Sample records for alpha-chlorohydrin-induced infertile rats

  1. Genome-wide profiling of gene expression in the epididymis of alpha-chlorohydrin-induced infertile rats using an oligonucleotide microarray

    PubMed Central

    2010-01-01

    Background As one of the chlorinated antifertility compounds, alpha-chlorohydrin (ACH) can inhibit glyceraldehyde-3-phosphate dehydrogenase (G3PDH) activity in epididymal sperm and affect sperm energy metabolism, maturation and fertilization, eventually leading to male infertility. Further studies demonstrated that the inhibitory effect of ACH on G3PDH is not only confined to epididymal sperm but also to the epididymis. Moreover, little investigation on gene expression changes in the epididymis after ACH treatment has been conducted. Therefore, gene expression studies may indicate new epididymal targets related to sperm maturation and fertility through the analysis of ACH-treated infertile animals. Methods Rats were treated with ACH for ten consecutive days, and then each male rat copulated with two female rats in proestrus. Then sperm maturation and other fertility parameters were analyzed. Furthermore, we identified epididymal-specific genes that are associated with fertility between control and ACH groups using an Affymetrix Rat 230 2.0 oligo-microarray. Finally, we performed RT-PCR analysis for several differentially expressed genes to validate the alteration in gene expression observed by oligonucleotide microarray. Results Among all the differentially expressed genes, we analyzed and screened the down-regulated genes associated with metabolism processes, which are considered the major targets of ACH action. Simultaneously, the genes that were up-regulated by chlorohydrin were detected. The genes that negatively regulate sperm maturation and fertility include apoptosis and immune-related genes and have not been reported previously. The overall results of PCR analysis for selected genes were consistent with the array data. Conclusions In this study, we have described the genome-wide profiles of gene expression in the epididymides of infertile rats induced by ACH, which could become potential epididymal specific targets for male contraception and infertility

  2. Genome-wide profiling of gene expression in the epididymis of alpha-chlorohydrin-induced infertile rats using an oligonucleotide microarray.

    PubMed

    Xie, Shuwu; Zhu, Yan; Ma, Li; Lu, Yingying; Zhou, Jieyun; Gui, Youlun; Cao, Lin

    2010-04-22

    As one of the chlorinated antifertility compounds, alpha-chlorohydrin (ACH) can inhibit glyceraldehyde-3-phosphate dehydrogenase (G3PDH) activity in epididymal sperm and affect sperm energy metabolism, maturation and fertilization, eventually leading to male infertility. Further studies demonstrated that the inhibitory effect of ACH on G3PDH is not only confined to epididymal sperm but also to the epididymis. Moreover, little investigation on gene expression changes in the epididymis after ACH treatment has been conducted. Therefore, gene expression studies may indicate new epididymal targets related to sperm maturation and fertility through the analysis of ACH-treated infertile animals. Rats were treated with ACH for ten consecutive days, and then each male rat copulated with two female rats in proestrus. Then sperm maturation and other fertility parameters were analyzed. Furthermore, we identified epididymal-specific genes that are associated with fertility between control and ACH groups using an Affymetrix Rat 230 2.0 oligo-microarray. Finally, we performed RT-PCR analysis for several differentially expressed genes to validate the alteration in gene expression observed by oligonucleotide microarray. Among all the differentially expressed genes, we analyzed and screened the down-regulated genes associated with metabolism processes, which are considered the major targets of ACH action. Simultaneously, the genes that were up-regulated by chlorohydrin were detected. The genes that negatively regulate sperm maturation and fertility include apoptosis and immune-related genes and have not been reported previously. The overall results of PCR analysis for selected genes were consistent with the array data. In this study, we have described the genome-wide profiles of gene expression in the epididymides of infertile rats induced by ACH, which could become potential epididymal specific targets for male contraception and infertility treatment.

  3. Ameliorative effects of pine bark extract on spermatotoxicity by α-chlorohydrin in rats.

    PubMed

    Kim, Sung-Hwan; Lee, In-Chul; Baek, Hyung-Seon; Moon, Changjong; Bae, Chun-Sik; Kim, Sung-Ho; Park, Seung-Chun; Kim, Hyoung-Chin; Kim, Jong-Choon

    2014-03-01

    We investigated the protective effects of pine bark extract (Pycnogenol®, PYC, Horphag Research Ltd., Route de Belis, France) against α-chlorohydrin (ACH)-induced spermatotoxicity in rats. Rats were orally administered ACH (30 mg/kg/day) with or without PYC (20 mg/kg/day) for 7 days. Administration of ACH significantly decreased sperm motility. α-Chlorohydrin also caused histopathological alterations and apoptotic changes in caput epididymides. An increased malondialdehyde concentration and decreased glutathione content, as well as catalase and glutathione peroxidase activities were also found. In contrast, PYC treatment significantly prevented ACH-induced spermatotoxicity, including decreased sperm motility, histopathological lesions, and apoptotic changes in the caput epididymis. Pycnogenol® also had an antioxidant benefit by decreasing malondialdehyde and increasing levels of the antioxidant glutathione and the activities of the antioxidant enzymes catalase and peroxidase in epididymal tissues. These results indicate that PYC treatment attenuated ACH-induced spermatotoxicity through antioxidant and antiapoptotic effects. Copyright © 2013 John Wiley & Sons, Ltd.

  4. (S)-α-Chlorohydrin Inhibits Protein Tyrosine Phosphorylation through Blocking Cyclic AMP - Protein Kinase A Pathway in Spermatozoa

    PubMed Central

    Zheng, Weiwei; Yang, Bei; Pi, Jingbo; He, Gengsheng; Qu, Weidong

    2012-01-01

    α-Chlorohydrin is a common contaminant in food. Its (S)-isomer, (S)-α-chlorohydrin (SACH), is known for causing infertility in animals by inhibiting glycolysis of spermatozoa. The aim of present work was to examine the relationship between SACH and protein tyrosine phosphorylation (PTP), which plays a critical role in regulating mammalian sperm capacitation. In vitro exposure of SACH 50 µM to isolated rat epididymal sperm inhibited PTP. Sperm-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDS) activities, the intracellular adenosine 5′-triphosphate (ATP) levels, 3′-5′-cyclic adenosine monophosphate (cAMP) levels and phosphorylation of protein kinase A (PKA) substrates in rat sperm were diminished dramatically, indicating that both glycolysis and the cAMP/PKA signaling pathway were impaired by SACH. The inhibition of both PTP and phosphorylation of PKA substrates by SACH could be restored by addition of cAMP analog dibutyryl-cAMP (dbcAMP) and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Moreover, addition of glycerol protected glycolysis, ATP levels, phosphorylation of PKA substrates and PTP against the influence of SACH. These results suggested SACH inhibited PTP through blocking cAMP/PKA pathway in sperm, and PTP inhibition may play a role in infertility associated with SACH. PMID:22916194

  5. (S)-α-chlorohydrin inhibits protein tyrosine phosphorylation through blocking cyclic AMP - protein kinase A pathway in spermatozoa.

    PubMed

    Zhang, Hao; Yu, Huan; Wang, Xia; Zheng, Weiwei; Yang, Bei; Pi, Jingbo; He, Gengsheng; Qu, Weidong

    2012-01-01

    α-Chlorohydrin is a common contaminant in food. Its (S)-isomer, (S)-α-chlorohydrin (SACH), is known for causing infertility in animals by inhibiting glycolysis of spermatozoa. The aim of present work was to examine the relationship between SACH and protein tyrosine phosphorylation (PTP), which plays a critical role in regulating mammalian sperm capacitation. In vitro exposure of SACH 50 µM to isolated rat epididymal sperm inhibited PTP. Sperm-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDS) activities, the intracellular adenosine 5'-triphosphate (ATP) levels, 3'-5'-cyclic adenosine monophosphate (cAMP) levels and phosphorylation of protein kinase A (PKA) substrates in rat sperm were diminished dramatically, indicating that both glycolysis and the cAMP/PKA signaling pathway were impaired by SACH. The inhibition of both PTP and phosphorylation of PKA substrates by SACH could be restored by addition of cAMP analog dibutyryl-cAMP (dbcAMP) and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Moreover, addition of glycerol protected glycolysis, ATP levels, phosphorylation of PKA substrates and PTP against the influence of SACH. These results suggested SACH inhibited PTP through blocking cAMP/PKA pathway in sperm, and PTP inhibition may play a role in infertility associated with SACH.

  6. Efficacy of alpha-chlorhydrin in sewer rat control.

    PubMed Central

    Andrews, R. V.; Belknap, R. W.

    1983-01-01

    A single application of the male chemosterilant, alpha-chlorhydrin, to a problem sewer rat infestation resulted in reductions of rat numbers and distribution which was comparable to effects of warfarin baiting methods. Rat numbers were reduced by more than 85% by both methods. More rapid mortality and recruitment were evident for warfarin effects; the alpha-chlorhydrin treated population had a longer lag phase of growth so that reinfestation of sewer habitat to pre-treatment numbers, and distribution over a 40 square block area, required approximately 1.5-2 times longer after alpha-chlorhydrin treatment when compared with warfarin treatment. Comparisons of changes in rat densities in infested sewers following the two treatments indicate that recovery of warfarin treated populations is achieved by reproductive recruitment followed by dispersal while alpha-chlorhydrin treated populations recover by slower immigration and later reproductive recruitment. Alpha-chlorohydrin should be a useful addition to a limited arsenal of rat control agents because of its specificity for the Norway rat, its single dose effectiveness as a toxicant-chemosterilant, and its short environmental half-life. PMID:6644013

  7. Spermatotoxic effects of α-chlorohydrin in rats

    PubMed Central

    Kim, Sung-Hwan; Lee, In-Chul; Lim, Jeong-Hyeon; Moon, Changjong; Bae, Chun-Sik; Kim, Sung-Ho; Shin, Dong-Ho; Kim, Hyoung-Chin

    2012-01-01

    This study was conducted to investigate the potential effects of α-chlorohydrin (ACH) on epididymal function and antioxidant system in male rats. The test chemical was administered to male rats by gavage at doses of 0, 3, 10, and 30 mg/kg/day for 7 days. Twenty-four male rats were randomly assigned to four experimental groups, with six rats in each group. Spermatotoxicity was assessed by measurement of reproductive organ weight, testicular sperm head count, epididymal sperm motility and morphology, histopathologic examination, and oxidative damage analysis in rats. At 30 mg/kg/day, an increase in the incidence of clinical signs, epididymis weight, and gross necropsy findings of the epididymis, a decrease in the sperm motility, and an increased incidence of histopathological changes of the epididymis were observed in a dose-dependent manner. At 10 mg/kg/day, an increased incidence of clinical signs and histopathological changes and decreased sperm motility were observed. In the oxidative damage analysis, an increase in the malondialdehyde concentration and a decrease in the glutathione content and glutathione peroxidase and catalase activities in the epididymal tissue were detected at ≥3 mg/kg/day. The results show that graded doses of ACH elicit depletion of the antioxidant defense system and that the spermatotoxicity of ACH may be due to the induction of oxidative stress. PMID:22474469

  8. Evaluating the anti-fertility potential of α-chlorohydrin on testis and spermatozoa in the adult male wild Indian house rat (Rattus rattus).

    PubMed

    Madhu, Nithar Ranjan; Sarkar, Bhanumati; Biswas, Surjyo Jyoti; Behera, Biplab Kumar; Patra, Ashis

    2011-01-01

    To examine the effects of α-chlorohydrin on testis and cauda epididymis in the male house rat (Rattus rattus), 24 adult male rats were segregated into two groups. Group I rats were force-fed daily by intragastric intubation with α-chlorohydrin at a single dose of 1.0 mg/100 g body weight/d for 5, 15, and 45 days. Another group was fed with distilled water, which served as the control. The treated male rats were paired with 24 adult proestrus female rats for 5 days after the last oral treatment and fertility was tested. At the end of the experiments, all of the male rats were weighed and killed by cervical dislocation. The right testes were removed, weighed, and processed for ultrastructural changes of spermatozoa from the cauda epididymis and testis under scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The seminiferous tubular area, nuclear diameter of the Sertoli and Leydig cells, percentage of spermatogonia, primary spermatocytes, secondary spermatocytes, spermatids, spermatozoa, and Sertoli cells in each group were compared morphometrically. Our results showed that the percentages of primary spermatocytes steadily increased from 5 to 15 days, but primary and secondary spermatocytes decreased significantly at 45 days. There was a steady decline in the percentages of spermatozoa and spermatids at all fixation intervals in the treated animals, but the percentages of spermatogonia and Sertoli cells increased significantly at 15 and 45 days. Seminiferous tubular areas, nuclear diameter of Leydig and Sertoli cells, and fertility rates were reduced after 45 days of treatment. SEM and TEM studies revealed severe morphological abnormalities in the spermatozoa, including deglutination of the acrosomal part, loss of head capsules, and fragmentation of tail fibrils. There was an enhanced anti-fertility effect and a lower number of implantation sites in the rats treated for 5 days. Our results validate α-chlorohydrin as a successful anti

  9. Improvement of sperm density in neem-oil induced infertile male albino rats by Ipomoea digitata Linn.

    PubMed

    Mahajan, Ghanashyam Keshav; Mahajan, Raghunath Totaram; Mahajan, Arun Y

    2015-01-01

    Investigation has been carried out to validate folkloric claim of the potential of Ipomoea digitata (ID) based on reproductive health status in experimentally induced male albino rats. Emulsified neem oil fed albino rats were orally administered root powder of ID suspended in water for the doses of 250 and 500 mg/kg body weight for 40 days. Change in organ weight, sperm density and motility, serum hormonal levels and histomorphological changes were evaluated. Significant increase in the sperm density and the sperm motility (P < 0.01) along with increase in the testis, and epididymes weight in neem-oil induced infertile rats treated with ID at both dose levels. This effect is vis-à-vis to serum hormonal levels. Presence of β-sitosterol in the root of ID likely to enhance the process of spermatogenesis as it is evident from histomorphological studies. Results of the present investigation reveal that ID is a good candidate for the management of male infertility.

  10. Mode of action of α-chlorohydrin as a male anti-fertility agent. Inhibition of the metabolism of ram spermatozoa by α-chlorohydrin and location of block in glycolysis

    PubMed Central

    Brown-Woodman, Patricia D. C.; Mohri, Hideo; Mohri, Toshiko; Suter, Dai; White, Ian G.

    1978-01-01

    1. The effect of α-chlorohydrin on the metabolism of glycolytic and tricarboxylate-cycle substrates by ram spermatozoa was investigated. The utilization and oxidation of fructose and triose phosphate were much more sensitive to inhibition by α-chlorohydrin (0.1–1.0mm) than lactate or pyruvate. Inhibition of glycolysis by α-chlorohydrin is concluded to be between triose phosphate and pyruvate formation. Oxidation of glycerol was not as severely inhibited as that of the triose phosphate. This unexpected finding can be explained in terms of competition between glycerol and α-chlorohydrin. A second, much less sensitive site, of α-chlorohydrin inhibition appears to be associated with production of acetyl-CoA from exogenous and endogenous fatty acids. 2. Measurement of the glycolytic intermediates after incubation of spermatozoal suspensions with 15mm-fructose in the presence of 3mm-α-chlorohydrin showed a `block' in the conversion of glyceraldehyde 3-phosphate into 3-phosphoglycerate. α-Chlorohydrin also caused conversion of most of the ATP in spermatozoa into AMP. After incubation with 3mm-α-chlorohydrin, glyceraldehyde 3-phosphate dehydrogenase and triose phosphate isomerase activities were decreased by approx. 90% and 80% respectively, and in some experiments aldolase was also inhibited. Other glycolytic enzymes were not affected by a low concentration (0.3mm) of α-chlorohydrin. Loss of motility of spermatozoa paralleled the decrease in glyceraldehyde 3-phosphate dehydrogenase activity. α-Chlorohydrin, however, did not inhibit glyceraldehyde 3-phosphate dehydrogenase or triose phosphate isomerase in sonicated enzyme preparations when added to the assay cuvette. 3. Measurement of intermediates and glycolytic enzymes in ejaculated spermatozoa before, during and after injection of rams with α-chlorohydrin (25mg/kg body wt.) confirmed a severe block in glycolysis in vivo at the site of triose phosphate conversion into 3-phosphoglycerate within 24h of the

  11. Effects of alpha lipoic acid on acrylamide-induced hepatotoxicity in rats.

    PubMed

    Al-Qahtani, F A; Arafah, M; Sharma, B; Siddiqi, N J

    2017-07-31

    Acrylamide (ACR) is a neurotoxicant, reproductive toxicant, and carcinogen in animal species.  It is used in many industries and has been found to form naturally in foods cooked at high temperatures. Alpha-lipoic acid (ALA) is a naturally occurring antioxidant whose therapeutic effect has been related to its antioxidant activity.  This study was carried out to study the protective effect of alpha lipoic acid on acrylamide induced perturbations in rat liver.  Four groups of rats were studied viz., control rats, acrylamide treated rats, alpha lipoic acid treated rats, and alpha lipoic acid plus acrylamide treated rats. ACR and ALA treatment alone and together caused a signifi-cant increase in hepatic reduced glutathione content while a decrease in hepatic ascorbic content was observed when compared to control group.  ALA pretreatment of acrylamide exposed rats caused no a signifi-cant alteration in superoxide dismutase activity but resulted in a tendency towards restoration of glutathione peroxidase and catalase activity to near normal levels.  Gel electrophoresis showed fragmentation of DNA in the treated groups.  The dose of ALA used in the present study afforded partial restoration of oxidative indices altered by ACR in rat liver.

  12. Alpha-lipoic acid treatment of acetaminophen-induced rat liver damage.

    PubMed

    Mahmoud, Y I; Mahmoud, A A; Nassar, G

    2015-01-01

    Acetaminophen (paracetamol) is a well-tolerated analgesic and antipyretic drug when used at therapeutic doses. Overdoses, however, cause oxidative stress, which leads to acute liver failure. Alpha lipoic acid is an antioxidant that has proven effective for ameliorating many pathological conditions caused by oxidative stress. We evaluated the effect of alpha lipoic acid on the histological and histochemical alterations of liver caused by an acute overdose of acetaminophen in rats. Livers of acetaminophen-intoxicated rats were congested and showed centrilobular necrosis, vacuolar degeneration and inflammatory cell infiltration. Necrotic hepatocytes lost most of their carbohydrates, lipids and structural proteins. Liver sections from rats pre-treated with lipoic acid showed fewer pathological changes; the hepatocytes appeared moderately vacuolated with moderate staining of carbohydrates and proteins. Nevertheless, alpha lipoic acid at the dose we used did not protect the liver fully from acetaminophen-induced acute toxicity.

  13. Protective effect of mirtazapine and hesperidin on cyclophosphamide-induced oxidative damage and infertility in rat ovaries

    PubMed Central

    2015-01-01

    Cyclophosphamide (CP) causes infertility due to ovarian toxicity. The toxicity mechanism suggests oxidative stress. We assessed whether mirtazapine (MTZ) and hesperidin (HSP) could promote ovarian protection against damage due to CP chemotherapy. Female Wistar rats aged 14 weeks were used. Animals were divided into four groups: control vehicle group (n = 8); CP group (n = 8, rats received 150 mg/kg of CP, single intraperitoneal [i.p.] injection); CP + MTZ group (n = 8, rats received same dose of CP + 30 mg/kg of MTZ, orally, daily); and HSP + CP group (n = 8, rats received same dose of CP + 100 mg/kg of HSP, orally, daily). After eight days of medication, ovaries were removed and ovarian toxicity was assessed by counting follicles and corpora lutea. Nitric oxide (NO) and malondialdehyde (MDA) levels, myeloperoxidase (MPO), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities were estimated in ovarian tissue. NO level, MDA level, and MPO activity were increased (P < 0.001), while, GPx and SOD activities were lowered significantly (P < 0.001) in CP-treated group compared with control vehicle. In addition, ovulation, number of follicles, and ovarian weight were reduced by CP treatment. On the contrary, rats pretreated with MTZ and HSP showed significant decrease in NO, MDA levels, and MPO activity, while, activities of SOD and GPx were increased (P < 0.001). Oxidative stress induced by CP in the rat ovary causes infertility in the female rats. HSP and MTZ could reverse this effect and provide protection of fertility against CP-induced toxicity. PMID:25787947

  14. Interleukin 1 alpha-induced expression of manganous superoxide dismutase reduces myocardial reperfusion injury in the rat.

    PubMed

    Nogae, C; Makino, N; Hata, T; Nogae, I; Takahashi, S; Suzuki, K; Taniguchi, N; Yanaga, T

    1995-10-01

    We investigated the effects of pretreatment with interleukin (IL)-1 alpha on the expression of manganous (Mn) superoxide dismutase (SOD) mRNA and reperfusion-induced arrhythmias and the size of myocardial infarct in rats. Male Wistar rats received 10 mg intraperitoneal injections of human recombinant IL-1 alpha. Their hearts were thereafter isolated at 6, 12, 24, 36 h. A Northern analysis showed that Mn-SOD mRNA was mainly expressed in the heart and slightly in kidney, but not in any other organs. The expression of Mn-SOD mRNA peaked at 6 h after the injection of IL-1 alpha. The Mn-SOD protein content was most increased 12 h after injection. In the isolated heart model, the rats were pretreated with IL-1 alpha 24 h earlier and their hearts were perfused by the Langendorff method. After 20 min of ischemia which was induced by a ligation of a coronary artery, reperfusion-induced arrhythmias were observed. There were no significant differences in the incidence of ventricular arrhythmias between the IL-1 alpha pretreated and the untreated hearts. IL-1 alpha pretreatment significantly reduced the mean duration of the ventricular arrhythmias and also delayed the onset of arrhythmias. The effect of IL-1 alpha pretreatment was also investigated in a 30-min model of ischemia followed by a 3-min reperfusion in anesthetized rats. The infarct size expressed as a percentage of the area at risk was significantly reduced in the IL-1 alpha pretreated hearts compared with the untreated hearts. The left ventricular systolic pressure increased significantly in rat hearts pretreated with IL-1 alpha. Our results therefore showed that the pretreatment with IL-1 alpha induced the overexpression of Mn-SOD mRNA in the rat hearts and also suggested that pretreatment with IL-1 alpha 24 h before ischemia reduced the risk of ischemia-reperfusion injury.

  15. Effects of Cynodon dactylon on Stress-Induced Infertility in Male Rats

    PubMed Central

    Chidrawar, VR; Chitme, HR; Patel, KN; Patel, NJ; Racharla, VR; Dhoraji, NC; Vadalia, KR

    2011-01-01

    Cynodon dactylon (Family: Poaceae) is known to be a tackler in Indian mythology and is offered to Lord Ganesha. It is found everywhere, even on waste land, road side, dry places, and spreads vigorously on cultivated ground. This study was carried out with an objective to test if the constituents of this plant are useful in coping stress-induced sexual In this study, we considered immobilization stress to induce male infertility and the effect of C. dactylon in restoration of the dysfunction was evaluated by considering sexual behavioral observations, sexual performance, fructose content of the seminal vesicles, epididymal sperm concentration and histopathological examinations as parameters. Treatment of rats under stress with methanolic extract of C. dactylon has shown a promising effect in overcoming stress-induced sexual dysfunction, sexual performance, fructose content, sperm concentration and its effect on accessory sexual organs and body weight. We conclude that active constituents of C. dactylon present in methanolic extract have a potent aphrodisiac and male fertility activity. PMID:21607051

  16. Aging increases amyloid beta-peptide-induced 8-iso-prostaglandin F2alpha release from rat brain.

    PubMed

    Brunetti, Luigi; Michelotto, Barbara; Orlando, Giustino; Recinella, Lucia; Di Nisio, Chiara; Ciabattoni, Giovanni; Vacca, Michele

    2004-01-01

    In order to investigate whether amyloid beta-peptide-induced oxidative damage in the brain could be related to aging, we studied the release of 8-iso-prostaglandin (PG)F2alpha, a stable marker of cellular oxidative stress, in brain synaptosomes from Wistar rats of different ages (3, 6, 12, 18 months old), both basally and after amyloid beta-peptide (1-40) perfusion. We found that basal release of 8-iso-PGF2alpha was not significantly different among all age groups of rats. Either phospholipase A2 activation induced by calcium ionophore A23187 (10 nM) or amyloid beta-peptide (5 microM) did not modify isoprostane release, when these substances were used alone. In contrast, amyloid beta-peptide (1-5 microM) preincubation caused a dose-dependent increase of A23187-stimulated 8-iso-PGF2alpha release in each age group, which was also strikingly correlated to aging of rats. Furthermore, ferric ammonium sulfate stimulates isoprostane production to levels comparable to those induced by amyloid beta-peptide. In conclusion, although 8-iso-PGF2alpha production from rat brain synaptosomes is independent from aging in the basal state, aging renders neurons more vulnerable to amyloid beta-peptide-induced oxidative toxicity.

  17. [Induction of hypoxia-inducible factor-1alpha in two kinds of rats asphyxiation death models].

    PubMed

    Zhang, Bei-lei; Yang, Zhi-hui; Ran, Peng; Liang, Wei-bo; Zhou, Bin; Zhang, Geng-qian; Lu, Mei-li; Zhang, Lin

    2007-02-15

    To investigate the expression of hypoxia-inducible factor 1-alpha (HIF1-alpha) in the heart, lung, liver and kidney in rats died of two typical models of asphyxia. Two asphyxia models were made and tissue samples of the dead rats were collected from different groups at various postmortem duration. The expression and the changes of HIF1-alpha in various tissues were examined by immunohistochemistry and image analysis techniques. Results Significant expression of HIF1-alpha was observed in the myocardial fibers, kidney cells, liver cells and lung cells in both asphyxia models, but not in the control group. The expression of HIF1-alpha in various tissues in the rat died of nitrogen gas breathing was found in the nuclei at 0 hour and the expression level decreased gradually thereafter. The HIF1-alpha expression level and duration in various tissues of the rat died of hanging were higher and longer than that of the former group, with a peak of the expression level observed 6 hours after death, and then started to decline in all tissues except the heart where the expression still showed an increase 24 hours after death. The control groups showed a steady expression in the cytoplasm but not in the nuclei. HIF1-alpha appears to be a valuable biomarker in the diagnosis of asphyxia within 24 hours after death.

  18. A diet containing the soy phytoestrogen genistein causes infertility in female rats partially deficient in UDP glucuronyltransferase

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Seppen, Jurgen, E-mail: j.seppen@amc.uva.nl

    Soy beans contain genistein, a natural compound that has estrogenic effects because it binds the estrogen receptor with relatively high affinity. Genistein is therefore the most important environmental estrogen in the human diet. Detoxification of genistein is mediated through conjugation by UDP-glucuronyltransferase 1 and 2 (UGT1 and UGT2) isoenzymes. Gunn rats have a genetic deficiency in UGT1 activity, UGT2 activities are not affected. Because our Gunn rats stopped breeding after the animal chow was changed to a type with much higher soy content, we examined the mechanism behind this soy diet induced infertility. Gunn and control rats were fed dietsmore » with and without genistein. In these rats, plasma levels of genistein and metabolites, fertility and reproductive parameters were determined. Enzyme assays showed reduced genistein UGT activity in Gunn rats, as compared to wild type rats. Female Gunn rats were completely infertile on a genistein diet, wild type rats were fertile. Genistein diet caused a persistent estrus, lowered serum progesterone and inhibited development of corpora lutea in Gunn rats. Concentrations of total genistein in Gunn and control rat plasma were identical and within the range observed in humans after soy consumption. However, Gunn rat plasma contained 25% unconjugated genistein, compared to 3.6% in control rats. This study shows that, under conditions of reduced glucuronidation, dietary genistein exhibits a strongly increased estrogenic effect. Because polymorphisms that reduce UGT1 expression are prevalent in the human population, these results suggest a cautionary attitude towards the consumption of large amounts of soy or soy supplements. -- Highlights: ► Gunn rats are partially deficient in detoxification by UDP glucuronyltransferases. ► Female Gunn rats are infertile on a soy containing diet. ► Soy contains genistein, a potent phytoestrogen. ► Inefficient glucuronidation of genistein causes female infertility.« less

  19. Occurrence of fatty acid chlorohydrins in jellyfish lipids.

    PubMed

    White, R H; Hager, L P

    1977-11-01

    Fatty acid chlorohydrins are characterized as lipid components of an edible jellyfish. The four isomers 9-chloro-10-hydroxypalmitic acid, 10-chloro-9-hydroxypalmitic acid, 9-chloro-10-hydroxystearic acid, and 10-chloro-9-hydroxystearic acid were identified by gas chromatography-mass spectrometry comparison of the methyl esters and their trimethylsilyl derivatives with known synthetic samples. Two additional isomers, 11-chloro-12-hydroxystearic acid and 12-chloro-11-hydroxystearic acid, were also found in the lipid by the identification of the expected mass spectral fragments of the trimethylsilyl (Me3Si) derivative of their methyl esters. These six isomeric compounds represented approximately 1.4% of the total extractable jellyfish lipid and were released from the lipid as methyl esters by boron trifluoride-methanol treatment. These isomers account for only about 30% of the organic chlorine in the lipid. Evidence is given that the remaining organic chlorine is also present as fatty acid chlorohydrins containing more than one hydroxyl group.

  20. A Role for Presynaptic alpha(sub 2)-Adrenoceptors in Angiotensin 2-Induced Drinking in Rats

    NASA Technical Reports Server (NTRS)

    Fregly, Melvin J.; Rowland, Neil E.; Greenleaf, John E.

    1984-01-01

    Studies from this laboratory have shown that either central or peripheral administration of clonidine, the alpha(sub 2)-adrenoceptor agonist, can attenuate a variety of dipsogenic stimuli in rats. Further, yohimbine and tolazoline, alpha(sub 2)-adrenoceptor antagonists, augment the drinking response to both peripherally administered isoproterenol and angiotensin 2. Studies reported here establish a dose-inhibition relationship between the dose of clonidine administered (2 to 32 micrograms/kg) intracerebroventricularly (IVT) and inhibition of the drinking response to peripherally administered angiotensin 2 (200 micrograms/kg, SC). DI(sub 50) was approximately 4 micrograms/kg. Yohimbine (300 micrograms/kg, SC) reversed the antidipsogenic effect of centrally administered clonidine (32 micrograms/kg, IVT) on angiotensin 2-induced (200 micrograms/kg, SC) water intake. Phenylephrine, an alpha(sub 2)-adrenoceptor agonist, administered IVT (40 and 80 micrograms/kg) also inhibited angiotensin 2-induced drinking in a dose-related fashion. The antidipsogenic effect of phenylephfine (80 micrograms/kg) was blocked by administration of yohimbine (100 micrograms/kg, SC). Thus, this effect of phenylephrine most likely occurs by way of alpha(sub 2)- adrenoceptors. These results support a role for the pre-synaptic alpha(sub 2)-adrenoceptor in the mediation of drinking in rats. Activation of alpha(sub 2)-adrenoceptors is accompanied by reduced water intake while inhibition of these receptors enhances water intake.

  1. Transforming growth factor-alpha stimulates enterocyte proliferation and accelerates intestinal recovery following methotrexate-induced intestinal mucositis in a rat and a cell culture model.

    PubMed

    Sukhotnik, Igor; Shteinberg, Dan; Ben Lulu, Shani; Bashenko, Yulia; Mogilner, Jorge G; Ure, Benno M; Shaoul, Ron; Shamian, Benhoor; Coran, Arnold G

    2008-12-01

    Recent evidence suggests that transforming growth factor-alpha (TGF-alpha) enhances enterocyte proliferation and exerts a gut trophic effect. The purpose of the present study was to evaluate the effect of TGF-alpha on enterocyte proliferation and intestinal recovery following methotrexate (MTX)-induced intestinal mucositis in rats and in Caco-2 cells. Nonpretreated Caco-2 cells and those pretreated with MTX were incubated with increasing concentrations of TGF-alpha. Cell proliferation was determined by FACS cytometry. Adult rats were divided into three groups: control rats treated with vehicle, MTX rats treated with one dose (20 microg/kg) of MTX given intraperitoneally, and MTX-TGF-alpha rats treated with one dose of MTX followed by two doses of TGF-alpha (75 microg/kg a day). Three days after MTX injection, rats were sacrificed. Intestinal mucosal damage (Park's score), mucosal structural changes, and enterocyte proliferation were measured at sacrifice. Western blotting was used to determine the level of extracellular signal-related kinase (ERK) protein, a marker of cell proliferation. A nonparametric Kruskal-Wallis ANOVA test was used for statistical analysis with P value less than 0.05 considered statistically significant. The in vitro experiment demonstrated that treatment with TGF-alpha of Caco-2 cells resulted in a significant stimulation of cell proliferation in a dose-dependent manner. The in vivo experiment showed that treatment with TGF-alpha resulted in a significant increase in bowel and mucosal weight, DNA and protein content in jejunum and ileum, villus height in jejunum and ileum, crypt depth in ileum, and increased cell proliferation in jejunum and ileum compared to the MTX group. MTX-TGF-alpha rats also had a significantly lower intestinal injury score in ileum when compared to MTX animals. The increase in levels of cell proliferation in MTX-TGF-alpha rats corresponded with the increase in ERK protein levels in intestinal mucosa. Treatment with

  2. LH responses to single doses of exogenous GnRH by social Mashona mole-rats: a continuum of socially induced infertility in the family Bathyergidae.

    PubMed Central

    Bennett, N C; Faulkes, C G; Spinks, A C

    1997-01-01

    The Mashona mole-rat, Cryptomys darlingi, exhibits an extreme reproductive division of labour. Reproduction in the colony is restricted to a single breeding pair. The non-reproductive male and female colony members are restrained from sexual activity by being familiar and related to one another and the reproductive animals. Circulating basal concentrations of luteinizing hormone (LH) as well as LH levels measured in response to a single exogenous gonadotropin releasing hormone (GnRH) challenge are not significantly different between the reproductive and non-reproductive groups of either sex. Socially induced infertility in both non-reproductive males and females does not result from a reduced pituitary secretion of LH or decreased sensitivity to hypothalamic GnRH, but rather appears to result from an inhibition of reproductive behaviour in these obligate outbreeders. The African mole-rats exhibit a continuum of socially induced infertility with differing social species inhabiting regions of varying degrees of aridity. In this continuum a transition from a predominantly behavioural repression in a social mesic-adapted species through to complete physiological suppression lacking incest avoidance in an arid-adapted eusocial species occurs in this endemic African family of rodents. PMID:9263467

  3. LH responses to single doses of exogenous GnRH by social Mashona mole-rats: a continuum of socially induced infertility in the family Bathyergidae.

    PubMed

    Bennett, N C; Faulkes, C G; Spinks, A C

    1997-07-22

    The Mashona mole-rat, Cryptomys darlingi, exhibits an extreme reproductive division of labour. Reproduction in the colony is restricted to a single breeding pair. The non-reproductive male and female colony members are restrained from sexual activity by being familiar and related to one another and the reproductive animals. Circulating basal concentrations of luteinizing hormone (LH) as well as LH levels measured in response to a single exogenous gonadotropin releasing hormone (GnRH) challenge are not significantly different between the reproductive and non-reproductive groups of either sex. Socially induced infertility in both non-reproductive males and females does not result from a reduced pituitary secretion of LH or decreased sensitivity to hypothalamic GnRH, but rather appears to result from an inhibition of reproductive behaviour in these obligate outbreeders. The African mole-rats exhibit a continuum of socially induced infertility with differing social species inhabiting regions of varying degrees of aridity. In this continuum a transition from a predominantly behavioural repression in a social mesic-adapted species through to complete physiological suppression lacking incest avoidance in an arid-adapted eusocial species occurs in this endemic African family of rodents.

  4. Inhibition of HIF-1{alpha} activity by BP-1 ameliorates adjuvant induced arthritis in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shankar, J.; Thippegowda, P.B., E-mail: btprabha@uic.edu; Kanum, S.A.

    Rheumatoid arthritis (RA) is a chronic inflammatory, angiogenic disease. Inflamed synovitis is a hallmark of RA which is hypoxic in nature. Vascular endothelial growth factor (VEGF), one of the key regulators of angiogenesis, is overexpressed in the pathogenesis of RA. VEGF expression is regulated by hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), a master regulator of homeostasis which plays a pivotal role in hypoxia-induced angiogenesis. In this study we show that synthetic benzophenone analogue, 2-benzoyl-phenoxy acetamide (BP-1) can act as a novel anti-arthritic agent in an experimental adjuvant induced arthritis (AIA) rat model by targeting VEGF and HIF-1{alpha}. BP-1 administered hypoxic endothelial cells andmore » arthritic animals clearly showed down regulation of VEGF expression. Further, BP-1 inhibits nuclear translocation of HIF-1{alpha}, which in turn suppresses transcription of the VEGF gene. These results suggest a further possible clinical application of the BP-1 derivative as an anti-arthritic agent in association with conventional chemotherapeutic agents.« less

  5. 5-Methoxy-N,N-dimethyltryptamine-induced analgesia is blocked by alpha-adrenoceptor antagonists in rats.

    PubMed Central

    Archer, T.; Danysz, W.; Jonsson, G.; Minor, B. G.; Post, C.

    1986-01-01

    The effects of the alpha-adrenoceptor antagonists prazosin, phentolamine and yohimbine upon 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)-induced analgesia were tested in the hot-plate, tail-flick and shock-titration tests of nociception with rats. Intrathecally injected yohimbine and phentolamine blocked or attenuated the analgesia produced by systemic administration of 5-MeODMT in all three nociceptive tests. Intrathecally administered prazosin attenuated the analgesic effects of 5-MeODMT in the hot-plate and tail-flick tests, but not in the shock titration test. Intrathecal yohimbine showed a dose-related lowering of pain thresholds in saline and 5-MeODMT-treated animals. Phentolamine and prazosin produced normal dose-related curves in the hot-plate test and biphasic effects in the shock titration and tail-flick tests. These results demonstrate a functional interaction between alpha 2-adrenoceptors and 5-HT agonist-induced analgesia at a spinal level in rats. PMID:2877697

  6. [Effect of Xinmailong on hypoxia-inducible factor-1alpha expression in neonatal rats with asphyxia].

    PubMed

    Huang, Li-Xin; Wu, Xing-Heng

    2009-08-01

    Xinmailong, a compound extracted from Periplaneta americana, is used for the treatment of cardiovascular diseases. This study investigated the effects of Xinmailong on myocardial hypoxia-inducible factor-1alpha (HIF-1alpha) and plasma endothelin-1(ET-1) levels in neonatal rats with asphyxia and explored the protection mechanism of Xinmailong in hypoxia-ischemic myocardial injury. Seven-day-old Sprague-Dawley rats were randomly divided into three groups (n=30 each): sham-operated, asphyxia, Xinmailong-treated asphyxia. Each group was randomly subdivided into three groups according to the observed time points: 6 hrs, 24 hrs and 72 hrs. Xinmailong (5 mg/kg) was intraperitoneally injected to the rats in the Xinmailong-treated group five minutes before asphyxia. Myocardial HIF-1alpha expression, and plasma ET-1 and creatine kinase (CK) levels were measured. The histopathologic changes of the myocardium were observed by hematoxylin-eosin staining. Four rats died in the asphyxia group while only one died in the Xinmailong-treated group during the experiment. The plasma ET-1 and CK levels as well as myocardial HIF-1alpha expression increased at 6 hrs, reached a peak at 24 hrs, and declined at 72 hrs after asphyxia in the asphyxia group, being higher than that in the sham-operated group (P<0.01). Myocardial ischemia was observed in the three time points, and cell necrosis occurred at 24 hrs after asphyxia in the asphyxia group. Myocardial HIF-1alpha expression was positively correlated with plasma ET-1 levels (r=0.876, P<0.01). In the Xinmailong-treated group, plasma levels of CK and ET-1 as well as myocardial HIF-1alpha expression were significantly lower than those in the asphyxia group (P<0.01). Myocardial ischemia was alleviated and no cell necrosis was found in the Xinmailong-treated group. Asphyxia leads to increase in myocardial HIF-1alpha expression and plasma levels of ET-1 and CK. Xinmailong can reduce the myocardial expression of HIF-1alpha and decrease plasma ET

  7. Comparative gene expression profiles induced by PPAR{gamma} and PPAR{alpha}/{gamma} agonists in rat hepatocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rogue, Alexandra; Universite de Rennes 1, 35065 Rennes Cedex; Biologie Servier, 45520 Gidy

    2011-07-01

    Species-differential toxic effects have been described with PPAR{alpha} and PPAR{gamma} agonists between rodent and human liver. PPAR{alpha} agonists (fibrates) are potent hypocholesterolemic agents in humans while they induce peroxisome proliferation and tumors in rodent liver. By contrast, PPAR{gamma} agonists (glitazones) and even dual PPAR{alpha}/{gamma} agonists (glitazars) have caused idiosyncratic hepatic and nonhepatic toxicities in human without evidence of any damage in rodent during preclinical studies. The mechanisms involved in such differences remain largely unknown. Several studies have identified the major target genes of PPAR{alpha} agonists in rodent liver while no comprehensive analysis has been performed on gene expression changes inducedmore » by PPAR{gamma} and dual PPAR{alpha}/{gamma} agonists. Here, we investigated transcriptomes of rat hepatocytes after 24 h treatment with two PPAR{gamma} (troglitazone and rosiglitazone) and two PPAR{alpha}/{gamma} (muraglitazar and tesaglitazar) agonists. Although, hierarchical clustering revealed a gene expression profile characteristic of each PPAR agonist class, only a limited number of genes was specifically deregulated by glitazars. Functional analyses showed that many genes known as PPAR{alpha} targets were also modulated by both PPAR{gamma} and PPAR{alpha}/{gamma} agonists and quantitative differences in gene expression profiles were observed between these two classes. Moreover, most major genes modulated in rat hepatocytes were also found to be deregulated in rat liver after tesaglitazar treatment. Taken altogether, these results support the conclusion that differential toxic effects of PPAR{alpha} and PPAR{gamma} agonists in rodent liver do not result from transcriptional deregulation of major PPAR target genes but rather from qualitative and/or quantitative differential responses of a small subset of genes.« less

  8. Selective inhibition by chloramphenicol of pregnenolone-16. cap alpha. -carbonitrile-inducible rat liver cytochrome P-450 isozymes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Graves, P.E.; Kaminsky, L.S.; Halpert, J.

    Pregnenolone-16 ..cap alpha..-carbonitrile (PCN) has been shown to induce, in male rats, cytochrome P-450 isozymes responsible for the formation of R-10-hydroxywarfarin and R-dehydrowarfarin. Antibodies to the major PCN-inducible isozyme (PB/PCN-E) inhibit both activities in microsomal preparations. Recently the authors have shown that PCN treatment of female rats also induces the formation of both R-warfarin metabolites. However, in both sexes chloramphenicol (CAP) treatment selectively inhibits only the rate of formation of the R-dehydrowarfarin. A decrease in microsomal P-450 content occurs after in vivo administration of CAP to PCN-treated rats of both sexes. This is in contrast to the lack of effectmore » of CAP on P-450 levels in phenobarbital-treated rats. Covalent binding of /sup 14/C-CAP to microsomal protein in vitro was increased 3 to 4-fold following PCN treatment. Chromatographic evidences suggests the presence of at least two PCN-induced isozymes of similar molecular weights in both male and female rat liver microsomes. These data are consistent with the multiplicity of PCN-inducible P-450 in rat liver.« less

  9. Peroxisome proliferator-activated receptor {alpha} agonist-induced down-regulation of hepatic glucocorticoid receptor expression in SD rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen Xiang; Li Ming; Sun Weiping

    2008-04-18

    It was reported that glucocorticoid production was inhibited by fenofibrate through suppression of type-1 11{beta}-hydroxysteroid dehydrogenase gene expression in liver. The inhibition might be a negative-feedback regulation of glucocorticoid receptor (GR) activity by peroxisome proliferator-activated receptor alpha (PPAR{alpha}), which is quickly induced by glucocorticoid in the liver. However, it is not clear if GR expression is changed by fenofibrate-induced PPAR{alpha} activation. In this study, we tested this possibility in the liver of Sprague-Dawley rats. GR expression was reduced by fenofibrate in a time- and does-dependent manner. The inhibition was observed in liver, but not in fat and muscle. The corticosteronemore » level in the blood was increased significantly by fenofibrate. These effects of fenofibrate were abolished by PPAR{alpha} inhibitor MK886, suggesting that fenofibrate activated through PPAR{alpha}. In conclusion, inhibition of GR expression may represent a new molecular mechanism for the negative feedback regulation of GR activity by PPAR{alpha}.« less

  10. PPAR alpha and PPAR gamma coactivation rapidly induces Egr-1 in the nuclei of the dorsal and ventral urinary bladder and kidney pelvis urothelium of rats.

    PubMed

    Egerod, Frederikke Lihme; Svendsen, Jette Eldrup; Hinley, Jennifer; Southgate, Jennifer; Bartels, Annette; Brünner, Nils; Oleksiewicz, Martin B

    2009-12-01

    To facilitate studies of the rat bladder carcinogenicity of dual-acting PPAR alpha+gamma agonists, we previously identified the Egr-1 transcription factor as a candidate carcinogenicity biomarker and developed rat models based on coadministration of commercially available specific PPAR alpha and PPAR gamma agonists. Immunohistochemistry for Egr-1 with a rabbit monoclonal antibody demonstrated that male vehicle-treated rats exhibited minimal urothelial expression and specifically, no nuclear signal. In contrast, Egr-1 was induced in the nuclei of bladder, as well as kidney pelvis, urothelia within one day (2 doses) of oral dosing of rats with a combination of 8 mg/kg rosiglitazone and 200 mg/kg fenofibrate (specific PPAR gamma and PPAR alpha agonists, respectively). These findings were confirmed by Western blotting using a different Egr-1 antibody. Egr-1 was induced to similar levels in the dorsal and ventral bladder urothelium, arguing against involvement of urinary solids. Egr-1 induction sometimes occurred in a localized fashion, indicating physiological microheterogeneity in the urothelium. The rapid kinetics supported that Egr-1 induction occurred as a result of pharmacological activation of PPAR alpha and PPAR gamma, which are coexpressed at high levels in the rat urothelium. Finally, our demonstration of a nuclear localization supports that the Egr-1 induced by PPAR alpha and PPAR gamma coactivation in the rat urothelium may be biologically active.

  11. Functional coupling of rat myometrial alpha 1-adrenergic receptors to Gh alpha/tissue transglutaminase 2 during pregnancy.

    PubMed

    Dupuis, Morgan; Lévy, Arlette; Mhaouty-Kodja, Sakina

    2004-04-30

    Gh alpha protein, which exhibits both transglutaminase and GTPase activities, represents a new class of GTP-binding proteins. In the present study, we characterized Gh alpha in rat uterine smooth muscle (myometrium) and followed its expression during pregnancy by reverse transcription-PCR and Western blot. We also measured transglutaminase and GTP binding functions and used a smooth muscle cell line to evaluate the role of Gh alpha in cell proliferation. The results show that pregnancy is associated with an up-regulation of Gh alpha expression at both the mRNA and protein level. Gh alpha induced during pregnancy is preferentially localized to the plasma membrane. This was found associated with an increased ability of plasma membrane preparations to catalyze Ca(2+)-dependent incorporation of [(3)H]putrescine into casein in vitro. In the cytosol, significant changes in the level of immunodetected Gh alpha and transglutaminase activity were seen only at term. Activation of alpha1-adrenergic receptors (alpha1-AR) enhanced photoaffinity labeling of plasma membrane Gh alpha. Moreover, the level of alpha1-AR-coupled Gh alpha increased progressively with pregnancy, which parallels the active period of myometrial cell proliferation. Overexpression of wild type Gh alpha in smooth muscle cell line DDT1-MF2 increased alpha1-AR-induced [(3)H]thymidine incorporation. A similar response was obtained in cells expressing the transglutaminase inactive mutant (C277S) of Gh alpha. Together, these findings underscore the role of Gh alpha as signal transducer of alpha1-AR-induced smooth muscle cell proliferation. In this context, pregnant rat myometrium provides an interesting physiological model to study the mechanisms underlying the regulation of the GTPase function of Gh alpha

  12. Mucosal tolerance induced by an immunodominant peptide from rat alpha3(IV)NC1 in established experimental autoimmune glomerulonephritis.

    PubMed

    Reynolds, John; Abbott, Danielle S; Karegli, Julieta; Evans, David J; Pusey, Charles D

    2009-06-01

    Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture's disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the noncollagenous domain of the alpha 3 chain of type IV collagen, alpha3(IV)NC1. Recent studies have identified an immunodominant peptide, pCol (24-38), from the N-terminus of rat alpha3(IV)NC1; this peptide contains the major B- and T-cell epitopes in EAG and can induce crescentic nephritis. In this study, we investigated the mechanisms of mucosal tolerance in EAG by examining the effects of the nasal administration of this peptide after the onset of disease. A dose-dependent effect was observed: a dose of 300 microg had no effect, a dose of 1000 microg resulted in a moderate reduction in EAG severity, and a dose of 3000 microg produced a marked reduction in EAG severity accompanied by diminished antigen-specific, T-cell proliferative responses. These results demonstrate that mucosal tolerance in EAG can be induced by nasal administration of an immunodominant peptide from the N-terminus of alpha3(IV)NC1 and should be of value in designing new therapeutic strategies for patients with Goodpasture's disease and other autoimmune disorders.

  13. The effect of alpha-lipoic acid on mitochondrial superoxide and glucocorticoid-induced hypertension.

    PubMed

    Ong, Sharon L H; Vohra, Harpreet; Zhang, Yi; Sutton, Matthew; Whitworth, Judith A

    2013-01-01

    To examine the effect of alpha-lipoic acid, an antioxidant with mitochondrial superoxide inhibitory properties, on adrenocorticotrophic hormone- (ACTH-HT) and dexamethasone-induced hypertensions (DEX-HT) in rats and if any antihypertensive effect is mediated via mitochondrial superoxide inhibition. In a prevention study, rats received ground food or alpha-lipoic-acid-laced food (10 mg/rat/day) for 15 nights. Saline, adrenocorticotrophic hormone (ACTH, 0.2 mg/kg/day), or dexamethasone (DEX, 10  μ g/rat/day) was injected subcutaneously from day 5 to day 11. In a reversal study, rats received alpha-lipoic-acid-laced food 4 days after commencement of saline or DEX. Tail-cuff systolic blood pressure (SBP) was measured second daily. Kidney mitochondrial superoxide was examined using (MitoSOX) Red (MitoSOX) via flow cytometry. SBP was increased by ACTH (P < 0.0005) and DEX (P < 0.0005). Alpha-lipoic acid alone did not alter SBP. With alpha-lipoic acid pretreatment, SBP was increased by ACTH (P' < 0.005) but not by DEX. Alpha-lipoic partially prevented ACTH-HT (P' < 0.0005) and fully prevented DEX-HT (P' < 0.0005) but failed to reverse DEX-HT. ACTH and DEX did not increase MitoSOX signal. In ACTH-hypertensive rats, high-dose alpha-lipoic acid (100 mg/rat/day) did not decrease SBP further but raised MitoSOX signal (P < 0.001), suggesting prooxidant activity. Glucocorticoid-induced hypertension in rats is prevented by alpha-lipoic acid via mechanisms other than mitochondrial superoxide reduction.

  14. The Effect of Alpha-Lipoic Acid on Mitochondrial Superoxide and Glucocorticoid-Induced Hypertension

    PubMed Central

    Ong, Sharon L. H.; Vohra, Harpreet; Zhang, Yi; Sutton, Matthew; Whitworth, Judith A.

    2013-01-01

    Aims. To examine the effect of alpha-lipoic acid, an antioxidant with mitochondrial superoxide inhibitory properties, on adrenocorticotrophic hormone- (ACTH-HT) and dexamethasone-induced hypertensions (DEX-HT) in rats and if any antihypertensive effect is mediated via mitochondrial superoxide inhibition. Methods. In a prevention study, rats received ground food or alpha-lipoic-acid-laced food (10 mg/rat/day) for 15 nights. Saline, adrenocorticotrophic hormone (ACTH, 0.2 mg/kg/day), or dexamethasone (DEX, 10 μg/rat/day) was injected subcutaneously from day 5 to day 11. In a reversal study, rats received alpha-lipoic-acid-laced food 4 days after commencement of saline or DEX. Tail-cuff systolic blood pressure (SBP) was measured second daily. Kidney mitochondrial superoxide was examined using (MitoSOX) Red (MitoSOX) via flow cytometry. Results. SBP was increased by ACTH (P < 0.0005) and DEX (P < 0.0005). Alpha-lipoic acid alone did not alter SBP. With alpha-lipoic acid pretreatment, SBP was increased by ACTH (P′ < 0.005) but not by DEX. Alpha-lipoic partially prevented ACTH-HT (P′ < 0.0005) and fully prevented DEX-HT (P′ < 0.0005) but failed to reverse DEX-HT. ACTH and DEX did not increase MitoSOX signal. In ACTH-hypertensive rats, high-dose alpha-lipoic acid (100 mg/rat/day) did not decrease SBP further but raised MitoSOX signal (P < 0.001), suggesting prooxidant activity. Conclusion. Glucocorticoid-induced hypertension in rats is prevented by alpha-lipoic acid via mechanisms other than mitochondrial superoxide reduction. PMID:23533693

  15. Expression and function of CD8 alpha/beta chains on rat and human mast cells.

    PubMed

    Kim, Mi-Sun; Kim, Sung-Hoon; Lee, Hye-Jung; Kim, Hyung-Min

    2004-03-01

    The expression and functional role of CD8 glycoprotein, a marker of cytotoxic/suppressor T lymphocytes and NK cells, were not studied on freshly isolated connective tissue type rat peritoneal mast cells, a rat mucosal type mast cell line (RBL 2H3), or human mast cell line (HMC-1). We used the reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, immunohistochemistry and enzyme-linked immunosorbent assay. RT-PCR and Western blot analysis identified the presence of CD8 alpha/beta chains on the mast cells, and immunohistochemistry confirmed CD8alpha expression on rat or human mast cells. Functional studies demonstrated that stimulation of CD8 alpha/beta chains on rat mast cells induced the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), which are regarded as important mediators during infection. However, co-stimulation with stem cell factor had no effect on CD8-induced mediator secretion. Our findings demonstrate novel biological roles of CD8 molecules in mast cells.

  16. Hippocampal 3alpha,5alpha-THP may alter depressive behavior of pregnant and lactating rats.

    PubMed

    Frye, Cheryl A; Walf, Alicia A

    2004-07-01

    The 5alpha-reduced metabolite of progesterone (P), 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), may mediate progestins' effects to reduce depressive behavior of female rats in part through actions in the hippocampus. To investigate, forced swim test behavior and plasma and hippocampal progestin levels were assessed in groups of rats expected to differ in their 3alpha,5alpha-THP levels due to endogenous differences (pregnant and postpartum), administration of a 5alpha-reductase inhibitor (finasteride; 50 mg/kg sc), and/or gestational stress [prenatal stress (PNS)], an animal model of depression. Pregnant rats had higher plasma and hippocampal 3alpha,5alpha-THP levels and less depressive behavior (decreased immobility, increased struggling and swimming) in the forced swim test than did postpartum rats. Finasteride, compared to vehicle-administration, reduced plasma and hippocampal 3alpha,5alpha-THP levels and increased depressive behavior (increased immobility, decreased struggling and swimming). PNS was associated with lower hippocampal, but not plasma, 3alpha,5alpha-THP levels and increased swimming compared to that observed in control rats. Together, these data suggest that 3alpha,5alpha-THP in the hippocampus may mediate antidepressive behavior of female rats.

  17. Antioxidant and anti-inflammatory activities of alpha lipoic acid protect against indomethacin-induced gastric ulcer in rats.

    PubMed

    Gomaa, Asmaa M S; Abd El-Mottaleb, Nashwa A; Aamer, Hazem A

    2018-05-01

    Little is known about the role of tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1), and inducible nitric oxide synthase (iNOS) in the gastric ulcer and the effect of alpha lipoic acid (ALA) in their modulation. Hence, this experimental study was designed to assess the possible protective effect of ALA against indomethacin (IND)-induced gastric ulcer in rats, as well as to determine the possible underlying mechanisms with a special focus on TNF-α, PAI-1, and iNOS. Adult male rats (n = 28) were divided into four equal groups: the control group received distilled water, the vehicle group received 0.5% carboxymethylcellulose, the ulcer group received a single oral dose of IND (50 mg/kg) and the ALA-treated group received ALA (100 mg/kg) orally for 3 days before ulcer induction. Four hours after IND administration, all rats were sacrificed. The ulcer index, and gastric tissue homogenate contents of total antioxidant capacity (TAC), malondialdehyde (MDA), TNF-α, and PAI-1 were evaluated. Immunohistochemical evaluation of iNOS protein expression and histopathological examination of gastric tissue were investigated. The results revealed that ALA pretreatment significantly decreased the ulcer index, the gastric levels of MDA, TNF-α, PAI-1, and iNOS protein expression while increased the gastric levels of TAC as well as improved the histopathological appearance of gastric tissues. In conclusion, ALA ameliorated the IND-induced gastric ulceration. This could be attributed to its antioxidant and anti-inflammatory activities via suppression of TNF-α-induced elevation of both PAI-1 level and iNOS expression in the gastric tissue. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  18. Restoration of Spermatogenesis Using a New Combined Herbal Formula of Epimedium koreanum Nakai and Angelica gigas Nakai in an Luteinizing Hormone-Releasing Hormone Agonist-Induced Rat Model of Male Infertility

    PubMed Central

    2017-01-01

    Purpose We investigated the protective effect of a mixture of 2 herbal extracts, KH-465, which consisted of Epimedium koreanum Nakai and Angelica gigas Nakai, on spermatogenesis in a luteinizing hormone-releasing hormone (LHRH) agonist-induced rat model of male infertility. Materials and Methods Seventy-five 12-week-old male Sprague-Dawley rats were randomly divided into 5 groups, containing 15 rats each: a normal control group that received no treatment and 4 experimental groups (I, II, III, and IV) in which an LHRH agonist was administered for 4 weeks to induce spermatogenic failure. Group I received distilled water, and groups II, III, and IV received 200 mg/kg/day of KH-465, 400 mg/kg/day KH-465, and depo-testosterone for 4 weeks, respectively. Weight changes of the testis and epididymis, sperm count motility, and levels of testosterone (T), free T, follicle-stimulating hormone (FSH), luteinizing hormone (LH), superoxide dismutase (SOD), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were estimated. Results Body, testis, and epididymis weight showed no significant differences among the control and experimental groups. Treatment with KH-465 increased the sperm count and motility. Serum hormone levels of T, free T, and FSH were not significantly different in the experimental groups, while the LH level was higher than in the LHRH agonist-induced control group, but not to a significant extent. Levels of SOD were higher and 8-OHdG were lower in the groups that received KH-465 than in the LHRH agonist-induced control group. Conclusions Our results suggest that KH-465 increased sperm production via reducing oxidative stress and had a positive effect in a male infertility model. PMID:29076302

  19. Effect of alpha lipoic acid on intracerebroventricular streptozotocin model of cognitive impairment in rats.

    PubMed

    Sharma, Monisha; Gupta, Y K

    2003-08-01

    In the present study, the effect of alpha lipoic acid, a potent free radical scavenger, was investigated against the intracerebroventricular streptozotocin model of cognitive impairment in rats, which is characterized by a progressive deterioration of memory, cerebral glucose and energy metabolism, and oxidative stress. Wistar rats were injected with intracerebroventricular streptozotocin bilaterally. The rats were treated chronically with alpha lipoic acid (50, 100 and 200 mg/kg) orally for 21 days starting from day 1 of streptozotocin injection in separate groups. The learning and memory behavior was evaluated and the rats were sacrificed for estimation of oxidative stress. The intracerebroventricular streptozotocin rats treated with alpha lipoic acid (200 mg/kg, p.o.) showed significantly less cognitive impairment as compared to the vehicle treated rats. There was also an insignificant increase in oxidative stress in the alpha lipoic acid treated groups. The study demonstrated the effectiveness of alpha lipoic acid in preventing cognitive impairment and oxidative stress induced by intracerebroventricular streptozotocin and its potential in dementia associated with age and age related neurodegenerative disorders where oxidative stress is involved such as Alzheimer's disease.

  20. Insulin induces alpha1B-adrenergic receptor phosphorylation and desensitization.

    PubMed

    García-Sáinz, J Adolfo; Romero-Avila, M Teresa; Molina-Muñoz, Tzindilú; Medina, Luz del Carmen

    2004-09-03

    The ability of insulin to induce alpha1B-adrenoceptor phosphorylation and desensitization was tested in two model systems: rat-1 cells that stably express alpha1B-adrenoceptors, through transfection, and endogenously express insulin receptors and DDT1 MF2 cells that endogenously express both receptors. Insulin induced concentration-dependent increases in the phosphorylation state of the adrenergic receptors in the two models with similar EC50 values (0.5-2 nM). The effect was rapid in the two systems but it was sustained in rat-1 cells and transient in DDT1 MF2 cells. In both cell lines, the insulin-mediated phosphorylation of alpha1B-adrenoceptors was blocked by wortmannin and LY 294002, and by staurosporine and bisindolylmaleimide I, indicating that the effect involved phosphoinositide 3-kinase and protein kinase C activities. The adrenoceptor phosphorylation induced by insulin was associated to desensitization as evidences by a diminished elevation of intracellular calcium in response to noradrenaline. Inhibitors of phosphoinositide 3-kinase and protein kinase C blocked the functional desensitization induced by insulin.

  1. Effects of OPC-6535 on lipopolysaccharide-induced acute liver injury in the rat: involvement of superoxide and tumor necrosis factor-alpha from hepatic macrophages.

    PubMed

    Hasegawa, Tadashi; Sakurai, Kazushi; Kambayashi, Yasuhiro; Saniabadi, Abby R; Nagamoto, Hisashi; Tsukada, Katsuhiko; Takahashi, Atsushi; Kuwano, Hiroyuki; Nakano, Minoru

    2003-11-01

    The objective of this study was to investigate the effects of OPC-6535 on Propionibacterium acnes-primed and lipopolysaccharide-induced liver injury in the rat. P. acnes was administered intravenously to the rat at 16 mg/kg 7 days before the experiments. In liver perfusion experiments, lipopolysaccharide was mixed in perfusion buffer at 2.5 microg/mL. The chemiluminescence method and histochemical reduction of nitro blue tetrazolium were used for detecting superoxide. Release of cytokines into the perfusate was examined. In in vivo experiments, lipopolysaccharide was administered intravenously to the rat at 200 microg/kg. Concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and cytokines were determined in the plasma, and myeloperoxidase activity was measured in the liver tissue. OPC-6535 was given intravenously at 1 mg/kg 30 minutes before lipopolysaccharide challenge, and was then, in perfusion experiments, added to the buffer at 10 micromol/L. In perfusion experiments, P. acnes and lipopolysaccharide caused dramatic production of superoxide, tumor necrosis factor-alpha (TNF-alpha) and growth-related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1). Superoxide was mainly from hepatic macrophages. Treatment with OPC-6535 suppressed superoxide and TNF-alpha but did not affect GRO/CINC-1. In in vivo experiments, P. acnes and lipopolysaccharide increased the level of TNF-alpha, GRO/CINC-1, AST and ALT in the plasma, and myeloperoxidase activity in the liver. OPC-6535 reduced TNF-alpha, AST, and ALT, but did not affect GRO/CINC-1 or myeloperoxidase. Attenuation of liver injury by OPC-6535 is believed to be due to its inhibitory effects on superoxide and TNF-alpha production by hepatic macrophages in P. acnes- and lipopolysaccharide-treated rats.

  2. Effect of transforming growth factor-alpha on enterocyte apoptosis is correlated with EGF receptor expression along the villus-crypt axis during methotrexate-induced intestinal mucositis in a rat.

    PubMed

    Sukhotnik, Igor; Shteinberg, Dan; Ben Lulu, Shani; Bashenko, Yulia; Mogilner, Jorge G; Ure, Benno M; Shaoul, Ron; Coran, Arnold G

    2008-11-01

    The purpose of the present study was to evaluate the effect of transforming-growth factor-alpha (TGF-alpha) on enterocyte apoptosis following methotrexate (MTX) induced intestinal mucositis in a rat and in Caco-2 cells. Non-pretreated and pretreated with MTX Caco-2 cells were incubated with increasing concentrations of TGF-alpha. Cell apoptosis was determined by FACS cytometry. Adult rats were divided into four groups: Control, Control-TGF-alpha, MTX, and MTX- TGF-alpha rats. Three days later rats were sacrificed. Enterocyte apoptosis were measured at sacrifice. RT-PCR and Western Blotting was used to determine the level of Bax and Bcl-2 mRNA and protein. Real time PCR was used to measure epidermal growth factor receptor (EGFr) expression along the villus-crypt axis. The in vitro experiment has shown that treatment with TGF-alpha of Caco-2 cells results in a significant inhibition of cell apoptosis in a dose-dependent manner. In vivo experiment, a decreased levels of apoptosis in MTX- TGF-alpha rats corresponded with the decrease in Bax and with the increase in Bcl-2 at both mRNA and protein levels. The inhibiting effect of TGF-alpha on enterocyte apoptosis was strongly correlated with EGFr expression along the villus-crypt axis. In conclusion, treatment with TGF-alpha inhibits enterocyte apoptosis following MTX- injury in the rat.

  3. Pharmacological dose of alpha-tocopherol induces cardiotoxicity in Wistar rats determined by echocardiography and histology

    USDA-ARS?s Scientific Manuscript database

    The effect of pharmacological dose of alpha-tocopherol on heart health was determined in Wistar rats. Animals were randomly assigned to either C (control, n = 11) or E (alpha-tocopherol, n = 11) group. Animals received corn oil (C) or alpha-tocopherol dissolved in corn oil (250 mg alpha-tocopherol/[...

  4. Thyroxine-induced changes in the glycosylation pattern and in brain and serum levels of rat alpha-fetoprotein.

    PubMed

    Naval, J; Calvo, M; Lampreave, F; Piñeiro, A

    1986-01-01

    We have studied the effect of thyroid disfunction during the postnatal period, on the serum and brain levels of rat alpha-fetoprotein (AFP) and albumin. Hypothyroidism was induced by treatment of pregnant rats and their newborn pups with 2-mercapto-1-methylimidazole(methimazole). Hyperthyroidism was provoked in newborns by daily injections of thyroxine (0.25 micrograms/g body wt) from the 3rd postnatal day weaning. Impaired growth, lower brain size, altered behaviour and morphological features observed were according to an altered thyroid status. Hypothyroid rats showed a significantly reduction in serum AFP concentration (78% of control values at 8 days of age) and a slight increase in that of albumin. level could be appreciated. Thyroxine supplementation (0.2 micrograms/rat/day) corrected most of these alterations. Hyperthyroidism induced a drastic fall in both serum and brain AFP levels (about 48% of the corresponding control values). Albumin concentration in serum was augmented significantly from the 12th postnatal day, but its brain levels did not change significantly. In hyperthyroid rats, a significant reduction (37% relative to controls) in the concanavalin A-non reactive microform of AFP, was observed. This alteration of the glycosylation pattern of AFP could be due to the inhibition by thyroxine of the activity of the hepatic enzyme GlcNAc-transferase III.

  5. Macrophage-induced angiogenesis is mediated by tumour necrosis factor-alpha.

    PubMed

    Leibovich, S J; Polverini, P J; Shepard, H M; Wiseman, D M; Shively, V; Nuseir, N

    Macrophages are important in the induction of new blood vessel growth during wound repair, inflammation and tumour growth. We show here that tumour necrosis factor-alpha (TNF-alpha), a secretory product of activated macrophages that is believed to mediate tumour cytotoxicity, is a potent inducer of new blood vessel growth (angiogenesis). In vivo, TNF-alpha induces capillary blood vessel formation in the rat cornea and the developing chick chorioallantoic membrane at very low doses. In vitro, TNF-alpha stimulates chemotaxis of bovine adrenal capillary endothelial cells and induces cultures of these cells grown on type-1 collagen gels to form capillary-tube-like structures. The angiogenic activity produced by activated murine peritoneal macrophages is completely neutralized by a polyclonal antibody to TNF-alpha, suggesting immunological features are common to TNF-alpha and the protein responsible for macrophage-derived angiogenic activity. In inflammation and wound repair, TNF-alpha could augment repair by stimulating new blood vessel growth; in tumours, TNF-alpha might both stimulate tumour development by promoting vessel growth and participate in tumour destruction by direct cytotoxicity.

  6. Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4alpha and PGC1alpha.

    PubMed

    Dietrich, Christoph G; Martin, Ina V; Porn, Anne C; Voigt, Sebastian; Gartung, Carsten; Trautwein, Christian; Geier, Andreas

    2007-09-01

    Fasting induces numerous adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4alpha/PGC-1alpha-pathway. Because HNF4alpha has been identified as central regulator of basolateral bile acid transporters and a previous study reports increased basolateral bile acid uptake into the liver during fasting, we hypothesized that HNF4alpha is involved in fasting-induced bile acid uptake via upregulation of basolateral bile acid transporters. In rats, mRNA of Ntcp, Oatp1, and Oatp2 were significantly increased after 48 h of fasting. Protein expression as determined by Western blot showed significant increases for all three transporters 72 h after the onset of fasting. Whereas binding activity of HNF1alpha in electrophoretic mobility shift assays remained unchanged, HNF4alpha binding activity to the Ntcp promoter was increased significantly. In line with this result, we found significantly increased mRNA expression of HNF4alpha and PGC-1alpha. Functional studies in HepG2 cells revealed an increased endogenous NTCP mRNA expression upon cotransfection with either HNF4alpha, PGC-1alpha, or a combination of both. We conclude that upregulation of the basolateral bile acid transporters Ntcp, Oatp1, and Oatp2 in fasted rats is mediated via the HNF4alpha/PGC-1alpha pathway.

  7. The effect of Eurycoma longifolia on sperm quality of male rats.

    PubMed

    Chan, Kit-Lam; Low, Bin-Seng; Teh, Chin-Hoe; Das, Prashanta K

    2009-10-01

    The present study investigated the effects of a standardized methanol extract of E. longifolia Jack containing the major quassinoid constituents of 13alpha(21)-epoxyeurycomanone (1), eurycomanone (2), 13alpha,21-dihydroeurycomanone (3) and eurycomanol (4) on the epididymal spermatozoa profile of normal and Andrographis paniculata induced infertile rats. The standardized MeOH extract at doses of 50, 100 and 200 mg/kg, the EtOAc fraction (70 mg/kg), and standardized MeOH extract at 200 mg/kg co-administered with the EtOAc fraction of A. paniculata at 70 mg/kg were each given orally to male Sprague-Dawley albino rats for 48 consecutive days. The spermatozoa count, morphology, motility, plasma testosterone level and Leydig cell count of the animals were statistically analyzed by ANOVA with a post-hoc Tukey HSD test. The results showed that the sperm count of rats given the standardized MeOH extract alone at doses of 50, 100 and 200 mg/kg were increased by 78.9, 94.3 and 99.2%, respectively when compared with that of control (p < 0.01). The low count, poor motility and abnormal morphology of the spermatozoa induced by the A. paniculata fraction were significantly reversed by the standardized MeOH extract of E. longifolia (p < 0.001). The plasma testosterone level of the rats treated with the standardized MeOH extract at 200 mg/kg was significantly increased (p < 0.01) when compared with that of the control and infertile animals. The spermatocytes in the seminiferous tubules and the Leydig cells appeared normal. Testosterone level was significantly higher in the testes (p < 0.01) than in the plasma after 30 days of oral treatment with the standardized MeOH extract. Interestingly, eurycomanone (2) alone was detected in the rat testis homogenates by HPLC-UV and confirmed by LC/MS, and may have contributed towards the improvement of sperm quality. Thus, the plant may potentially be suitable for the management of male infertility.

  8. Therapeutic potential of alpha-ketoglutarate against acetaminophen-induced hepatotoxicity in rats

    PubMed Central

    Mehra, Lalita; Hasija, Yasha; Mittal, Gaurav

    2016-01-01

    Objective: Alpha-ketoglutarate (α-KG) is a cellular intermediary metabolite of Krebs cycle, involved in energy metabolism, amino acid synthesis, and nitrogen transport. It is available over-the-counter and marketed as a nutritional supplement. There is a growing body of evidence to suggest that dietary α-KG has the potential to maintain cellular redox status and thus can protect various oxidative stress induced disease states. The aim of the present study was to investigate the hepatoprotective role of α-KG in acetaminophen (APAP) induced toxicity in rats. Materials and Methods: Animals were divided into three groups of six animals each. Group I (Vehicle control): Normal Saline, Group II (APAP): A single intraperitoneal injection of 0.6 g/kg, Group III (APAP + α-KG): APAP as in Group II with α-KG treatment at a dose of 2 g/kg, orally for 5 days. Then the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) with oxidative stress markers including malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and histopathology were analyzed. Results: The results indicate that APAP caused significant elevations in ALT, AST, ALP, and MDA levels, while GSH, SOD, and CAT were significantly depleted while co-administration of α-KG showed a significant (P < 0.05) reduction in the severity of these damages. Histologically, the liver showed inflammation and necrosis after APAP treatment, which were significantly restored with co-administration of α-KG. Conclusion: These results indicate the possible therapeutic potential of α-KG in protecting liver damage by APAP in rats. PMID:28216953

  9. Induction of nitric oxide synthase in rat intestine by interleukin-1alpha may explain diarrhea associated with zinc deficiency.

    PubMed

    Cui, L; Takagi, Y; Wasa, M; Iiboshi, Y; Khan, J; Nezu, R; Okada, A

    1997-09-01

    Synthesis of inducible nitric oxide synthase (iNOS) in the intestine may result in local tissue damage. We investigated whether a challenge with interleukin-1alpha could give rise to intestinal iNOS expression and diarrhea in rats of differing zinc status. Weaning male rats were fed a zinc-deficient (ZD) diet (2 mg zinc/kg) for 4 wk to induce zinc deficiency or a zinc-supplemented diet [50.8 mg zinc/kg; controls, including pair-fed (PF ) and ad libitum (AL) consumption groups], and then subcutaneously injected with interleukin-1alpha (2 x 10(7) units/kg body wt). Without the interleukin-1alpha challenge, ZD rats had significantly lower plasma zinc concentration than the other groups. Intestinal metallothionein-1 mRNA abundance was lower in ZD rats than in AL rats. iNOS was expressed in the intestine of ZD rats but not in the others. None of the rats experienced diarrhea during the feeding period. Interleukin-1alpha led to a reduction in plasma zinc concentration, enhancement in intestinal metallothionein-1 mRNA levels, and expression of the intestinal iNOS gene in all groups. However, the abundance of iNOS mRNA was significantly higher in ZD rats than in the other groups. The presence of iNOS protein was demonstrated by immunohistochemical staining in the intestine of ZD rats that had been treated with interleukin-1alpha 12 h earlier. In addition, diarrhea occurred in most of the ZD rats and some of the PF rats but not in AL rats after interleukin-1alpha treatment. We conclude that ZD rats respond to interleukin-1alpha challenge more severely than controls, reflected by a more marked and prolonged iNOS expression and a greater incidence of diarrhea.

  10. Evaluation of GABAergic neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one as a neurobiological substrate for the anti-anxiety effect of ethanol in rats.

    PubMed

    Hirani, Khemraj; Sharma, Ajay N; Jain, Nishant S; Ugale, Rajesh R; Chopde, Chandrabhan T

    2005-07-01

    Acute systemic ethanol administration is known to elevate plasma and cerebral levels of neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one (3alpha, 5alpha-THP; allopregnanolone) to a concentration sufficient to potentiate GABA(A) receptors. We have earlier demonstrated that 3alpha, 5alpha-THP mediates the antidepressant-like effect of ethanol in Porsolt forced swim test. The aim of the present study is to explain the relationship between endogenous GABAergic neurosteroids and anxiolytic effect of ethanol in Sprague-Dawley rats. The mediation of 3alpha, 5alpha-THP in the anti-anxiety effect of ethanol was assessed by pharmacological interactions of ethanol with various endogenous neurosteroidal modulators and using simulated physiological conditions of altered neurosteroid content in elevated plus maze (EPM) test. Pretreatment of 3alpha, 5alpha-THP (0.5-2.5 mug/rat, i.c.v.) or neurosteroidogenic agents such as 3alpha, 5alpha-THP precursor progesterone (5 or 10 mg/kg, i.p.), 11-beta hydroxylase inhibitor metyrapone (50 or 100 mg/kg, i.p.) or the GABA(A) receptor agonist muscimol (25 ng/rat, i.c.v.) significantly potentiated the anti-anxiety effect of ethanol (1 g/kg, i.p.). On the other hand, the GABAergic antagonistic neurosteroid dehydroepiandrosterone sulphate (DHEAS) (1 mg/kg, i.p.), the GABA(A) receptor blocker bicuculline (1 mg/kg, i.p.), the 5alpha-reductase inhibitor finasteride (50 x 2 mg/kg, s.c.) or the mitochondrial diazepam binding inhibitory receptor antagonist PK11195 (1 mg/kg, i.p.) reduced ethanol-induced preference of time spent and number of entries into open arms. Anti-anxiety effect of ethanol was abolished in adrenalectomized (ADX) rats as compared to sham-operated control. This ADX-induced blockade was restored by prior systemic injection of progesterone, signifying the contribution of peripheral steroidogenesis in ethanol anxiolysis. Socially isolated animals known to exhibit decreased brain 3alpha, 5alpha-THP and GABA(A) receptor

  11. Protective effect of alpha-lipoic acid in methotrexate-induced ovarian oxidative injury and decreased ovarian reserve in rats.

    PubMed

    Soylu Karapinar, Oya; Pinar, Neslihan; Özcan, Oğuzhan; Özgür, Tümay; Dolapçıoğlu, Kenan

    2017-08-01

    To determine whether the possible oxidative effect of methotrexate (Mtx) on ovary and to evaluate the effectiveness of alpha lipoic acid (ALA), which may be useful in many oxidative stress models. Thirty-two female Wistar-albino rats were randomly divided into four groups; control group, alpha lipoic acid group (ALA 100 mg/kg, 10 days), multiple dose Mtx group (Mtx 1 mg/kg 1, 3, 5, 7 days) and Mtx and ALA group (Mtx 1 mg/kg 1, 3, 5, 7 days and ALA 100 mg/kg, 10 days). Serum total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI), tumor necrosis factor-alpha (TNF-α), tissue malondialdehyde (MDA) and activities of glutathione peroxidase (GSH-Px) and catalase (CAT) and anti-Mullerian hormone (AMH) and total ovarian follicle count were evaluated. Mtx administration caused a significant decrease in TAS, a significant increase in TOS and OSI, a significant increase in MDA levels and a decrease in GSH-Px and CAT activity. Moreover the proinflammatory cytokine (TNF-α) was increased in the Mtx group. And AMH values and total follicle count were significantly decreased in Mtx group. However, ALA treatment reversed biochemical results and AMH levels and total follicle count. Alpha lipoic acid ameliorates methotrexate induced oxidative damage of ovarian in rats.

  12. Alpha-adrenoceptor antagonistic and calcium antagonistic effects of nicergoline in the rat isolated aorta.

    PubMed

    Heitz, C; Descombes, J J; Miller, R C; Stoclet, J C

    1986-04-16

    The activity of the alpha-adrenoceptor antagonist nicergoline, a molecule composed of two constituent parts, ergoline and bromonicotinic acid, was investigated in the rat isolated aorta. Nicergoline (10 nM-0.1 microM) displaced concentration-effect curves elicited by noradrenaline and phenylephrine to the right and inhibited maximal responses elicited by both alpha-adrenoceptor agonists without significantly affecting prostaglandin F2 alpha-induced contractions. Higher concentrations of nicergoline (1 microM-50 microM) displaced to the right the concentration-effect curves elicited by calcium in a depolarizing medium. This calcium antagonist activity was not shared by either of the constituent parts. Nicergoline 100 microM abolished the 45Ca influx induced into rat aorta by 100 mM K+-containing physiological solution. The selectivity of nicergoline for alpha 1-adrenoceptors seen in binding experiments also depends on the presence of the bromonicotinic moiety of the molecule. It is concluded that nicergoline, but not its substituent parts, displays both alpha 1-adrenoceptor and calcium antagonism. The latter property may account for some of the observed effects of this compound.

  13. Gliclazide inhibits diabetic neuropathy irrespective of blood glucose levels in streptozotocin-induced diabetic rats.

    PubMed

    Qiang, X; Satoh, J; Sagara, M; Fukuzawa, M; Masuda, T; Miyaguchi, S; Takahashi, K; Toyota, T

    1998-08-01

    N-acetylcysteine and pentoxifylline, free radical scavengers and inhibitors of tumor necrosis factor-alpha (TNF-alpha) production, inhibit the development of peripheral neuropathy in streptozotocin (STZ)-induced diabetic rats. This study was designed to elucidate the effect of gliclazide, an oral hypoglycemic sulfonylurea, on diabetic neuropathy, because it has been indicated to be a free radical scavenger and TNF-alpha inhibitor. Rats were fed with powder chow mixed with gliclazide or glibenclamide as a control ad libitum. Blood glucose levels and body weight were remarkably higher and lower in diabetic than in nondiabetic rats, respectively, while gliclazide and glibenclamide had no effect on these in both diabetic and nondiabetic rats throughout a 24-week experiment. Serum lipoperoxide levels and lipopolysaccharide (LPS)-induced serum TNF-alpha activities were significantly increased in diabetic rats, whereas these were significantly inhibited in gliclazide-treated rats. Motor nerve conduction velocity (MNCV) of the tibial nerve significantly slowed in diabetic rats compared with nondiabetic rats. On the other hand, the slowed MNCV was significantly inhibited in gliclazide-treated diabetic rats after 16 experimental weeks. Morphometric analysis showed that gliclazide prevented decreased myelinated fiber area (P < .05), increased fiber density (P < .001), and decreased axon/myelin ratio (P < .05) in diabetic rats. Glibenclamide treatment did not affect serum lipoperoxide, TNF-alpha, MNCV, or nerve morphology in this experiment. These results indicate that gliclazide has a beneficial effect on peripheral neuropathy in STZ-induced diabetic rats, irrespective of blood glucose levels.

  14. Environmentally Induced Epigenetic Transgenerational Inheritance of Altered Sertoli Cell Transcriptome and Epigenome: Molecular Etiology of Male Infertility

    PubMed Central

    Guerrero-Bosagna, Carlos; Savenkova, Marina; Haque, Md. Muksitul; Nilsson, Eric; Skinner, Michael K.

    2013-01-01

    Environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset disease, including testis disease and male infertility. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell (Sertoli cell) that influences the onset of a specific disease (male infertility). A gestating female rat (F0 generation) was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. As previously observed, enhanced spermatogenic cell apoptosis was observed. The Sertoli cells provide the physical and nutritional support for the spermatogenic cells. Over 400 genes were differentially expressed in the F3 generation control versus vinclozolin lineage Sertoli cells. A number of specific cellular pathways were identified to be transgenerationally altered. One of the key metabolic processes affected was pyruvate/lactate production that is directly linked to spermatogenic cell viability. The Sertoli cell epigenome was also altered with over 100 promoter differential DNA methylation regions (DMR) modified. The genomic features and overlap with the sperm DMR were investigated. Observations demonstrate that the transgenerational sperm epigenetic alterations subsequently alters the development of a specific somatic cell (Sertoli cell) epigenome and transcriptome that correlates with adult onset disease (male infertility). The environmentally induced epigenetic transgenerational inheritance of testis disease appears to be a component of the molecular etiology of male infertility. PMID:23555832

  15. Inhibitory effect of troglitazone on diabetic neuropathy in streptozotocin-induced diabetic rats.

    PubMed

    Qiang, X; Satoh, J; Sagara, M; Fukuzawa, M; Masuda, T; Sakata, Y; Muto, G; Muto, Y; Takahashi, K; Toyota, T

    1998-11-01

    Free-radical scavengers and inhibitors of tumour necrosis factor-alpha (TNF-alpha) such as N-acetylcysteine and pentoxifylline have been shown to inhibit the development of peripheral neuropathy in streptozotocin(STZ)-induced diabetic rats. In this study we examined the effect of troglitazone, an anti-diabetic thiazolidinedione, on diabetic neuropathy, since it also is a free-radical scavenger and a TNF-alpha inhibitor. Rats were fed powder chow mixed with troglitazone at 0.5% and 0.125% ad libitum. Although blood glucose concentrations were remarkably higher and body weight lower in diabetic than in nondiabetic rats, troglitazone had no effect on these throughout the 24-week experiment. Serum lipoperoxide concentrations, tibial nerve lipoperoxide content and serum TNF-alpha activity induced by lipopolysaccharide was increased in diabetic rats, but inhibited in troglitazone-treated rats. Motor nerve conduction velocity (MNCV) of the tibial nerve slowed in diabetic rats, compared with that in nondiabetic rats. On the other hand, the slowed MNCV was (p < 0.05-0.01) inhibited after weeks 12 and 16 of the experiment in diabetic rats treated with high and low doses of troglitazone, respectively. Morphometric analysis showed that troglitazone suppressed the decrease of the myelinated fibre area (p < 0.05), axon/myelin ratio (p < 0.01) and fascicular area (p < 0.05) and suppressed the increase of myelinated fibre density (p < 0.001) in diabetic rats. These results indicate that troglitazone has a beneficial effect on peripheral neuropathy in STZ-induced diabetic rats irrespective of blood glucose concentrations.

  16. Membrane remodeling, an early event in benzo[alpha]pyrene-induced apoptosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tekpli, Xavier; Rissel, Mary; Huc, Laurence

    2010-02-15

    Benzo[alpha]pyrene (B[alpha]P) often serves as a model for mutagenic and carcinogenic polycyclic aromatic hydrocarbons (PAHs). Our previous work suggested a role of membrane fluidity in B[alpha]P-induced apoptotic process. In this study, we report that B[alpha]P modifies the composition of cholesterol-rich microdomains (lipid rafts) in rat liver F258 epithelial cells. The cellular distribution of the ganglioside-GM1 was markedly changed following B[alpha]P exposure. B[alpha]P also modified fatty acid composition and decreased the cholesterol content of cholesterol-rich microdomains. B[alpha]P-induced depletion of cholesterol in lipid rafts was linked to a reduced expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). Aryl hydrocarbon receptor (AhR) and B[alpha]P-related H{submore » 2}O{sub 2} formation were involved in the reduced expression of HMG-CoA reductase and in the remodeling of membrane microdomains. The B[alpha]P-induced membrane remodeling resulted in an intracellular alkalinization observed during the early phase of apoptosis. In conclusion, B[alpha]P altered the composition of plasma membrane microstructures through AhR and H{sub 2}O{sub 2} dependent-regulation of lipid biosynthesis. In F258 cells, the B[alpha]P-induced membrane remodeling was identified as an early apoptotic event leading to an intracellular alkalinization.« less

  17. Effect of alpha-tocopherol on lipid peroxidation and antioxidant system in fibrosarcoma bearing rats.

    PubMed

    Vasavi, H; Thangaraju, M; Sachdanandam, P

    1994-02-23

    The anticarcinogenic activity of alpha-tocopherol (Vitamin E) was tried in fibrosarcoma induced rats through its antioxidative potential. The rate of formation of malondialdehyde (MDA), the end product of lipid peroxidation was analysed in alpha-tocopherol (400 mg/kg body weight) treated and untreated fibrosarcoma bearing rats with respective controls. The levels of non-enzymic antioxidants like, glutathione and vitamin E, and enzymic antioxidants viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione-S-transferase (GST) were assayed as well. Significantly increased (p < 0.001) level of lipid peroxide was observed with concomitant decreases in the level of enzymic and non-enzymic antioxidants in fibrosarcoma bearing rats when compared with control animals. In alpha-tocopherol supplemented animals, the corrected level of these parameters were observed likely to near normal values. Thus, alpha-tocopherol can be accepted to pose first line of defense mechanism against excessively formed reactive species due to impaired antioxidant systems in fibrosarcoma conditions, that cause membrane damage leading to deleterious effects.

  18. Aerosol-administered alpha-tocopherol attenuates lung inflammation in rats given lipopolysaccharide intratracheally.

    PubMed

    Hybertson, Brooks M; Chung, Jin H; Fini, Mehdi A; Lee, Young M; Allard, Jenny D; Hansen, Brian N; Cho, Okyong J; Shibao, Gayle N; Repine, John E

    2005-04-01

    Intrapulmonary administration of bacterial lipopolysaccharide (LPS) induces a well-characterized lung inflammatory response involving alveolar macrophage activation, proinflammatory cytokine elaboration, and neutrophil influx. Vitamin E, a lipophilic antioxidant consisting of a family that includes tocopherols and tocotrienols, has previously been shown to have a variety of anti-inflammatory effects, raising interest in its possible uses in disease prevention or therapy. Because aerosol delivery is a specific and rapid way to administer agents to the lungs, the authors undertook to determine whether inhaled vitamin E aerosols would have an anti-inflammatory effect in the lungs. Using a rat model of acute lung inflammation caused by intratracheally administered LPS (10 microg Pseudomonas aeruginosa LPS), the authors examined the effect of aerosol-administered vitamin E, in this case alpha-tocopherol, on several indices of lung inflammation which are increased by LPS treatment. It was found that inhaled alpha-tocopherol aerosol, but not inhaled alpha-tocopherol acetate aerosol, decreased tumor necrosis factor alpha (TNFalpha) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA levels in lung tissue, TNFalpha and CINC-1 immunoreactive protein levels in lung lavage, and the number of neutrophils recoverable by lung lavage from rats given LPS intratracheally. These results contribute to the increasing body of work describing immunomodulatory functions of alpha-tocopherol, and support the idea that direct aerosol administration of alpha-tocopherol may play a beneficial role in strategies to control inflammatory lung illnesses.

  19. Influence of alpha-lipoic acid on nicotine-induced lung and liver damage in experimental rats.

    PubMed

    Ateyya, Hayam; Nader, Manar A; Attia, Ghalia M; El-Sherbeeny, Nagla A

    2017-05-01

    Nicotine mediates some of the injurious effects caused by consuming tobacco products. This work aimed at investigating the defensive role of alpha-lipoic acid (ALA) with its known antioxidant and antiinflammatory effect in nicotine-induced lung and liver damage. Rats were arranged into 4 groups: control, nicotine, ALA, and ALA-nicotine groups. Oxidative stress and antioxidant status were determined by assessing thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH) levels in lung and liver. Liver enzymes and lipid profiles were measured and pulmonary and hepatic damage were assessed by histopathological examination. Also, serum levels of transforming growth factor beta 1 (TGF-β1) and vascular cell adhesion molecule 1 (VCAM-1) were determined. The results revealed an increase in TBARS in tissues and a reduction in both SOD and GSH activity in the nicotine-treated rats. Nicotine induced high levels of liver enzymes, TGF-β1, VCAM-1, and dyslipidemia with histopathological changes in the lung and liver. ALA administration along with nicotine attenuated oxidative stress and normalized the SOD and GSH levels, ameliorated dyslipidemia, and improved TGF-β1 and VCAM-1 with better histopathology of the lung and liver. The study data revealed that ALA may be beneficial in alleviating nicotine-induced oxidative stress, dyslipidemia, and both lung and liver damage.

  20. Expression of TNF-alpha and immunohistochemical distribution of hepatic macrophage surface markers in carbon tetrachloride-induced chronic liver injury in rats.

    PubMed

    Orfila, C; Lepert, J C; Alric, L; Carrera, G; Beraud, M; Vinel, J P; Pipy, B

    1999-10-01

    In liver injury induced by carbon tetrachloride, secondary hepatic injury occurs from inflammatory processes originating from products released by activated Kupffer cells, which play a central role in hepatic inflammation. The purpose of our study was to demonstrate, in rats, the relationships between a function of the hepatic macrophages, TNF-alpha production and the state of activation of these cells, characterized by their phenotype, in the different phases of the process and development of fibrosis in a carbon tetrachloride-induced cirrhosis model. The immunohistochemical localization of proinflammatory cytokine TNF-alpha and surface surface makers (ED1 and ED2) was studied in hepatitis and cirrhosis in response to 3 and 9 weeks ingestion of carbon tetrachloride. After carbon tetrachloride ingestion, accompanying the increased necrosis, immunohistochemical analysis of liver tissue sections demonstrated the significantly increased number of cells expressing ED1, ED2 and TNF-alpha, compared to normal. The number of cells expressing the surface phenotypic markers of liver macrophages increased and this change was concomitantly associated with an increased cellular expression of TNF-alpha. Local macrophage proliferation and influx of newly recruited blood monocytes resulted in an increase of the macrophage population. The populational changes involved difference in functional activity and enhanced TNF-alpha expression. This cytokine expressed in the carbon tetrachloride-induced inflammatory process is associated with the development of fibrosis and may contribute to disease severity.

  1. d-Limonene-induced male rat-specific nephrotoxicity: Evaluation of the association between d-limonene and alpha 2u-globulin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lehman-McKeeman, L.D.; Rodriguez, P.A.; Takigiku, R.

    1989-06-15

    d-Limonene is a naturally occurring monoterpene, which when dosed orally, causes a male rat-specific nephrotoxicity manifested acutely as the exacerbation of protein droplets in proximal tubule cells. Experiments were conducted to examine the retention of (/sup 14/C)d-limonene in male and female rat kidney, to determine whether d-limonene or one or more of its metabolites associates with the male rat-specific protein, alpha 2u-globulin, and if so, to identify the bound material. The results indicated that, 24 hr after oral administration of 3 mmol d-limonene/kg, the renal concentration of d-limonene equivalents was approximately 2.5 times higher in male rats than in femalemore » rats. Equilibrium dialysis in the presence or absence of sodium dodecyl sulfate indicated that approximately 40% of the d-limonene equivalents in male rat kidney associated with proteins in a reversible manner, whereas no significant association was observed between d-limonene equivalents and female rat kidney proteins. Association between d-limonene and male rat kidney proteins was characterized by high-performance gel filtration and reverse-phase chromatography. Gel filtration HPLC indicated that d-limonene in male rat kidney is associated with a protein fraction having a molecular weight of approximately 20,000. Separation of alpha 2u-globulin from other kidney proteins by reverse-phase HPLC indicated that d-limonene associated with a protein present only in male rat kidney which was definitively identified as alpha 2u-globulin by amino acid sequencing. The major metabolite associated with alpha 2u-globulin was d-limonene-1,2-oxide. Parent d-limonene was also identified as a minor component in the alpha 2u-globulin fraction.« less

  2. Genomic structure of rat 3alpha-hydroxysteroid/dihydrodiol dehydrogenase (3alpha-HSD/DD, AKR1C9).

    PubMed

    Lin, H K; Hung, C F; Moore, M; Penning, T M

    1999-11-01

    Rat liver 3alpha-hydroxysteroid/dihydrodiol dehydrogenase (3alpha-HSD/DD) is a member of the aldo-keto reductase (AKR) superfamily. It is involved in the inactivation of steroid hormones and the metabolic activation of polycyclic aromatic hydrocarbons (PAH) by converting trans-dihydrodiols into reactive and redox-active o-quinones. The structure of the 5'-flanking region of the gene and factors involved in the constitutive and regulated expression of this gene have been reported [H.-K. Lin, T.M. Penning, Cloning, sequencing, and functional analysis of the 5'-flanking region of the rat 3alpha-hydroxysteroid/dihydrodiol dehydrogenase gene, Cancer Res. 55 (1995) 4105-4113]. We now describe the complete genomic structure of the rat type 1 3alpha-HSD/DD gene. Charon 4A and P1 genomic clones contained at least three rat genes (type 1, type 2 and type 3 3alpha-HSD/DD) each of which encoded for the same open reading frame (ORF) but differed in their exon-intron organization. 5'-RACE confirmed that the type 1 3alpha-HSD/DD gene encodes for the dominant transcript in rat liver and it was the regulation of this gene that was previously studied. The rat type 1 3alpha-HSD/DD gene is 30 kb in length and consists of nine exons and eight introns. Exon 9 encodes +931 to 966 bp of the ORF and the 1292 bp 3'-UTR implicated in mRNA stability. This genomic structure is nearly identical to the homologous human genes, type 1 3alpha-HSD (chlordecone reductase/DD4, AKR1C4), type 2 3alpha-HSD (AKR1C3) and type 3 3alpha-HSD (bile-acid binding protein, AKR1C2) genes. Three different cDNA's containing identical ORFs for 3alpha-HSD have been reported suggesting that all three genes may be expressed in rat liver. Using 5' primers corresponding to the 5'-UTR's of the three different cDNA's only one PCR fragment was obtained and corresponded to the type 1 3alpha-HSD/DD gene. These data suggested that the type 2 and type 3 3alpha-HSD/DD genes are not abundantly expressed in rat liver. It is unknown

  3. Induced expression of mRNA for IL-5, IL-6, TNF-alpha, MIP-2 and IFN-gamma in immunologically activated rat peritoneal mast cells: inhibition by dexamethasone and cyclosporin A.

    PubMed

    Williams, C M; Coleman, J W

    1995-10-01

    We examined the capacity of purified rat peritoneal connective tissue-type mast cells (PMC) to express mRNA for several cytokines. Stimulation of PMC with anti-IgE for 4 hr induced the expression of mRNA encoding interleukin-5 (IL-5), IL-6, tumour necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Unstimulated PMC expressed detectable mRNA for TNF-alpha but not for the other four cytokines. Incubation of PMC with cyclosporin A (CsA) or dexamethasone (DEX), each at 10(-6) M for 24 hr, significantly inhibited the induced expression of mRNA for each of the five cytokines, and also inhibited release of biologically active TNF-alpha. Throughout these experiments mRNA levels of the housekeeping gene G3PDH were not altered by stimulation with anti-IgE or incubation with CsA or DEX. We conclude that immunological activation of rat PMC induces gene expression of several cytokines and that expression of these genes can be inhibited by immunosuppressive drugs.

  4. Induced expression of mRNA for IL-5, IL-6, TNF-alpha, MIP-2 and IFN-gamma in immunologically activated rat peritoneal mast cells: inhibition by dexamethasone and cyclosporin A.

    PubMed Central

    Williams, C M; Coleman, J W

    1995-01-01

    We examined the capacity of purified rat peritoneal connective tissue-type mast cells (PMC) to express mRNA for several cytokines. Stimulation of PMC with anti-IgE for 4 hr induced the expression of mRNA encoding interleukin-5 (IL-5), IL-6, tumour necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Unstimulated PMC expressed detectable mRNA for TNF-alpha but not for the other four cytokines. Incubation of PMC with cyclosporin A (CsA) or dexamethasone (DEX), each at 10(-6) M for 24 hr, significantly inhibited the induced expression of mRNA for each of the five cytokines, and also inhibited release of biologically active TNF-alpha. Throughout these experiments mRNA levels of the housekeeping gene G3PDH were not altered by stimulation with anti-IgE or incubation with CsA or DEX. We conclude that immunological activation of rat PMC induces gene expression of several cytokines and that expression of these genes can be inhibited by immunosuppressive drugs. Images Figure 1 Figure 2 Figure 3 PMID:7490125

  5. Blood and tissue tocopherol levels in rats following intraperitoneally administered alpha-tocopheryl acetate.

    PubMed

    McGee, C D; Greenwood, C E; Jeejeebhoy, K N

    1990-01-01

    The correction or maintenance of blood and tissue alpha-tocopherol (alpha-Toc) levels by intraperitoneally administered all-rac-alpha-tocopheryl acetate (alpha-Tac) was compared with RRR- alpha-tocopherol (alpha-Toc) in vitamin E-depleted and control rats. Rats received 1.3 TE vitamin E daily for 7 days. alpha-Tac was detected in plasma of one-third of alpha-Tac-treated rats 24 hr after the first treatment, although not in subsequent samplings. Both alpha-Tac and alpha-Toc increased tocopherol levels in plasma and liver of E-deprived rats, while little or no change was observed in adipose tissue and brain. Similarly, control rats treated with alpha-Tac or alpha-Toc had significantly greater (p less than 0.05) plasma and liver alpha-Toc levels at day 3 and day 7 than did saline-treated rats. There was no significant difference in adipose alpha-Toc levels among treatment groups of control rats. The results of this study suggest that alpha-Tac is rapidly hydrolyzed to its biologically active alcohol form and results in similar effects to that of intraperitoneally administered alpha-Toc.

  6. Recombinant human acetylcholine receptor alpha-subunit induces chronic experimental autoimmune myasthenia gravis.

    PubMed

    Lennon, V A; Lambert, E H; Leiby, K R; Okarma, T B; Talib, S

    1991-04-01

    A synthetic gene encoding the 210 N-terminal residues of the alpha-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human alpha 1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 micrograms. With 6.6 to 22 micrograms, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 micrograms or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the alpha 1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.

  7. Abnormal TNF-alpha production in diabetes-prone BB rats: enhanced TNF-alpha expression and defective PGE2 feedback inhibition.

    PubMed Central

    Rothe, H; Ongören, C; Martin, S; Rösen, P; Kolb, H

    1994-01-01

    Upon stimulation with lipopolysaccharide (LPS), peritoneal macrophages from diabetes-prone Bio-Breeding (BB) rats secrete more tumour necrosis factor-alpha (TNF-alpha) than macrophages from diabetes-resistant BB or normal Wistar rats. Enhanced transcription was demonstrated by Northern blot analysis and at the single cell level by mRNA: RNA hybridization. Cytofluorometry analysis showed 2-4 times more plasma membrane and total cell-associated TNF-alpha in macrophages of diabetes-prone BB rats. The analysis of fluorescence intensity showed a single peak, and TNF-alpha mRNA was found in > 90% of macrophages. These findings exclude TNF hypersecretion as being due to an abnormal subfraction of cells. TNF-alpha gene hyperexpression in diabetes-prone BB rats was not due to mutations in the regulatory regions of the promoter, which could be shown by cloning and sequencing of the TNF-alpha promoter in the three rat strains. When searching for other regulatory defects we found the production of prostaglandin E2 (PGE2) in response to LPS to be up to 10 times lower in macrophages from diabetes-prone BB rats than from Wistar rats. Furthermore, BB rats macrophages required significantly higher concentrations of PGE2 for suppression of TNF-alpha secretion. We conclude that abnormal TNF-alpha production in macrophages from diabetes-prone BB rats is due to enhanced gene transcription and translation and that this is associated with defective PGE2 feedback inhibition. Images Figure 1 Figure 2 PMID:8206514

  8. Characterization of alpha-ketobutyrate metabolism in rat tissues: effects of dietary protein and fasting.

    PubMed

    Steele, R D; Weber, H; Patterson, J I

    1984-04-01

    The oxidative decarboxylation of alpha-ketobutyrate was studied in rat tissue preparations. Decarboxylation was confined to the mitochondrial fraction and required coenzyme A, NAD, TPP and FAD for optimal activity in solubilized preparations. The pH optimum for this reaction in liver was 7.8, somewhat higher than that reported for other alpha-keto acid dehydrogenases. An apparent Km of 0.63 mM for alpha-ketobutyrate was determined for the rat liver system. Competition by other alpha-keto acids at 10 mM concentrations inhibited enzyme activity up to 75%. Tissue distribution of alpha-ketobutyrate dehydrogenase activity relative to liver activity was (in percent): liver, 100; heart, 127; brain, 63; kidney, 57; skeletal muscle, 38; and small intestine, 7. Total liver alpha-ketobutyrate dehydrogenase was decreased by 40% after a 24-hour fast. Similar results were found for kidney and heart activity. alpha-Aminobutyrate-pyruvate aminotransferase activity in liver or kidney was not affected by fasting; however, it was induced in liver by 50% after feeding a 40% casein diet for 10 days compared to rats fed a 20% casein diet. Increasing the dietary casein content from 6 through 40% of the diet resulted in about a fivefold increase in liver alpha-ketobutyrate dehydrogenase activity. The substantial extrahepatic capacity for alpha-ketobutyrate metabolism makes it unlikely that a loss of liver function results in an inability to metabolize alpha-ketobutyrate. Whether alpha-ketobutyrate is decarboxylated by a specific enzyme or by an already characterized complex such as pyruvate dehydrogenase or the branched-chain keto acid dehydrogenase remains to be established.

  9. Ca2+ permeability through rat cloned alpha9-containing nicotinic acetylcholine receptors.

    PubMed

    Fucile, Sergio; Sucapane, Antonietta; Eusebi, Fabrizio

    2006-04-01

    We investigated the functional properties of rat alpha9 and alpha9alpha10 nicotinic acetylcholine receptors (nAChRs) expressed by transient transfection in the rat GH4C1 cell line, using both Ca(2+) imaging and whole-cell recording. Acute applications of ACh generated short-delay fast-rising and quick-decaying Ca(2+) transients, suppressed in Ca(2+)-free medium and invariably accompanied by the activation of whole-cell inward currents. The mean amplitude of ACh-induced currents was as small as -16 pA in alpha9 subunit cDNA-transfected GH4C1 cells (alpha9-GH4C1), while they were much larger (range: -150 to -300 pA) in alpha9alpha10 subunit cDNAs-transfected GH4C1 cells (alpha9alpha10-GH4C1). Currents were not activated by nicotine, were blocked by methyllycaconitine and were ACh concentration-dependent. Because the Ca(2+) permeability of alpha9-containing nAChRs has been estimated in immortalized cochlear UB/OC-2 mouse cells, we also characterized the ACh-induced responses in these cells. Unlike alpha9- and alpha9alpha10-GH4C1 cells, UB/OC-2 cells responded to ACh with both long-delay methyllycaconitine-insensitive whole-cell currents and long-lasting Ca(2+) transients, the latter being detected in the absence of Ca(2+) in the extracellular medium and being suppressed by the Ca(2+)-ATPase inhibitor thapsigargin, known to deplete IP(3)-sensitive stores. These results indicated the involvement of muscarinic nAChRs and the lack of functional ACh-gated receptor channels in UB/OC-2 cells. Thus, we measured the fractional Ca(2+) current (P(f), i.e. the percentage of total current carried by Ca(2+) ions) in alpha9alpha10-GH4C1, obtaining a P(f) value of 22 +/- 4%; this is the largest value estimated to date for a ligand-gated receptor channel. The physiological role played by Ca(2+) entry through alpha9-containing nAChRs gated by ACh is discussed.

  10. The permissive effect of zinc deficiency on uroguanylin and inducible nitric oxide synthase gene upregulation in rat intestine induced by interleukin 1alpha is rapidly reversed by zinc repletion.

    PubMed

    Cui, Li; Blanchard, Raymond K; Cousins, Robert J

    2003-01-01

    Deficient intake of zinc from the diet upregulates both uroguanylin (UG) and inducible nitric oxide synthase (iNOS) expression in rats. Because these changes influence intestinal fluid secretion and intestinal cell pathophysiology, they relate to the incidence of diarrheal disease and its reversal by zinc as well as intestinal inflammation in general. A model of moderate zinc deficiency in rats, which changes molecular indices of zinc deficiency, was used to further explore the effects of the proinflammatory cytokine interleukin (IL)-1alpha and zinc repletion on these changes. IL-1alpha has been shown to have a role in the intestinal inflammation that occurs with bacterial infection. Our results showed a permissive effect of zinc deficiency on both UG and iNOS expression. Specifically, UG expression was responsive to zinc deficiency and IL-1alpha challenge, which were additive when combined, whereas iNOS expression was upregulated by IL-1alpha only during the deficiency. Immunohistochemistry showed that the increase in UG was limited to enterocytes of the upper villus but, in contrast, the increase in iNOS was principally in cells of the lamina propria of IL-1alpha-treated rats. Cells exhibiting UG upregulation did not co-express serotonin. Repletion with zinc reversed upregulation of the iNOS gene within 1 d, whereas UG upregulation required 3-4 d to return to normal. This differential response to repletion suggests that mechanisms of UG and iNOS dysregulation are different. Dysregulation of both genes may contribute to the severity of zinc-responsive diarrheal disease and intestinal inflammatory disease.

  11. Effects of alpha-tocopherol treatment on newborn rat lung development and injury in hyperoxia.

    PubMed

    Bucher, J R; Roberts, R J

    1982-01-01

    The efficacy of alpha-tocopherol treatment to influence the pattern or extent of lung injury resulting during exposure of newborn rats to hyperoxia was assessed following six-day exposures to FIO2 0.21, 0.4, and greater than 0.95. Alpha-Tocopherol treatment was found incapable of preventing the developmental arrest of the lung that occurs during hyperoxic exposure, shown by assessments of wet lung weights, lung DNA, lung volumes, and the progress of secondary septal and capillary development. However alpha-tocopherol treatment was found effective in preventing the hyperoxic-induced lessening of lung compliance and in preventing the deterioration of gas exchange capacity in the lung of the hyperoxic-exposed newborn rat. These findings suggest alpha-tocopherol treatment may not be capable of preventing major alterations in lung morphology in infants with chronic lung disease may be lessened by preserving gas exchange capabilities.

  12. Co-regulation of the atrial natriuretic factor and cardiac myosin light chain-2 genes during alpha-adrenergic stimulation of neonatal rat ventricular cells. Identification of cis sequences within an embryonic and a constitutive contractile protein gene which mediate inducible expression.

    PubMed

    Knowlton, K U; Baracchini, E; Ross, R S; Harris, A N; Henderson, S A; Evans, S M; Glembotski, C C; Chien, K R

    1991-04-25

    To study the mechanisms which mediate the transcriptional activation of cardiac genes during alpha adrenergic stimulation, the present study examined the regulated expression of three cardiac genes, a ventricular embryonic gene (atrial natriuretic factor, ANF), a constitutively expressed contractile protein gene (cardiac MLC-2), and a cardiac sodium channel gene. alpha 1-Adrenergic stimulation activates the expression and release of ANF from neonatal ventricular cells. As assessed by RNase protection analyses, treatment with alpha-adrenergic agonists increases the steady-state levels of ANF mRNA by greater than 15-fold. However, a rat cardiac sodium channel gene mRNA is not induced, indicating that alpha-adrenergic stimulation does not lead to an increase in the expression of all cardiac genes. Studies employing a series of rat ANF luciferase and rat MLC-2 luciferase fusion genes identify 315- and 92-base pair cis regulatory sequences within an embryonic gene (ANF) and a constitutively expressed contractile protein gene (MLC-2), respectively, which mediate alpha-adrenergic-inducible gene expression. Transfection of various ANF luciferase reporters into neonatal rat ventricular cells demonstrated that upstream sequences which mediate tissue-specific expression (-3003 to -638) can be segregated from those responsible for inducibility. The lack of inducibility of a cardiac Na+ channel gene, and the segregation of ANF gene sequences which mediate cardiac specific from those which mediate inducible expression, provides further insight into the relationship between muscle-specific and inducible expression during cardiac myocyte hypertrophy. Based on these results, a testable model is proposed for the induction of embryonic cardiac genes and constitutively expressed contractile protein genes and the noninducibility of a subset of cardiac genes during alpha-adrenergic stimulation of neonatal rat ventricular cells.

  13. Olfactory Bulb [alpha][subscript 2]-Adrenoceptor Activation Promotes Rat Pup Odor-Preference Learning via a cAMP-Independent Mechanism

    ERIC Educational Resources Information Center

    Shakhawat, Amin MD.; Harley, Carolyn W.; Yuan, Qi

    2012-01-01

    In this study, three lines of evidence suggest a role for [alpha][subscript 2]-adrenoreceptors in rat pup odor-preference learning: olfactory bulb infusions of the [alpha][subscript 2]-antagonist, yohimbine, prevents learning; the [alpha][subscript 2]-agonist, clonidine, paired with odor, induces learning; and subthreshold clonidine paired with…

  14. Apoptosis induced by tumor necrosis factor-alpha in rat hepatocyte cell lines expressing hepatitis B virus.

    PubMed Central

    Guilhot, S.; Miller, T.; Cornman, G.; Isom, H. C.

    1996-01-01

    Three well differentiated SV40-immortalized rat hepatocyte cell lines, CWSV1, CWSV2, and CWSV14, and Hepatitis B Virus (HBV)-producing cell lines derived from them were examined for sensitivity to tumor necrosis factor (TNF)-alpha. CWSV1, CWSV2, and CWSV14 cells were co-transfected with a DNA construct containing a dimer of the HBV genome and the neo gene and selected in G418 to generate stable cell lines. Characterization of these cell lines indicated that they contain integrated HBV DNA, contain low molecular weight HBV DNA compatible with the presence of HBV replication intermediates, express HBV transcripts, and produce HBV proteins. The viability of CWSV1, CWSV2, and CWSV2 cells was not significantly altered when they were treated with TNF-alpha at concentrations as high as 20,000 U/ml. The HBV-expressing CWSV1 cell line, SV1di36, and the HBV-expressing CWSV14 cell line, SV14di208, were also not killed when treated with TNF-alpha. However, the HBV-expressing CWSV2 cell line, SV2di366, was extensively killed when treated with TNF-alpha at concentrations ranging from 200 to 20,000 U/ml. Analysis of several different HBV-producing CWSV2 cell lines indicated that TNF-alpha killing depended upon the level of HBV expression. The TNF-alpha-induced cell killing in high HBV-producing CWSV2 cell lines was accompanied by the presence of an oligonucleosomal DNA ladder characteristic of apoptosis. Images Figure 2 Figure 3 Figure 4 Figure 6 Figure 9 Figure 10 Figure 11 PMID:8774135

  15. Complexation of cytochrome P-450 isozymes in hepatic microsomes from SKF 525-A-induced rats.

    PubMed

    Murray, M

    1988-05-01

    Potassium ferricyanide-elicited reactivation of steroid hydroxylase activities, in hepatic microsomes from SKF 525-A-induced male rats, was used as an indicator of complex formation between individual cytochrome P-450 isozymes and the SKF 525-A metabolite. Induction of male rats with SKF 525-A (50 mg/kg for three days) led to apparent increases in androst-4-ene-3,17-dione 16 beta- and 6 beta-hydroxylation to 6.7- and 3-fold of control activities. Steroid 7 alpha-hydroxylase activity was decreased to 0.8-fold of control and 16 alpha-hydroxylation was unchanged. Ferricyanide-elicited dissociation of the SKF 525-A metabolite-P-450 complex revealed an even greater induction of 16 beta- and 6 beta-hydroxylase activities (to 1.8- and 1.6-fold of activities in the absence of ferricyanide). Androst-4-ene-3,17-dione 16 alpha-hydroxylase activity increased 2-fold after ferricyanide but 7 alpha-hydroxylase activity was unaltered. An antibody directed against the male-specific cytochrome P-450 UT-A decreased androst-4-ene-3,17-dione 16 alpha-hydroxylase activity to 13% of control in hepatic microsomes from untreated rats. In contrast, 16 alpha-hydroxylase activity in microsomes from SKF 525-A-induced rats, before and after dissociation with ferricyanide, was reduced by anti UT-A IgG to 32 and 19% of the respective uninhibited controls. Considered together, these observations strongly suggest that the phenobarbital-inducible cytochrome P-450 isozymes PB-B and PCN-E are present in an inactive complexed state in microsomes from SKF 525-A-induced rat liver. Further, the increased susceptibility of androst-4-ene-3,17-dione 16 alpha-hydroxylase activity to inhibition by an antibody to cytochrome P-450 UT-A, following ferricyanide treatment of microsomes, suggests that this male sexually differentiated enzyme is also complexed after in vivo SKF 525-A dosage. In contrast, the constitutive isozyme cytochrome P-450 UT-F, which is active in steroid 7 alpha-hydroxylation, does not appear

  16. Aliskiren ameliorates chlorhexidine digluconate-induced peritoneal fibrosis in rats.

    PubMed

    Ke, Chun-Yen; Lee, Chia-Chi; Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Hsu, Bang-Gee

    2010-04-01

    Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of aliskiren on chlorhexidine digluconate-induced PF in rats. The PF was induced in Sprague-Dawley rats by daily administration of 0.5 mL 0.1% chlorhexidine digluconate in normal saline via PD tube for 1 week. Rats received daily intravenous injections of low-dose aliskiren (1 mg kg(-1)) or high-dose aliskiren (10 mg kg(-1)) for 1 week. After 7 days, conventional 4.25% Dianeal (30 mL) was administered via a PD catheter with a dwell time of 4 h and assessed of peritoneal function. At the end of dialysis, rats were sacrificed and the liver peritoneum was harvested for microscopically and immunohistochemistry. There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D(4)/P(4) urea level was reduced, the D(4)/D(0) glucose level, serum and dialysate transforming growth factor-beta1 (TGF-beta1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF) were elevated in the PS group compared with the vehicle group. Aliskiren decreased the serum and dialysate TGF-beta1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-beta1, alpha-SMA, fibronectin, collagen, and VEGF-positive cells in liver peritoneum. Moreover, high-dose aliskiren had better protective effects against PF than low dose in rats. Aliskiren protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-beta1 production.

  17. Alpha 2-adrenoceptor blockade, pituitary-adrenal hormones, and agonistic interactions in rats.

    PubMed

    Haller, J; Barna, I; Kovács, J L

    1994-08-01

    The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. Alpha 2 adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an alpha 2 adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different alpha 2 adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the alpha 2 adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed.

  18. [The effects of nicergoline on the heart rate in the normotensive or spontaneously hypertensive rat. Possible participation of central alpha-1 receptors].

    PubMed

    Huchet, A M; Schmitt, H

    1986-01-01

    The cardiovascular effects of nicergoline, a preferential alpha 1-adrenoceptor blocking drug, were studied in anaesthetized normotensive or spontaneously hypertensive (SH) rats. Nicergoline (300 micrograms/kg, i.v.) significantly reduced blood pressure and heart rate in control, bivagotomized or beta-blocked normotensive or SH rats. In bilaterally vagotomized and beta-blocked rats, nicergoline reduced mean blood pressure but did no longer modify heart rate. Thus, it is postulated that nicergoline could reduce the sympathetic tone and increase the vagal nerve activity, possibly by inhibiting central alpha 1-adrenoceptors. The nicergoline--induced bradycardia was greater in bivagotomized SHR than in normotensive ones. Intracerebroventricular injections of nicergoline (30 micrograms/kg) did not modify heart rate in normotensive control, bivagotomized or beta-blocked rats. On the contrary, nicergoline (30 micrograms/kg) injected into the cisterna magna induced a significant bradycardia in the three groups of normotensive rats. Blood pressure was reduced in the same way in all groups centrally treated by nicergoline. In conclusion, it seems that nicergoline reduces blood pressure by peripheral alpha-adrenoceptor blockade and modulates the autonomic nervous activity by inhibiting alpha 1-adrenoceptors mainly localized in the brainstem.

  19. Cloning and characterization of the rat HIF-1 alpha prolyl-4-hydroxylase-1 gene.

    PubMed

    Cobb, Ronald R; McClary, John; Manzana, Warren; Finster, Silke; Larsen, Brent; Blasko, Eric; Pearson, Jennifer; Biancalana, Sara; Kauser, Katalin; Bringmann, Peter; Light, David R; Schirm, Sabine

    2005-08-01

    Prolyl-4-hydroxylase domain-containing enzymes (PHDs) mediate the oxygen-dependent regulation of the heterodimeric transcription factor hypoxia-inducible factor-1 (HIF-1). Under normoxic conditions, one of the subunits of HIF-1, HIF-1alpha, is hydroxylated on specific proline residues to target HIF-1alpha for degradation by the ubiquitin-proteasome pathway. Under hypoxic conditions, the hydroxylation by the PHDs is attenuated by lack of the oxygen substrate, allowing HIF-1 to accumulate, translocate to the nucleus, and mediate HIF-mediated gene transcription. In several mammalian species including humans, three PHDs have been identified. We report here the cloning of a full-length rat cDNA that is highly homologous to the human and murine PHD-1 enzymes and encodes a protein that is 416 amino acids long. Both cDNA and protein are widely expressed in rat tissues and cell types. We demonstrate that purified and crude baculovirus-expressed rat PHD-1 exhibits HIF-1alpha specific prolyl hydroxylase activity with similar substrate affinities and is comparable to human PHD-1 protein.

  20. Genetically-induced Estrogen Receptor Alpha mRNA (Esr1) Overexpression Does Not Adversely Affect Fertility or Penile Development in Male Mice

    PubMed Central

    Heath, John; Abdelmageed, Yazeed; Braden, Tim D.; Williams, Carol S.; Williams, John W.; Paulose, Tessie; Hernandez-Ochoa, Isabel; Gupta, Rupesh; Flaws, Jodi A.; Goyal, Hari O.

    2011-01-01

    Previously, we reported that estrogen receptor alpha mRNA (Esr1) or protein (ESR1) overexpression resulting from neonatal exposure to estrogens in rats was associated with infertility and mal-developed penis characterized by reduced length and weight and abnormal accumulation of fat cells. The objective of this study was to determine if mutant male mice overexpressing Esr1 are naturally infertile or have reduced fertility and/or develop abnormal penis. The fertility parameters, including fertility and fecundity indices, numbers of days from the day of cohabitation to the day of delivery, and numbers of pups per female, were not altered from controls, as a result of Esr1 overexpression. Likewise, penile morphology, including the length, weight, and diameter and os penis development, was not altered from controls. Conversely, weights of the seminal vesicles and bulbospongiosus and levator ani (BS/LA) muscles were significantly (P < 0.05) lower as compared to controls; however, the weight of the testis, the morphology of the testis and epididymis, and the plasma and testicular testosterone concentration were not different from controls. Hence, the genetically-induced Esr1 overexpression alone, without an exogenous estrogen exposure during the neonatal period, is unable to adversely affect the development of the penis as well as other male reproductive organs, except limited, but significant, reductions in weights of the seminal vesicles and BS/LA muscles. PMID:20930192

  1. Quantitative immuno-electron microscopic analysis of depolarization-induced expression of PGC-1alpha in cultured rat visual cortical neurons.

    PubMed

    Meng, Hui; Liang, Huan Ling; Wong-Riley, Margaret

    2007-10-17

    Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC- 1alpha) is a coactivator of nuclear receptors and other transcription factors that regulate several metabolic processes, including mitochondrial biogenesis, energy homeostasis, respiration, and gluconeogenesis. PGC-1alpha plays a vital role in stimulating genes that are important to oxidative metabolism and other mitochondrial functions in brown adipose tissue and skeleton muscles, but the significance of PGC-1alpha in the brain remains elusive. The goal of our present study was to determine by means of quantitative immuno-electron microscopy the expression of PGC-1alpha in cultured rat visual cortical neurons under normal conditions as well as after depolarizing stimulation for varying periods of time. Our results showed that: (a) PGC-1alpha was normally located in both the nucleus and the cytoplasm. In the nucleus, PGC-1alpha was associated mainly with euchromatin rather than heterochromatin, consistent with active involvement in transcription. In the cytoplasm, it was associated mainly with free ribosomes. (b) Neuronal depolarization by KCl for 0.5 h induced a significant increase in PGC-1alpha labeling density in both the nucleus and the cytoplasm (P<0.01). The heightened expression continued after 1 and 3 h of depolarizing treatment (P<0.01), but decreased from 5 h onward and returned to baseline level by 10 h. These results indicate that PGC-1alpha responds very early to increased neuronal activity by synthesizing more proteins in the cytoplasm and translocating them to the nucleus for gene activation. PGC-1alpha level in neurons is, therefore, tightly regulated by neuronal activity.

  2. Hazard evaluation of chemicals that cause accumulation of alpha 2u-globulin, hyaline droplet nephropathy, and tubule neoplasia in the kidneys of male rats.

    PubMed Central

    Hard, G C; Rodgers, I S; Baetcke, K P; Richards, W L; McGaughy, R E; Valcovic, L R

    1993-01-01

    This review paper examines the relationship between chemicals inducing excessive accumulation of alpha 2u-globulin (alpha 2u-g) (CIGA) in hyaline droplets in male rat kidneys and the subsequent development of nephrotoxicity and renal tubule neoplasia in the male rat. This dose-responsive hyaline droplet accumulation distinguishes CIGA carcinogens from classical renal carcinogens. CIGA carcinogens also do not appear to react with DNA and are generally negative in short-term tests for genotoxicity, CIGA or their metabolites bind specifically, but reversibly, to male rat alpha 2u-g. The resulting complex appears to be more resistant to hydrolytic degradation in the proximal tubule than native, unbound alpha 2u-g. Single cell necrosis of the tubule epithelium, with associated granular cast formation and papillary mineralization, is followed by sustained regenerative tubule cell proliferation, foci of tubule hyperplasia in the convoluted proximal tubules, and renal tubule tumors. Although structurally similar proteins have been detected in other species, including humans, renal lesions characteristic of alpha 2u-g nephropathy have not been observed. Epidemiologic investigation has not specifically examined the CIGA hypothesis for humans. Based on cancer bioassays, hormone manipulation studies, investigations in an alpha 2u-g-deficient strain of rat, and other laboratory data, an increased proliferative response caused by chemically induced cytotoxicity appears to play a role in the development of renal tubule tumors in male rats. Thus, it is reasonable to suggest that the renal effects induced in male rats by chemicals causing alpha 2u-g accumulation are unlikely to occur in humans. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 8. FIGURE 9. FIGURE 10. FIGURE 11. FIGURE 12. FIGURE 13. PMID:7686485

  3. Increased choline kinase activity in 1,2-dimethylhydrazine-induced rat colon cancer.

    PubMed

    Nakagami, K; Uchida, T; Ohwada, S; Koibuchi, Y; Morishita, Y

    1999-11-01

    Cancer cells acquire particular characteristics that benefit their proliferation. We previously reported that human colon cancers examined had increased choline kinase activity and phosphocholine levels. The elevated phosphocholine levels were in part due to both activation of choline kinase and increased choline kinase alpha protein levels. In this report, we analyzed choline kinase, which catalyzes the phosphorylation of choline to produce phosphocholine, in rat 1,2-dimethylhydrazine (DMH)-induced colon cancer. This study is the first to demonstrate increased choline kinase alpha enzymatic activity, protein levels, and mRNA levels in DMH-induced colon cancer as well as human colon cancer, although phosphocholine was not increased in DMH-induced rat cancer. The increase in the mRNA level was partly due to an increase in the transcription of the choline kinase alpha gene. The increased choline kinase activity may be a specific characteristic acquired by cancer cells that benefits their proliferation.

  4. The involvement of peripheral alpha 2-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain.

    PubMed

    Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Ugresić, Nenad D; Paranos, Sonja Lj; Prostran, Milica S; Bosković, Bogdan

    2007-11-01

    We studied whether peripheral alpha2-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective alpha2-adrenoceptor antagonist), BRL 44408 (selective alpha(2A)-adrenoceptor antagonist), MK-912 (selective alpha2C-adrenoceptor antagonist), and clonidine (alpha2-adrenoceptor agonist) on the antihyperalgesic effect of oxcarbazepine in the rat model of inflammatory pain. Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: 1) the development of hyperalgesia induced by Con A; 2) the effects of oxcarbazepine (i.pl.) on Con A-induced hyperalgesia; and 3) the effects of i.pl. yohimbine, BRL 44408, MK-912 and clonidine on the oxcarbazepine antihyperalgesia. Both oxcarbazepine (1000-3000 nmol/paw; i.pl.) and clonidine (1.9-7.5 nmol/paw; i.pl.) produced a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by Con A. Yohimbine (260 and 520 nmol/paw; i.pl.), BRL 44408 (100 and 200 nmol/paw; i.pl.) and MK-912 (10 and 20 nmol/paw; i.pl.) significantly depressed the antihyperalgesic effects of oxcarbazepine (2000 nmol/paw; i.pl.) in a dose-dependent manner. The effects of antagonists were due to local effects since they were not observed after administration into the contralateral hindpaw. Oxcarbazepine and clonidine administered jointly in fixed-dose fractions of the ED(50) (1/4, 1/2, and 3/4) caused significant and dose-dependent reduction of hyperalgesia induced by Con A. Isobolographic analysis revealed an additive antihyperalgesic effect. Our results indicate that the peripheral alpha2A and alpha2C adrenoceptors could be involved in the antihyperalgesic effects of oxcarbazepine in a rat model of inflammatory hyperalgesia.

  5. Genomic organization of the rat alpha 2u-globulin gene cluster.

    PubMed

    McFadyen, D A; Addison, W; Locke, J

    1999-05-01

    The alpha 2u-globulin are a group of similar proteins, belonging to the lipocalin superfamily of proteins, that are synthesized in a subset of secretory tissues in rats. The many alpha 2u-globulin isoforms are encoded by a multigene family that exhibits extensive homology. Despite a high degree of sequence identity, individual family members show diverse expression patterns involving complex hormonal, tissue-specific, and developmental regulation. Analysis suggests that there are approximately 20 alpha 2u-globulin genes in the rat genome. We have used fluorescence in situ hybridization (FISH) to show that the alpha 2u-globulin genes are clustered at a single site on rat Chromosome (Chr) 5 (5q22-24). Southern blots of rat genomic DNA separated by pulsed field gel electrophoresis indicated that the alpha 2u-globulin genes are contained on two NruI fragments with a total size of 880 kbp. Analysis of three P1 clones containing alpha 2u-globulin genes indicated that the alpha 2u-globulin genes are tandemly arranged in a head-to-tail fashion. The organization of the alpha 2u-globulin genes in the rat as a tandem array of single genes differs from the homologous major urinary protein genes in the mouse, which are organized as tandem arrays of divergently oriented gene pairs. The structure of these gene clusters may have consequences for the proposed function, as a pheromone transporter, for the protein products encoded by these genes.

  6. Dissociation between PGC-1alpha and GLUT-4 expression in skeletal muscle of rats fed a high-fat diet.

    PubMed

    Higashida, Kazuhiko; Higuchi, Mitsuru; Terada, Shin

    2009-12-01

    It has recently been reported that a 4-wk high-fat diet gradually increases skeletal muscle peroxisome proliferator activated receptor (PPAR) gamma coactivator-1alpha (PGC-1alpha) protein content, which has been suggested to regulate GLUT-4 gene transcription. However, it has not been reported that a high-fat diet enhances GLUT-4 mRNA expression and protein content in skeletal muscle, suggesting that an increase in PGC-1alpha protein content is not sufficient to induce muscle GLUT-4 biogenesis in a high-fat fed animal. Therefore, we first evaluated the relationship between PGC-1alpha and GLUT-4 expression in skeletal muscle of rats fed a high-fat diet for 4 wk. The PGC-1alpha protein content in rat epitrochlearis muscle significantly increased by twofold after the 4-wk high-fat diet feeding. However, the high-fat diet had no effect on GLUT-4 protein content and induced a 30% decrease in GLUT-4 mRNA expression in rat skeletal muscle (p<0.05). To clarify the mechanism by which a high-fat diet downregulates GLUT-4 mRNA expression, we next examined the effect of PPARdelta activation, which is known to occur in response to a high-fat diet, on GLUT-4 mRNA expression in L6 myotubes. Incubation with 500 nM GW501516 (PPARdelta activator) for 24 h significantly decreased GLUT-4 mRNA in L6 myotubes. Taken together, these findings suggest that a high-fat diet downregulates GLUT-4 mRNA, possibly through the activation of PPARdelta, despite an increase in PGC-1alpha protein content in rat skeletal muscle, and that a posttranscriptional regulatory mechanism maintains GLUT-4 protein content in skeletal muscle of rats fed a high-fat diet.

  7. The influence of tumour necrosis factor-alpha on the cardiovascular system of anaesthetized rats.

    PubMed

    Tabrizchi, R

    2001-03-01

    The effects of two vasoactive agents (adenosine A2A agonist, CGS 21680, and adrenoceptor agonist, noradrenaline) were examined on cardiac output (CO), heart rate (HR), blood pressure (BP), mean circulatory filling pressure (Pmcf), resistance to venous return, arterial resistance, dP/dt, plasma levels of NO2-/NO3-, and inducible nitric oxide synthase (iNOS) activity in lungs ex vivo, following treatment with tumour necrosis factor-alpha (TNF-alpha; 30 microg/kg) in anaesthetized rats. Treatment with TNF-alpha produced significant reduction in CO (41+/-2%), dP/dt (26+/-3%), BP (26+/-2%) and Pmcf (27+/-4%; n=6; mean+/-SEM), but increased arterial resistance. There were no significant changes in the plasma levels of NO2-/NO3-levels over time following treatment with TNF-alpha, but there was a significant increase (approximately twofold) in the activity of the iNOS in the lungs of animals treated with TNF-alpha. Administration of CGS 21680 (1.0 microg/kg per min) significantly increased CO (44+/-6%), HR (12+/-2%), Pmcf (24+/-4%) and dP/dt (24+/-5%) in TNF-alpha-treated rats. CGS 21680 also significantly reduced arterial resistance (33+/-2%) without altering resistance to venous return in TNF-alpha-treated rats. While noradrenaline (1.0 microg/kg per min) infusion did not significantly increase CO, it did significantly increase HR (12+/-1%), BP (55+/-9%), Pmcf (47+/-5%), dP/dt (65+/-7%), resistance to venous return (64+/-20%), and arterial resistance (41+/-16%) in TNF-alpha-treated animals. The reduction in BP due to administration of TNF-alpha is the result of significant reduction in CO. Consequently, the decline in CO can be attributed to a combination of a negative inotropic effect as well as a reduction in Pmcf. It is evident that infusion with CGS 21680 could reverse the negative impact of TNF-alpha on CO by increasing dP/dt, Pmcf and HR as well as a reduction in arterial resistance. The fact that noradrenaline did not significantly increase CO in TNF-alpha

  8. Carbachol induces TGF-alpha expression and colonic epithelial cell proliferation in sensory-desensitised rats.

    PubMed

    Bulut, Kerem; Felderbauer, Peter; Hoeck, Karoline; Schmidt, Wolfgang E; Hoffmann, Peter

    2010-03-01

    Signals for the expression of the peptide growth factors epidermal growth factor and transforming growth factor-alpha (TGFalpha) in the gastrointestinal mucosa are largely unknown. We have shown earlier that extrinsic afferents in the gastrointestinal tract induce TGFalpha expression in colonic mucosa via the deliberation of neurotransmitters substance P and calcitonin gene-related peptide. The aim of our present study was to determine the effects of carbachol on mucosal TGFalpha expression and epithelial cell proliferation in vivo. Rats were divided in three groups. Group 1 was treated with vehicle only, group 2 received one single subcutaneous injection of 250 microg/kg of carbachol and animals in group 3 were sensory-desensitised prior to the injection of 250 microg/kg carbachol. TGFalpha expression and epithelial cell proliferation was evaluated by polymerase chain reaction, Western blot analysis and bromodeoxyuridine staining. Carbachol induced a significant increase in mucosal epithelial cell proliferation and TGFalpha expression. Sensory desensitisation did neither abolish the increased TGFalpha expression nor the increase in epithelial cell proliferation. Parasympathetic pathways are involved in the control of TGFalpha expression in gastrointestinal mucosa as well as in epithelial cell proliferation.

  9. Alpha2-adrenoceptor modulation of long-term potentiation elicited in vivo in rat occipital cortex.

    PubMed

    Mondaca, Mauricio; Hernández, Alejandro; Pérez, Hernán; Valladares, Luis; Sierralta, Walter; Fernández, Victor; Soto-Moyano, Rubén

    2004-09-24

    Pretreatment with the alpha(2)-adrenoceptor agonist clonidine (31.25, 62.5, or 125 microg/kg, i.p.) dose-dependently reduced long-term potentiation (LTP) elicited in vivo in the occipital cortex of anesthetized rats, whereas pretreatment with the alpha(2)-adrenoceptor antagonist yohimbine (0.133, 0.4, or 1.2 mg/kg, i.p.) increased neocortical LTP in a dose-dependent fashion. These effects could be related to the reported disruptive and facilitatory actions induced on memory formation by pretreatment with alpha(2)-adrenoceptor agonists and antagonists, respectively.

  10. Localization of alpha 1-adrenoceptors in rat and human hearts by immunocytochemistry.

    PubMed

    Schulze, W; Fu, M L

    1996-01-01

    The localization of the alpha 1 adrenoceptors (alpha 1-AR) in the heart tissues from rat and human and in the cultured heart cells from neonatal rats was studied by indirect immunofluorescence and postembedding electronmicroscopical immuno-gold technique. With antipeptide antibodies directed against the second extracellular loop of the human alpha 1-AR (AS sequence 192-218), this receptor was found to be localized along the sarcolemma in both human and rat hearts. Similar localization sites were detected in cultivated rat neonatal cardiomyocytes. Beside the localization in cardiomyocytes, alpha 1-AR were identified in endothelial cells of capillaries and smooth muscle cells of coronary vessels, in neuronal endings, in mast cells of cultivated heart cells but not, or in less amount in fibroblasts. Interestingly, in the right atrium of rat heart the localization of alpha 1-AR was found to be near or on atrial natriuretic factor (ANF) granules, providing the basis for the alpha-adrenergic influence on ANF release. The immunocytochemical studies further confirm and complete the findings known by using autoradiographic binding studies with specific ligands.

  11. Dexmedetomidine-induced Contraction Involves Phosphorylation of Caldesmon by JNK in Endothelium-denuded Rat Aortas

    PubMed Central

    Baik, Jiseok; Ok, Seong-Ho; Cho, Hyunhoo; Yu, Jongsun; Kim, Woochan; Nam, In-Koo; Choi, Mun-Jeoung; Lee, Heon-Keun; Sohn, Ju-Tae

    2014-01-01

    Caldesmon, an inhibitory actin binding protein, binds to actin and inhibits actin-myosin interactions, whereas caldesmon phosphorylation reverses the inhibitory effect of caldesmon on actin-myosin interactions, potentially leading to enhanced contraction. The goal of this study was to investigate the cellular signaling pathway responsible for caldesmon phosphorylation, which is involved in the regulation of the contraction induced by dexmedetomidine (DMT), an alpha-2 adrenoceptor agonist, in endothelium-denuded rat aortas. SP600125 (a c-Jun NH2-terminal kinase [JNK] inhibitor) dose-response curves were generated in aortas that were pre-contracted with DMT or phorbol 12,13-dibutyrate (PDBu), a protein kinase C (PKC) activator. Dose-response curves to the PKC inhibitor chelerythrine were generated in rat aortas pre-contracted with DMT. The effects of SP600125 and rauwolscine (an alpha-2 adrenoceptor inhibitor) on DMT-induced caldesmon phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) were investigated by western blot analysis. PDBu-induced caldesmon and DMT-induced PKC phosphorylation in rat aortic VSMCs was investigated by western blot analysis. The effects of GF109203X (a PKC inhibitor) on DMT- or PDBu-induced JNK phosphorylation in VSMCs were assessed. SP600125 resulted in the relaxation of aortas that were pre-contracted with DMT or PDBu, whereas rauwolscine attenuated DMT-induced contraction. Chelerythrine resulted in the vasodilation of aortas pre-contracted with DMT. SP600125 and rauwolscine inhibited DMT-induced caldesmon phosphorylation. Additionally, PDBu induced caldesmon phosphorylation, and GF109203X attenuated the JNK phosphorylation induced by DMT or PDBu. DMT induced PKC phosphorylation in rat aortic VSMCs. These results suggest that alpha-2 adrenoceptor-mediated, DMT-induced contraction involves caldesmon phosphorylation that is mediated by JNK phosphorylation by PKC. PMID:25332685

  12. [Influence of bear bile on rat hepatocarcinoma induced by diethylnitrosamine].

    PubMed

    Zhou, Jian-Yin; Yin, Zhen-Yu; Wang, Sheng-Yu; Yan, Jiang-Hua; Zhao, Yi-Lin; Wu, Duan; Liu, Zheng-Jin; Zhang, Sheng; Wang, Xiao-Min

    2012-11-01

    To investigate the influence of bear bile on rat hepatocarcinoma induced by diethylnitrosamine (DEN), a total of 40 rats were randomly divided into 4 groups: normal control group, model group, and two bear bile treatment groups. The rat liver cancer model was induced by breeding with water containing 100 mg x L(-1) DEN for 14 weeks. The rats of the bear bile groups received bear bile powder (200 or 400 mg x kg(-1)) orally 5 times per week for 18 weeks. The general condition and the body weight of rats were examined every day. After 18 weeks the activities of serum alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin (TBIL) were detected. Meanwhile, the pathological changes of liver tissues were observed after H&E staining. The expression of proliferative cell nuclear antigen (PCNA) and a-smooth muscle actin (alpha-SMA) in liver tissue were detected by immunohistochemical method. After 4 weeks the body weights of rats in normal group were significantly more than that in other groups (P < 0.05); and that in the two bile groups was significantly more than that in the model group. Compared with normal group, the level of serum glutamic-pyruvic transaminase and total bilirubin increased significantly in other groups; compared with model group, these two indexes decreased significantly in two bile groups. Hepatocellular carcinoma occurred in all rats except for normal group; there were classic cirrhosis and cancer in model group while there were mild cirrhosis and high differentiation in two bile groups. There were almost no expressions of PCNA and alpha-SMA in normal group while there were high expressions in model group; the two bile groups had some expressions but were inferior to the model group, and alpha-SMA reduced markedly. It indicated that bear bile restrained the development of liver cancer during DEN inducing rat hepatocarcinoma, which may be related to its depressing hepatic stellate cell activation and relieving hepatic lesion and

  13. Role of cortical alpha-2 adrenoceptors in alcohol withdrawal-induced depression and tricyclic antidepressants

    PubMed Central

    Getachew, Bruk; Hauser, Sheketha R.; Csoka, Antonei B.; Taylor, Robert E.; Tizabi, Yousef

    2017-01-01

    Introduction Although a role for alpha-2 adrenoceptors (alpha-2 ARs) in alcohol use disorder (AUD) and depression is suggested, very little information on a direct interaction between alcohol and these receptors is available. Methods In this study adult female Wistar and Wistar-Kyoto (WKY) rats, a putative animal model of depression, were exposed to alcohol vapor 3 h daily for 10 days (blood alcohol concentration ~150 mg%) followed by daily injection of 10 mg/kg of imipramine (IMP, a selective norepinephrine NE/serotonin reuptake inhibitor) or nomifensine (NOMI, a selective NE/dopamine reuptake inhibitor). On day 11 animals were tested for open field locomotor activity (OFLA) and forced swim test (FST) and were sacrificed 2 h later for measurement of alpha-2 ARs densities in the frontal cortex and hippocampus using [3H]RX 821002 as the specific ligand. Results Chronic alcohol treatment increased the immobility in the FST, without affecting OFLA in both Wistar and WKY rats, suggesting induction of depressive-like behavior in Wistar rats and an exacerbation of this behavior in WKY rats. Alcohol treatment also resulted in an increase in cortical but not hippocampal alpha-2 ARs densities in both Wistar and WKY rats. The behavioral effects of alcohol were completely blocked by IMP and NOMI and the neurochemical effects (increases in alpha-2 ARs) were significantly attenuated by both drugs in both strains. Conclusions The results suggest a role for cortical alpha-2 ARs in alcohol withdrawal-induced depression and that selective subtype antagonists of these receptors may be of adjunct therapeutic potential in AUD-depression co-morbidity. PMID:28414989

  14. Effects of orally administered OP-1206 alpha-CD with loxoprofen-Na on walking dysfunction in the rat neuropathic intermittent claudication model.

    PubMed

    Nakai, Katsuhiko; Takenobu, Yoshifumi; Takimizu, Hideyuki; Akimaru, Shinji; Ito, Hidenori; Maegawa, Hitoshi; Marsala, Martin; Katsube, Nobuo

    2003-10-01

    An orally active prostaglandin E1 analogue, OP-1206 alpha-CD improves walking dysfunction in the rat spinal stenosis model. Loxoprofen-Na, a non-steroidal anti-inflammatory drug, is used to relieve chronic pain in patients with lumbar spinal canal stenosis. To determine whether the OP-1206 alpha-CD in combination with loxoprofen-Na could induce a greater therapeutical effect on walking dysfunction and spinal cord blood flow (SCBF) than OP-1206 alpha-CD treatment alone after chronic spinal stenosis in the rat. Spinal stenosis was induced by placing two pieces of silicon rubber strips in the lumbar (L4 and L6) epidural space of rats. After surgery, walking function was measured using a treadmill apparatus and SCBF was measured using a laser-Doppler flow meter. Drugs were administered orally twice a day for 11 days from the day 3 post-surgery. OP-1206 alpha-CD elicited a significant improvement of walking dysfunction on days 7 and 14 post-surgery and significantly increased spinal cord blood flow on day 15, whereas walking dysfunction and SCBF of rats treated with loxoprofen-Na alone remained unchanged. Combined treatment of OP-1206 alpha-CD with loxoprofen-Na did not provide additive therapeutical effect. These results suggest that a significant improvement seen after OP-1206 alpha-CD treatment is primarily mediated by improvement of the local spinal cord blood flow. This effect is not ameliorated or potentiated by a combined treatment with loxoprofen-Na.

  15. Effect of alpha-lipoic acid on endometrial implants in an experimental rat model.

    PubMed

    Pınar, Neslihan; Soylu Karapınar, Oya; Özcan, Oğuzhan; Özgür, Tümay; Bayraktar, Suphi

    2017-10-01

    To investigate the antioxidant and anti-inflammatory effects of alpha-lipoic acid (ALA) in the treatment of endometriosis in an experimental rat model by evaluating biochemical and histopathologic parameters. Experimental endometriosis was induced by the peritoneal implantation of autologous endometrial tissue. The rats were randomly divided into two groups with eight rats each. Group I was intraperitoneally administered ALA 100 mg/kg/day for 14 days. Group II was intraperitoneally administered saline solution at the same dosage and over the same period. Endometrial implant volume was measured in both groups both pre- and post-treatment. Tumor necrosis factor alpha (TNF-α) was measured in peritoneal fluid. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were assessed in serum. The implants were histopathologically evaluated. In the ALA group, the serum TOS and OSI levels, the endometrial implant volumes, the TNF-α levels in serum and peritoneal fluid, and the histopathologic scores were significantly lower compared to the control group (P < 0.05). Alpha-lipoic acid may have a therapeutic potential in the treatment of endometriosis due to its antioxidant and anti-inflammatory effects. © 2017 Société Française de Pharmacologie et de Thérapeutique.

  16. The radioprotective activities of turpentine-induced inflammation and alpha2-macroglobulin: the effect of dexamethasone on the radioprotective efficacy of the inflammation.

    PubMed

    Sevaljević, Ljiljana; Dobrić, Silva; Bogojević, Desanka; Petrović, Miodrag; Koricanać, Goran; Vulović, Mojca; Kanazir, Dusan; Ribarac-Stepić, Nevena

    2003-03-01

    This work was aimed at the radioprotective efficacy of turpentine oil (TO), alpha2-Macroglobulin (alpha2-M), Amifostine (Ami) and/or dexamethasone (Dex). These agents were administrated, alone or in combination, prior to irradiation of rats with 6.7 Gy (LD(50/30)). The survival was recorded daily for 4 weeks after irradiation and body weight, peripheral leukocytes and thrombocytes were measured. The plasma concentration of alpha2-M and other acute phase proteins were determined by crossed immunoelectrophoresis. All rats receiving alpha2-M and Ami alone or in combination survived the radiation injury, whereas the rate of survival of TO-treated rats was 90%. Radiation and therapy-induced changes in the expression of acute phase protein genes were atypical for the acute phase reaction. Dex alone was lethal for 45% and 55% of control and irradiated rats, respectively. Pretreatment with 1mg Dex reduced radioprotective efficacy of TO and Ami to 30% and 40%, respectively. Given together TO and Ami provided 70% protection to rats receiving Dex. The TO and alpha2-M enhanced the rate of survival from 50% to 90% and 100%, respectively. In the presence of 1mg Dex the TO-induced radioprotectors and Ami exhibited radiosensitizing rather than radioprotecting activities.

  17. Inhibitory effects of crude alpha-mangostin, a xanthone derivative, on two different categories of colon preneoplastic lesions induced by 1, 2-dimethylhydrazine in the rat.

    PubMed

    Nabandith, Viengvansay; Suzui, Masumi; Morioka, Takamitsu; Kaneshiro, Tatsuya; Kinjo, Tatsuya; Matsumoto, Kenji; Akao, Yukihiro; Iinuma, Munekazu; Yoshimi, Naoki

    2004-01-01

    The purpose of this study was to examine whether crude alpha-mangostin (a major xanthone derivative in mangosteen pericarp (Garcinia mangostana)) has short-term chemopreventive effects on putative preneoplastic lesions involved in rat colon carcinogenesis. The crude preparation was obtained by simple recrystallization of an ethylacetate extract of mangosteen pericarps. A total of 33 five-week-old male F344 rats were randomly divided into 5 experimental groups. Rats in groups 1-3 were given a subcutaneous injection of 1,2-dimethylhydrazine (DMH)(40 mg/kg body weight) once a week for 2 weeks. Starting one week before the first injection of DMH, rats in groups 2 and 3 were fed a diet containing 0.02% and 0.05% crude alpha-mangostin, respectively, for 5 weeks. Rats in group 4 also received the diet containing 0.05% crude alpha-mangostin, while rats in group 5 served as untreated controls. The experiment was terminated 5 weeks after the start. Dietary administration of crude alpha-mangostin at both doses significantly inhibited the induction and/or development of aberrant crypt foci (ACF) (P<0.05 for 0.02% crude alpha-mangostin, P<0.01 for 0.05% crude alpha-mangostin), when compared to the DMH-treated group (group 1). Moreover, treatment of rats with 0.05% crude alpha-mangostin significantly decreased dysplastic foci (DF) (P<0.05) and beta-catenin accumulated crypts (BCAC) (P<0.05), to below the group 1 values. The proliferating cell nuclear antigen (PCNA) labeling indices of colon epithelium and focal lesions in groups 2 and 3 were also significantly lower than in group 1 and this effect occurred in a dose dependent manner of the crude alpha-mangostin. This finding that crude alpha-mangostin has potent chemopreventive effects in our short-term colon carcinogenesis bioassay system suggests that longer exposure might result in suppression of tumor development.

  18. Prophylactic effect of four prescriptions of traditional Chinese medicine on alpha-naphthylisothiocyanate and carbon tetrachloride induced toxicity in rats.

    PubMed

    Lin, K J; Chen, J C; Tsauer, W; Lin, C C; Lin, J G; Tsai, C C

    2001-12-01

    To study the prophylactic effects of four Chinese traditional prescriptions against experimental liver injury. Liver toxins, alpha-naphthylisothiocyanate (ANIT), and carbon tetrachloride (CCl4) were used to induce acute liver injury. Simo Yin(SMY), Guizhi Fuling Wan (GFW), Xieqing Wan (XQW), and Sini San (SNS) were fed (500 mg/kg, in saline, po) to the rats before toxin administration. All the animals were killed 48 h after toxin insulted. Serum index of liver function and hepatic lipid peroxidation (LPO) were estimated. Histopathological observation was conducted simultaneously. The rats treated with ANIT exhibited elevations of serum total bilirubin (TBI), alkaline phosphatase (ALP), glutamate-oxalate- transaminase (GOT), glutamate-pyruvate-transaminase (GPT), as well as cholestasis and parenchyma necrosis. In rats, challenged with ANIT, receiving the pre-treatment of prescriptions of SMY, XQW, and SNS, the biochemical and morphological parameters of liver injury were significantly reduced. The increased LPO level in liver tissue, associated with the provoked serum GOT and GPT levels were the salient features observed in CCl4-insulting rats. Pre-treatment of four prescriptions showed a remarkable protective effect, and also was effective in counteracting the free radical toxicity by bringing about a significant decrease in peroxidative level. These recipes ameliorate liver damage induced by both ANIT and CCl4 despite the differences in their mechanisms of injury. Therefore they may be able to exert hepatoprotective effects through more than one mechanism of action because they contained a mixture of anti-hepatotoxic ingredients with mutual reinforcement and assistance.

  19. Ginkgo biloba leaf extract and alpha-tocopherol attenuate haloperidol-induced orofacial dyskinesia in rats: Possible implication of antiapoptotic mechanisms by preventing Bcl-2 decrease and Bax elevation.

    PubMed

    An, Hui Mei; Tan, Yun Long; Shi, Jing; Wang, Zhiren; Lv, Meng Han; Soares, Jair C; Zhou, Dongfeng; Yang, Fude; Zhang, Xiang Yang

    2016-12-01

    Tardive dyskinesia (TD) is a serious side effect of long-term administration of typical neuroleptics, such as haloperidol. The pathophysiology of TD remains unclear, but the experimental evidence suggests that free radical-induced neuronal apoptosis in the basal ganglia may play an important role. This study was to investigate changes in Bax and Bcl-2 expression levels in TD-associated brain regions and the effects of the antioxidant EGb761 on Bax and Bcl-2 levels in an animal model of TD. Thirty-two rats were randomly divided into four study groups: saline control (saline), haloperidol-alone (haloperidol), EGb761-haloperidol (EGb), and alpha-tocopherol-haloperidol (vitamin E). Rats were treated with daily intraperitoneal haloperidol injections (2 mg/kg/day) for 5 weeks. EGb761 (50 mg/kg/day) and alpha-tocopherol (20 mg/kg/day) were then administered for another 5 weeks during the withdrawal period. Behavioral assessments were performed, and Bax and Bcl-2 protein expression levels were immunohistochemically analyzed in four brain regions, including the prefrontal cortex, striatum, substantia nigra, and globus pallidum. We found that increased vacuous chewing movements (VCMs) were associated with increased proapoptotic Bax protein expression, decreased antiapoptotic Bcl-2 protein expression, and an increased Bax/Bcl-2 ratio. EGb761 and alpha-tocopherol treatment reversed the increase in VCMs, decreased Bax expression, increased Bcl-2 expression, and decreased the Bax/Bcl-2 ratio. These results demonstrate that long-term haloperidol administration may affect Bcl-2 protein family expression and promote neuronal apoptosis in the basal ganglia. In combination with their antioxidant capacity, EGb761 and alpha-tocopherol's antiapoptotic effects through Bcl-2 might account for the symptom improvement observed in haloperidol-induced TD rats. Copyright © 2016 Elsevier GmbH. All rights reserved.

  20. Cypermethrin induced reproductive toxicity in male Wistar rats: protective role of Tribulus terrestris.

    PubMed

    Sharma, Poonam; Huq, Amir Ul; Singh, Rambir

    2013-09-01

    The present study was designed to investigate role of ethanolic extract of Tribulus terrestris (EETT) against alpha-cypermethrin induced reproductive toxicity in male Wistar rats. 24 male Wistar rats weighing about 250-300g were divided in four groups. Group-I was control. alpha-cypermethrin (3.38 mg kg-1b.wt.) was given to group-IlI for 28 days. In Group-Ill, alpha-cypermethrin and EETT (100 mg kg -1b.wt.) were administered in combination for 28 days. Rats in group-IV were given EETT for 28 days. At the end of the experiment, rats were sacrificed, testes and epididymis were removed and sperm characteristics, sex hormones and various biochemical parameters were studied. Decrease in weight of testes and epididymis, testicular sperm head count, sperm motility, live sperm count, serum testosterone (T), follicle stimulating hormone (FSH), leutinizing hormone (LH), catalase (CAT), superoxide dismutase (SOD), glutathione S transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), total protein content and increase in sperm abnormalities and lipid peroxidation (LPO) level was observed in rats exposed to cypermethrin. In combination group-Ill, EETT treatment ameliorated alpha-cypermethrin induced damage. EETT treatment in group-IV increased testes and epididymis weight, sperm head counts, sperm motility, live sperm counts, testosterone, FSH, LH, GSH, CAT, SOD, GST, GR, GPx and total protein content. The study suggested that Tribulus terrestris plant possess reproductive system enhancement and antioxidant activity.

  1. Daily treatment with {alpha}-naphthoflavone enhances follicular growth and ovulation rate in the rat

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Barreiro, Karina A.; Di Yorio, Maria P.; Artillo-Guida, Romina D.

    2011-04-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and the first protein involved in a variety of physiological and toxicological processes, including those of xenobiotic metabolizing enzymes. AhR has been found in the ovary of many species and seems to mediate the ovarian toxicity of many environmental contaminants, which are AhR ligands. However, the role of AhR in the ovarian function is unknown. Therefore, the aim of this work was to study the action of {alpha}-naphthoflavone ({alpha}NF), known to be an AhR antagonist, on both follicular growth and ovulation. Immature Sprague-Dawley rats were daily injected intraperitoneally with {alpha}NFmore » (0.1-80 mg/kg) or vehicle for 12 days, and primed with gonadotrophins (eCG/hCG) to induce follicular growth and ovulation. Ovaries were obtained 20 h after hCG administration. By means of immunohistochemistry, we found that the numbers of primordial, primary and antral follicles were increased in rats treated with 80 mg/kg {alpha}NF and that there were no differences with other doses. Likewise, the ovarian weight and the ovulation rate, measured by both number of oocytes within oviducts and corpora lutea in ovarian sections, were increased when the rats received either 1 or 10 mg/kg daily. Although further studies are necessary to know the mechanism of action of {alpha}NF, it is possible that the different ovarian processes can be differentially responsive to the presence of different levels of {alpha}NF, and that the same or different endogenous AhR ligands can be involved in these ovarian processes in a cell type-dependent manner.« less

  2. Involvement of alpha-adrenoceptors in myometrial responses in the pro-oestral rat.

    PubMed Central

    Acritopoulou-Fourcroy, S.; Marçais-Collado, H.

    1988-01-01

    1. Myometrial responses to different agents acting on adrenoceptors were examined in vivo in the pro-oestrous rat. Changes in spontaneous uterine mechanical activity were recorded isometrically and evaluated in terms of amplitude and duration of uterine contractions. 2. Phenylephrine (10 micrograms kg-1) markedly increased the amplitude and duration of contractions and 40 micrograms kg-1 gave rise to tetanic contractions. 3. Administration of either nicergoline (400 micrograms kg-1) or phentolamine (1000 micrograms kg-1) to phenylephrine-primed rat uterus reduced the strength of contractions and phentolamine abolished the phenylephrine-induced uterine contracture. 4. Following blockade of alpha 2-adrenoceptors by yohimbine (1000 micrograms kg-1) and beta-adrenoceptors by propranolol (2400 micrograms kg-1), a single injection of phenylephrine (100 micrograms kg-1) increased the amplitude of uterine contractions by 30%. 5. Noradrenaline reduced the amplitude of contractions and caused elevation of the baseline level. The response of myometrium to the combination of both propranolol and noradrenaline was the establishment of uterine contracture with subsequent increase of the duration of contractions. 6. These results clearly demonstrate the involvement of alpha-adrenoceptors in the myometrial activity of the rat in vivo during pro-oestrus. PMID:2832026

  3. Simultaneous quantification of GABAergic 3alpha,5alpha/3alpha,5beta neuroactive steroids in human and rat serum.

    PubMed

    Porcu, Patrizia; O'Buckley, Todd K; Alward, Sarah E; Marx, Christine E; Shampine, Lawrence J; Girdler, Susan S; Morrow, A Leslie

    2009-01-01

    The 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone enhance GABAergic neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory effects. Despite substantial information on the progesterone derivative (3alpha,5alpha)-3-hydroxypregnan-20-one (3alpha,5alpha-THP, allopregnanolone), the physiological significance of the other endogenous GABAergic neuroactive steroids has remained elusive. Here, we describe the validation of a method using gas chromatography-mass spectrometry to simultaneously identify serum levels of the eight 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone. The method shows specificity, sensitivity and enhanced throughput compared to other methods already available for neuroactive steroid quantification. Administration of pregnenolone to rats and progesterone to women produced selective effects on the 3alpha,5alpha- and 3alpha,5beta-reduced neuroactive steroids, indicating differential regulation of their biosynthetic pathways. Pregnenolone administration increased serum levels of 3alpha,5alpha-THP (+1488%, p<0.001), (3alpha,5alpha)-3,21-dihydroxypregnan-20-one (3alpha,5alpha-THDOC, +205%, p<0.01), (3alpha,5alpha)-3-hydroxyandrostan-17-one (3alpha,5alpha-A, +216%, p<0.001), (3alpha,5alpha,17beta)-androstane-3,17-diol (3alpha,5alpha-A-diol, +190%, p<0.01). (3alpha,5beta)-3-hydroxypregnan-20-one (3alpha,5beta-THP) and (3alpha,5beta)-3-hydroxyandrostan-17-one (3alpha,5beta-A) were not altered, while (3alpha,5beta)-3,21-dihydroxypregnan-20-one (3alpha,5beta-THDOC) and (3alpha,5beta,17beta)-androstane-3,17-diol (3alpha,5beta-A-diol) were increased from undetectable levels to 271+/-100 and 2.4+/-0.9 pg+/-SEM, respectively (5/8 rats). Progesterone administration increased serum levels of 3alpha,5alpha-THP (+1806%, p<0.0001), 3alpha,5beta-THP (+575%, p<0.001), 3alpha,5alpha

  4. Nilotinib ameliorates lipopolysaccharide-induced acute lung injury in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    El-Agamy, Dina S., E-mail: dinaagamy1@yahoo.com

    The present study aimed to investigate the effect of the new tyrosine kinase inhibitor, nilotinib on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and explore its possible mechanisms. Male Sprague-Dawley rats were given nilotinib (10 mg/kg) by oral gavage twice daily for 1 week prior to exposure to aerosolized LPS. At 24 h after LPS exposure, bronchoalveolar lavage fluid (BALF) samples and lung tissue were collected. The lung wet/dry weight (W/D) ratio, protein level and the number of inflammatory cells in the BALF were determined. Optical microscopy was performed to examine the pathological changes in lungs. Malondialdehyde (MDA) content,more » superoxidase dismutase (SOD) and reduced glutathione (GSH) activities as well as nitrite/nitrate (NO{sub 2}{sup -}/NO{sub 3}{sup -}) levels were measured in lung tissues. The expression of inflammatory cytokines, tumor necrosis factor-{alpha} (TNF-{alpha}), transforming growth factor-{beta}{sub 1} (TGF-{beta}{sub 1}) and inducible nitric oxide synthase (iNOS) were determined in lung tissues. Treatment with nilotinib prior to LPS exposure significantly attenuated the LPS-induced pulmonary edema, as it significantly decreased lung W/D ratio, protein concentration and the accumulation of the inflammatory cells in the BALF. This was supported by the histopathological examination which revealed marked attenuation of LPS-induced ALI in nilotinib treated rats. In addition, nilotinib significantly increased SOD and GSH activities with significant decrease in MDA content in the lung. Nilotinib also reduced LPS mediated overproduction of pulmonary NO{sub 2}{sup -}/NO{sub 3}{sup -} levels. Importantly, nilotinib caused down-regulation of the inflammatory cytokines TNF-{alpha}, TGF-{beta}{sub 1} and iNOS levels in the lung. Taken together, these results demonstrate the protective effects of nilotinib against the LPS-induced ALI. This effect can be attributed to nilotinib ability to counteract the inflammatory cells

  5. Spermatogonial stem cells alone are not sufficient to re-initiate spermatogenesis in the rat testis following adjudin-induced infertility*

    PubMed Central

    Mok, Ka-Wai; Mruk, Dolores D.; Lee, Will M.; Cheng, C. Yan

    2011-01-01

    The blood-testis barrier (BTB) is a unique ultrastructure in the testis which creates a specialized microenvironment in the seminiferous epithelium for post-meiotic germ cell development and to maintain an immunological barrier. In this report, we have demonstrated unequivocally that a functional and intact BTB is crucial for initiation of spermatogenesis in particular differentiation of spermatogonial stem cells (SSCs). It was shown that adult rats (~300 gm body weight, b.w.) treated with adjudin at 50 (low-dose) or 250 (high-dose) mg/kg b.w. by gavage led to germ cell depletion from the seminiferous tubules and >98% of the tubules were devoid of germ cells by ~2-week and rats became infertile in both groups after the sperm reserve in the epididymis was exhausted. While the population of SSC/spermatogonia in the seminiferous tubules from both groups was similar to normal rats, only rats from the low-dose group were capable of re-initiating spermatogenesis by 20-week and by 30-week, greater than 75% of the tubules displayed normal spermatogenesis and the fertility of these rats rebounded. Detailed analysis by dual-labeled immunofluorescence analysis and a functional BTB integrity assay revealed that in both treatment groups, the BTB was disrupted from 6- to 12-week. However, the disrupted BTB “resealed” in the low, but not in the high, dose group. Our findings illustrate that that SSC/spermatogonia failed to differentiate into spermatocytes beyond Aaligned spermatogonia in the high-dose group with a disrupted BTB. In short, these findings illustrate the critical significance of BTB for re-initiation of spermatogenesis besides SSC and spermatogonia. PMID:21696392

  6. Rat epileptic seizures evoked by BmK {alpha}IV and its possible mechanisms involved in sodium channels

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chai Zhifang; Bai Zhantao; Zhang Xuying

    2007-05-01

    This study showed that rat unilateral intracerebroventricular injection of BmK {alpha}IV, a sodium channel modulator derived from scorpion Buthus martensi Karsch, induced clusters of spikes, epileptic discharges and convulsion-related behavioral changes. BmK {alpha}IV potently promoted the release of endogenous glutamate from rat cerebrocortical synaptosomes. In vitro examination of the effect of BmK {alpha}IV on intrasynaptosomal free calcium concentration [Ca{sup 2+}]{sub i} and sodium concentration [Na{sup +}]{sub i} revealed that BmK {alpha}IV-evoked glutamate release from synaptosomes was associated with an increase in Ca{sup 2+} and Na{sup +} influx. Moreover, BmK {alpha}IV-mediated glutamate release and ion influx was completely blocked by tetrodotoxin,more » a blocker of sodium channel. Together, these results suggest that the induction of BmK {alpha}IV-evoked epileptic seizures may be involved in the modulation of BmK {alpha}IV on tetrodotoxin-sensitive sodium channels located on the nerve terminal, which subsequently enhances the Ca{sup 2+} influx to cause an increase of glutamate release. These findings may provide some insight regarding the mechanism of neuronal action of BmK {alpha}IV in the central nervous system for understanding epileptogenesis involved in sodium channels.« less

  7. Protective Effect of Decursin Extracted from Angelica gigas in Male Infertility via Nrf2/HO-1 Signaling Pathway.

    PubMed

    Bae, Woong Jin; Ha, U Syn; Choi, Jin Bong; Kim, Kang Sup; Kim, Su Jin; Cho, Hyuk Jin; Hong, Sung Hoo; Lee, Ji Youl; Wang, Zhiping; Hwang, Sung Yeoun; Kim, Sae Woong

    2016-01-01

    Higher testicular temperature results in altered spermatogenesis due to heat-related oxidative stress. We examined the effects of decursin extracted from Angelica gigas Nakai on antioxidant activity in vitro and in a cryptorchidism-induced infertility rat model. TM3 Leydig cell viability was measured based on oxidative stress according to treatment. Either distilled water or AG 400 mg/kg of A. gigas extract was administered orally for 4 weeks after unilateral cryptorchidism was induced. After 1, 2, and 4 weeks, six rats from the control group and six rats from treatment group were sacrificed. Testicular weight, semen quality, antioxidant activities, nuclear factor erythroid 2-related factor 2 (Nrf2) protein, and mRNA expression of Nrf2-regulated genes were analyzed. Treatment with A. gigas extract (1) protected TM3 cells against oxidative stress in a dose-dependent manner, (2) improved the mean weight of the cryptorchid testis, (3) maintained sperm counts, motility, and spermatogenic cell density, (4) decreased levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and increased levels of superoxide dismutase (SOD), (5) significantly increased Nrf2 and heme oxygenase-1 (HO-1), and (6) significantly decreased apoptosis. This study suggests that decursin extracted from A. gigas is a supplemental agent that can reduce oxidative stress by Nrf2-mediated upregulation of HO-1 in rat experimentally induced unilateral cryptorchidism and may improve cryptorchidism-induced infertility.

  8. Dietary exposure to aflatoxin in human male infertility in Benin City, Nigeria.

    PubMed

    Ibeh, I N; Uraih, N; Ogonar, J I

    1994-01-01

    To discover the relationship between aflatoxin levels, if any, in serum of infertile men in comparison with random controls from the community. In a parallel experiment, adult male rats were given an aflatoxin-contaminated diet. 100 adult males, yielding 50 semen samples, from men attending Infertility Clinics at a university teaching hospital and 50 normal men in the same community. The staple foods of the men were assayed for aflatoxin content. The rats were given the aflatoxin-rich diet, and their spermatozoa were examined and their ability to reproduce assessed. A random sampling of semen from 100 adult males comprising 50 samples drawn from infertile men and 50 drawn from normal individuals within the same community revealed the presence of aflatoxins in 20 semen samples from the infertile group (40.0%) and four samples from the fertile group (8.0%). The mean aflatoxin concentrations were 1.660 +/- 0.04 micrograms/mL (infertile men) and 1.041 +/- 0.01 micrograms/mL (fertile men). Infertile men with aflatoxin in their semen showed a higher percentage of spermatozoal abnormality (50.0%) than the fertile men (10.0-15.0%). Dietary exposure of adult male Albino rats to aflatoxin (8.5 micrograms AF1/g of Guinea growers feed for 14 days) produced deleterious effects on the spermatozoa of the affected rats, producing features that resemble those seen in semen of infertile men exposed to aflatoxin.

  9. Linking two opposites of pregnancy loss: Induced abortion and infertility in Yoruba society, Nigeria.

    PubMed

    Koster, Winny

    2010-11-01

    Involuntary infertility and induced abortion exist on opposite sides of the spectrum: the first being the unwanted loss of childbearing potential while the second is the intentional termination of pregnancy. However, this paper proposes that these two poles of pregnancy loss are in fact related in Yoruba society, Nigeria. This argument is supported by qualitative and quantitative data drawn from an applied research project in communities and health institutions of Lagos State, from 1996 to 1999, where a total of 693 women recounted 1114 personal abortion experiences, and 233 women shared their experiences of fertility problems. Study statistics show that 37% of secondary infertility was most probably the result of induced abortion and that half of women with abortion complications interviewed in a referral hospital will have fertility problems. This paper provides insight into the reasons why single and married women decide to abort, and use unsafe methods, despite awareness of the serious health risks, including infertility. This is paradoxical given that fear of infertility is a major reason why women do not use modern contraceptives when trying to prevent unwanted pregnancy. By analysing the relations between infertility and abortion within the socio-cultural, economic, and services-related structures that influence women's decisions, this paper suggests ways of addressing the problems related to both types of pregnancy loss. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. AMP-activated protein kinase confers protection against TNF-{alpha}-induced cardiac cell death.

    PubMed

    Kewalramani, Girish; Puthanveetil, Prasanth; Wang, Fang; Kim, Min Suk; Deppe, Sylvia; Abrahani, Ashraf; Luciani, Dan S; Johnson, James D; Rodrigues, Brian

    2009-10-01

    Although a substantial role for 5' adenosine monophosphate-activated protein kinase (AMPK) has been established in regulating cardiac metabolism, a less studied action of AMPK is its ability to prevent cardiac cell death. Using established AMPK activators like dexamethasone (DEX) or metformin (MET), the objective of the present study was to determine whether AMPK activation prevents tumour necrosis factor-alpha (TNF-alpha) induced apoptosis in adult rat ventricular cardiomyocytes. Cardiomyocytes were incubated with DEX, MET, or TNF-alpha for varying durations (0-12 h). TNF-alpha-induced cell damage was evaluated by measuring caspase-3 activity and Hoechst staining. Protein and gene estimation techniques were employed to determine the mechanisms mediating the effects of AMPK activators on TNF-alpha-induced cardiomyocyte apoptosis. Incubation of myocytes with TNF-alpha for 8 h has increased caspase-3 activation and apoptotic cell death, an effect that was abrogated by DEX and MET. The beneficial effect of DEX and MET was associated with stimulation of AMPK, which led to a rapid and sustained increase in Bad phosphorylation. This event reduced the interaction between Bad and Bcl-xL, limiting cytochrome c release and caspase-3 activation. Addition of Compound C to inhibit AMPK reduced Bad phosphorylation and prevented the beneficial effects of AMPK against TNF-alpha-induced cytotoxicity. Our data demonstrate that although DEX and MET are used as anti-inflammatory agents or insulin sensitizers, respectively, their common property to phosphorylate AMPK promotes cardiomyocyte cell survival through its regulation of Bad and the mitochondrial apoptotic mechanism.

  11. alpha1B-Adrenergic receptor phosphorylation and desensitization induced by transforming growth factor-beta.

    PubMed Central

    Romero-Avila, M Teresa; Flores-Jasso, C Fabián; García-Sáinz, J Adolfo

    2002-01-01

    Transforming growth factor-beta (TGF-beta) induced alpha(1B)-adrenergic receptor phosphorylation in Rat-1 fibroblasts stably expressing these adrenoceptors. This effect of TGF-beta was rapid, reaching a maximum within 30 min and decreasing thereafter, and concentration-dependent (EC(50) 0.3 pM). The phosphoinositide 3-kinase inhibitors wortmannin and LY294002, and the protein kinase C inhibitors staurosporine, Ro 318220 and bisindolylmaleimide, blocked the effect of this growth factor. alpha(1B)-Adrenergic receptor phosphorylation was associated with desensitization, as indicated by a reduction in the adrenergic-mediated production of [(3)H]inositol phosphates. Phosphorylation of alpha(1B)-adrenergic receptors by TGF-beta was also observed in Cos-1 cells transfected with the receptor. Co-transfection of the dominant-negative mutant of the regulatory subunit of phosphoinositide 3-kinase (Deltap85) inhibited the phosphorylation of alpha(1B)-adrenergic receptors induced by TGF-beta. Our results indicate that activation of TGF-beta receptors induces alpha(1B)-adrenergic receptor phosphorylation and desensitization. The data suggest that phosphoinositide 3-kinase and protein kinase C play key roles in this effect of TGF-beta. PMID:12234252

  12. alpha1B-Adrenergic receptor phosphorylation and desensitization induced by transforming growth factor-beta.

    PubMed

    Romero-Avila, M Teresa; Flores-Jasso, C Fabián; García-Sáinz, J Adolfo

    2002-12-01

    Transforming growth factor-beta (TGF-beta) induced alpha(1B)-adrenergic receptor phosphorylation in Rat-1 fibroblasts stably expressing these adrenoceptors. This effect of TGF-beta was rapid, reaching a maximum within 30 min and decreasing thereafter, and concentration-dependent (EC(50) 0.3 pM). The phosphoinositide 3-kinase inhibitors wortmannin and LY294002, and the protein kinase C inhibitors staurosporine, Ro 318220 and bisindolylmaleimide, blocked the effect of this growth factor. alpha(1B)-Adrenergic receptor phosphorylation was associated with desensitization, as indicated by a reduction in the adrenergic-mediated production of [(3)H]inositol phosphates. Phosphorylation of alpha(1B)-adrenergic receptors by TGF-beta was also observed in Cos-1 cells transfected with the receptor. Co-transfection of the dominant-negative mutant of the regulatory subunit of phosphoinositide 3-kinase (Deltap85) inhibited the phosphorylation of alpha(1B)-adrenergic receptors induced by TGF-beta. Our results indicate that activation of TGF-beta receptors induces alpha(1B)-adrenergic receptor phosphorylation and desensitization. The data suggest that phosphoinositide 3-kinase and protein kinase C play key roles in this effect of TGF-beta.

  13. Effects of alpha-lipoic acid on spatial learning and memory, oxidative stress, and central cholinergic system in a rat model of vascular dementia.

    PubMed

    Zhao, Ran-Ran; Xu, Fei; Xu, Xiao-Chen; Tan, Guo-Jun; Liu, Liang-Min; Wu, Ning; Zhang, Wen-Zhong; Liu, Ji-Xiang

    2015-02-05

    Brain oxidative stress due to chronic cerebral hypoperfusion was considered to be the major risk factor in the pathogenesis of vascular dementia. In this study, we investigated the protective efficacy of alpha-lipoic acid, an antioxidant, against vascular dementia in rats, as well as the potential mechanism. Bilateral common carotid arteries occlusion (BCCAO) induced severe cognitive deficits tested by Morris water maze (MWM), along with oxidative stress and disturbance of central cholinergic system. However, administration of alpha-lipoic acid (50mg/kg, i.p.) for 28 days significantly restored cognitive deficits induced by BCCAO. Biochemical determination revealed that alpha-lipoic acid markedly decreased the production of malondialdehyde (MDA) and the generation of reactive oxidative species (ROS), and increased the level of reduced glutathione (GSH) in the hippocampal tissue. Additionally, alpha-lipoic acid raised the level of acetylcholine (ACh) and choline acetyltransferase (ChAT) and decreased the activity of acetycholinesterase (AChE) in the hippocampus. These results indicated that treatment with alpha-lipoic acid significantly improved behavioral alterations, protected against oxidative stress, and restored central cholinergic system in the rat model of vascular dementia induced by BCCAO. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Alterations in lenticular proteins during ageing and selenite-induced cataractogenesis in Wistar rats.

    PubMed

    Sakthivel, Muniyan; Elanchezhian, Rajan; Thomas, Philip A; Geraldine, Pitchairaj

    2010-03-16

    To determine putative alterations in the major lenticular proteins in Wistar rats of different ages and to compare these alterations with those occurring in rats with selenite-induced cataract. Lenticular transparency was determined by morphological examination using slit-lamp biomicroscopy. Alterations in lenticular protein were determined by sodium dodecyl sulfate-PAGE (SDS-PAGE) and confirmed immunologically by western blot. Morphological examination did not reveal observable opacities in the lenses of the rats of different age groups; however, dense nuclear opacities were noted in lenses of rats in the selenite-cataract group. Western blot assays revealed age-related changes in soluble and urea-soluble lenticular proteins. Decreased alphaA- and betaB1-crystallins in the soluble fraction and aggregation of alphaA-crystallin, in addition to the degraded fragment of betaB1-crystallin, in the urea-soluble fraction appeared to occur in relation to increasing age of the rats from which the lenses were taken; similarly, cytoskeletal proteins appeared to decline with increasing age. The lenses from rats in the selenite-cataract group exhibited similar changes, except that there was also high molecular weight aggregation of alphaA-crystallin. The results of this study suggest that there is loss, as well as aggregation, of alphaA-crystallin in the aging rat lens, although there is no accompanying loss of lenticular transparency.

  15. Involvement of reversible binding to alpha 2u-globulin in 1,4-dichlorobenzene-induced nephrotoxicity.

    PubMed

    Charbonneau, M; Strasser, J; Lock, E A; Turner, M J; Swenberg, J A

    1989-06-01

    Similarly to unleaded gasoline, 1,4-dichlorobenzene (1,4-DCB) administered for 2 years caused a dose-related increase in the incidence of renal tumors in male but not in female rats or in either sex of mice. Unleaded gasoline and 2,2,4-trimethylpentane (TMP), a component of unleaded gasoline, increased protein droplet formation and cell proliferation in male but not in female rat kidneys. These protein droplets contained, alpha 2u-globulin, a male rat-specific low-molecular-weight protein and 2,4,4-trimethyl-2-pentanol, a metabolite of TMP that was reversibly bound to this protein. Studies were undertaken to determine if 1,4-DCB produced similar effects; 1,2-DCB was used for comparison since it did not produce renal carcinogenesis in male rats. Gel filtration chromatography of a 116,000g supernatant prepared from kidneys of 1,4-[14C]DCB-treated rats showed that radiolabel coeluted with alpha 2u-globulin as one sharp peak as opposed to a multipeak pattern observed for 1,2-[14C]DCB; the maximal quantity of radiolabel for 1,4-DCB was twice that for 1,2-DCB. Equilibrium dialysis of kidney cytosol in the presence or absence of sodium dodecyl sulfate demonstrated that the radiolabel was reversibly bound to alpha 2u-globulin; the amount for 1,4-[14C]DCB-treated rats was almost twice as much as that for 1,2-[14C]DCB-treated rats. 1,2-DCB was also shown to be covalently bound to renal alpha 2u-globulin, and covalently bound to liver and plasma high-molecular-weight proteins. 1,4-DCB and, to a minor extent, 2,5-dichlorophenol, the major metabolite of 1,4-DCB, were reversibly bound to renal alpha 2u-globulin from 1,4-DCB-treated rats. 1,4-DCB increased protein droplet formation in male but not in female rat kidneys, whereas equimolar doses of 1,2-DCB showed no effect in either sex. Renal cell proliferation, measured by [3H]thymidine incorporation into renal DNA, was increased after 1,4-DCB but not after 1,2-DCB treatment. Nephrotoxicity and biochemical alterations induced by

  16. Grape seed proanthocyanidins ameliorates isoproterenol-induced myocardial injury in rats by stabilizing mitochondrial and lysosomal enzymes: an in vivo study.

    PubMed

    Karthikeyan, K; Sarala Bai, B R; Niranjali Devaraj, S

    2007-11-30

    This study was designed to examine the effects of grape seed proanthocyanidins (GSP) against myocardial injury (MI) induced by isoproterenol (ISO), in a rat model. Induction of rats with ISO (85 mg/kg body weight, subcutaneously) for 2 days resulted in a significant decrease in the activities of heart mitochondrial enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and alpha-ketoglutarate dehydrogenase) and respiratory chain enzymes (NADH dehydrogenase and cytochrome c oxidase). The activities of lysosomal enzymes (alpha-d-glucuronidase, alpha-d-N-acetylglucosaminidase, cathepsin-D, acid phosphatases and alpha-d-galactosidase) were increased significantly in the heart and serum of ISO-induced rats. The prior administration of GSP for 6 days a week for 5 weeks significantly increased the activities of mitochondrial and respiratory chain enzymes and significantly decreased the activities of lysosomal enzymes in the heart tissues of ISO-induced rats, which proves the stress stabilizing action of GSP. Oral administration of grape seed proanthocyanidins alone (50, 100 and 150 mg/kg) to normal rats did not show any significant effect in all the parameters studied. These biochemical functional alterations were supported by the macroscopic enzyme mapping assay of ischemic myocardium. Thus, this study shows that 100 and 150 mg/kg of GSP gives protection against ISO-induced MI and demonstrates that GSP has a significant effect in the protection of heart.

  17. Different susceptibility of rat pancreatic alpha and beta cells to hypoxia.

    PubMed

    Bloch, Konstantin; Vennäng, Julia; Lazard, Daniel; Vardi, Pnina

    2012-06-01

    Insulin-producing beta cells are known to be highly susceptible to hypoxia, which is a major factor in their destruction after pancreatic islet transplantation. However, whether the glucagon-producing pancreatic islet alpha cells are sensitive to hypoxia is not known. Our objective was to compare the sensitivity of alpha and beta cells to hypoxia. Isolated rat pancreatic islets were exposed to hypoxia (1% oxygen, 94% N(2), 5% CO(2)) for 3 days. The viability of the alpha and beta cells, as well as the stimulus-specific secretion of glucagon and insulin, was evaluated. A quantitative analysis of the proportion of beta to alpha cells indicated that, under normoxic conditions, islet cells were composed mainly of beta cells (87 ± 3%) with only 13 ± 3% alpha cells. Instead, hypoxia treatment significantly increased the proportion of alpha cells (40 ± 13%) and decreased the proportion of beta cells to 60 ± 13%. Using the fluorescent TUNEL assay we found that only a few percent of beta cells and alpha cells were apoptotic in normoxia. In contrast, hypoxia induced an abundance of apoptotic beta cells (61 ± 22%) and had no effect on the level of apoptosis in alpha cells. In conclusion, this study demonstrates that hypoxia results in severe functional abnormality in both beta and alpha cells while alpha cells display significantly decreased rate of apoptosis compared to intensive apoptotic injury of beta cells. These findings have implications for the understanding of the possible role of hypoxia in the pathophysiology of diabetes.

  18. Cinnamon extract ameliorates ionizing radiation-induced cellular injury in rats.

    PubMed

    Azab, Khaled Sh; Mostafa, Abdel-Halem A; Ali, Ehab M M; Abdel-Aziz, Mohamed A S

    2011-11-01

    The present study aimed to investigate the protective role of cinnamon extract against inflammatory and oxidative injuries in gamma irradiated rats. Rats were subjected to fractionated doses of gamma radiation. Cinnamon extract were daily administrated before starting irradiation and continued after radiation exposure. The results obtained revealed that the administration of cinnamon extract to irradiated rats significantly ameliorated the changes induced in liver antioxidant system; catalase, superoxide dismutase and glutathione peroxidase activities as well as reduced glutathione concentration. The liver's lipid peroxidation and protein oxidation indices were significantly decreased when compared with their equivalent values in irradiated rats. Furthermore, the changes induces in xanthine oxidoreductase system were significantly diminished. In addition, the changes in liver nitric oxide contents, serum tumor necrosis factor alpha and C-reactive protein levels were markedly improved. In conclusion, the administration of cinnamon extract might provide substantial protection against radiation-induced oxidative and inflammatory damages. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Protective potential of royal jelly against cadmium-induced infertility in male rats.

    PubMed

    Ahmed, Mohamed M; El-Shazly, Samir A; Alkafafy, Mohamed E; Mohamed, Alaa A; Mousa, Ahmed A

    2018-06-01

    This study aimed to investigate the protective potential of Royal jelly (RJ) against cadmium (Cd)-induced testicular dysfunction in rats. Thirty-five adult male Wistar rats were assigned into five groups. G I; (control) injected intraperitoneally with saline, G II injected intraperitoneally with a single dose of CdCl 2 (1 mg/kg BW), G III received RJ (100 mg/kg BW/day) orally, G IV was pre-treated with RJ for 1 week then, treated with CdCl 2 , and G V was co-treated with RJ and CdCl 2 . After day 56, serum and tissue samples were collected and analysed. The results showed decreased serum testosterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), superoxide dismutase, glutathione reductase, sperm motility and count while increased malondialdehyde, nitric oxide, tumour necrosis factor-α (TNF-α) and sperm abnormalities, along with a severely damaged seminiferous tubules epithelium with cytoplasmic and nuclear disruptions following Cd toxicity. Additionally, Cd stimulated testicular mRNA expression of TNF-α while inhibited those of steroidogenic acute regulatory protein, cytochrome P450 cholesterol side chain cleavage enzyme androgen binding protein, FSH-receptor, LH-receptor, androgen receptor, 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, and cytochrome P450 17A1. These negative alterations of cadmium were greatly reduced by RJ treatment. This study concluded that RJ protects against Cd-induced testicular toxicity. © 2018 Blackwell Verlag GmbH.

  20. GENE ARRAYS FOR ELUCIDATING MECHANISTIC DATA FROM MODELS OF MALE INFERTILITY AND CHEMICAL EXPOSURE IN MICE, RATS AND HUMANS

    EPA Science Inventory

    Gene arrays for elucidating mechanistic data from models of male infertility and chemical exposure in mice, rats and humans
    John C. Rockett and David J. Dix
    Gamete and Early Embryo Biology Branch, Reproductive Toxicology Division, National Health and Environmental Effects ...

  1. Protective Effect of Decursin Extracted from Angelica gigas in Male Infertility via Nrf2/HO-1 Signaling Pathway

    PubMed Central

    Bae, Woong Jin; Ha, U. Syn; Choi, Jin Bong; Kim, Kang Sup; Kim, Su Jin; Cho, Hyuk Jin; Hong, Sung Hoo; Lee, Ji Youl; Wang, Zhiping; Hwang, Sung Yeoun; Kim, Sae Woong

    2016-01-01

    Higher testicular temperature results in altered spermatogenesis due to heat-related oxidative stress. We examined the effects of decursin extracted from Angelica gigas Nakai on antioxidant activity in vitro and in a cryptorchidism-induced infertility rat model. TM3 Leydig cell viability was measured based on oxidative stress according to treatment. Either distilled water or AG 400 mg/kg of A. gigas extract was administered orally for 4 weeks after unilateral cryptorchidism was induced. After 1, 2, and 4 weeks, six rats from the control group and six rats from treatment group were sacrificed. Testicular weight, semen quality, antioxidant activities, nuclear factor erythroid 2-related factor 2 (Nrf2) protein, and mRNA expression of Nrf2-regulated genes were analyzed. Treatment with A. gigas extract (1) protected TM3 cells against oxidative stress in a dose-dependent manner, (2) improved the mean weight of the cryptorchid testis, (3) maintained sperm counts, motility, and spermatogenic cell density, (4) decreased levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and increased levels of superoxide dismutase (SOD), (5) significantly increased Nrf2 and heme oxygenase-1 (HO-1), and (6) significantly decreased apoptosis. This study suggests that decursin extracted from A. gigas is a supplemental agent that can reduce oxidative stress by Nrf2-mediated upregulation of HO-1 in rat experimentally induced unilateral cryptorchidism and may improve cryptorchidism-induced infertility. PMID:27034737

  2. Effect of astaxanthin in combination with alpha-tocopherol or ascorbic acid against oxidative damage in diabetic ODS rats.

    PubMed

    Nakano, Masako; Onodera, Aya; Saito, Emi; Tanabe, Miyako; Yajima, Kazue; Takahashi, Jiro; Nguyen, Van Chuyen

    2008-08-01

    The present study was performed to investigate the effect of astaxanthin in combination with other antioxidants against oxidative damage in streptozotocin (STZ)-induced diabetic Osteogenic Disorder Shionogi (ODS) rats. Diabetic-ODS rats were divided into five groups: control, astaxanthin, ascorbic acid, alpha-tocopherol, and tocotrienol. Each of the four experimental groups was administered a diet containing astaxanthin (0.1 g/kg), in combination with ascorbic acid (3.0 g/kg), alpha-tocopherol (0.1 g/kg), or tocotrienol (0.1 g/kg) for 20 wk. The effects of astaxanthin with other antioxidants on lipid peroxidation, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) excretion, serum creatinine (Cr) level, creatinine clearance (Ccr), and urinary protein content were assessed. The serum lipid peroxide levels and chemiluminescent (CL) intensity in the liver of the alpha-tocopherol and tocotrienol groups were significantly reduced in comparison to that of the control group. In the alpha-tocopherol group, urinary 8-OHdG excretion, serum Cr level, Ccr, urinary albumin excretion, and urinary protein concentration were significantly decreased as compared with those in the control group. Additionally, the CL intensity in the kidney of the alpha-tocopherol group was significantly lower, but that of the ascorbic acid group was significantly higher than that in the control group. These results indicate that dietary astaxanthin in combination with alpha-tocopherol has an inhibitory effect on oxidative stress. On the other hand, our study suggests that excessive ascorbic acid intake increases lipid peroxidation in diabetic rats.

  3. Effect of alpha(1)-acid glycoprotein on the pharmacokinetics of tamsulosin in rats treated with turpentine oil.

    PubMed

    Matsushima, H; Watanabe, T; Higuchi, S

    2000-04-01

    The pharmacokinetics of tamsulosin (TAM) was investigated using male Sprague-Dawley rats in which plasma alpha(1)-acid glycoprotein (alpha(1)-AGP) levels were elevated by the subcutaneous injection of 0.2 mL/kg of turpentine oil. alpha(1)-AGP levels increased about eight times after turpentine oil treatment, causing a threefold decrease in plasma unbound fraction (f(u)) of TAM. When 0.3 mg/kg of TAM was dosed intravenously, total and nonrenal clearances (CL(tot) and CL(nr)) in turpentine-treated rats were 47% and 44% lower than those in nontreated controls, respectively. The area under the concentration-time curve of plasma unbound TAM (AUC(inf,u)) was lower than that in the control. When 1 mg/kg of TAM was dosed orally, oral clearance (CL(oral)) in alpha1-AGP-induced rats was 65% lower than in the control. The AUC(inf,u) and unbound oral clearance (CL(oral,u)) were nearly equal in both groups. Moreover, a positive correlation was observed between fu and CL(oral) of TAM (r(2) = 0.603, P < 0.01), whereas no correlation was observed between f(u) and CL(oral,u). The absolute bioavailability (BA) increased from 19.2% to 46.9% by induction of alpha(1)-AGP. These results suggest that decreased f(u) caused by the elevation of plasma alpha(1)-AGP level affects the pharmacokinetics of TAM, but does not affect the CL(oral,u,) which represents the hepatic metabolism of TAM. Copyright 2000 Wiley-Liss, Inc.

  4. Tissue-specific and hormonally regulated expression of a rat alpha 2u globulin gene in transgenic mice.

    PubMed Central

    Soares, V da C; Gubits, R M; Feigelson, P; Costantini, F

    1987-01-01

    To investigate the tissue-specific and hormonal regulation of the rat alpha 2u globulin gene family, we introduced one cloned member of the gene family into the mouse germ line and studied its expression in the resulting transgenic mice. Alpha 2u globulingene 207 was microinjected on a 7-kilobase DNA fragment, and four transgenic lines were analyzed. The transgene was expressed at very high levels, specifically in the liver and the preputial gland of adult male mice. The expression in male liver was first detected at puberty, and no expression was detected in female transgenic mice. This pattern of expression is similar to the expression of endogenous alpha 2u globulin genes in the rat but differs from the expression of the homologous mouse major urinary protein (MUP) gene family in that MUPs are synthesized in female liver and not in the male preputial gland. We conclude that these differences between rat alpha 2u globulin and mouse MUP gene expression are due to evolutionary differences in cis-acting regulatory elements. The expression of the alpha 2u globulin transgene in the liver was abolished by castration and fully restored after testosterone replacement. The expression could also be induced in the livers of female mice by treatment with either testosterone or dexamethasone, following ovariectomy and adrenalectomy. Therefore, the cis-acting elements responsible for regulation by these two hormones, as well as those responsible for tissue-specific expression, are closely linked to the alpha 2u globulin gene. Images PMID:2446121

  5. The toxicity of N-methyl-alpha-methyldopamine to freshly isolated rat hepatocytes is prevented by ascorbic acid and N-acetylcysteine.

    PubMed

    Carvalho, Márcia; Remião, Fernando; Milhazes, Nuno; Borges, Fernanda; Fernandes, Eduarda; Carvalho, Félix; Bastos, Maria Lourdes

    2004-08-05

    In the past decade, clinical evidence has increasingly shown that the liver is a target organ for 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") toxicity. The aims of the present in vitro study were: (1) to evaluate and compare the hepatotoxic effects of MDMA and one of its main metabolites, N-methyl-alpha-methyldopamine (N-Me-alpha-MeDA) and (2) to investigate the ability of antioxidants, namely ascorbic acid and N-acetyl-L-cysteine (NAC), to prevent N-Me-alpha-MeDA-induced toxic injury, using freshly isolated rat hepatocytes. Cell suspensions were incubated with MDMA or N-Me-alpha-MeDA in the final concentrations of 0.1, 0.2, 0.4, 0.8, and 1.6 mM for 3 h. To evaluate the potential protective effects of antioxidants, cells were preincubated with ascorbic acid in the final concentrations of 0.1 and 0.5 mM, or NAC in the final concentrations of 0.1 and 1 mM for 15 min before treatment with 1.6 mM N-Me-alpha-MeDA for 3 h (throughout this incubation period the cells were exposed to both compounds). The toxic effects were evaluated by measuring the cell viability, glutathione (GSH) and glutathione disulfide (GSSG), ATP, and the cellular activities of GSH peroxidase (GPX), GSSG reductase (GR), and GSH S-transferase (GST). MDMA induced a concentration- and time-dependent GSH depletion, but had a negligible effect on cell viability, ATP levels, or on the activities of GR, GPX, and GST. In contrast, N-Me-alpha-MeDA was shown to induce not only a concentration- and time-dependent depletion of GSH, but also a depletion of ATP levels accompanied by a loss in cell viability, and decreases in the antioxidant enzyme activities. For both compounds, GSH depletion was not accompanied by increases in GSSG levels, which seems to indicate GSH depletion by adduct formation. Importantly, the presence of ascorbic acid (0.5 mM) or NAC (1 mM) prevented cell death and GSH depletion induced by N-Me-alpha-MeDA. The results provide evidence that MDMA and its metabolite N-Me-alpha

  6. Sequence of rat alpha- and gamma-casein mRNAs: evolutionary comparison of the calcium-dependent rat casein multigene family.

    PubMed Central

    Hobbs, A A; Rosen, J M

    1982-01-01

    The complete sequences of rat alpha- and gamma-casein mRNAs have been determined. The 1402-nucleotide alpha- and 864-nucleotide gamma-casein mRNAs both encode 15 amino acid signal peptides and mature proteins of 269 and 164 residues, respectively. Considerable homology between the 5' non-coding regions, and the regions encoding the signal peptides and the phosphorylation sites, in these mRNAs as compared to several other rodent casein mRNAs, was observed. Significant homology was also detected between rat alpha- and bovine alpha s1-casein. Comparison of the rodent and bovine sequences suggests that the caseins evolved at about the time of the appearance of the primitive mammals. This may have occurred by intragenic duplication of a nucleotide sequence encoding a primitive phosphorylation site, -(Ser)n-Glu-Glu-, and intergenic duplication resulting in the small casein multigene family. A unique feature of the rat alpha-casein sequence is an insertion in the coding region containing 10 repeated elements of 18 nucleotides each. This insertion appears to have occurred 7-12 million years ago, just prior to the divergence of rat and mouse. Images PMID:6298707

  7. Advantages of the Alpha-lipoic Acid Association with Chlorpromazine in a Model of Schizophrenia Induced by Ketamine in Rats: Behavioral and Oxidative Stress evidences.

    PubMed

    Sampaio, Luis Rafael Leite; Cysne Filho, Francisco Maurício Sales; de Almeida, Jamily Cunha; Diniz, Danilo Dos Santos; Patrocínio, Cláudio Felipe Vasconcelos; de Sousa, Caren Nádia Soares; Patrocínio, Manoel Cláudio Azevedo; Macêdo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2018-03-01

    Schizophrenia is a chronic mental disorder reported to compromise about 1% of the world's population. Although its pathophysiological process is not completely elucidated, evidence showing the presence of an oxidative imbalance has been increasingly highlighted in the literature. Thus, the use of antioxidant substances may be of importance for schizophrenia treatment. The objective of this study was to evaluate the behavioral and oxidative alterations by the combination of chlorpromazine (CP) and alpha-lipoic acid (ALA), a potent antioxidant, in the ketamine (KET) model of schizophrenia in rats. Male Wistar rats (200-300 g) were treated for 10 days with saline, CP or ALA alone or in combination with CP previous to KET and the behavioral (open field, Y-maze and PPI tests) and oxidative tests were performed on the last day of treatment. The results showed that KET induced hyperlocomotion, impaired working memory and decreased PPI. CP alone or in combination with ALA prevented KET-induced behavioral effects. In addition, the administration of KET decreased GSH and increased nitrite, lipid peroxidation and myeloperoxidase activity. CP alone or combined with ALA prevented the oxidative alterations induced by KET. In conclusion, the treatment with KET in rats induced behavioral impairments accompanied by hippocampal oxidative alterations, possibly related to NMDA receptors hypofunction. Besides that, CP alone or combined with ALA prevented these effects, showing a beneficial activity as antipsychotic agents. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. The increased gastroprotective effect of pioglitazone in cholestatic rats: role of nitric oxide and tumour necrosis factor alpha.

    PubMed

    Moezi, Leila; Janahmadi, Zeinab; Amirghofran, Zahra; Nekooeian, Ali Akbar; Dehpour, Ahmad R

    2014-02-01

    The prevalence of gastric ulcers is high in cholestatic patients, but the exact mechanism of this increased frequency remains uncertain. It has been shown that pioglitazone accelerates the healing of pre-existing gastric ulcers. The present study was designed to investigate the effect of pioglitazone, on the gastric mucosal lesions in cholestatic rats. Cholestasis was induced by surgical ligation of common bile duct and sham-operated rats served as control. Different groups of sham and cholestatic animals received solvent or pioglitazone (5, 15, 30 mg/kg) for 7 days. On the day eight rats were killed after oral ethanol administration and the area of gastric lesions was measured. The serums of rats were also collected to determine serum levels of tumour necrosis factor alpha (TNF-α), IL-1β and bilirubin. The ethanol-induced gastric mucosal damage was significantly more severe in cholestatic rats than sham-operated ones. Pretreatment with pioglitazone dose-dependently attenuated gastric lesions induced by ethanol in both sham and cholestatic rats, but this effect was more prominent in cholestatic ones. The effect of pioglitazone was associated with a significant fall in serum levels of TNF-α in cholestatic rats. L-NAME, a non-selective nitric oxide synthase (NOS) inhibitor, and decreased pioglitazone-induced gastroprotective effect in cholestatic rats, while aminoguanidine, a selective inducible NOS inhibitor, potentiated pioglitazone-induced gastroprotective effect in the cholestatic rats. Chronic treatment with pioglitazone exerts an enhanced gastroprotective effect on the stomach ulcers of cholestatic rats compared to sham rats probably due to constitutive NOS induction and/or inducible NOS inhibition and attenuating release of TNF-α. © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.

  9. Synthetic. cap alpha. subunit peptide 125-147 of human nicotinic acetylcholine receptor induces antibodies to native receptor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McCormick, D.J.; Griesmann, G.E.; Huang, Z.

    1986-03-05

    A synthetic peptide corresponding to residues 125-147 of the Torpedo acetylcholine receptor (AChR) ..cap alpha.. subunit proved to be a major antigenic region of the AChR. Rats inoculated with 50 ..mu..g of peptide (T ..cap alpha.. 125-147) developed T cell immunity and antibodies to native AChR and signs of experimental autoimmune myasthenia gravis. They report the synthesis and preliminary testing of a disulfide-looped peptide comprising residues 125-147 of the human AChR ..cap alpha.. subunit. Peptide H ..cap alpha.. 125-147 differs from T ..cap alpha.. 125-147 at residues 139 (Glu for Gln) and 143 (Ser for Thr). In immunoprecipitation assays, antibodiesmore » to Torpedo AChR bound /sup 125/I-labelled H..cap alpha.. 125-147 antibody bound H..cap alpha.. 125-147, but monoclonal antibodies to an immunodominant region of native AChR bound neither H..cap alpha.. 125-147 nor T ..cap alpha.. 125-147. Rats immunized with H ..cap alpha.. 125-147 produced anti-mammalian muscle AChR antibodies that induced modulation of AChRs from cultured human myotubes. Thus, region 125-147 of the human AChR ..cap alpha.. subunit is extracellular in muscle, and is both antigenic and immunogenic. It remains to be determined whether or not autoantibodies to this region may in part cause the weakness or myasthenia gravis in man.« less

  10. Divergent effects of estradiol and the estrogen receptor-alpha agonist PPT on eating and activation of PVN CRH neurons in ovariectomized rats and mice.

    PubMed

    Thammacharoen, Sumpun; Geary, Nori; Lutz, Thomas A; Ogawa, Sonoko; Asarian, Lori

    2009-05-01

    Eating is modulated by estradiol in females of many species and in women. To further investigate the estrogen receptor mechanism mediating this effect, ovariectomized rats and mice were treated with estradiol benzoate or the estrogen receptor-alpha (ER-alpha)-selective agonist PPT. PPT inhibited eating in rats much more rapidly than estradiol (approximately 2-6 h versus >24 h). In contrast, the latencies to vaginal estrus after PPT and estradiol were similar (>24 h). PPT also inhibited eating within a few hours in wild-type mice, but failed to inhibit eating in transgenic mice deficient in ER-alpha (ERalphaKO mice). PPT, but not estradiol, induced the expression of c-Fos in corticotrophin-releasing hormone (CRH)-expressing cells of the paraventricular nucleus (PVN) of the hypothalamus within 90-180 min in rats. Both PPT and estradiol reduced c-Fos expression in an ER-alpha-containing area of the nucleus of the solitary tract. The anomalously rapid eating-inhibitory effect of PPT suggests that PPT's neuropharmacological effect differs from estradiol's, perhaps because PPT differentially activates membrane versus nuclear ER-alpha or because PPT activates non-ER-alpha membrane estrogen receptors in addition to ER-alpha. The failure of PPT to inhibit eating in ERalphaKO mice, however, indicates that ER-alpha is necessary for PPT's eating-inhibitory action and that any PPT-induced activation of non-ER-alpha estrogen receptors is not sufficient to inhibit eating. Finally, the rapid induction of c-Fos in CRH-expressing cells in the PVN by PPT suggests that PPT elicits a neural response that is similar to that elicited by stress or aversive emotional stimuli.

  11. Stromal cell derived factor-1alpha protects stem cell derived insulin-producing cells from glucotoxicity under high glucose conditions in-vitro and ameliorates drug induced diabetes in rats

    PubMed Central

    2013-01-01

    Background Diabetes mellitus is affecting more than 300 million people worldwide. Current treatment strategies cannot prevent secondary complications. Stem cells due to their regenerative power have long been the attractive target for the cell-based therapies. Mesenchymal stem cells (MSCs) possess the ability to differentiate into several cell types and to escape immune recognition in vitro. MSCs can be differentiated into insulin-producing cells (IPCs) and could be an exciting therapy for diabetes but problems like poor engraftment and survivability need to be confronted. It was hypothesized that stromal cell derived factor- 1alpha (SDF-1alpha) will enhance therapeutic potential of stem cell derived IPCs by increasing their survival and proliferation rate. Methods Novel culture conditions were developed to differentiate bone marrow derived mesenchymal stem cells (BMSCs) into IPCs by using endocrine differentiation inducers and growth factors via a three stage protocol. In order to enhance their therapeutic potential, we preconditioned IPCs with SDF-1alpha. Results Our results showed that SDF-1alpha increases survival and proliferation of IPCs and protects them from glucotoxicity under high glucose conditions in vitro. SDF-1alpha also enhances the glucose responsive insulin secretion in IPCs in vitro. SDF-1alpha preconditioning reverses hyperglycemia and increase serum insulin in drug induced diabetic rats. Conclusions The differentiation of BMSCs into IPCs and enhancement of their therapeutic potential by SDF-1alpha preconditioning may contribute to cell based therapies for diabetes. PMID:23648189

  12. Amelioration of tamoxifen-induced liver injury in rats by grape seed extract, black seed extract and curcumin.

    PubMed

    El-Beshbishy, Hesham A; Mohamadin, Ahmed M; Nagy, Ayman A; Abdel-Naim, Ashraf B

    2010-03-01

    Liver injury was induced in female rats using tamoxifen (TAM). Grape seeds (Vitis vinifera) extract (GSE), black seed (Nigella sativa) extract (NSE), curcumin (CUR) or silymarin (SYL) were orally administered to TAM-intoxicated rats. Liver histopathology of TAM-intoxicated:rats showed pathological changes. TAM-intoxication elicited declines in liver antioxidant enzymes levels (glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase), reduced glutathione (GSH) and GSH/GSSG ratio plus the hepatic elevations in lipid peroxides, oxidized glutathione (GSSG), tumor necrosis factor-alpha (TNF-alpha) and serum liver enzymes; alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase and gamma glutamyl transferase levels. Oral intake of NSE, GSE, CUR or SYL to TAM-intoxicated rats, attenuated histopathological changes and corrected all parameters mentioned above. Improvements were prominent in case of NSE (similarly SYL) > CUR > GSE. Data indicated that NSE, GSE or CUR act as free radicals scavengers and protect TAM-induced liver injury in rats.

  13. Topically applied standardized aqueous extract of Curcuma longa Linn. suppresses endotoxin-induced uveal inflammation in rats.

    PubMed

    Agarwal, Renu; Gupta, S K; Agarwal, Puneet; Srivastava, Sushma

    2013-10-01

    Aqueous extract of C. longa when administered 4 h after induction of E. coli lipopolysaccharide-induced uveitis in rats showed significantly suppressed inflammation with a significantly lower mean clinical grade, histopathological grade and aqueous humor (AH) protein level compared to vehicle treated group. Although, prednisolone group showed significantly lower clinical grade, histopathological grades and AH protein levels compared to C. longa group, TNF-alpha levels did not differ significantly. Moreover, when the aqueous extract was administered starting from 3 days before induction of uveitis, the mean clinical and histopathological grade as well as AH protein and TNF-alpha levels were comparable to C. longa group when treatment was administered 4 h after induction of uveitis. It is concluded that topically applied standardized aqueous extract of C. longa suppresses endotoxin-induced uveitis in rats by reducing TNF-alpha activity.

  14. Carbachol inhibits TNF-α-induced endothelial barrier dysfunction through alpha 7 nicotinic receptors.

    PubMed

    Li, Yu-zhen; Liu, Xiu-hua; Rong, Fei; Hu, Sen; Sheng, Zhi-yong

    2010-10-01

    To test whether carbachol can influence endothelial barrier dysfunction induced by tumor necrosis factor (TNF)-α and whether the alpha 7 nicotinic receptor can mediate this process. Rat cardiac microvascular endothelial cells were exposed to carbachol followed by TNF-α treatment in the presence or the absence of α-bungarotoxin (an antagonist of the alpha 7 nicotinic receptor). Permeability of endothelial cells cultured on Transwell filters was assayed using FITC-albumin. F-actin was stained with FITC- phalloidin. Expression of vascular endothelial cadherin, intercellular adhesion molecule 1 (ICAM-1), phosphor-ERK1/2 and phosphor-JNK was detected using Western blot. Carbachol (2 μmol/L-2 mmol/L) prevented increase in endothelial cell permeability induced by TNF-α (500 ng/mL) in a dose-dependent manner. Further, it attenuated the down-regulation of vascular endothelial cadherin and the up-regulation of ICAM-1 induced by TNF-α. In addition, treatment of endothelial cells with carbachol decreased phosphor-ERK1/2 and phosphor-JNK. These effects of carbachol were blocked by α-bungarotoxin 3 μg/mL. These data suggest that the inhibitory effect of carbachol on TNF-α-induced endothelial barrier dysfunction mediated by the alpha 7 nicotinic receptor.

  15. Carbachol inhibits TNF-α-induced endothelial barrier dysfunction through alpha 7 nicotinic receptors

    PubMed Central

    Li, Yu-zhen; Liu, Xiu-hua; Rong, Fei; Hu, Sen; Sheng, Zhi-yong

    2010-01-01

    Aim: To test whether carbachol can influence endothelial barrier dysfunction induced by tumor necrosis factor (TNF)-α and whether the alpha 7 nicotinic receptor can mediate this process. Methods: Rat cardiac microvascular endothelial cells were exposed to carbachol followed by TNF-α treatment in the presence or the absence of α-bungarotoxin (an antagonist of the alpha 7 nicotinic receptor). Permeability of endothelial cells cultured on Transwell filters was assayed using FITC-albumin. F-actin was stained with FITC- phalloidin. Expression of vascular endothelial cadherin, intercellular adhesion molecule 1 (ICAM-1), phosphor-ERK1/2 and phosphor-JNK was detected using Western blot. Results: Carbachol (2 μmol/L-2 mmol/L) prevented increase in endothelial cell permeability induced by TNF-α (500 ng/mL) in a dose-dependent manner. Further, it attenuated the down-regulation of vascular endothelial cadherin and the up-regulation of ICAM-1 induced by TNF-α. In addition, treatment of endothelial cells with carbachol decreased phosphor-ERK1/2 and phosphor-JNK. These effects of carbachol were blocked by α-bungarotoxin 3 μg/mL. Conclusion: These data suggest that the inhibitory effect of carbachol on TNF-α-induced endothelial barrier dysfunction mediated by the alpha 7 nicotinic receptor. PMID:20871620

  16. Determination of ethylene oxide, ethylene chlorohydrin, and ethylene glycol in aqueous solutions and ethylene oxide residues in associated plastics.

    PubMed

    Ball, N A

    1984-09-01

    A gas chromatographic (GC) method was developed for the determination of ethylene oxide and its two reaction products, ethylene chlorohydrin and ethylene glycol, in aqueous ophthalmic solutions. Propylene oxide was used as an internal standard. All three components were determined in one isothermal chromatographic analysis in less than 15 min. An extraction method for the determination of ethylene oxide residues in plastic components was also developed, and certain plastics with different ethylene oxide retention characteristics were identified.

  17. Protection effect of piper betel leaf extract against carbon tetrachloride-induced liver fibrosis in rats.

    PubMed

    Young, Shun-Chieh; Wang, Chau-Jong; Lin, Jing-Jing; Peng, Pei-Ling; Hsu, Jui-Ling; Chou, Fen-Pi

    2007-01-01

    Piper betel leaves (PBL) are used in Chinese folk medicine for the treatment of various disorders. PBL has the biological capabilities of detoxication, antioxidation, and antimutation. In this study, we evaluated the antihepatotoxic effect of PBL extract on the carbon tetrachloride (CCl(4))-induced liver injury in a rat model. Fibrosis and hepatic damage, as reveled by histology and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were induced in rats by an administration of CCl(4) (8%, 1 ml/kg body weight) thrice a week for 4 weeks. PBL extract significantly inhibited the elevated AST and ALT activities caused by CCl(4) intoxication. It also attenuated total glutathione S-transferase (GST) activity and GST alpha isoform activity, and on the other hand, enhanced superoxide dismutase (SOD) and catalase (CAT) activities. The histological examination showed the PBL extract protected liver from the damage induced by CCl(4) by decreasing alpha-smooth muscle actin (alpha-sma) expression, inducing active matrix metalloproteinase-2 (MMP2) expression though Ras/Erk pathway, and inhibiting TIMP2 level that consequently attenuated the fibrosis of liver. The data of this study support a chemopreventive potential of PBL against liver fibrosis.

  18. Alpha1- and alpha2-containing GABAA receptor modulation is not necessary for benzodiazepine-induced hyperphagia.

    PubMed

    Morris, H V; Nilsson, S; Dixon, C I; Stephens, D N; Clifton, P G

    2009-06-01

    Benzodiazepines increase food intake, an effect attributed to their ability to enhance palatability. We investigated which GABA(A) receptor subtypes may be involved in mediating benzodiazepine-induced hyperphagia. The role of the alpha2 subtype was investigated by observing the effects of midazolam, on the behavioural satiety sequence in mice with targeted deletion of the alpha2 gene (alpha2 knockout). Midazolam (0.125, 0.25 and 0.5mg/kg) increased food intake and the amount of time spent feeding in alpha2 knockout mice, suggesting that BZ-induced hyperphagia does not involve alpha2-containing GABA(A) receptors. We further investigated the roles of alpha1- and alpha3-containing GABA(A) receptors in mediating BZ-induced hyperphagia. We treated alpha2(H101R) mice, in which alpha2-containing receptors are rendered benzodiazepine insensitive, with L-838417, a compound which acts as a partial agonist at alpha2-, alpha3- and alpha5-receptors but is inactive at alpha1-containing receptors. L-838417 (10 and 30 mg/kg) increased food intake and the time spent feeding in both wildtype and alpha2(H101R) mice, demonstrating that benzodiazepine-induced hyperphagia does not require alpha1- and alpha2-containing GABA(A) receptors. These observations, together with evidence against the involvement of alpha5-containing GABA(A) receptors, suggest that alpha3-containing receptors mediate BZ-induced hyperphagia in the mouse.

  19. [Effects of Jianpi Qinghua Decoctions on immune inflammatory injury in adriamycin-induced nephropathic rats MA].

    PubMed

    Ma, Xiao-Hong; He, Li-Qun

    2014-01-01

    To investigate the effects of Jianpi Qinghua Decoctions on the inflammation injury mediated by the cellular immunity in the focal segmental glomurular Sclerosis (FSGS) nephropathy rats. The FSGS nephropathy rat model was established by the method of intravenous injection of Adriamycin after the removal of one kidney. After the treatment of Jianpi Qinghua Decoctions, the blood, spleen and kidney samples of each rat were collected for the detection of splenocytes CD4+/CD8+ ratio, renal tubulointerstitial fibronectin (FN) mRNA, Col III mRNA, and the expression levels of TNF-alpha and IL6. The treatment of Jianpi Qinghua Decoctions decreased the levels of CD4+/CD8+, tubulointerstitial FN mRNA, Col III mRNA, TNF-alpha and IL6 significantly in FSGS nephropathy rats. Jianpi Qinghua Decoctions could improve renal FSGS damage in adriamycin-induced nephropathy rats.

  20. Thalidomide in rat liver cirrhosis: blockade of tumor necrosis factor-alpha via inhibition of degradation of an inhibitor of nuclear factor-kappaB.

    PubMed

    Paul, Shelley Chireyath; Lv, Peng; Xiao, Yan-Jv; An, Ping; Liu, Shi-Quan; Luo, He-Sheng

    2006-01-01

    Thalidomide inhibited tumor necrosis factor-alpha (TNF-alpha) effectively in many trials. The aim of this study was to investigate the effect of thalidomide on the expression of nuclear factor-kappaB (NF-kappaB), inhibitor of NF-kappaB (IkappaB) and TNF-alpha in a rat model of liver cirrhosis. Liver cirrhosis was achieved by intraperitoneal injection of carbon tetrachloride thrice weekly, and thalidomide (10 or 100 mg/kg/day) was given daily by intragastric route for 8 weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), prealbumin (PA), hyaluronic acid (HA) and laminin (LN), and hydroxyproline (HYP), NF-kappaBp65, alpha-smooth muscle actin (alpha-SMA) protein and TNF-alpha mRNA were studied in the liver, IkappaBalpha and TNF-alpha protein in the cytoplasm and NF-kappaBp65 protein in the nucleus. Compared with nontreated cirrhotic rats, the histopathology of rats given thalidomide (100 mg/kg) was significantly better. Serum ALT, AST, HA and LN and HYP content in the liver were significantly decreased and PA was elevated (p < 0.01) in this group; the expression of TNF-alpha mRNA and protein, NF-kappaBp65 and alpha-SMA were significantly decreased and IkappaBalpha protein was also elevated (p < 0.01). Thalidomide downregulates NF-kappaB-induced TNF-alpha and activates hepatic stellate cells (HSC) via inhibition of IkappaB degradation to prevent liver cirrhosis. Copyright 2006 S. Karger AG, Basel.

  1. The potential antifibrotic impact of apocynin and alpha-lipoic acid in concanavalin A-induced liver fibrosis in rats: Role of NADPH oxidases 1 and 4.

    PubMed

    Fayed, Mostafa R; El-Naga, Reem N; Akool, El-Sayed; El-Demerdash, Ebtehal

    2018-01-01

    Liver fibrosis results from chronic inflammation that precipitates excessive accumulation of extracellular matrix. Oxidative stress is involved in its pathogenesis. This study aimed to elucidate the potential antifibrotic effect of the NADPH oxidase (NOX) inhibitor, apocynin against concanavalin A (ConA)-induced immunological model of liver fibrosis, and to investigate the ability of the antioxidant, alpha-lipoic acid (α-LA) to potentiate this effect. Rats were treated with apocynin and/or α-LA for six weeks. Hepatotoxicity indices, oxidative stress, insulin, NOXs, inflammatory and liver fibrosis markers were assessed. Treatment of animals with apocynin and α-LA significantly ameliorated the changes in liver functions and histopathological architecture induced by ConA. Liver fibrosis induced by ConA was evident where alpha-smooth muscle actin and transforming growth factor- beta1 were elevated, which was further confirmed by Masson's trichrome stain and increased hydroxyproline. Co-treatment with apocynin and α-LA significantly reduced their expression. Besides, apocynin and α-LA significantly ameliorated oxidative stress injury evoked by ConA, as evidenced by enhancing reduced glutathione content, antioxidant enzymes activities and decreasing lipid peroxides. ConA induced a significant elevation in serum insulin level and inflammatory markers; tumor necrosis factor-alpha, interleukin-6 and nuclear factor kappa b. Furthermore, the mRNA tissue expression of NOXs 1 and 4 was found to be elevated in the ConA group. All these elevations were significantly reduced by apocynin and α-LA co-treatment. These findings indicate that using apocynin and α-LA in combination possess marked antifibrotic effects, and that NOX enzymes are partially involved in the pathogenesis of ConA-induced liver fibrosis.

  2. The effects of alpha2-adrenoceptor agents on anti-hyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory pain.

    PubMed

    Vucković, Sonja M; Tomić, Maja A; Stepanović-Petrović, Radica M; Ugresić, Nenad; Prostran, Milica S; Bosković, Bogdan

    2006-11-01

    In this study, the effects of yohimbine (alpha2-adrenoceptor antagonist) and clonidine (alpha2-adrenoceptor agonist) on anti-hyperalgesia induced by carbamazepine and oxcarbazepine in a rat model of inflammatory pain were investigated. Carbamazepine (10-40 mg/kg; i.p.) and oxcarbazepine (40-160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A, intraplantarly) in a paw pressure test in rats. Yohimbine (1-3 mg/kg; i.p.) significantly depressed the anti-hyperalgesic effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Both drug mixtures (carbamazepine-clonidine and oxcarbazepine-clonidine) administered in fixed-dose fractions of the ED50 (1/2, 1/4 and 1/8) caused significant and dose-dependent reduction of the hyperalgesia induced by Con A. Isobolographic analysis revealed a significant synergistic (supra-additive) anti-hyperalgesic effect of both combinations tested. These results indicate that anti-hyperalgesic effects of carbamazepine and oxcarbazepine are, at least partially, mediated by activation of adrenergic alpha2-receptors. In addition, synergistic interaction for anti-hyperalgesia between carbamazepine and clonidine, as well as oxcarbazepine and clonidine in a model of inflammatory hyperalgesia, was demonstrated.

  3. The influence of interferon alpha on the rat liver injured by chronic administration of carbon tetrachloride.

    PubMed

    Madro, Agnieszka; Słomka, Maria; Celiński, Krzysztof; Chibowski, Daniel; Czechowska, Grazyna; Kleinrok, Zdzisław; Karpińska, Agnieszka

    2002-01-01

    Due to their complex and not fully known etiopathogenesis as well as difficulties in treatment, chronic hepatitis and cirrhosis still remain one of the main problems of hepatologists. Nowadays, the use of IFN alpha is considered the most effective method of treatment in chronic hepatitis. Recently, a new property of IFN, i.e. its effects on the reduction of fibrosis, has been discovered. The aim of the paper was to examine the effects of IFN alpha on biochemical parameters (AlAt and AspAt activities), on the metabolic function of the liver and its morphologic picture observed under the light and electron microscope after the 3- and 6-week CCl4-induced damage. The experiments were carried out in Wistar male rats. To evaluate the liver function, the test of aminophenazone elimination in the isolated perfused rat livers was used according to Miller modified by Hafte. Additionally, AspAt and AlAt activities were determined. The liver specimens were analysed under the light and electron microscope and using immunohistochemical methods. The findings show that after the 3-week CCl4-induced liver damage, IFN alpha does not significantly affect AlAt and AspAt activities, irrespective of the dose used. IFN alpha administered after the 6-week damage significantly changes those activities when the doses used are high. It was found that carbon tetrachloride does not result in evident cirrhotic changes, however it activates Ito cells, causes focal retraction of the stroma and fibrosis. The increased number of Ito cells in Disse's space observed in immunohistochemical and ultrastructural examinations is indicative of the activation of liver fibrotic processes following CCl4 administration in both variants used. IFN alpha substantially weakens fibrogenesis of the CCl4-damaged liver which is visible in the decreased number of Ito cells and weaker expression of the stroma retraction. Moreover, IFN alpha administered to the experimental animals after the CCl4-induced injury of the

  4. Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine.

    PubMed

    Sagara, M; Satoh, J; Wada, R; Yagihashi, S; Takahashi, K; Fukuzawa, M; Muto, G; Muto, Y; Toyota, T

    1996-03-01

    N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor alpha (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velocity (MNCV) was significantly decreased in streptozotocin-induced-diabetic Wistar rats compared to control rats. Oral administration of NAC reduced the decline of MNCV in diabetic rats. Structural analysis of the sural nerve disclosed significant reduction of fibres undergoing myelin wrinkling and inhibition of myelinated fibre atrophy in NAC-treated diabetic rats. NAC treatment had no effect on blood glucose levels or on the nerve glucose, sorbitol and cAMP contents, whereas it corrected the decreased GSH levels in erythrocytes, the increased lipid peroxide levels in plasma and the increased lipopolysaccharide-induced TNF activity in sera of diabetic rats. Thus, NAC inhibited the development of functional and structural abnormalities of the peripheral nerve in streptozotocin-induced diabetic rats.

  5. Halothane reduces the early lipopolysaccharide-induced lung inflammation in mechanically ventilated rats.

    PubMed

    Giraud, O; Seince, P F; Rolland, C; Leçon-Malas, V; Desmonts, J M; Aubier, M; Dehoux, M

    2000-12-01

    Several studies suggest that anesthetics modulate the immune response. The aim of this study was to investigate the effect of halothane and thiopental on the lung inflammatory response. Rats submitted or not to intratracheal (IT) instillation of lipopolysaccharides (LPS) were anesthetized with either halothane (0. 5, 1, or 1.5%) or thiopental (60 mg. kg(-1)) and mechanically ventilated for 4 h. Control rats were treated or not by LPS without anesthesia. Lung inflammation was assessed by total and differential cell counts in bronchoalveolar lavage fluids (BALF) and by cytokine measurements (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6], macrophage inflammatory protein-2 [MIP-2], and monocyte chemoattractant protein-1 [MCP-1]) in BALF and lung homogenates. In the absence of LPS treatment, neither halothane nor thiopental modified the moderate inflammatory response induced by tracheotomy or mechanical ventilation. Cell recruitment and cytokine concentrations were increased in all groups receiving IT LPS. However, in halothane-anesthetized rats (halothane > or = 1%), but not in thiopental-anesthetized rats, the LPS-induced lung inflammation was altered in a dose-dependent manner. Indeed, when using 1% halothane, polymorphonuclear leukocyte (PMN) recruitment was decreased by 55% (p < 0.001) and TNF-alpha, IL-6, and MIP-2 concentrations in BALF and lung homogenates were decreased by more than 60% (p < 0.001) whereas total protein and MCP-1 concentrations remained unchanged. The decrease of MIP-2 (observed at the protein and messenger RNA [mRNA] level) was strongly correlated to the decrease of PMN recruitment (r = 0.73, p < 0.05). This halothane-reduced lung inflammatory response was transient and was reversed 20 h after the end of the anesthesia. Our study shows that halothane > or = 1%, delivered during 4 h by mechanical ventilation, but not mechanical ventilation per se, alters the early LPS-induced lung inflammation in the rat, suggesting a specific

  6. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague-Dawley rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chatterjee, A.; Chatterji, U., E-mail: urmichatterji@gmail.com

    2011-12-15

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin-eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression ofmore » the estrogen receptor (ER{alpha}), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ER{alpha}, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: Black

  7. Phosphorylation and desensitization of alpha1d-adrenergic receptors.

    PubMed Central

    García-Sáinz, J A; Vázquez-Cuevas, F G; Romero-Avila, M T

    2001-01-01

    In rat-1 fibroblasts stably expressing rat alpha(1d)-adrenoceptors, noradrenaline and PMA markedly decreased alpha(1d)-adrenoceptor function (noradrenaline-elicited increases in calcium in whole cells and [(35)S]guanosine 5'-[gamma-thio]triphosphate binding in membranes), suggesting homologous and heterologous desensitizations. Photoaffinity labelling, Western blotting and immunoprecipitation identified alpha(1d)-adrenoceptors as a broad band of 70-80 kDa. alpha(1d)-Adrenoceptors were phosphorylated in the basal state and noradrenaline and PMA increased it. The effect of noradrenaline was concentration-dependent (EC(50) 75 nM), rapid (maximum at 1 min) and transient. Phorbol ester-induced phosphorylation was concentration-dependent (EC(50) 25 nM), slightly slower (maximum at 5 min) and stable for at least 60 min. Inhibitors of protein kinase C decreased the effect of phorbol esters but not that of noradrenaline. Evidence of cross-talk of alpha(1d)-adrenoceptors with receptors endogenously expressed in rat-1 fibroblasts was given by the ability of endothelin, lysophosphatidic acid and bradykinin to induce alpha(1d)-adrenoceptor phosphorylation. In summary, it is shown for the first time here that alpha(1d)-adrenoceptors are phosphoproteins and that receptor phosphorylation is increased by the natural ligand, noradrenaline, by direct activation of protein kinase C and via cross-talk with other receptors endogenously expressed in rat-1 fibroblasts. Receptor phosphorylation has functional repercussions. PMID:11171057

  8. Depletion of brain alpha-MSH alters prostaglandin and interleukin fever in rats.

    PubMed

    Martin, S M; Malkinson, T J; Veale, W L; Pittman, Q J

    1990-09-03

    Alpha-melanocyte stimulating hormone (alpha-MSH), a putative endogenous antipyretic agent, is synthesized largely within neurons in the arcuate nucleus. To test the hypothesis that destruction of this area would increase the febrile response, male Wistar rats, treated as neonates with intraperitoneal injections of monosodium glutamate (MSG) or saline, were given intracerebroventricular (i.c.v.) injections of prostaglandin E1 (20 ng; 200 ng) or purified interleukin-1 (20 U) and body temperature was monitored. The fevers displayed by the MSG-treated animals were significantly greater (P less than 0.05) than those of the controls for the lower dose of PGE1 at 10-30 min and for IL-1 at 3-6 h after the injections. MSG-treated rats showed significant reduction (P less than 0.01) in alpha-MSH content of the medial basal hypothalamus and lateral septum when compared to saline controls. Body temperature response of non-febrile animals to high ambient temperature was not affected by the MSG treatment. These data support the hypothesis that alpha-MSH is an endogenous antipyretic in the rat.

  9. Prostaglandin mediates endotoxaemia-induced hypophagia by activation of pro-opiomelanocortin and corticotrophin-releasing factor neurons in rats.

    PubMed

    Rorato, Rodrigo; Menezes, Aline Motta; Giusti-Paiva, Alexandre; de Castro, Margaret; Antunes-Rodrigues, José; Elias, Lucila Leico Kagohara

    2009-03-01

    Corticotrophin-releasing factor (CRF) and alpha-melanocyte-stimulating hormone (alpha-MSH), both of which are synthesized by hypothalamic neurons, play an essential role in the control of energy homeostasis. Neuroendocrine and behavioural responses induced by lipopolyssacharide (LPS) have been shown to involve prostaglandin-mediated pathways. This study investigated the effects of prostaglandin on CRF and alpha-MSH neuronal activities in LPS-induced anorexia. Male Wistar rats were pretreated with indomethacin (10 mg kg(-1); i.p.) or vehicle; 15 min later they received LPS (500 microg kg(-1); i.p.) or saline injection. Food intake, hormone responses and Fos-CRF and Fos-alpha-MSH immunoreactivity in the paraventricular and arcuate nuclei, respectively, were evaluated. In comparison with saline treatment, LPS administration induced lower food intake and increased plasma ACTH and corticosterone levels, as well as an increase in Fos-CRF and Fos-alpha-MSH double-labelled neurons in vehicle-pretreated rats. In contrast, indomethacin treatment partly reversed the hypophagic effect, blunted the hormonal increase and blocked the Fos-CRF and Fos-alpha-MSH hypothalamic double labelling increase in response to the LPS stimulus. These data demonstrate that the activation of pro-opiomelanocortin and CRF hypothalamic neurons following LPS administration is at least partly mediated by the prostaglandin pathway and is likely to be involved in the modulation of feeding behaviour during endotoxaemia.

  10. Protection against dexamethasone-induced muscle atrophy is related to modulation by testosterone of FOXO1 and PGC-1{alpha}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Qin, Weiping, E-mail: weiping.qin@mssm.edu; Department of Medicine, Mount Sinai School of Medicine, NY; Pan, Jiangping

    Research highlights: {yields} In rat gastrocnemius muscle, dexamethasone reduced PGC-1{alpha} cellular and nuclear levels without altering mRNA levels for this factor. {yields} Dexamethasone reduced phosphorylating of p38 MAPK, which stabilizes PGC-1{alpha} and promotes its nuclear entry. {yields} Co-administration of testosterone with dexamethasone increased cellular and nuclear levels of PGC-1{alpha} protein without changing its mRNA levels. {yields} Co-administration of testosterone restored p38 MAPK levels to those of controls. -- Abstract: Glucocorticoid-induced muscle atrophy results from muscle protein catabolism and reduced protein synthesis, associated with increased expression of two muscle-specific ubiquitin ligases (MAFbx and MuRF1), and of two inhibitors of protein synthesis,more » REDD1 and 4EBP1. MAFbx, MuRF1, REDD1 and 4EBP1 are up-regulated by the transcription factors FOXO1 and FOXO3A. The transcriptional co-activator PGC-1{alpha} has been shown to attenuate many forms of muscle atrophy and to repress FOXO3A-mediated transcription of atrophy-specific genes. Dexamethasone-induced muscle atrophy can be prevented by testosterone, which blocks up-regulation by dexamethasone of FOXO1. Here, an animal model of dexamethasone-induced muscle atrophy was used to further characterize effects of testosterone to abrogate adverse actions of dexamethasone on FOXO1 levels and nuclear localization, and to determine how these agents affect PGC-1{alpha}, and its upstream activators, p38 MAPK and AMPK. In rat gastrocnemius muscle, testosterone blunted the dexamethasone-mediated increase in levels of FOXO1 mRNA, and FOXO1 total and nuclear protein. Dexamethasone reduced total and nuclear PGC-1{alpha} protein levels in the gastrocnemius; co-administration of testosterone with dexamethasone increased total and nuclear PGC-1{alpha} levels above those present in untreated controls. Testosterone blocked dexamethasone-induced decreases in activity of p38 MAPK in the

  11. Selenomethionine and alpha-tocopherol do not inhibit prostate carcinogenesis in the testosterone plus estradiol-treated NBL rat model.

    PubMed

    Ozten, Nur; Horton, Lori; Lasano, Salamia; Bosland, Maarten C

    2010-03-01

    Previous studies with selenium and/or vitamin E in prostate carcinogenesis animal models have been negative, but these models may not involve oxidative stress mechanisms. In this study, we examined the potential of selenomethionine and alpha-tocopherol to modulate prostate cancer development in the testosterone plus estradiol-treated NBL rat, a model that does involve sex hormone-induced oxidative stress mechanisms and prostatic inflammation. One week following the implantation with hormone-filled Silastic implants, rats were fed diets containing l-selenomethionine (1.5 or 3.0 mg/kg), DL-alpha-tocopherol acetate (2,000 or 4,000 mg/kg), or a natural ingredient control diet (NIH-07). The development of prostate carcinomas was not affected by dietary treatment with either agent. Food intake, body weight, and mortality were also not affected. The high dose of selenomethionine reduced the severity of epithelial dysplasia in the lateral prostate that was not associated with inflammation, and alpha-tocopherol reduced in a dose-related fashion the incidence of marked inflammation and marked epithelial dysplasia in the lateral prostate, regardless of whether these lesions were associated with inflammation. alpha-Tocopherol significantly increased the incidence of adenocarcinomas of the mammary glands at both dietary concentrations. Collectively, our findings suggest that selenomethionine and alpha-tocopherol supplementation does not prevent prostate cancer in rats fed diets with nutritionally adequate levels of selenium and vitamin E. Importantly, the results of the current animal studies and those reported previously were fully predictive of the outcome of the Selenium and Vitamin E Cancer Prevention Trial.

  12. [Effect of paeoniflorin on level of glucocorticoid receptor of peripheral blood monocytes in rats of collagen-induced arthritis].

    PubMed

    Yi, Jian-Feng

    2014-03-01

    The study is to explore the effect of paeoniflorin on the level of glucocorticoid receptor, including glucocorticoid receptor-alpha (GCRalpha) and glucocorticoid receptor-beta (GCRbeta), of peripheral blood mononuclear cells (PBMCs) in rats of collagen-induced arthritis (CIA). CIA is induced in Wistar rats by an intradermal injection of bovine type II collagen emulsified with complete adjuvant. From the 14th day after primary immunization, the CIA rats were intragastrically administered paeoniflorin 25, 50 and 100 mg x kg(-1) or triptolde 20 microg x kg(-1) or paeoniflorin 50 mg x kg(-1) + RU486 15 mg x kg(-1), once a day, for 28 consecutive days. After administration, apart from PF + RU486 group all experimental rats were took blood by removalling eyeball, then separated PBMCs. The level of GCRalpha, GCRbeta in PBMCs were examined by ELISA, and the mRNA expression of GCRalpha, GCRbeta was detected by RT-PCR. All rats were sacrificed and took the joint with no immunization. The expression of IL-1beta, NF-kappaB p65, TNF-alpha, PGE2 of synovial tissue was detected by immunohistochemistry. Paeoniflorin was able to inhibit the expression of IL-1beta, NF-kappaB p65, TNF-alpha, PGE2 of synovial tissue in CIA rats. While RU486, glucocorticoid receptor's blocker, could weaken the fuction of paeoniflorin. Meanwhile, paeoniflorin obviously induced the expression of GCRalpha and GCRalpha mRNA, while obviously inhibited the expression of GCRbeta and GCRbeta mRNA. These results indicat paeoniflorine suppresses inflammatory mediator production may be relating with it regulating GCR in PBMCs of CIA rats.

  13. Effects of glutamate and {alpha}2-noradrenergic receptor antagonists on the development of neurotoxicity produced by chronic rotenone in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Alam, Mesbah; Danysz, Wojciech; Schmidt, Werner Juergen

    2009-10-15

    Systemic inhibition of complex I by rotenone in rats represents a model of Parkinson's disease (PD). The aim of this study was to elucidate whether neramexane (NMDA, nicotinic {alpha}9/{alpha}10 and 5-HT{sub 3} receptor antagonist), idazoxan ({alpha}{sub 2}-adrenoceptor antagonist) or 2-methyl-6-(phenyl-ethyl)-pyrimidine (MPEP, metabotropic glutamate receptor 5 antagonist) prevents rotenone-induced parkinsonian-like behaviours and neurochemical changes in rats. Rotenone (2.5 mg/kg i.p. daily) was administered over 60 days together with saline, neramexane (5 mg/kg i.p., b.i.d.), idazoxan (2.5 mg/kg i.p., b.i.d.) or MPEP (2.5 mg/kg i.p., b.i.d.). The same doses of neramexane, idazoxan and MPEP were administered to rats treated with vehicle insteadmore » of rotenone. Treatment-related effects on parkinsonian-like behaviours, such as hypokinesia/rigidity and locomotor activity, were evaluated. Moreover, concentrations of dopamine, serotonin and their metabolites were measured in rats from each experimental group. Over the 60-day treatment period, the rotenone + saline treated animals developed hypokinesia, expressed as an increase in the bar and grid descent latencies in the catalepsy test, and a decrease in locomotor activity. Neramexane and idazoxan partially prevented the development of catalepsy in rotenone-treated rats. Co-administration of MPEP with rotenone resulted only in a decrease in descent latency in the grid test on day 60. Chronic rotenone treatment reduced concentrations of dopamine and serotonin in the anterior striatum, which was blocked by co-treatment with neramexane or idazoxan but not with MPEP. Only neramexane treatment blocked the rotenone-induced decrease in dopamine levels in the substantia nigra pars compacta. In conclusion, neramexane and idazoxan counteracted to some extent the development of parkinsonian symptoms and neurochemical alterations in the rotenone model of Parkinson's disease.« less

  14. Human umbilical cord blood-derived mesenchymal stem cells attenuate hyperoxia-induced lung injury in neonatal rats.

    PubMed

    Chang, Yun Sil; Oh, Wonil; Choi, Soo Jin; Sung, Dong Kyung; Kim, Soo Yoon; Choi, Eun Yang; Kang, Saem; Jin, Hye Jin; Yang, Yoon Sun; Park, Won Soon

    2009-01-01

    Recent evidence suggests mesenchymal stem cells (MSCs) can downmodulate bleomycin-induced lung injury, and umbilical cord blood (UCB) is a promising source for human MSCs. This study examined whether intratracheal or intraperitoneal transplantation of human UCB-derived MSCs can attenuate hyperoxia-induced lung injury in immunocompetent newborn rats. Wild-type Sprague-Dawley rats were randomly exposed to 95% oxygen or air from birth. In the transplantation groups, a single dose of PKH26-labeled human UCB-derived MSCs was administered either intratracheally (2 x 10(6) cells) or intraperitoneally (5 x 10(5) cells) at postnatal day (P) 5. At P14, the harvested lungs were examined for morphometric analyses of alveolarization and TUNEL staining, as well as the myeoloperoxidase activity, the level of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and transforming growth factor (TGF)-beta mRNA, alpha-smooth muscle actin (SMA) protein, and collagen levels. Differentiation of MSCs to the respiratory epithelium was also evaluated both in vitro before transplantation and in vivo after transplantation. Despite one fourth dosage of MSCs, significantly more PKH26-labeled donor cells were recovered with intratracheal administration than with intraperitoneal administration both during normoxia and hyperoxia. The hyperoxia-induced increase in the number of TUNEL-positive cells, myeloperoixdase activity, and the level of IL-6 mRNA were significantly attenuated with both intratracheal and intraperitoneal MSCs transplantation. However, the hyperoxia-induced impaired alveolarization and increased the level of TNF-alpha and TGF-beta mRNA, alpha-SMA protein, and collagen were significantly attenuated only with intratracheal MSCs transplantation. MSCs differentiated into respiratory epithelium in vitro and a few PKH26-positive donor cells were colocalized with pro surfactant protein C in the damaged lungs. In conclusion, intratracheal transplantation of human UCB-derived MSCs is

  15. Cytokine appearance and effects of anti-tumor necrosis factor alpha antibodies in a neonatal rat model of group B streptococcal infection.

    PubMed Central

    Teti, G; Mancuso, G; Tomasello, F

    1993-01-01

    Cytokines are suspected of playing an important role in the pathophysiology of septic shock. This study was undertaken to determine whether tumor necrosis factor alpha (TNF-alpha) induces the production of other cytokines and mediates mortality in a neonatal rat model of sepsis caused by group B streptococci (GBS). We have measured TNF-alpha, interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), and gamma interferon (IFN-gamma) levels in neonatal rats infected with different strains (H738, 259, and 90) and doses (1 50% lethal dose [LD50] and 5 90% lethal doses [LD90]) of type III GBS. TNF-alpha and IL-6 were detected by the L929 cytotoxicity and the B9 proliferation assays, respectively, in serial plasma samples. IL-1 alpha and IFN-gamma were measured in spleen homogenates by enzyme-linked immunosorbent assay kits by using antibodies raised against the corresponding mouse cytokines. Plasma TNF-alpha levels significantly rose above baseline values within 12 h after intraperitoneal challenge with 5 LD90 of GBS strain H738, corresponding to 3 x 10(3) CFU. A mean peak TNF-alpha concentration of 232 +/- 124 U/ml was reached at 20 h. Peak IL-1 alpha and IL-6 levels of 766 +/- 404 U/g and 1,033 +/- 520 U/ml, respectively, were reached at 24 h after bacterial challenge. Maximal spleen concentrations of IFN-gamma (449 +/- 283 U/g) were measured at 36 h. Concentrations of TNF-alpha, but not other cytokines, remained significantly elevated at 72 h, a time when mortality approached 100%. Significant correlations were found between concentrations of each of the cytokines tested and the logs of CFU concentrations in the blood. In order to ascertain whether TNF-alpha influenced the production of other cytokines, rat pups received two injections of anti-murine TNF-alpha or normal rabbit serum at 2 h before and at 26 h after challenge with live GBS. Plasma TNF-alpha bioactivity was undetectable in anti-TNF-alpha-treated animals, while IL-6 and IFN-gamma, but not IL-1 alpha

  16. Evaluation of the alpha-1 and alpha-2 adrenoceptor-mediated effects of a series of dimethoxy-substituted tolazoline derivatives in the cardiovascular system of the pithed rat.

    PubMed

    Ruffolo, R R; Messick, K

    1985-01-01

    The alpha-1 and alpha-2 adrenoceptor-mediated effects of a series of dimethoxy-substituted tolazoline derivatives were investigated in the cardiovascular system of the pithed rat. The 2,5- and 3,5-dimethoxy-substituted tolazoline derivatives produced vasopressor responses that were inhibited by the alpha-1 adrenoceptor antagonist, prazosin (0.1 mg/kg i.v.), and were not affected by the alpha-2 adrenoceptor antagonist, yohimbine (1 mg/kg i.v.), suggesting that these derivatives selectively activate postsynaptic vascular alpha-1 adrenoceptors. The 2,5- and 3,5-dimethoxy-substituted derivatives of tolazoline did not produce an alpha-2 adrenoceptor-mediated inhibition of neurogenic tachycardia in cord-stimulated pithed rats and were therefore presumed to be devoid of alpha-2 adrenoceptor agonist activity. In contrast, 2,3-dimethoxytolazoline produced a vasopressor effect that was inhibited by yohimbine but not by prazosin, suggesting selective activation of postsynaptic vascular alpha-2 adrenoceptors. Consistent with this observation is the fact that 2,3-dimethoxytolazoline elicited a dose-dependent, alpha-2 adrenoceptor-mediated inhibition of neurogenic tachycardia in cord-stimulated pithed rat. 3,4-Dimethoxytolazoline was a weak alpha-1 adrenoceptor agonist in the vasculature of the pithed rat and was devoid of agonist activity at alpha-2 adrenoceptors. However, 3,4-dimethoxytolazoline was found to be an alpha-2 adrenoceptor antagonist of similar potency as yohimbine. The results of the present study indicate that dimethoxy-substituted derivatives of tolazoline possess different activities and selectivities at alpha-1 and alpha-2 adrenoceptors depending upon the positions of substitution.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. [Modified Jujing No.2 Decoction for varicocele-induced male infertility].

    PubMed

    Sun, Zhi-Xing; Zhou, Yu-Chun; Liu, Tao; Fan, Qian; Huang, Xin-Fei; Huang, Jian; Wang, Qing; Ni, Liang-Yu; Xue, Jian-Guo; Ning, Ke-Qin

    2016-07-01

    To investigate the clinical effect of Jujing No.2 Decoction on male infertility induced by varicocele. We equally randomized 70 male patients with varicocele-induced infertility into a treatment group and a control group, the former treated with modified Jujing No.2 Decoction (1 dose a day, bid) and the latter given Danshen Tablets (4 tablets once, tid) plus Liu Wei Di Huang Wan (8 pills once, tid), both for 3 months. We examined the spermatic veins of the patients by ultrasonography and performed seminal analysis before and after medication. Compared with the controls, the patients in the treatment group showed significant improvement after medication in sperm concentration ([12.35±2.12] vs [18.56±4.16] ×10⁶/ml, P<0.05), progressively motile sperm ([16.18±6.34] vs [24.63±8.51] %, P<0.05), and morphologically normal sperm ([11.59±5.31] vs [14.17±6.02] %, P<0.05). In the control group, sperm concentration was increased from (12.29±2.07) ×10⁶/ml at the baseline to (13.13±3.13) ×10⁶/ml after medication, progressively motile sperm from (16.13±6.45) % to (20.55±7.30) % (P<0.05), and morphologically normal sperm from (11.62±5.35) % to (12.69±5.77) %. The total effectiveness rate was significantly higher in the treatment than in the control group (71.88% vs 46.67%, P<0.05). The inner diameter of the left spermatic vein was decreased from (0.32±0.05) mm at the baseline to [0.26±0.05] mm after medication in the treatment group (P<0.05) and from (0.32±0.03) mm to (0.29±0.04) mm in the control (P<0.05), with statistically significant difference between the two groups after medication (P<0.05). Jujing No.2 Decoction is effective in the treatment of varicocele-induced male infertility.

  18. Factor structure of the General Health Questionnaire-28 (GHQ-28) from infertile women attending the Yazd Research and Clinical Center for Infertility.

    PubMed

    Shayan, Zahra; Pourmovahed, Zahra; Najafipour, Fatemeh; Abdoli, Ali Mohammad; Mohebpour, Fatemeh; Najafipour, Sedighe

    2015-12-01

    Nowadays, infertility problems have become a social concern, and are associated with multiple psychological and social problems. Also, it affects the interpersonal communication between the individual, familial, and social characteristics. Since women are exposed to stressors of physical, mental, social factors, and treatment of infertility, providing a psychometric screening tool is necessary for disorders of this group. The aim of this study was to determine the factor structure of the general health questionnaire-28 to discover mental disorders in infertile women. In this study, 220 infertile women undergoing treatment of infertility were selected from the Yazd Research and Clinical Center for Infertility with convenience sampling in 2011. After completing the general health questionnaire by the project manager, validity and, reliability of the questionnaire were calculated by confirmatory factor structure and Cronbach's alpha, respectively. Four factors, including anxiety and insomnia, social dysfunction, depression, and physical symptoms were extracted from the factor structure. 50.12% of the total variance was explained by four factors. The reliability coefficient of the questionnaire was obtained 0.90. Analysis of the factor structure and reliability of General Health Questionnaire-28 showed that it is suitable as a screening instrument for assessing general health of infertile women.

  19. [Age-related change in the alpha-tocopherolquinone/alpha-tocopherol ratio in the rat erythrocyte membrane].

    PubMed

    Yanagawa, K; Takeda, H; Matsumiya, T; Takasaki, M

    1999-05-01

    alpha-Tocopherol (alpha-Toc), a lipophilic phenolic antioxidant that is localized mainly in the biomembrane, protects cells against oxidation-associated cytotoxicity by prevention of membrane lipid peroxidation, maintenance of the redox balance intracellular thiols and stabilization of the membrane structure. We investigated the age-related changes in redox dynamics of alpha-Toc in plasma and erythrocyte membrane of an elderly (66 weeks old) and young group (10 weeks old). Total, alpha-, beta + gamma-, delta-Toc and alpha-tocopherolquinone (alpha-TocQ) in plasma and erythrocyte membrane were determined by high-performance liquid chromatography (HPLC) with a series of multiple coulometric working electrodes (CWE). Rat venous blood sample was divided into plasma and erythrocyte layers by centrifugation, and then erythrocyte membrane sample was prepared according to the method of Dodge et al. under a stream of nitrogen. In plasma, total and alpha-Toc concentrations were increased, and beta + gamma-, delta-Toc and alpha-TocQ concentrations were decreased age-dependently. In the erythrocyte membrane, total, alpha-TocQ concentrations and three fractions of tocopherols decreased age-dependently. Also, a decrease in the alpha-TocQ/alpha-Toc ratio in erythrocyte membrane was observed in the elderly group. These findings suggest that the alpha-Toc uptake in erythrocyte membrane and utilization rate of alpha-Toc in erythrocyte membrane decline age-dependently. This decline may promote membrane lipid peroxidation. alpha-Toc redox dynamics in erythrocyte membrane were useful to investigate the pathophysiology of aging mechanisms related to oxidative stress.

  20. Bovine alpha-lactalbumin stimulates mucus metabolism in gastric mucosa.

    PubMed

    Ushida, Y; Shimokawa, Y; Toida, T; Matsui, H; Takase, M

    2007-02-01

    Bovine alpha-lactalbumin (alpha-LA), a major milk protein, exerts strong gastroprotective activity against rat experimental gastric ulcers induced by ethanol or stress. To elucidate the mechanisms underlying this activity, the influence of alpha-LA on gastric mucus metabolism was investigated in vitro and in vivo. For the in vitro study, RGM1 cells (a rat gastric epithelial cell line) were selected for observation of the direct activity of alpha-LA on gastric mucosal cells and cultured in the presence of either alpha-LA or ovalbumin (OVA), a reference protein showing no gastroprotective activity. Amounts of synthesized and secreted mucin, a major component of mucus, were determined using [3H]glucosamine as a tracer, and prostaglandin E2 (PGE2) levels in the culture medium were determined by RIA. For the in vivo study, the thickness of the mucus gel layer, a protective barrier for gastric mucosa, was evaluated histochemically in rat gastric mucosa. alpha-Lactalbumin (3 mg/mL) significantly stimulated mucin synthesis and secretion in RGM1 cells and also increased PGE2 levels in the culture medium. In contrast, OVA showed no enhancing effects under identical conditions. Neither indomethacin, a cyclo-oxygenase inhibitor, nor AH23848, a prostaglandin EP4 receptor antagonist, affected alpha-LA-induced enhancement of mucin synthesis and secretion. In vivo, oral administration of alpha-LA (300 mg/kg x 3 times/d x 7 d) increased the thickness of the mucus gel layer in rats. These results indicate that alpha-LA fortifies the mucus gel layer by stimulating mucin production and secretion in gastric mucus-producing cells, and that this enhancing effect is independent of endogenous PGE2. Comparison of the efficacy of alpha-LA with OVA suggests that the activities observed in RGM1 cells are closely related to the gastroprotective effects in rat gastric ulcer models. In conclusion, alpha-LA stimulates mucus metabolism, and this action may be responsible for its gastroprotective

  1. Fluid shear stress inhibits TNF-alpha-induced apoptosis in osteoblasts: a role for fluid shear stress-induced activation of PI3-kinase and inhibition of caspase-3

    NASA Technical Reports Server (NTRS)

    Pavalko, Fredrick M.; Gerard, Rita L.; Ponik, Suzanne M.; Gallagher, Patricia J.; Jin, Yijun; Norvell, Suzanne M.

    2003-01-01

    In bone, a large proportion of osteoblasts, the cells responsible for deposition of new bone, normally undergo programmed cell death (apoptosis). Because mechanical loading of bone increases the rate of new bone formation, we hypothesized that mechanical stimulation of osteoblasts might increase their survival. To test this hypothesis, we investigated the effects of fluid shear stress (FSS) on osteoblast apoptosis using three osteoblast cell types: primary rat calvarial osteoblasts (RCOB), MC3T3-E1 osteoblastic cells, and UMR106 osteosarcoma cells. Cells were treated with TNF-alpha in the presence of cyclohexamide (CHX) to rapidly induce apoptosis. Osteoblasts showed significant signs of apoptosis within 4-6 h of exposure to TNF-alpha and CHX, and application of FSS (12 dyne/cm(2)) significantly attenuated this TNF-alpha-induced apoptosis. FSS activated PI3-kinase signaling, induced phosphorylation of Akt, and inhibited TNF-alpha-induced activation of caspase-3. Inhibition of PI3-kinase, using LY294002, blocked the ability of FSS to rescue osteoblasts from TNF-alpha-induced apoptosis and blocked FSS-induced inhibition of caspase-3 activation in osteoblasts treated with TNF-alpha. LY294002 did not, however, prevent FSS-induced phosphorylation of Akt suggesting that activation of Akt alone is not sufficient to rescue cells from apoptosis. This result also suggests that FSS can activate Akt via a PI3-kinase-independent pathway. These studies demonstrate for the first time that application of FSS to osteoblasts in vitro results in inhibition of TNF-alpha-induced apoptosis through a mechanism involving activation of PI3-kinase signaling and inhibition of caspases. FSS-induced activation of PI3-kinase may promote cell survival through a mechanism that is distinct from the Akt-mediated survival pathway. Copyright 2002 Wiley-Liss, Inc.

  2. Influence of thyroid status on hepatic alpha 1-adrenoreceptor responsiveness.

    PubMed

    Daza, F J; Parrilla, R; Martín-Requero, A

    1997-12-01

    The present work aimed to elucidate the influence of thyroid functional status on the alpha 1-adrenoreceptor-induced activation of hepatic metabolic functions. The experiments were performed in either a nonrecirculating liver perfusion system featuring continuous monitoring of portal pressure, PO2, pCa, and pH, or isolated hepatocytes from euthyroid, hyperthyroid, and hypothyroid rats. Hypothyroidism decreased the alpha 1-adrenergic stimulation of respiration, glycogen breakdown, and gluconeogenesis. These effects were accompanied by a decreased intracellular Ca2+ mobilization corroborating that those processes are regulated by the Ca(2+)-dependent branch of the alpha 1-adrenoreceptor signaling pathway. Moreover, in hyperthyroid rats the alpha 1-adrenergic-induced increase in cytosolic Ca2+ was enhanced, and glucose synthesis or mobilization was not altered. The thyroid status influenced neither the alpha 1-adrenergic stimulation of vascular smooth muscle contraction nor the alpha 1-agonist-induced intracellular alkalinization and protein kinase C (PKC) activation. Thus the distinct impairment of the Ca(2+)-dependent branch of the alpha 1-adrenoreceptor signaling pathway by thyroid status provides a useful tool to investigate the role played by each signaling pathway, Ca2+ or PKC, in controlling hepatic functions.

  3. Biomarker and Drug Target Discovery Using Proteomics in a New Rat Model of Sepsis-Induced Acute Renal Failure

    PubMed Central

    Holly, Mikaela K.; Dear, James W.; Hu, Xuzhen; Schechter, Alan N.; Gladwin, Mark T.; Hewitt, Stephen M.; Yuen, Peter S.T.; Star, Robert A.

    2008-01-01

    Background Sepsis is one of the common causes of acute renal failure (ARF). The objective of this study was to identify new biomarkers and therapeutic targets. We present a new rat model of sepsis-induced ARF based on cecal ligation and puncture (CLP). We used this model to find urinary proteins which may be potential biomarkers and/or drug targets. Methods Aged rats were treated with fluids and antibiotics after CLP. Urinary proteins from septic rats without ARF and urinary proteins from septic rats with ARF were compared by difference in-gel electrophoresis (DIGE). Results CLP surgery elevated IL-6 and IL-10 serum cytokines and blood nitrite compared with sham-operated rats. However there was a range of serum creatinine values at 24 hrs (0.4–2.3 mg/dL) and only 24% developed ARF. Histology confirmed renal injury in these rats. 49% of rats did not develop ARF. Rats without ARF also had less liver injury. The mortality rate at 24 hrs was 27% but was increased by housing the post-surgery rats in metabolic cages. Creatinine clearance and urine output 2–8 hours after CLP was significantly reduced in rats which died within 24 hours. Using DIGE we identified changes in a number of urinary proteins including albumin, brush-border enzymes (eg., meprin-1-alpha) and serine protease inhibitors. The meprin-1-alpha inhibitor actinonin prevented ARF in aged mice. Conclusion In summary we describe a new rat model of sepsis-induced ARF which has a heterogeneous response similar to humans. This model allowed us to use DIGE to find changes in urinary proteins and this approach identified a potential biomarker and drug target – meprin-1-alpha. PMID:16760904

  4. Protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine induced acute liver injury in rats.

    PubMed

    Akashi, Iwao; Kagami, Keisuke; Hirano, Toshihiko; Oka, Kitaro

    2009-04-01

    The protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine (LPS/D-GalN) induced acute liver injury in rats were investigated. Wistar rats were orally administered saline (control) or one of the test compounds (caffeine, chlorogenic acid, trigonelline, nicotinic acid or eight pyrazinoic acids) at a dose of 100 mg/kg, respectively. This was followed by intraperitoneal injection with LPS (100 mug/kg)/D-GalN (250 mg/kg) 1 h after administration of the test compounds. Blood samples were collected up to 12 h after LPS/D-GalN injection, followed by determination of plasma aspartate aminotransferase, alanine aminotransferase, tumour necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) levels. Plasma aspartate aminotransferase and alanine aminotransferase levels were significantly increased after LPS/D-GalN-treatment, but were suppressed by pretreatment with caffeine (n = 5), nicotinic acid, non-substituted pyrazinoic acid or 5-methylpyrazinoic acid (n = 6, respectively) 12 h after LPS/D-GalN-treatment (P < 0.01, respectively). Moreover, the animals pretreated with these test compounds showed significantly higher survival rates (83-100%) compared with the control (23%). Only pretreatment with caffeine significantly suppressed the LPS/D-GalN induced elevation of plasma TNF-alpha levels 1 and 2 h after LPS/D-GalN-treatment (P < 0.01, respectively). Pretreatment with caffeine, nicotinic acid or non-substituted pyrazinoic acid activated the LPS/D-GalN induced elevation of plasma IL-10 levels at 1 and 2 h, although there were no statistically significant differences in IL-10 levels between control and nicotinic acid or non-substituted pyrazinoic acid treated rats. The results suggest that caffeine, nicotinic acid, non-substituted pyrazinoic acid and 5-methylpyrazinoic acid can protect against LPS/D-GalN induced acute liver injury, which may be mediated by the reduction of TNF-alpha production and/or increasing IL-10 production.

  5. Osthole attenuates the development of carrageenan-induced lung inflammation in rats.

    PubMed

    Li, Zhipeng; Ji, Haijie; Song, Xiuyun; Hu, Jinfeng; Han, Ning; Chen, Naihong

    2014-05-01

    Osthole has been reported to possess a variety of pharmacological activities, such as antiinflammatory effect. In the present study, we have investigated the effect of osthole on lung inflammation associated with carrageenan-induced pleurisy in rats. The result showed that osthole could inhibit significantly pleural exudates formation and PMNs infiltration. Histological examination revealed osthole could reduce lung inflammation in rats treated with carrageenan. The myeloperoxidase (MPO) level was examined in pleural exudates. The result showed that osthole could attenuate MPO level in pleural exudates. Further studies showed osthole could decrease tumor necrosis factor alpha (TNF-α) and interleukin 1beta (IL-1β) levels in the lungs. Taken together, the present results suggested that osthole could inhibit lung inflammation on carrageenan-induced pleurisy in rats and that could be related to a reduction of PMNs infiltration and release of inflammatory factors. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mitra, Mayurranjan S.; Donthamsetty, Shashikiran; White, Brent

    Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK/STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. A LD{sub 10} dose (8 mg doxorubicin/kg, ip) administered on day 43 of the HFD feeding regimen ledmore » to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-{alpha}, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9 {+-} 14.0 nmol/min/g heart in ND versus 400.2 {+-} 11.8 nmol/min/g heart in OB), (5) decreased mitochondrial AMP-{alpha}2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK/STAT3 pathway. In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and

  7. Effect of S 17092, a novel prolyl endopeptidase inhibitor, on substance P and alpha-melanocyte-stimulating hormone breakdown in the rat brain.

    PubMed

    Bellemère, Gaëlle; Morain, Philippe; Vaudry, Hubert; Jégou, Sylvie

    2003-03-01

    In the present study, we have investigated the effects of a novel prolyl endopeptidase (EC 3.4.21.26, PEP) inhibitor, compound S 17092, on substance P (SP) and alpha-melanocyte-stimulating hormone (alpha-MSH) metabolism in the rat brain. In vitro experiments revealed that S 17092 inhibits in a dose-dependent manner PEP activity in rat cortical extracts (IC50 = 8.3 nm). In addition, S 17092 totally abolished the degradation of SP and alpha-MSH induced by bacterial PEP. In vivo, a significant decrease in PEP activity was observed in the medulla oblongata after a single oral administration of S 17092 at doses of 10 and 30 mg/kg (-78% and -82%, respectively) and after chronic oral treatment with S 17092 at doses of 10 and 30 mg/kg per day (-75% and -88%, respectively). Concurrently, a single administration of S 17092 (30 mg/kg) caused a significant increase in SP- and alpha-MSH-like immunoreactivity (LI) in the frontal cortex (+41% and +122%, respectively) and hypothalamus (+84% and +49%, respectively). In contrast, chronic treatment with S 17092 did not significantly modify SP- and alpha-MSH-LI in the frontal cortex and hypothalamus. Collectively, the present results show that S 17092 elevates SP and alpha-MSH concentrations in the rat brain by inhibiting PEP activity. These data suggest that the effect of S 17092 on memory impairment can be accounted for, at least in part, by inhibition of catabolism of promnesic neuropeptides such as SP and alpha-MSH.

  8. Anti-inflammatory effects of compounds alpha-humulene and (-)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea.

    PubMed

    Fernandes, Elizabeth S; Passos, Giselle F; Medeiros, Rodrigo; da Cunha, Fernanda M; Ferreira, Juliano; Campos, Maria M; Pianowski, Luiz F; Calixto, João B

    2007-08-27

    This study evaluated the anti-inflammatory properties of two sesquiterpenes isolated from Cordia verbenacea's essential oil, alpha-humulene and (-)-trans-caryophyllene. Our results revealed that oral treatment with both compounds displayed marked inhibitory effects in different inflammatory experimental models in mice and rats. alpha-humulene and (-)-trans-caryophyllene were effective in reducing platelet activating factor-, bradykinin- and ovoalbumin-induced mouse paw oedema, while only alpha-humulene was able to diminish the oedema formation caused by histamine injection. Also, both compounds had important inhibitory effects on the mouse and rat carrageenan-induced paw oedema. Systemic treatment with alpha-humulene largely prevented both tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) generation in carrageenan-injected rats, whereas (-)-trans-caryophyllene diminished only TNFalpha release. Furthermore, both compounds reduced the production of prostaglandin E(2) (PGE(2)), as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) expression, induced by the intraplantar injection of carrageenan in rats. The anti-inflammatory effects of alpha-humulene and (-)-trans-caryophyllene were comparable to those observed in dexamethasone-treated animals, used as positive control drug. All these findings indicate that alpha-humulene and (-)-trans-caryophyllene, derived from the essential oil of C. verbenacea, might represent important tools for the management and/or treatment of inflammatory diseases.

  9. Hypoglycemic and hypolipidemic effects of Saururus chinensis Baill in streptozotocin-induced diabetic rats.

    PubMed

    Hwang, Ji-Yeon; Zhang, Jian; Kang, Min-Jung; Lee, Soo-Kyung; Kim, Hyun-A; Kim, Jong-Jin; Kim, Jung-In

    2007-01-01

    Saururus chinensis Baill was reported to inhibit alpha-glucosidase in vitro and flatten postprandial increase in blood glucose in streptozotocin (STZ)-induced diabetic rats. We studied the effect of chronic consumption of S. chinensis Baill on blood glucose and lipid profile in STZ-induced diabetic male rats fed high fat diet. Male rats weighing 100-120 g were fed 30% fat diet with and without 10% freeze-dried leaves of S. chinensis Baill for 7 weeks after 1 week of adaptation. The rats were rendered diabetic by intravenous injection of STZ (60 mg/kg) after 6-week feeding of the assigned diets. At 1 week after the injection, the rats were sacrificed after an overnight fast. Plasma glucose (380.2 +/- 14.4 mg/dL), total cholesterol (93.9 +/- 7.9 mg/dL) and triglyceride levels (123.6 +/- 7.5 mg/dL) of the S. chinensis Baill group were significantly lower than those of the control group (418.1 +/- 12.0 mg/dL, 119.9 +/- 9.4 mg/dL, 152.0 +/- 10.3 mg/dL, respectively, p<0.05). Chronic consumption of S. chinesis Baill significantly decreased maltase activity of the small intestinal mucosa (120.1 +/- 8.7 U/g protein) compared with the control group (96.8 +/- 7.0 U/g protein, p<0.05). These results suggest that S. chinensis Baill have hypoglycemic and hypolipidemic effects by inhibiting alpha-glucosidase activity in the animal model of diabetes mellitus.

  10. Anti-inflammatory activity of Pistacia lentiscus essential oil: involvement of IL-6 and TNF-alpha.

    PubMed

    Maxia, Andrea; Sanna, Cinzia; Frau, Maria Assunta; Piras, Alessandra; Karchuli, Manvendra Singh; Kasture, Veena

    2011-10-01

    The topical anti-inflammatory activity of essential oil of Pistacia lentiscus L. was studied using carrageenan induced rat paw edema and cotton pellet induced granuloma. The effect on serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in rats inserted with cotton pellet was also investigated. On topical application, the oil exhibited a significant decrease in paw edema. The oil also inhibited cotton pellet-induced granuloma, and reduced serum TNF-alpha and IL-6. It can be concluded that the essential oil of Pistacia lentiscus reduces leukocyte migration to the damaged tissue and exhibits anti-inflammatory activity.

  11. Regulation of 5alpha-reductase isoforms by oxytocin in the rat ventral prostate.

    PubMed

    Assinder, S J; Johnson, C; King, K; Nicholson, H D

    2004-12-01

    Oxytocin (OT) is present in the male reproductive tract, where it is known to modulate contractility, cell growth, and steroidogenesis. Little is known about how OT regulates these processes. This study describes the localization of OT receptor in the rat ventral prostate and investigates if OT regulates gene expression and/or activity of 5alpha-reductase isoforms I and II. The ventral prostates of adult male Wistar rats were collected following daily sc administration of saline (control), OT, a specific OT antagonist or both OT plus antagonist for 3 d. Expression of the OT receptor was identified in the ventral prostate by RT-PCR and Western blot, and confirmed to be a single active binding site by radioreceptor assay. Immunohistochemistry localized the receptor to the epithelium of prostatic acini and to the stromal tissue. Real-time RT-PCR determined that OT treatment significantly reduced expression of 5alpha-reductase I but significantly increased 5alpha-reductase II expression in the ventral prostate. Activity of both isoforms of 5alpha-reductase was significantly increased by OT, resulting in increased concentration of prostatic dihydrotestosterone. In conclusion, OT is involved in regulating conversion of testosterone to the biologically active dihydrotestosterone in the rat ventral prostate. It does so by differential regulation of 5alpha-reductase isoforms I and II.

  12. Is male factor infertility associated with midlife low-grade inflammation? A population based study.

    PubMed

    Hærvig, Katia Keglberg; Kierkegaard, Lene; Lund, Rikke; Bruunsgaard, Helle; Osler, Merete; Schmidt, Lone

    2018-06-01

    Male factor infertility is associated with an increased risk of disease and mortality, which has been related to markers of chronic systemic inflammation. The objective of this study was to investigate the association between male factor infertility and low-grade inflammation and furthermore to examine the lifetime prevalence of male factor infertility and overall infertility (also including female and couple infertility). The study population consisted of 2140 members of the Metropolit 1953 Danish Male Birth Cohort who had participated in the Copenhagen Aging and Midlife Biobank data collection in 2009-2011. Information on male factor infertility and overall infertility was obtained from a questionnaire, and low-grade inflammation was evaluated as the highest plasma levels of C-reactive protein, interleukin-6 and tumour necrosis factor-alpha in the population. The level of interleukin-6 was significantly higher among men with male factor infertility compared with other men adjusted for potential confounders. This was not found for the two other inflammatory markers. The lifetime prevalence of male factor infertility and overall infertility were 10.2% and 17.9%, respectively. The findings suggest that male factor infertility might be associated with an increased level of interleukin-6.

  13. Treatment with captopril abrogates the altered expression of alpha1 macroglobulin and alpha1 antiproteinase in sera of spontaneously hypertensive rats

    PubMed Central

    2012-01-01

    Background Proteins that are associated with hypertension may be identified by comparing the 2-dimensional gel electrophoresis (2-DE) profiles of the sera of spontaneously hypertensive rats (SHR) with those generated from normotensive Spraque-Dawley rats (SDR). Results Five proteins of high abundance were found to be significantly altered when the 2-DE serum profiles of the SHR were compared to those that were similarly generated from the SDR. Analysis by mass spectrometry and database search identified the proteins as retinol binding protein 4, complement C3, albumin (19.9 kDa fragment), alpha1 macroglobulin and alpha1 antiproteinase, which are all known to be associated with hypertension. The altered expression of the two latter proteins was found to be abrogated when similar analysis was performed on sera of the SHR that were treated with captopril. Conclusion Our data suggests that serum alpha1 macroglobulin and alpha1 antiproteinase are potentially useful complementary biomolecular indicators for monitoring of hypertension. PMID:22416803

  14. Inhibitory effects of 1alpha, 25dihydroxyvitamin D3 and Ajuga iva extract on oxidative stress, toxicity and hypo-fertility in diabetic rat testes.

    PubMed

    Hamden, K; Carreau, S; Jamoussi, K; Ayadi, F; Garmazi, F; Mezgenni, N; Elfeki, A

    2008-09-01

    The aim of the current study is to investigate the therapeutic and preventive effects of 1alpha, 25dihydroxyvitaminD3 (1,25 (OH)2 D3) and Afuga iva (AI) extract on diabetes toxicity in rats testes. Thus diabetic rats were treated with 1alpha, 25dihydroxyvitaminD3 or Ajuga iva extract as both therapeutic and preventive treatments on diabetes toxicity in rats testes. Our results showed that diabetes induced a decrease in testosterone and 17beta-estradiol levels in testes and plasma. Besides, a fall in testicular antioxidant capacity appeared by a decrease in both antioxidant (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities) and nonenzymatic antioxidant (copper (Cu), magnesium (Mg) and iron (Fe) levels). All theses changes enhanced testicular toxicity (increase in testicular aspartate amino transaminase (AST), alanine amino transaminase (ALT), lactate dehydrogenase (LDH) activities and the lipid peroxidation and triglyceride (TG) levels). In addition, a decrease in testicular total cholesterol (TCh) level was observed in diabetic rats testes. All the changes lead to a decrease in the total number and mobility of epididymal spermatozoa. The administration of 1alpha,25dihydroxyvitaminD3 and Ajuga iva extract three weeks before and after diabetes induction interfered and prevented diabetes toxicity in the reproductive system. 1,25 (OH)2 D3 and Ajuga iva extract blunted all changes observed in diabetic rats. To sum up, the data suggested that 1,25 (OH)2 D3 and Ajuga iva extract have a protective effect on alloxan-induced damage in reproductive system by enhancing the testosterone and 17beta-estradiol levels, consequently protecting from oxidative stress, cellular toxicity and maintaining the number and motility of spermatozoids.

  15. Hypotensive effect of alpha-lipoic acid after a single administration in rats.

    PubMed

    Dudek, Magdalena; Razny, Katarzyna; Bilska-Wilkosz, Anna; Iciek, Malgorzata; Sapa, Jacek; Wlodek, Lidia; Filipek, Barbara

    2016-05-01

    The effect of alpha-lipoic acid on blood pressure was investigated many times in chronic studies, but there are no studies on the effect of this compound after a single administration. Alpha-lipoic acid is a drug used in diabetic neuropathy, often in obese patients, to treat hypertension. Therefore, knowledge of the potential antihypertensive effect of alpha-lipoic acid even after a single dose and possibly too much pressure reduction is interesting and useful. The mechanism of the hypotensive effect of alpha-lipoic acid was examined in normotensive rats in vivo after a single intraperitoneal administration, blood pressure in the left carotid artery of the rats was measured prior to the administration of the compounds (alpha- lipoic acid and/or glibenclamide) and 80 min thereafter. Alpha-lipoic acid at a dosage of 50 mg/kg b.w. i.p. significantly decreased the blood pressure from the 50th min after drug administration. This cardiovascular effect of this compound was reversed by glibenclamide, a selective KATP blocker. Glibenclamide alone at this dose did not significantly affect the blood pressure. Statistical significance was evaluated using two-way ANOVA. This suggests that alpha-lipoic acid affects ATP-dependent potassium channels. It is possible that this is an indirect effect of hydrogen sulfide because alpha-lipoic acid can increase its concentration. The results obtained in this study are very important because the patients taking alpha-lipoic acid may be treated for co-existing hypertension. Therefore, the possibility of blood pressure lowering by alpha-lipoic acid should be taken into account, although it does not lead to excessive orthostatic hypotension.

  16. Therapeutic and prophylactic thalidomide in TNBS-induced colitis: synergistic effects on TNF-alpha, IL-12 and VEGF production.

    PubMed

    Carvalho, Ana Teresa; Souza, Heitor; Carneiro, Antonio Jose; Castelo-Branco, Morgana; Madi, Kalil; Schanaider, Alberto; Silv, Flavia; Pereira Junior, Fernando Antonio; Pereira, Marcia G; Tortori, Claudio; Dines, Ilana; Carvalho, Jane; Rocha, Eduardo; Elia, Celeste

    2007-04-21

    To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necrosis factor alpha (TNF-alpha), IL-12, and vascular endothelial growth factor (VEGF), hallmarks of intestinal inflammation in Crohnos disease (CD). Male Wistar rats were divided in five groups of ten animals each. Four groups received a rectal infusion of TNBS in ethanol. The first group was sacrificed 7 d after colitis induction. The second and third groups received either thalidomide or placebo by gavage and were sacrificed at 14 d. The fourth group received thalidomide 6 h before TNBS administration, and was sacrificed 7 d after induction. The fifth group acted as the control group and colitis was not induced. Histological inflammatory scores of the colon were performed and lamina propria CD4+ T cells, macrophages, and VEGF+ cells were detected by immunohistochemistry. TNF-alpha and IL-12 were quantified in the supernatant of organ cultures by ELISA. Significant reduction in the inflammatory score and in the percentage of VEGF+ cells was observed in the group treated with thalidomide compared with animals not treated with thalidomide. Both TNF-alpha and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide. TNF-alpha levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-alpha and IL-12 were significantly correlated with the inflammatory score and the number of VEGF+ cells. Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-alpha, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD.

  17. Flavocoxid attenuates gentamicin-induced nephrotoxicity in rats.

    PubMed

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Suddek, Ghada M; Salem, Hatem A

    2015-12-01

    Gentamicin is a widely used antibiotic against serious and life-threatening infections; however, its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine whether flavocoxid has a protective effect against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of flavocoxid on gentamicin induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was determined. Twenty-four male Wistar albino rats were randomly divided into three groups, namely control, gentamicin (100 mg/kg, i.p.) and gentamicin plus flavocoxid (20 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood, urine samples and kidneys were collected for further analysis. Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated renal somatic index (RSI), serum creatinine, blood urea nitrogen, serum lactate dehydrogenase, and protein in urine with a concomitant reduction in serum albumin and normalized creatinine clearance value as compared with the controls. Moreover, a significant increase in renal contents of malondialdehyde, myeloperoxidase, and tumor necrosis factor-alpha with a significant decrease in renal reduced glutathione and superoxide dismutase activities was detected upon gentamicin administration together with increasing the sensitivity of isolated urinary bladder rings to ACh. Exposure to gentamicin induced necrosis of renal tubular epithelial cells. Flavocoxid protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by gentamicin treatment. In addition, flavocoxid significantly reduced the responses of isolated bladder rings to ACh. The results from our study indicate that flavocoxid supplement attenuates gentamicin-induced renal injury via the amelioration of

  18. Creatine kinase and alpha-actin mRNA levels decrease in diabetic rat hearts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Popovich, B.; Barrieux, A.; Dillmann, W.H.

    1987-05-01

    Diabetic cardiomyopathy is associated with cardiac atrophy and isoenzyme redistribution. To determine if tissue specific changes occur in mRNAs coding for ..cap alpha..-actin and creatine kinase (CK), they performed RNA blot analysis. Total ventricular RNA from control (C) and 4 wk old diabetic (D) rats were hybridized with /sup 32/P cDNA probes for ..cap alpha..-actin and CK. A tissue independent cDNA probe, CHOA was also used. Signal intensity was quantified by photodensitometry. D CK mRNA was 47 +/- 16% lower in D vs C. Insulin increases CK mRNA by 20% at 1.5 hs, and completely reverses the deficit after 4more » wks. D ..cap alpha..-actin mRNA is 66 +/- 18% lower in D vs C. Insulin normalized ..cap alpha..-actin mRNA by 5 hs. CHOA mRNA is unchanged in D vs C, but D + insulin CHOA mRNA is 30 +/- 2% lower than C. In rats with diabetic cardiomyopathy, muscle specific CK and ..cap alpha..-actin mRNAs are decreased. Insulin treatment reverses these changes.« less

  19. Intermittent hypoxia activates peptidylglycine alpha-amidating monooxygenase in rat brain stem via reactive oxygen species-mediated proteolytic processing.

    PubMed

    Sharma, Suresh D; Raghuraman, Gayatri; Lee, Myeong-Seon; Prabhakar, Nanduri R; Kumar, Ganesh K

    2009-01-01

    Intermittent hypoxia (IH) associated with sleep apneas leads to cardiorespiratory abnormalities that may involve altered neuropeptide signaling. The effects of IH on neuropeptide synthesis have not been investigated. Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the alpha-amidation of neuropeptides, which confers biological activity to a large number of neuropeptides. PAM consists of O(2)-sensitive peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) activities. Here, we examined whether IH alters neuropeptide synthesis by affecting PAM activity and, if so, by what mechanisms. Experiments were performed on the brain stem of adult male rats exposed to IH (5% O(2) for 15 s followed by 21% O(2) for 5 min; 8 h/day for up to 10 days) or continuous hypoxia (0.4 atm for 10 days). Analysis of brain stem extracts showed that IH, but not continuous hypoxia, increased PHM, but not PAL, activity of PAM and that the increase of PHM activity was associated with a concomitant elevation in the levels of alpha-amidated forms of substance P and neuropeptide Y. IH increased the relative abundance of 42- and 35-kDa forms of PHM ( approximately 1.6- and 2.7-fold, respectively), suggesting enhanced proteolytic processing of PHM, which appears to be mediated by an IH-induced increase of endoprotease activity. Kinetic analysis showed that IH increases V(max) but has no effect on K(m). IH increased generation of reactive oxygen species in the brain stem, and systemic administration of antioxidant prevented IH-evoked increases of PHM activity, proteolytic processing of PHM, endoprotease activity, and elevations in substance P and neuropeptide Y amide levels. Taken together, these results demonstrate that IH activates PHM in rat brain stem via reactive oxygen species-dependent posttranslational proteolytic processing and further suggest that PAM activation may contribute to IH-mediated peptidergic

  20. Ginger extract mitigates ethanol-induced changes of alpha and beta - myosin heavy chain isoforms gene expression and oxidative stress in the heart of male wistar rats.

    PubMed

    Shirpoor, Alireza; Zerehpoosh, Mitra; Ansari, Mohammad Hasan Khadem; Kheradmand, Fatemeh; Rasmi, Yousef

    2017-09-01

    The association between ethanol consumption and heart abnormalities, such as chamber dilation, myocyte damage, ventricular hypertrophy, and hypertension is well known. However, underlying molecular mediators involved in ethanol-induced heart abnormalities remain elusive. The aim of this study was to investigate the effect of chronic ethanol exposure on alpha and beta - myosin heavy chain (MHC) isoforms gene expression transition and oxidative stress in rats' heart. It was also planned to find out whether ginger extract mitigated the abnormalities induced by ethanol in rats' heart. Male wistar rats were divided into three groups of eight animals as follows: Control, ethanol, and ginger extract treated ethanolic (GETE) groups. After six weeks of treatment, the results revealed a significant increase in the β-MHC gene expression, 8- OHdG amount, and NADPH oxidase level. Furthermore, a significant decrease in the ratio of α-MHC/β-MHC gene expression to the amount of paraoxonase enzyme in the ethanol group compared to the control group was found. The consumption of Ginger extract along with ethanol ameliorated the changes in MHC isoforms gene expression and reduced the elevated amount of 8-OHdG and NADPH oxidase. Moreover, compared to the consumption of ethanol alone, it increased the paraoxonase level significantly. These findings indicate that ethanol-induced heart abnormalities may in part be associated with MHC isoforms changes mediated by oxidative stress, and that these effects can be alleviated by using ginger extract as an antioxidant molecule. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Alpha-hydroxytamoxifen, a genotoxic metabolite of tamoxifen in the rat: identification and quantification in vivo and in vitro.

    PubMed

    Boocock, D J; Maggs, J L; White, I N; Park, B K

    1999-01-01

    The metabolic formation of a-hydroxytamoxifen, a reactive metabolite of tamoxifen in rat liver, was characterized and quantified in vitro (hepatic microsomal incubations) and in vivo (bile-duct cannulated animals). This minor metabolite was identified by chromatographic and mass spectral comparisons with the authentic compound. The rates of formation of alpha-hydroxytamoxifen in incubations (30 min) of tamoxifen (25 microM) with liver microsomal preparations from women (pool of six), female CD1 mice or female Sprague-Dawley rats, as quantified by liquid chromatography-mass spectrometry (LC-MS), were 1.15+/-0.03, 0.30+/-0.05 and 2.70+/-0.35 pmol/min/mg protein, respectively. Selective inhibition of microsomal P450 indicated that alpha-hydroxylation was catalysed predominantly by CYP3A in humans. Bile-duct cannulated and anaesthetized female rats and mice given [14C]tamoxifen (43 micromol/kg, i.v.) excreted, respectively, 24 and 21% of the administered radioactivity in bile over 5 and 3.5 h. The major radiolabelled biliary metabolite in rats, characterized by LC-MS after enzymic hydrolysis of conjugates, was the glucuronide of 4-hydroxytamoxifen (10% of dose) and only 0.1% of the dose was recovered as alpha-hydroxytamoxifen. After administration of alpha-hydroxytamoxifen (43 micromol/kg, i.v.) to rats, only 1.19% of the administered compound was recovered from a glucuronide metabolite in bile, indicating a possible 0.84% alpha-hydroxylation of tamoxifen in vivo. There was, however, no indication of the presence in bile of either O-sulphonate or glutathione conjugates derived from alpha-hydroxytamoxifen. This study shows for the first time that alpha-hydroxytamoxifen can be glucuronylated in rat liver. Whereas sulphonation results in electrophilic genotoxic intermediates, glucuronidation may represent a means of detoxifying alpha-hydroxytamoxifen.

  2. Efficacy of DL-alpha-lipoic acid on methanol induced free radical changes, protein oxidative damages and hsp70 expression in folate deficient rat nervous tissue.

    PubMed

    Rajamani, Rathinam; Muthuvel, Arumugam; Manikandan, Sundaramahalingam; Srikumar, Ramasundaram; Sheeladevi, Rathinasamy

    2007-05-01

    DL-alpha-Lipoic acid (LPA) was reported to be effective in reducing free radicals generated by oxidative stress. The protective of effect of LPA on methanol (MeOH) induced free radical changes and oxidative damages in discrete regions of rat brain have been reported in this study. Folate deficient rat (FDD) model was used. The five animal groups (saline control, FDD control, FDD+MeOH, FDD+LPA+MeOH, LPA control) were used. The FDD+MeOH and FDD+LPA+MeOH animals were injected intraperitoneally with methanol (3gm/kg). After 24h, the level of free radical scavengers such as, superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione was estimated in six discrete regions of brain, retina and optic nerve. Level of protein thiol, protein carbonyl and lipid peroxidation was also estimated. Expression of heat shock protein 70 mRNA (hsp70) was studied in the cerebellum and hippocampus by reverse transcriptase PCR. All the samples showed elevation in the level of free radical scavenging enzymes and reduced level of glutathione in the FDD+MeOH group in relation to the other groups. hsp70 expression was more in FDD+MeOH group when compared to FDD+LPA+MeOH group. In conclusion, MeOH exposure leads to increased free radical generation and protein oxidative damages in the rat nervous tissue. Treatment with LPA prevents oxidative damage induced by MeOH exposure.

  3. Effects of Yohimbine and Tolazoline on Isoproterenol and Angiotensin 2-Induced Water Intake in Rats

    NASA Technical Reports Server (NTRS)

    Fregly, Melvin J.; Rowland, Neil E.; Greenleaf, John E.

    1983-01-01

    Subcutaneous administration of the alpha(sub 2)-adrenoreceptor antagonists, yohimbine and tolazoline, at doses up to 1000 micro-g/kg, had no effect on water intake of female rats. However, when these compounds were administered SC in combination with either the beta-adrenoreceptor agonist, isoproterenol (10 to 25 micro-g/kg, SC), or with angiotensin 2 (200 micro-g/kg, SC). water intake was enhanced. In contrast, intraventricular administration of either tolazoline (10 and 20 micro-g/kg) or yohimbine (300 micro-g/kg) failed to augment the dipsogenic response to angiotensin 2 (150 micro-g/kg, SC). Thus, the enhancing effect of these alpha(sub 2)-adrenoreceptor antagonists on isoproterenol- and angiotensin 2-induced water intakes appears to be manifested peripherally, rather than centrally. In view of the fact that clonidine, an alpha(sub 2)-adrenoreceptor agonist, has been shown to inhibit water intake induced by both isoproterenol and angiotensin 2, the results suggest that the alpha(sub 2)-adrenoreceptor may play a role in modulating water intake induced by these two dipsogenic agents.

  4. [The effect of high fat feeding and rosiglitazone intervention on pancreatic alpha cell in rats].

    PubMed

    Wang, Xin; Yang, Wen-ying; Xiao, Jian-zhong; Zhao, Wen-hui; Wang, Na; Liu, Xue-li; Pan, Lin

    2005-08-01

    To observe the effect of high-fat diet and rosiglitazone intervention on the function of pancreatic alpha cell of SD rats. 36 normal male SD rats, 8-week old, were randomly divided into 3 groups i.e., a normal chow group (CC, n = 12), an isocaloric high-fat diet group (CF, n = 12), and a rosiglitazone-treated group (Ro, n = 12, rosiglitazone 3 mg.kg(-1).d(-1) and isocaloric high fat diet). Triglyceride (TG) was measured every 4 weeks after feeding for 6 weeks. After 28 weeks, the secretion of insulin and glucagon (Gg) was assessed with intravenous glucose tolerance test (IVGTT) at 0, 3, 5, and 10 minutes. (3)H-2-deoxyglucose ((3)H-2-DG) uptake by tissues was measured to evaluate the insulin sensitivity. The ratio of intra-abdominal fat mass and body weight was higher in the rats of CF and Ro group than that in the rats of CC group. At the first 10 min of IVGTT, the Gg level was higher in the CF group than that in CC group [(119.3 +/- 12.4, 82.3 +/- 6.4, 72.2 +/- 5.8, 68.2 +/- 9.1) ng/L vs (96.8 +/- 9.1, 67.6 +/- 5.9, 57.9 +/- 5.3, 55.3 +/- 6.9) ng/L, P < 0.05] and Ro group [(78.4 +/- 6.0, 59.4 +/- 4.0, 49.9 +/- 6.2, 40.9 +/- 6.0) ng/L, P < 0.01], the level was even lower in the latter group than in CC group (P < 0.01). There was no difference of insulin level among the 3 groups. By using quantitative image analysis, the integrated A (area x A) of alpha cells was significantly higher in the CF group and Ro group as compared with that in the CC group (1661 +/- 130 and 1532 +/- 132 vs 1188 +/- 104, P < 0.05). In contrast, there was no difference among the 3 groups in the integrated A of beta cells. High-fat feeding induces insulin resistance in rats, which is associated with pancreatic alpha cell proliferation and abnormal Gg secretion.

  5. The effects of alpha-lipoic acid on breast of female albino rats exposed to malathion: Histopathological and immunohistochemical study.

    PubMed

    Omran, Ola M; Omer, Osama H

    2015-06-01

    The wide use of the organophosphate insecticide malathion is accompanied by the risk of human exposure and may be involved in the etiology of breast cancers, especially in developing countries. Alpha (α)-lipoic acid, a natural molecule, present in our diet has antioxidant and protective effects in cases such as aging, diabetes mellitus, and vascular and neurodegenerative diseases all in which free radicals are involved. However, there is only scarce data regarding the efficacy and biological activity of α-lipoic acid on malathion-induced breast histopathological changes. To investigate whether malathion can induce mammary histopathological changes, to immunohistochemically analyze the modulations in proliferation-apoptosis balance associated with these changes, to assess the associated metabolic parameters, antioxidant stress and hormonal profile changes and to elucidate the possible protective effect of α-lipoic acid on malathion induced alterations in rats. Forty Wistar female rats weighing 150-170g were divided into four groups. Group 1: control group were injected intraperitoneally (ip) with saline solution. Group2: animals were injected (ip) with malathion twice a day for five days. Group 3: animals were orally given α-lipoic acid, after three hours of treatment with malathion at the same dose given to group 2. Group 4: animals were treated with α-lipoic acid at the same dose given to group 3. Rats were sacrificed on the 90th day, and breast tissues were analyzed for histopathological and immunohistochemical alterations. Blood samples were collected for biochemical tests. α-Lipoic acid exhibited a striking reduction of malathion-induced mammary tumor incidence, and reversed intra-tumor histopathological alterations. Alpha lipoic acid suppressed proliferating cell nuclear antigen (PCNA) and p53 expression, induced apoptosis, upregulated proapoptotic protein Bax. Our results provide the experimental evidence that α-lipoic acid exerts chemopreventive

  6. Interleukin-1-induced anorexia in the rat. Influence of prostaglandins.

    PubMed Central

    Hellerstein, M K; Meydani, S N; Meydani, M; Wu, K; Dinarello, C A

    1989-01-01

    The anorexia associated with acute and chronic inflammatory or infectious conditions is poorly understood. Our objectives were to explore the anorexigenic effects of interleukin-1 (IL-1) in the rat. Recombinant human (rh) IL-1 beta, murine (rm) IL-1 alpha and to a lesser extent rhIL-1 alpha significantly reduced food intake at greater than or equal to 4.0 micrograms/kg i.p. but not at lower doses, in young (200-250 g) meal-fed rats on chow diets. The anorexic effect appears to be mediated by prostaglandins since pretreatment with ibuprofen completely blocked it, and a fish oil based diet abolished it, in comparison to corn oil or chow diets. Fish oil feeding also decreased basal and IL-1 stimulated prostaglandin E2 production by tissues in vitro (liver, brain, peritoneal macrophages) and in the whole body. Constant intravenous infusions of lower doses of IL-1 also diminished food intake, though intravenous boluses did not (reflecting rapid renal clearance). Chronic daily administration of IL-1 caused persistent inhibition of food intake for 7-17 d in chow and corn oil fed rats, but had no effect in fish oil fed rats. There was an attenuation of the effect (tachyphylaxis) after 7 d in corn oil and chow fed rats, but slowed weight gain and lower final weights were observed after 17-32 d of daily IL-1. Old (18-20 mo Fisher 344) rats showed less sensitivity to IL-1 induced anorexia. In conclusion, IL-1 is anorexigenic in the rat, but this is influenced by the structural form of IL-1, the route and chronicity of administration, the source of dietary fat, and the age of the animal. The ability of prior fat intake to influence the anorexic response to IL-1 represents a novel nutrient-nutrient interaction with potential therapeutic implications. PMID:2786888

  7. Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats.

    PubMed

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Abdel Rahim, Mona; Suddek, Ghada M; Salem, Hatem A

    2016-03-01

    The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.

  8. Comparison of alpha 1A- and alpha 1B-adrenoceptor coupling to inositol phosphate formation in rat kidney.

    PubMed

    Büscher, R; Erdbrügger, W; Philipp, T; Brodde, O E; Michel, M C

    1994-12-01

    We have compared the coupling mechanisms of rat renal alpha 1A- and alpha 1B-like adrenoceptors to inositol phosphate formation. The experiments were performed in parallel in native renal tissue preparations and in those where alpha 1B-adrenoceptors had been inactivated by treatment with 10 mumol/l chloroethylclonidine for 30 min at 37 degrees C; renal slices were used in most experiments but isolated renal cells were also used in some cases. The Ca2+ chelating agent, EGTA (5 mmol/l), reduced noradrenaline-stimulated inositol phosphate formation in native but enhanced it in chloroethylclonidine-treated renal slices. The inhibitory effect of EGTA was not mimicked by 100 nmol/l nifedipine. Inactivation of 87% of cellular Gi by 16-20 h treatment with 500 ng/ml pertussis toxin did not significantly affect noradrenaline-stimulated inositol phosphate formation in isolated renal cells but abolished the inhibitory effect of chloroethylclonidine. The adenylate cyclase activator, forskolin (20 mumol/l), inhibited noradrenaline-stimulated inositol phosphate formation in native and chloroethylclonidine-treated slices, and the inhibitory effects of chloroethylclonidine treatment and forskolin were additive. We conclude that in rat kidney inositol phosphate formation via alpha 1B-like adrenoceptors may involve the influx of extracellular Ca2+ and a pertussis toxin-sensitive G-protein but is insensitive to inhibition by forskolin. In contrast alpha 1A-like adrenoceptor-mediated inositol phosphate formation does not require the presence of extracellular Ca2+ or of Gi and is sensitive to inhibition by forskolin. In comparison to published data from other model systems we further conclude that the signaling mechanisms of alpha 1-adrenoceptor subtypes may depend on their cellular environment.

  9. Anti-inflammatory and antiproliferative activities of date palm pollen (Phoenix dactylifera) on experimentally-induced atypical prostatic hyperplasia in rats

    PubMed Central

    2011-01-01

    Background Atypical prostatic hyperplasia (APH) is a pseudoneoplastic lesion that can mimic prostate adenocarcinoma because of its cytologic and architectural features. Suspension of date palm pollen (DPP) is an herbal mixture that is widely used in folk medicine for male infertility. The aim of the present study was to evaluate the effect of DPP suspension and extract on APH-induced rats. Methods APH was induced in adult castrated Wistar rats by both s.c. injection of testosterone (0.5 mg/rat/day) and smearing citral on shaved skin once every 3 days for 30 days. Saw palmetto (100mg/kg), DPP suspension (250, 500 and 1000 mg/kg), and lyophilized DPP extract (150,300 and 600 mg/kg) were given orally daily for 30 days. All medications were started 7 days after castration and along with testosterone and citral. Results The histopathological feature in APH-induced prostate rats showed evidence of hyperplasia and inflammation. Immunohistochemical examination revealed that the expressions of IL-6, IL-8, TNF-α, IGF-1 and clusterin were increased, while the expression of TGF-β1 was decreased that correlates with presence of inflammation. Moreover, histopathological examination revealed increased cellular proliferation and reduced apoptosis in ventral prostate. Both saw palmetto and DPP treatment has ameliorated these histopathological and immunohistochemical changes in APH-induced rats. These improvements were not associated with reduction in the prostatic weight that may be attributed to the persistence of edema. Conclusion DPP may have a potential protective effect in APH-induced Wistar rats through modulation of cytokine expression and/or upregulation of their autocrine/paracrine receptors. PMID:22195697

  10. [Protective effect of curcumin on oleic-induced acute lung injury in rats].

    PubMed

    Zhu, Rui-fang; Zhou, Min; He, Jian-lin; Ding, Fu-yun; Yu, Shu-qin; Xu, Guang-lin

    2008-09-01

    To investigate the effect of curcumine on acute lung injury induced by oleic acid in rat and the possible mechanism of action. The rats were divided into 6 groups randomly: normal group, control group, curcumine groups (5, 10, 20 mg x kg(-1)) and dexamethasone group (1 mg x kg(-1)). During the experiment, acute lung injury was induced by oleic acid in rat. The changes of dynamic lung compliance were recorded by anrise 2005 pulmonary function test apparatus, light microscope was used to examine histological changes and lung index as well as wet to dry weight ratio was calculated by weighting method. Lung vascular permeability and protein level in BALF were detected by ultraviolet spectrophotometry, and the concentrations of TNF-alpha, IL-6 and IL-10 in BALF were measured by enzyme linked immunosorbent assay (ELISA). The result showed that the changes of pulmonary compliance were inhibited and pulmonary function was improved by curcumine. The OA-induced elevation of lung index was restrained, as well as wet to dry weight ratio, lung vascular permeability, protein level, TNF-alpha (250.4 +/- 21.6 vs. 172.53 +/- 14.88, 122.2 +/- 10.98, 108.69 +/- 3.39) ng x L(-1), IL-6 (763.6 +/- 88.33 vs. 207.41 +/- 15.55, 172.13 +/- 21.91, 142.92 +/- 4.32) ng x L(-1) in BALF in curcumine groups, IL-10 (98.90 +/- 2.99 vs. 208.44 +/- 16.30, 218.43 +/- 6.23, 252.70 +/- 20.58) ng x L(-1) in BALF was increased, respectively significantly. Light microscope findings shown that the impairment in curcumine groups was far less severe than that in model groups. Pretreatment of curcumine showed beneficial effect on acute lung injury induced by oleic acid in rats. The mediation of both proinflammatory factor and anti-inflammatory factor by curcumine may be involved in mechanism of action of curcumine effects.

  11. Stress-induced facilitation of host response to bacterial challenge in F344 rats is dependent on extracellular heat shock protein 72 and independent of alpha beta T cells.

    PubMed

    Campisi, Jay; Sharkey, Craig; Johnson, John D; Asea, Alexzander; Maslanik, Thomas; Bernstein-Hanley, Isaac; Fleshner, Monika

    2012-11-01

    Activation of the in vivo stress response can facilitate antibacterial host defenses. One possible mechanism for this effect is stress-induced release of heat shock protein 72 (Hsp72) into the extracellular environment. Hsp72 is a ubiquitous cellular protein that is up-regulated in response to cellular stress, and modulates various aspects of immune function including macrophage inflammatory/bactericidal responses and T-cell function when found in the extracellular environment. The current study tested the hypothesis that in vivo extracellular Hsp72 (eHsp72) at the site of inflammation contributes to stress-induced restricted development of bacteria, and facilitated recovery from bacteria-induced inflammation, and that this effect is independent of alpha beta (αβ) T cells. Male F344 rats were exposed to either inescapable electrical tail-shocks or no stress, and subcutaneously injected with Escherichia coli (ATCC 15746). The role of eHsp72 was investigated by Hsp72-immunoneutralization at the inflammatory site. The potential contribution of T cells was examined by testing male athymic (rnu/rnu) nude rats lacking mature αβ T cells and heterozygous thymic intact control (rnu/+) rats. The results were that stressor exposure increased plasma concentrations of eHsp72 and facilitated recovery from bacterial inflammation. Immunoneutralization of eHsp72 at the inflammatory site attenuated this effect. Stressor exposure impacted bacterial inflammation and eHsp72 equally in both athymic and intact control rats. These results support the hypothesis that eHsp72 at the site of inflammation, and not αβ T cells, contributes to the effect of stressor exposure on subcutaneous bacterial inflammation.

  12. Discovery of Ecopladib, an indole inhibitor of cytosolic phospholipase A2alpha.

    PubMed

    Lee, Katherine L; Foley, Megan A; Chen, Lihren; Behnke, Mark L; Lovering, Frank E; Kirincich, Steven J; Wang, Weiheng; Shim, Jaechul; Tam, Steve; Shen, Marina W H; Khor, Soopeang; Xu, Xin; Goodwin, Debra G; Ramarao, Manjunath K; Nickerson-Nutter, Cheryl; Donahue, Frances; Ku, M Sherry; Clark, James D; McKew, John C

    2007-03-22

    The synthesis and structure-activity relationship of a series of indole inhibitors of cytosolic phospholipase A2alpha (cPLA2alpha, type IVA phospholipase) are described. Inhibitors of cPLA2alpha are predicted to be efficacious in treating asthma as well as the signs and symptoms of osteoarthritis, rheumatoid arthritis, and pain. The introduction of a benzyl sulfonamide substituent at C2 was found to impart improved potency of these inhibitors, and the SAR of these sulfonamide analogues is disclosed. Compound 123 (Ecopladib) is a sub-micromolar inhibitor of cPLA2alpha in the GLU micelle and rat whole blood assays. Compound 123 displayed oral efficacy in the rat carrageenan air pouch and rat carrageenan-induced paw edema models.

  13. The water avoidance stress induces bladder pain due to a prolonged alpha1A adrenoceptor stimulation.

    PubMed

    Matos, Rita; Serrão, Paula; Rodriguez, Larissa; Birder, Lori Ann; Cruz, Francisco; Charrua, Ana

    2017-08-01

    Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) remains an elusive disease with the cause for the pain unclear. BPS/IC patients present increased sympathetic activity and high levels of urinary noradrenaline. At the experimental level, it has been shown that chronic adrenergic stimulation produces pain and bladder changes through an alpha 1A adrenoceptor mediated mechanism. Water avoidance stress (WAS) in rodents reproduces signs of nociception and bladder changes seen in BPS/IC patients. In this study, we explore the possible role of alpha 1A adrenoceptor in bladder pain and morphological changes. WAS was induced in a group of female Wistar rats. A separate WAS group received 0.2 mg/kg day silodosin (WAS + S). Lower abdominal pain was determined by performing sensitivity to Von Frey filaments. Bladder reflex activity was determined by cystometry in anaesthetised animals. Urine was collected for noradrenaline quantification by HPLC. Bladders were harvested and stained with Haematoxylin-eosin (to analyse urothelial morphology and to determine the disruption of surface umbrella cells) or with Toluidine Blue 0.1% to analyse mast cell infiltration. WAS increased urinary noradrenaline level and bladder frequency and decreased mechanical pain threshold, which was reversed by silodosin. WAS induced lymphocytic and mast cells infiltration in the mucosa and mild urothelial disruption, which was absent in WAS + S group. Alpha 1A adrenoceptor stimulation has an important role in the appearance of bladder pain in rats. Since BPS/IC patients present high levels of noradrenaline, alpha 1A stimulation may be an additional trigger for bladder dysfunction presented by these patients. Further studies will determine the clinical relevance of this finding in the treatment of BPS/IC patients.

  14. Lepidium meyenii (Maca) reversed the lead acetate induced -- damage on reproductive function in male rats.

    PubMed

    Rubio, Julio; Riqueros, Marissa I; Gasco, Manuel; Yucra, Sandra; Miranda, Sara; Gonzales, Gustavo F

    2006-07-01

    Rats were treated with 0, 8, 16 and 24 mg/kg of lead acetate (LA) (i.p.) for 35 days with or without Maca. Maca was co-administrated orally from day 18 to day 35. The lengths of stages of the seminiferous epithelium were assessed by transillumination. Also, sex organ weights, testicular and epididymal sperm count, sperm motility, daily sperm production, sperm transit rate and serum testosterone levels were measured. Lead acetate treatment resulted in a dose-response reduction of lengths of stages VIII and IX-XI, and serum testosterone levels. However, rats treated with 8 and 16 mg/kg but not 24 mg/kg of lead acetate showed a low number of testicular spermatids, low daily sperm production (DSP) and low epididymal sperm count. Administration of Maca to rats treated with lead acetate resulted in higher lengths of stages VIII and IX-XI with respect to lead acetate-treated rats. Moreover, treatment with Maca to lead acetate-treated rats resulted in lengths of stages VIII and IX-XI similar to the control group. Maca administration also reduced the deleterious effect on DSP caused by lead acetate treatment. Maca prevented LA-induced spermatogenic disruption in rats and it may become in a potential treatment of male infertility associated with lead exposure.

  15. S-allylcysteine ameliorates isoproterenol-induced cardiac toxicity in rats by stabilizing cardiac mitochondrial and lysosomal enzymes.

    PubMed

    Padmanabhan, M; Mainzen Prince, P Stanely

    2007-02-13

    This study was aimed to evaluate the preventive role of S-allylcysteine (SAC) on mitochondrial and lysosomal enzymes in isoproterenol (ISO)-induced rats. Male albino Wistar rats were pretreated with SAC (50, 100 and 150 mg/kg) daily for a period of 45 days. After the treatment period, ISO (150 mg/kg) was subcutaneously injected to rats at an interval of 24 h for two days. The activities of heart mitochondrial enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and alpha-ketoglutarate dehydrogenase) and respiratory chain enzymes (NADH dehydrogenase and cytochrome C oxidase) were decreased significantly (p<0.05) in ISO-induced rats. The activities of lysosomal enzymes (beta-glucuronidase, beta-N-acetyl glucosaminidase, beta-galactosidase, cathepsin-D and acid phosphatase) were increased significantly (p<0.05) in serum and heart of ISO-induced rats. Pretreatment with SAC (100 mg/kg and 150 mg/kg) for a period of 45 days increased significantly (p<0.05) the activities of mitochondrial and respiratory chain enzymes and decreased the activities of lysosomal enzymes significantly (p<0.05) in ISO-induced rats. Oral administration of SAC (50, 100 and 150 mg/kg) for a period of 45 days to normal rats did not show any significant (p<0.05) effect in all the parameters studied. The altered electrocardiogram (ECG) of ISO-treated rats was also restored to near normal by treatment with SAC (100 and 150 mg/kg). These results confirm the efficacy of SAC in alleviating ISO-induced cardiac damage.

  16. Muscarinic and alpha 1-adrenergic receptor binding characteristics of saw palmetto extract in rat lower urinary tract.

    PubMed

    Suzuki, Mayumi; Oki, Tomomi; Sugiyama, Tomomi; Umegaki, Keizo; Uchida, Shinya; Yamada, Shizuo

    2007-06-01

    To elucidate the in vitro and ex vivo effects of saw palmetto extract (SPE) on autonomic receptors in the rat lower urinary tract. The in vitro binding affinities for alpha 1-adrenergic, muscarinic, and purinergic receptors in the rat prostate and bladder were measured by radioligand binding assays. Rats received vehicle or SPE (0.6 to 60 mg/kg/day) orally for 4 weeks, and alpha 1-adrenergic and muscarinic receptor binding in tissues of these rats were measured. Saw palmetto extract inhibited specific binding of [3H]prazosin and [N-methyl-3H]scopolamine methyl chloride (NMS) but not alpha, beta-methylene adenosine triphosphate [2,8-(3)H]tetrasodium salt in the rat prostate and bladder. The binding activity of SPE for muscarinic receptors was four times greater than that for alpha 1-adrenergic receptors. Scatchard analysis revealed that SPE significantly reduced the maximal number of binding sites (Bmax) for each radioligand in the prostate and bladder under in vitro condition. Repeated oral administration of SPE to rats brought about significant alteration in Bmax for prostatic [3H]prazosin binding and for bladder [3H]NMS binding. Such alteration by SPE was selective to the receptors in the lower urinary tract. Saw palmetto extract exerts significant binding activity on autonomic receptors in the lower urinary tract under in vitro and in vivo conditions.

  17. Human induced pluripotent stem cells and male infertility: an overview of current progress and perspectives

    PubMed Central

    Li, Zili; Zhao, Qian; Li, Honggang; Xiong, Chengliang

    2018-01-01

    Abstract Recently, significant progress has been made in ART for the treatment of male infertility. However, current ART has failed to help infertile patients with non-obstructive azoospermia, unless donor sperm is used. In fact, most couples wish to have their own genetically related child. Human induced pluripotent stem cells (hiPSCs) can be generated from patients’ somatic cells and in vitro derivation of functional germ cells from patient-specific iPSCs may provide new therapeutic strategies for infertile couples. The overall developmental dynamics of human primordial germ cells are similar to that in mice, but accumulating evidence suggests that there are crucial differences between human and mouse PGC specification. Unlike mouse iPSCs (miPSCs) in naive state, hiPSCs exhibit a primed pluripotency which possess less potential for the germ cell fate. Based on research in mice, male germ cells at different stages have been derived from hiPSCs with different protocols, including spontaneous differentiation, overexpression of germ cell regulators, addition of cytokines, co-culture with gonadal cells in vitro and xeno-transplantation. The aim of this review is to summarize the current advances in derivation of male germ cells from hiPSCs and raise the perspectives of hiPSCs in medical application for male infertility, as well as in basic research for male germ cell development. PMID:29315416

  18. Effects of the pesticide amitraz and its metabolite BTS 27271 on insulin and glucagon secretion from the perfused rat pancreas: involvement of alpha2D-adrenergic receptors.

    PubMed

    Abu-Basha, E A; Yibchok-Anun, S; Hopper, D L; Hsu, W H

    1999-11-01

    The study purpose was to investigate the direct effect of amitraz, a formamidine insecticide/acaricide, and its active metabolite BTS 27271 on insulin and glucagon secretion from the perfused rat pancreas. Amitraz and BTS 27271 (0.01, 0.1, 1, and 10 micromol/L) inhibited insulin secretion in a concentration-dependent manner. Amitraz increased glucagon secretion at 10 micromol/L, whereas BTS 27271 increased glucagon secretion at 1 and 10 micromol/L. Amitraz- and BTS 27271-induced decreases in insulin secretion and increases in glucagon secretion were not abolished during the 10-minute washout period. During the arginine treatment, both amitraz and BTS 27271 groups (0.1, 1, and 10 micromol/L) had lower insulin secretion and higher glucagon secretion than the control group. Idazoxan, an alpha2A/2D-adrenergic receptor (AR) antagonist, prevented the inhibitory effect of amitraz on insulin secretion in a concentration-dependent manner, but prazosin, an alpha1- and alpha2B/2C-AR antagonist, failed to antagonize the effect of amitraz. These results demonstrate that (1) amitraz and BTS 27271 inhibit insulin and stimulate glucagon secretion from the perfused rat pancreas, (2) amitraz inhibits insulin secretion by activation of alpha2D-ARs, since rats have alpha2D- but not alpha2A-ARs, and (3) amitraz and BTS 27271 may have a high binding affinity to the alpha2D-ARs of pancreatic islets.

  19. Mechanism of protection of moderately diet restricted rats against doxorubicin-induced acute cardiotoxicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mitra, Mayurranjan S.; Donthamsetty, Shashikiran; White, Brent

    Clinical use of doxorubicin (Adriamycin (registered) ), an antitumor agent, is limited by its oxyradical-mediated cardiotoxicity. We tested the hypothesis that moderate diet restriction protects against doxorubicin-induced cardiotoxicity by decreasing oxidative stress and inducing cardioprotective mechanisms. Male Sprague-Dawley rats (250-275 g) were maintained on diet restriction [35% less food than ad libitum]. Cardiotoxicity was estimated by measuring biomarkers of cardiotoxicity, cardiac function, lipid peroxidation, and histopathology. A LD{sub 100} dose of doxorubicin (12 mg/kg, ip) administered on day 43 led to 100% mortality in ad libitum rats between 7 and 13 days due to higher cardiotoxicity and cardiac dysfunction, whereasmore » all the diet restricted rats exhibited normal cardiac function and survived. Toxicokinetic analysis revealed equal accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the ad libitum and diet restricted hearts. Mechanistic studies revealed that diet restricted rats were protected due to (1) lower oxyradical stress from increased cardiac antioxidants leading to downregulation of uncoupling proteins 2 and 3, (2) induction of cardiac peroxisome proliferators activated receptor-{alpha} and plasma adiponectin increased cardiac fatty acid oxidation (666.9 {+-}14.0 nmol/min/g heart in ad libitum versus 1035.6 {+-} 32.3 nmol/min/g heart in diet restriction) and mitochondrial AMP{alpha}2 protein kinase. The changes led to 51% higher cardiac ATP levels (17.7 {+-} 2.1 {mu}mol/g heart in ad libitum versus 26.7 {+-} 1.9 {mu}mol/g heart in diet restriction), higher ATP/ADP ratio, and (3) increased cardiac erythropoietin and decreased suppressor of cytokine signaling 3, which upregulates cardioprotective JAK/STAT3 pathway. These findings collectively show that moderate diet restriction renders resiliency against doxorubicin cardiotoxicity by lowering oxidative stress, enhancing ATP synthesis, and inducing the JAK/STAT3 pathway.« less

  20. Psychosocial Consequences of Infertility on Infertile Women.

    PubMed

    Fatima, P; Rahman, D; Hossain, H B; Hossain, H N; Mughi, C R

    2015-10-01

    This study explores to find out the qualitative and quantitative psychosocial consequences of infertility in women coming for infertility treatment in tertiary infertility center. A total of 400 infertile couples who agreed to participate in the study were asked to fill up the questionnaires and later interviewed to access the psychosocial consequences of infertility on their personal life in a tertiary infertility clinic in Dhaka at Center for Assisted Reproduction (CARe Hospital), Dhaka from June 2011 to December 2011 and agreed to participate in the study were included in the study. The data was analyzed and the quantitative and qualitative psychosocial factors were evaluated. Four hundred infertile couple who filled the questionnaires was included in the study. Sixty three percent of the women belonged to age group >20 30 years at the time of interview. Regarding age at marriage 43.8% of the women were married by 20 years, 51.3% were married between 20 30 years. Mean±SD duration of present married life was 7.20±4.45 (range 1 to 28) years and 74.4% of the women were living with their husbands. Of them 75.5% women were housewife. When asked whether they knew what was the reason of infertility in the couple, 32.5% knew the cause was in the female partner, 14.5%, knew the cause was in the male partner, 10.3% knew the cause was in both partners, 21.5% knew cause of infertility was not in any of the partners, and 21.3% had no idea about the cause of infertility. The male partner's response about the issue of prognosis and outcome of couple's infertility revealed 37.3% believed their wives will conceive someday, 31.3% had no intention for a second marriage, 13% were indifferent, 11.3% blamed their wives for infertility and 4.8% threatened for a second marriage. Only 2.5% of the male partners were suggested on consulting and continuing treatment by specialist. The family pressure by in-laws and relatives towards their infertility was that 57.3% insisted on consulting

  1. [Validation of the Questionnaire of Emotional Maladjustment and Adaptive Resources in Infertility (DERA)].

    PubMed

    Moreno-Rosset, Carmen; Antequera Jurado, Rosario; Jenaro Río, Cristina

    2009-02-01

    Validation of the Questionnaire of Emotional Maladjustment and Adaptive Resources in Infertility (DERA). Given the absence of measures to help psychologists working with infertile couples, this paper presents the process of developing a standardized measure to assess emotional maladjustment and adaptive resources in this population. A cross-sectional design was utilized to gather data from the assisted reproduction units of two public hospitals. Preliminary analyses were performed with a sample of 85 infertile patients. Psychometric properties of the measure were tested with a second sample of 490 infertile patients. Concerning reliability analyses, alpha indexes were adequate both for the measure and its factors. Concerning validity, second-order factor analysis yielded a four-factor solution that conjointly explains 56% of the total variance. Additional analyses with a third sample of 50 participants from the general population matched with a sample of 50 infertile participants were performed. In sum, this measure seems to be a useful psychological assessment tool to determine emotional adjustment, and individual, and interpersonal resources, for coping with infertility diagnosis and treatment.

  2. Cholestasis-induced fibrosis is reduced by interferon alpha-2a and is associated with elevated liver metalloprotease activity.

    PubMed

    Bueno, M R; Daneri, A; Armendáriz-Borunda, J

    2000-12-01

    Several drugs have been tested for the treatment of hepatic cirrhosis induced by various etiologic agents. Although interferon (IFN)alpha-2a has mostly been used to treat viral hepatitis, its anti-fibrogenic properties remain to be established. An experimental model of cholestasis-induced cirrhosis was used to test the effect of IFNalpha-2a. Cirrhosis was induced in rats via ligation of the common bile duct. IFNalpha-2a (100,000 IU/rat, s.c.) was administered daily throughout the experiment. Collagens and TIMP-1 mRNA transcripts were determined by semi-quantitative reverse transcriptase-polymerase chain reaction in liver tissue samples. Activity of metalloproteases (MMPs) was measured using gelatin (denatured collagen) as substrate and the specific size of the enzymes was estimated by zymograms. Histology was performed using Sirius red as a specific stain for collagenous material, and computer-assisted morphometric analyses were carried out. A polyclonal mouse anti-plasminogen activator inhibitor (PAI-1) antibody was used to evaluate the distribution during treatment with IFNalpha-2a. MMP-activity was up-regulated in bile duct ligated rats treated with IFNalpha-2a. MMP-activity in homogenates of total liver was minimal as compared with activity in non-parenchymal cells isolated from the same parental perfused liver, indicating a cryptic MMP activity which was completely abolished by EDTA and 1,10 phenanthroline. Three bands of gelatin degradation were detected by zymography, corresponding to 95, 75 and 65 kDa. IFNalpha-2a decreased PAI-1 immunoreactivity in liver tissue slices as well as biochemical activity in non-parenchymal cell extracts (3.3+/-0.08 vs 7.4+/-1.1 U/mg protein). Procollagen alpha1 (III) and alpha1 (IV) genes expression were also down-regulated 1.5 and 4-fold, respectively. Interestingly, TIMP-1 gene expression did not change. Functional hepatic tests: alanine aminotransferase, aspartate aminotransferase, bilirubins and alkaline phosphatase were

  3. [Rat cardiomyocyte remodeling after neonatal cryptosporidiosis. II. Elongation, excessive polyploidization and HIF-1alpha overexpression].

    PubMed

    Anatskaia, O V; Sidorenko, N V; Matveev, I V; Kropotov, A V; Vinogradov, A E

    2012-01-01

    Retrospective epidemyological studies evidence that infant diseases leave survivors with an increased susceptibility to cardiovascular diseases in later life. At the same time, the mechanisms of this link remain poorly understood. Based on medical statistics reporting that infectious gastroenteritis is the most common cause of maladies in babies, infants and children, we analysed the effects of moderate cryptosporidial gastroenteritis on the heart and ventricular cardiomyocyte remodelling in rats of the first month of life. The disease was challenged by a worldwide human protozoic pathogen Cryptosporidium parvum (Apicomplexa, Sporozoa). The main symptoms manifested in the growth retardation moderate diarrhea. Using real-time PCR, cytophotometry, confocal microscopy and image analysis, we indicated that cryptosporidiosis was associated, with the atrophy heart and the elongation, narrowing, protein content decrease and hyperpolyploidization of cardiomyocytes and the moderate overexpression of hypoxia inducible factor 1alpha (HIF-1alpha) mRNA. Cardiomyocyte shape remodeling and heart atrophy presented in all age groups. The severity of these changes, hovewer, declined gradually from younger to older groups. In contrast, hyperpolyploidization and HIF-1alpha mRNA overexpression were registered mainly among animals aged between 6 and 13 days, and were barely detected and non-significant in older age groups. In the rat the time period covering 6-13 days after birth is known to coincide with the intensive cardiomyocyte polyploidization and the switch from proliferation to hypertrophy. Thus, our data indicate that neonatal cryptosporidiosis may be potential cardiovascular diseases risk factor and that one of the critical time windows for the growing heart covers the time period when cardiomyocyte undergo polyploidization.

  4. Mild prenatal protein malnutrition increases alpha 2C-adrenoceptor expression in the rat cerebral cortex during postnatal life.

    PubMed

    Sierralta, Walter; Hernández, Alejandro; Valladares, Luis; Pérez, Hernán; Mondaca, Mauricio; Soto-Moyano, Rubén

    2006-05-15

    Mild reduction in the protein content in the diet of pregnant rats from 25 to 8% casein, calorically compensated by carbohydrates, does not alter body and brain weights of rat pups at birth, but results in significant changes of the concentration and release of cortical noradrenaline during postnatal life, together with impaired long-term potentiation and memory formation. Since some central noradrenergic receptors are critically involved in neuroplasticity, the present study evaluated, by utilizing immunohistochemical methods, the effect of mild prenatal protein malnutrition on the alpha 2C-adrenoceptor expression in the frontal and occipital cortices of 8- and 60-day-old rats. At day 8 of postnatal age, prenatally malnourished rats exhibited a three-fold increase of alpha 2C-adrenoceptor expression in both the frontal and the occipital cortices, as compared to well-nourished controls. At 60 days of age, prenatally malnourished rats showed normal expression levels scores of alpha 2C-adrenoceptor in the neocortex. Results suggest that overexpression of neocortical alpha 2C-adrenoceptors during early postnatal life, subsequent to mild prenatal protein malnutrition, could in part be responsible for neural and behavioral disturbances showing prenatally malnourished animals during the postnatal life.

  5. Splicing mutation in Sbf1 causes nonsyndromic male infertility in the rat.

    PubMed

    Liška, František; Chylíková, Blanka; Janků, Michaela; Šeda, Ondřej; Vernerová, Zdeňka; Pravenec, Michal; Křen, Vladimír

    2016-09-01

    In the inbred SHR/OlaIpcv rat colony, we identified males with small testicles and inability to reproduce. By selectively breeding their parents, we revealed the infertility to segregate as an autosomal recessive Mendelian character. No other phenotype was observed in males, and females were completely normal. By linkage using a backcross with Brown Norway strain, we mapped the locus to a 1.2Mbp segment on chromosome 7, harboring 35 genes. Sequencing of candidate genes revealed a G to A substitution in a canonical 'AG' splice site of intron 37 in Sbf1 (SET binding factor 1, alias myotubularin-related protein 5). This leads to either skipping exon 38 or shifting splicing one base downstream, invariantly resulting in frameshift, premature stop codon and truncation of the protein. Western blotting using two anti-Sbf1 antibodies revealed absence of the full-length protein in the mutant testis. Testicles of the mutant males were significantly smaller compared with SHR from 4weeks, peaked at 84% wild-type weight at 6weeks and declined afterward to 28%, reflecting massive germ cell loss. Histological examination revealed lower germ cell number; latest observed germ cell stage were round spermatids, resulting in the absence of sperm in the epididymis (azoospermia). SBF1 is a member of a phosphatase family lacking the catalytical activity. It probably modulates the activity of a phosphoinositol phosphatase MTMR2. Human homozygotes or compound heterozygotes for missense SBF1 mutations exhibit Charcot-Marie-Tooth disease (manifested mainly as progressive neuropathy), while a single mouse knockout reported in the literature identified male infertility as the only phenotype manifestation. © 2016 Society for Reproduction and Fertility.

  6. Effect of alpha 2-adrenoceptor agonists on gastric pepsin and acid secretion in the rat.

    PubMed Central

    Tazi-Saad, K.; Chariot, J.; Del Tacca, M.; Rozé, C.

    1992-01-01

    1. The purpose of the present study was to analyze the effects of the alpha 2-adrenoceptor agonists clonidine, guanabenz, detomidine and medetomidine on pepsin secretion in conscious rats provided with gastric chronic fistula and to compare this with acid secretion. 2. Basal interdigestive gastric secretion, which is mainly neurally driven in the rat, and the secretion directly stimulated by the two main stimulants of chief cells, cholecystokinin octapeptide (CCK8) and methacholine, were studied. 3. Basal secretion of pepsin and acid was inhibited by all four drugs with comparable EC50S. 4. CCK-stimulated pepsin and acid secretion was less sensitive than basal pepsin and acid secretion to alpha 2-adrenoceptor inhibition. 5. Methacholine-stimulated pepsin and acid secretion was not changed by clonidine and guanabenz; methacholine-stimulated acid was even marginally increased by clonidine. 6. These results do not favour the presence of alpha 2-receptors on chief cells in the rat stomach. They rather suggest that pepsin inhibition by alpha 2-adrenoceptor agonists is indirect and due to central or peripheral inhibition of the discharge of nerve fibres activating pepsin secretion. PMID:1356566

  7. Characterization of synthesis and storage of TGF-alpha in rat parotid acinar and intercalated duct cells.

    PubMed

    Login, G R; Yang, J; Bryan, K P; Digenis, E C; McBride, J; Elovic, A; Quissell, D O; Dvorak, A M; Wong, D T

    1997-03-01

    Although the expression and biological role of transforming growth factor-alpha (TGF-alpha) have been explored in a variety of normal cells in mammalian species, little is known about the storage of TGF-alpha in secretory cells of exocrine organs. Parotid glands from four rats were homogenized for RNA isolation followed by reverse transcription-polymerase chain reaction to determine the presence of TGF-alpha message. In situ hybridization using a hamster-specific TGF-alpha riboprobe was done on paraffin sections. Parotid gland and isolated acinar cells were processed for transmission electron microscopy (TEM) and postembedding immunogold labeled for TGF-alpha. Gold particles were counted on approximately 200 granules in 10 acinar cells and in 10 intercalated duct cells. Labeling density was calculated as the number of gold particles per square micrometer +/- SD. Statistical significance was calculated using one-way analysis of variance. Using multiple technologies, we have established that rat parotid acinar and intercalated duct cells synthesize TGF-alpha and store the precursor form of this cytokine in their secretory granules.

  8. The radioprotective effects of Moringa oleifera against mobile phone electromagnetic radiation-induced infertility in rats.

    PubMed

    Bin-Meferij, Mashael Mohammed; El-Kott, Attalla Farag

    2015-01-01

    The present study has investigated the effects of mobile phone electromagnetic radiation (EMR) on fertility in rats. The purpose of this study was to explore the capability of polyphenolic-rich Moringa oleifera leaf extract in protecting rat testis against EMR-induced impairments based on evaluation of sperm count, viability, motility, sperm cell morphology, anti-oxidants (SOD & CAT), oxidative stress marker, testis tissue histopathology and PCNA immunohistochemistry. The sample consisted of sixty male Wistar rats which were divided into four equal groups. The first group (the control) received only standard diet while the second group was supplemented daily and for eight weeks with 200 mg/kg aqueous extract of Moringa leaves. The third group was exposed to 900 MHz fields for one hour a day and for (7) days a week. As for the fourth group, it was exposed to mobile phone radiation and received the Moringa extract. The results showed that the EMR treated group exhibited a significantly decrease sperm parameters. Furthermore, concurrent exposure to EMR and treated with MOE significantly enhanced the sperm parameters. However, histological results in EMR group showed irregular seminiferous tubules, few spermatogonia, giant multinucleated cells, degenerated spermatozoa and the number of Leydig cells was significantly reduced. PCNA labeling indices were significant in EMR group versus the control group. Also, EMR affects spermatogenesis and causes to apoptosis due to the heat and other stress-related EMR in testis tissue. This study concludes that chronic exposure to EMR marked testicular injury which can be prevented by Moringa oleifera leaf extract.

  9. The radioprotective effects of Moringa oleifera against mobile phone electromagnetic radiation-induced infertility in rats

    PubMed Central

    Bin-Meferij, Mashael Mohammed; El-kott, Attalla Farag

    2015-01-01

    The present study has investigated the effects of mobile phone electromagnetic radiation (EMR) on fertility in rats. The purpose of this study was to explore the capability of polyphenolic-rich Moringa oleifera leaf extract in protecting rat testis against EMR-induced impairments based on evaluation of sperm count, viability, motility, sperm cell morphology, anti-oxidants (SOD & CAT), oxidative stress marker, testis tissue histopathology and PCNA immunohistochemistry. The sample consisted of sixty male Wistar rats which were divided into four equal groups. The first group (the control) received only standard diet while the second group was supplemented daily and for eight weeks with 200 mg/kg aqueous extract of Moringa leaves. The third group was exposed to 900 MHz fields for one hour a day and for (7) days a week. As for the fourth group, it was exposed to mobile phone radiation and received the Moringa extract. The results showed that the EMR treated group exhibited a significantly decrease sperm parameters. Furthermore, concurrent exposure to EMR and treated with MOE significantly enhanced the sperm parameters. However, histological results in EMR group showed irregular seminiferous tubules, few spermatogonia, giant multinucleated cells, degenerated spermatozoa and the number of Leydig cells was significantly reduced. PCNA labeling indices were significant in EMR group versus the control group. Also, EMR affects spermatogenesis and causes to apoptosis due to the heat and other stress-related EMR in testis tissue. This study concludes that chronic exposure to EMR marked testicular injury which can be prevented by Moringa oleifera leaf extract. PMID:26550159

  10. Gastroprotective effects of sulforaphane and thymoquinone against acetylsalicylic acid-induced gastric ulcer in rats.

    PubMed

    Zeren, Sezgin; Bayhan, Zulfu; Kocak, Fatma Emel; Kocak, Cengiz; Akcılar, Raziye; Bayat, Zeynep; Simsek, Hasan; Duzgun, Sukru Aydin

    2016-06-15

    Nonsteroidal anti-inflammatory drugs (NSAIDs) commonly cause gastric ulcers (GUs). We investigated the effects of sulforaphane (SF) and thymoquinone (TQ) in rats with acetylsalicylic acid (ASA)-induced GUs. Thirty-five male Wistar-Albino rats were divided into five groups: control; ASA; ASA with vehicle; ASA + SF; and ASA + TQ. Compounds were administered by oral gavage before GU induction. GUs were induced by intragastric administration of ASA. Four hours after GU induction, rats were killed and stomachs excised. Total oxidant status, total antioxidant status, total thiol, nitric oxide, asymmetric dimethylarginine, tumor necrosis factor-alpha levels, superoxide dismutase activity, and glutathione peroxidase activity in tissue were measured. Messenger RNA expression of dimethylarginine dimethylaminohydrolases, heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2, and nuclear factor kappa-light-chain-enhancer of activated B cells were analyzed. Renal tissues were evaluated by histopathologic and immunohistochemical means. SF and TQ reduced GU indices, apoptosis, total oxidant status, asymmetric dimethylarginine, and tumor necrosis factor-alpha levels, nuclear factor kappa-light-chain-enhancer of activated B cells, and inducible nitric oxide synthase expressions (P < 0.001, P = 0.001). Both examined compounds increased superoxide dismutase activity, glutathione peroxidase activity, total antioxidant status, total thiol, nitric oxide levels, endothelial nitric oxide synthase, dimethylarginine dimethylaminohydrolases, HO-1, nuclear factor erythroid 2-related factor 2, and HO-1 expressions (P < 0.001). These results suggest that pretreatment with SF or TQ can reduce ASA-induced GUs via anti-inflammatory, antioxidant, and antiapoptotic effects. These compounds may be useful therapeutic strategies to prevent the gastrointestinal adverse effects that limit nonsteroidal anti-inflammatory drugs use. Copyright © 2016 Elsevier Inc. All rights

  11. Protective effect of a coffee preparation (Nescafe pure) against carbon tetrachloride-induced liver fibrosis in rats.

    PubMed

    Shi, Hongyang; Dong, Lei; Zhang, Yong; Bai, Yanhua; Zhao, Juhui; Zhang, Li

    2010-06-01

    We examined the effects of a coffee preparation on liver fibrosis induced by carbon tetrachloride (CCl(4)) and explored the possible mechanisms. Rats were divided randomly into four groups: control, CCl(4), and two coffee preparation groups. Except for the control group, liver fibrosis was induced in male Sprague-Dawley (SD) rats by subcutaneous injection with 40% CCl(4) twice a week for 8 weeks. At the same time, a coffee preparation (300 mg/kg and 150 mg/kg) was administered to the two coffee preparation groups intragastrically once daily. Upon pathological examination, a coffee preparation treatment significantly reduced liver damage and symptoms of liver fibrosis. The mRNA expression of collagen I, collagen III, bcl-2, vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGF-beta1) were markedly increased by CCl(4) treatment but suppressed by a coffee preparation treatment. Whereas compared with the CCl(4) group, the mRNA expression of Bax was increased in the coffee preparation group. The protein expression of Bax and bcl-2 were confirmed by western blot. Intragastric administration of a coffee preparation reduced the protein expression of alpha-smooth muscle actin (alpha-SMA) and the glucose-regulated proteins (GRP) 78 and 94 in rats increased by CCl(4). Our data indicate that a coffee preparation can efficiently inhibit CCl(4)-induced liver fibrosis in rats. The coffee preparation may therefore be a potential functional food for preventing liver fibrosis. Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  12. α-Amyrin attenuates high fructose diet-induced metabolic syndrome in rats.

    PubMed

    Prabhakar, Pankaj; Reeta, K H; Maulik, Subir Kumar; Dinda, Amit Kumar; Gupta, Yogendra Kumar

    2017-01-01

    This study investigated the effect of α-amyrin (a pentacyclic triterpene) on high-fructose diet (HFD)-induced metabolic syndrome in rats. Male Wistar rats were randomly distributed into different groups. The control group was fed normal rat chow diet. The HFD group was fed HFD (60%; w/w) for 42 days. Pioglitazone (10 mg/kg, orally, once daily) was used as a standard drug. α-Amyrin was administered in 3 doses (50, 100, and 200 mg/kg, orally, once daily along with HFD). Plasma glucose, total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were estimated. Changes in blood pressure, oral glucose tolerance, and insulin tolerance were measured. Hepatic oxidative stress as well as messenger RNA (mRNA) and protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) were analyzed. A significant increase in systolic blood pressure, plasma glucose, total cholesterol, and plasma triglycerides and a significant decrease in HDL-C were observed in HFD rats as compared with control rats. Glucose tolerance and insulin tolerance were also significantly impaired with HFD. α-Amyrin prevented these changes in a dose-dependent manner. Hepatic oxidative stress as well as micro- and macrovesicular fatty changes in hepatocytes caused by HFD were also attenuated by α-amyrin. α-Amyrin preserved the hepatic mRNA and protein levels of PPAR-α, which was reduced in HFD group. This study thus demonstrates that α-amyrin attenuates HFD-induced metabolic syndrome in rats.

  13. Alpha-Driven MHD and MHD-Induced Alpha Loss in TFTR DT Experiments

    NASA Astrophysics Data System (ADS)

    Chang, Zuoyang

    1996-11-01

    Theoretical calculation and numerical simulation indicate that there can be interesting interactions between alpha particles and MHD activity which can adversely affect the performance of a tokamak reactor (e.g., ITER). These interactions include alpha-driven MHD, like the toroidicity-induced-Alfven-eigenmode (TAE) and MHD induced alpha particle losses or redistribution. Both phenomena have been observed in recent TFTR DT experiments. Weak alpha-driven TAE activity was observed in a NBI-heated DT experiment characterized by high q0 ( >= 2) and low core magnetic shear. The TAE mode appears at ~30-100 ms after the neutral beam turning off approximately as predicted by theory. The mode has an amplitude measured by magnetic coils at the edge tildeB_p ~1 mG, frequency ~150-190 kHz and toroidal mode number ~2-3. It lasts only ~ 30-70 ms and has been seen only in DT discharges with fusion power level about 1.5-2.0 MW. Numerical calculation using NOVA-K code shows that this type of plasma has a big TAE gap. The calculated TAE frequency and mode number are close to the observation. (2) KBM-induced alpha particle loss^1. In some high-β, high fusion power DT experiments, enhanced alpha particle losses were observed to be correlated to the high frequency MHD modes with f ~100-200 kHz (the TAE frequency would be two-times higher) and n ~5-10. These modes are localized around the peak plasma pressure gradient and have ballooning characteristics. Alpha loss increases by 30-100% during the modes. Particle orbit simulations show the added loss results from wave-particle resonance. Linear instability analysis indicates that the plasma is unstable to the kinetic MHD ballooning modes (KBM) driven primarily by strong local pressure gradients. ----------------- ^1Z. Chang, et al, Phys. Rev. Lett. 76 (1996) 1071. In collaberation with R. Nazikian, G.-Y. Fu, S. Batha, R. Budny, L. Chen, D. Darrow, E. Fredrickson, R. Majeski, D. Mansfield, K. McGuire, G. Rewoldt, G. Taylor, R. White, K

  14. Estrogen protects the liver and intestines against sepsis-induced injury in rats.

    PubMed

    Sener, Göksel; Arbak, Serap; Kurtaran, Pelin; Gedik, Nursal; Yeğen, Berrak C

    2005-09-01

    Sepsis is commonly associated with enhanced generation of reactive oxygen metabolites, leading to multiple organ dysfunctions. The aim of this study was to examine the putative protective role of estradiol against sepsis-induced oxidative organ damage. Sepsis was induced by cecal ligation and puncture method in Wistar albino rats. Sham-operated (control) and sepsis groups received saline or estradiol propionate (10 mg/kg) intraperitoneally immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and malondialdehyde, glutathione levels, and myeloperoxidase activity were determined in the liver and ileum, while oxidant-induced tissue fibrosis was determined by collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase, alanine aminotransferase levels, and lactate dehydrogenase were measured for the evaluation of liver functions and tissue damage, respectively. Tumor necrosis factor-alpha was also assayed in serum samples. In the saline-treated sepsis group, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity, and collagen content were increased in the tissues (P < 0.01 to P < 0.001), suggesting oxidative organ damage, which was also verified histologically. In the estradiol-treated sepsis group, all of these oxidant responses were reversed significantly (P < 0.05 to P < 0.01). Liver function tests and tumor necrosis factor-alpha levels, which were increased significantly (P < 0.001) following sepsis, were decreased (P < 0.05 to P < 0.001) with estradiol treatment. The results demonstrate the role of oxidative mechanisms in sepsis-induced tissue damage, and estradiol, by its antioxidant properties, ameliorates oxidative organ injury, implicating that treatment with estrogens might be applicable in clinical situations to ameliorate multiple organ damage induced by sepsis.

  15. Alpha-adrenoceptor blockade modifies neurally induced atrial arrhythmias.

    PubMed

    Richer, Louis-Philippe; Vinet, Alain; Kus, Teresa; Cardinal, René; Ardell, Jeffrey L; Armour, John Andrew

    2008-10-01

    Our objective was to determine whether neuronally induced atrial arrhythmias can be modified by alpha-adrenergic receptor blockade. In 30 anesthetized dogs, trains of five electrical stimuli (1 mA; 1 ms) were delivered immediately after the P wave of the ECG to mediastinal nerves associated with the superior vena cava. Regional atrial electrical events were monitored with 191 atrial unipolar electrodes. Mediastinal nerve sites were identified that reproducibly initiated atrial arrhythmias. These sites were then restimulated following 1 h (time control, n = 6), or the intravenous administration of naftopidil (alpha(1)-adrenergic blocker: 0.2 mg/kg, n = 6), yohimbine (alpha(2)-adrenergic blocker: 1 mg/kg, n = 6) or both (n = 8). A ganglionic blocker (hexamethonium: 1 mg/kg) was tested in four dogs. Stimulation of mediastinal nerves sites consistently elicited atrial tachyarrhythmias. Repeat stimulation after 1 h in the time-control group exerted a 19% decrease of the sites still able to induce atrial tachyarrhythmias. Hexamethonium inactivated 78% of the previously active sites. Combined alpha-adrenoceptor blockade inactivated 72% of the previously active sites. Bradycardia responses induced by mediastinal nerve stimulation were blunted by hexamethonium, but not by alpha(1,2)-adrenergic blockade. Naftopidil or yohimbine alone eliminated atrial arrhythmia induction from 31% and 34% of the sites (similar to time control). We conclude that heterogeneous activation of the intrinsic cardiac nervous system results in atrial arrhythmias that involve intrinsic cardiac neuronal alpha-adrenoceptors. In contrast to the global suppression exerted by hexamethonium, we conclude that alpha-adrenoceptor blockade targets intrinsic cardiac local circuit neurons involved in arrhythmia formation and not the flow-through efferent projections of the cardiac nervous system.

  16. Testicular membrane lipid damage by complex mixture of leachate from municipal battery recycling site as indication of idiopathic male infertility in rat

    PubMed Central

    Oboh, Ganiyu; Akindahunsi, Akintunde A.

    2013-01-01

    Leachate from a municipal battery recycling site is a potent source of mixed-metal released into the environment. The present study investigated the degree at which mixed-metal exposure to the municipal auto-battery leachate (MABL) and to the Elewi Odo municipal auto-battery recycling site leachate (EOMABRL) affected the lipid membrane of the testes in in vitro experiment. The results showed elevated level of mixed-metals over the permissible levels in drinking water, as recommended by regulatory authorities. In the leachate samples, the levels of malondialdehyde (MDA), a biomarker of lipid damage, was significantly (p<0.05) increased in rat testes in a dose-dependent manner. MDA induced by the municipal auto-battery leachate (MABL) was significantly (p<0.05) higher than the leachate from Elewi Odo municipal auto-battery recycling site (EOMABRL). The testicular lipid membrane capacity was compromised following treatment with leachate from the municipal battery recycling site, implicating mixed-metal exposure as the causative agent of testicular damage and male infertility. PMID:24678257

  17. Testicular membrane lipid damage by complex mixture of leachate from municipal battery recycling site as indication of idiopathic male infertility in rat.

    PubMed

    Akintunde, Jacob K; Oboh, Ganiyu; Akindahunsi, Akintunde A

    2013-12-01

    Leachate from a municipal battery recycling site is a potent source of mixed-metal released into the environment. The present study investigated the degree at which mixed-metal exposure to the municipal auto-battery leachate (MABL) and to the Elewi Odo municipal auto-battery recycling site leachate (EOMABRL) affected the lipid membrane of the testes in in vitro experiment. The results showed elevated level of mixed-metals over the permissible levels in drinking water, as recommended by regulatory authorities. In the leachate samples, the levels of malondialdehyde (MDA), a biomarker of lipid damage, was significantly (p<0.05) increased in rat testes in a dose-dependent manner. MDA induced by the municipal auto-battery leachate (MABL) was significantly (p<0.05) higher than the leachate from Elewi Odo municipal auto-battery recycling site (EOMABRL). The testicular lipid membrane capacity was compromised following treatment with leachate from the municipal battery recycling site, implicating mixed-metal exposure as the causative agent of testicular damage and male infertility.

  18. Effect of ascorbic acid and alpha tocopherol supplementation on acute restraint stress induced changes in testosterone, corticosterone and nor epinephrine levels in male Sprague Dawley rats.

    PubMed

    Lodhi, Ghulam Mustafa; Latif, Rabia; Hussain, Muhammad Mazhar; Naveed, Abdul Khaliq; Aslam, Muhammad

    2014-01-01

    Stress of various origins suppresses male reproductive functions through releasing stress hormones. Antioxidant like ascorbic acid (AA) and alpha tocopherol (AT) have been thought to protect the body against stress induced damage. Whether, these antioxidants confer protection against the stress induced increased levels of corticosterone and nor-epinephrine, and decreased testosterone secretion have been investigated in this study. This quasi experimental study was carried out at the Department of Physiology, Army Medical College Rawalpindi in collaboration with National Institute of Health, Islamabad during March to September 2009. Eighty male Sprague Dawley rats were divided into five groups with sixteen rats in each group. Group-I served as the control without stress while group-II was exposed to restraint stress for 6 hours, group-III was administered AA, group-IVAT and group-V was supplemented with both the antioxidants along with standard diet for one month. All antioxidant supplemented groups were exposed to restraint stress for 6 hours. Immediately after the stress episode, blood sample was obtained for the assay of serum testosterone, serum corticosterone by EIA and plasma nor-epinephrine levels by ELISA. Data were analyzed on SPSS-13 and p-value less than 0.05 was considered significant. Acute restraint stress resulted in a statistically significant rise in corticosterone and nor-epinephrine levels and fall in serum testosterone levels. AA supplementation for one month revealed insignificant changes in stress induced hormonal parameters. AT alone and in combination with ascorbic acid prevented the fall in testosterone level as well as rise in corticosterone, however nor-epinephrine levels remained unchanged. Supplementation with AT alone or in combination with AA prevent reduction in testosterone and rise in corticosterone levels while keeping the nor-epinephrine levels unchanged after acute restraint stress in Sprague Dawley rats.

  19. A novel vitamin E derivative (TMG) protects against gastric mucosal damage induced by ischemia and reperfusion in rats.

    PubMed

    Ichikawa, Hiroshi; Yoshida, Norimasa; Takano, Hiroshisa; Ishikawa, Takeshi; Handa, Osamu; Takagi, Tomohisa; Naito, Yuji; Murase, Hironobu; Yoshikawa, Toshikazu

    2003-01-01

    The aim of the present study was to investigate the antioxidative effects of water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), on ischemia-reperfusion (I/R) -induced gastric mucosal injury in rats. Gastric ischemia was induced by applying a small clamp to the celiac artery and reoxygenation was produced by removal of the clamp. The area of gastric mucosal erosion, the concentration of thiobarbituric acid-reactive substances, and the myeloperoxidase activity in gastric mucosa significantly increased in I/R groups compared with those of sham-operated groups. These increases were significantly inhibited by pretreatment with TMG. The contents of both mucosal TNF-alpha and CINC-2beta in I/R groups were also increased compared with the levels of those in sham-operated groups. These increases of the inflammatory cytokines were significantly inhibited by the treatment with TMG. It is concluded that TMG inhibited lipid peroxidation and reduced development of the gastric mucosal inflammation induced by I/R in rats.

  20. Infertility - resources

    MedlinePlus

    Resources - infertility ... The following organizations are good resources for information on infertility : US Centers for Disease Control and Prevention -- www.cdc/gov/reproductivehealth/infertility March of Dimes -- www.marchofdimes. ...

  1. Non-NMDA receptor antagonist-induced drinking in rat

    NASA Technical Reports Server (NTRS)

    Xu, Z.; Johnson, A. K.

    1998-01-01

    Glutamate has been implicated in the central control of mechanisms that maintain body fluid homeostasis. The present studies demonstrate that intracerebroventricular (i.c.v.) injections of the non-N-methyl-d-aspartate (NMDA) receptor antagonists 6, 7-dinitroquinoxaline-2,3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) induce drinking in rats. The dipsogenic effect of i.c.v. DNQX was antagonized by the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). The water intake induced by DNQX was also blocked by pretreatment with a NMDA receptor antagonist, MK-801, but not by angiotensin type 1 (AT1) or acetylcholine muscarinic receptor antagonists (losartan and atropine). The results indicate that non-NMDA receptors may exert a tonic inhibitory effect within brain circuits that control dipsogenic activity and that functional integrity of NMDA receptors may be required for the non-NMDA receptor antagonists to induce water intake. Copyright 1998 Published by Elsevier Science B.V.

  2. Oxidation enhances calpain-induced turbidity in young rat lenses.

    PubMed

    Nakamura, Y; Fukiage, C; Azuma, M; Shearer, T R

    1999-07-01

    To determine if oxidation enhances turbidity after proteolysis of rat lens crystallins by the calcium-activated protease calpain (EC 3.4.22.17). Total soluble proteins from young rat lens were hydrolyzed for 24 hr by endogenous lens calpain, and the proteins were further incubated with the oxidant diamide for up to 7 days. Turbidity was measured daily at 405 nm. To measure proteolysis and turbidity in cultured lenses, rat lenses were cultured for 6 days in low calcium medium and diamide. The lenses were then photographed to assess transmission of light. SDS-PAGE and immunoblotting assessed proteolysis of crystallins, alpha-spectrin, and activation of calpain. Appreciable in vitro turbidity occurred in soluble proteins from young rat lenses after proteolysis of crystallins by endogenous calpain. Calpain inhibitor E64, or anti-oxidants DTE and GSH, inhibited this turbidity. On the other hand, the oxidant diamide markedly enhanced calpain-induced turbidity. Cultured rat lenses showed elevated intralenticular calcium and proteolysis of crystallins by calpain, but no nuclear cataract. Addition of diamide to the culture medium caused development of nuclear cataract. Diamide enhanced turbidity only when crystallins were proteolyzed. Oxidation may be one of the factors promoting light scatter and insolubilization after proteolysis. These data are consistent with the hypothesis that proteolysis of crystallins from young rat lens may expose cysteine residues, which are then oxidized, become insoluble and scatter light.

  3. Serum IgG, IgM and slow alpha-globulin levels in carrageenan-treated rats.

    PubMed Central

    Fowler, E. F.; Thomson, A. W.

    1979-01-01

    Serum levels of IgM, IgG, slow alpha 1- and slow alpha 2-globulins were measured either by quantitative radial immunodiffusion (IgG) or immunoelectrophoresis (IgM and slow alpha-globulins) during the 3-week period after i.p. injection of 50 mg potassium carrageenan. There was a significant elevation in levels of IgM and slow alpha 1-globulin, maximal on Day 4 and returning to normal by Day 14. Slow alpha 2-globulin was detectable within 24 h, reached a peak at Day 2, and was no longer measurable in most rats by Day 14. Levels of IgG however, were unaffected by carrageenan injection. PMID:92333

  4. Demonstration of ameliorative effect of lacosamide: in a rat model of sepsis-induced critical illness polyneuropathy.

    PubMed

    Solmaz, Volkan; Aksoy, Dürdane; Yılmaz, Mustafa; Eser, Enes; Erbas, Oytun

    2015-09-01

    Critical illness neuropathy (CIN) is a condition that may occur in diseases with severe systemic response, particularly in sepsis. The aim of this study is to investigate the potential anti-inflammatory and lipid-peroxidation inhibiting activities of lacosamide by measuring tumour necrotizing factor-alpha (TNF-alpha), C-reactive protein (CRP), malondialdehyde (MDA) and white blood cells (WBC) using electroneuromyography (ENMG) in rats with sepsis-induced critical illness neuropathy (SICIN). Cecal ligation and puncture (CLP) procedure was performed on 39 rats to induce a sepsis model. The study groups were designed as follows: Group 1: normal (nonoperative); Group 2: (sham-operated); Group 3: CLP (untreated group); Group 4: CLP and lacosamide 20 mg/kg; Group 5: CLP and lacosamide 40 mg/kg. TNF-alpha, C reactive protein, MDA and WBC levels was measured and compound muscle action potential (CMAP) distal latans, amplitudes were measured by using ENMG in rats with SICIN. When untreated sepsis group was compared with both control and sham groups, CMAP amplitudes and latans were significantly lower (P < 000.1). When CLP, CLP+lacosamide 20 mg/kg and CLP+lacosamide 40 mg/kg groups were compared, plasma levels of TNF-alpha and MDA were significantly higher in the untreated CLP group (F = 12.74, P < 0.0001), (F = 19.43, P < 0.05). In the CLP+lacosamide 40 mg/kg group, CRP levels were significantly lower only compared to the CLP group (P < 0.001). We have showed that lacosamide may have beneficial effects on early SICIN by its potential anti-inflammatory and lipid peroxidation inhibiting activities; however, further comprehensive studies are required to clarify these effects.

  5. Protective role of Hibiscus sabdariffa calyx extract against streptozotocin induced sperm damage in diabetic rats

    PubMed Central

    Idris, Muhd Hanis Md; Budin, Siti Balkis; Osman, Mohamad; Mohamed, Jamaludin

    2012-01-01

    Diabetes mellitus contributes to male sexual dysfunction and infertility by modulating oxidative damage. To date, a number of studies have demonstrated antioxidant properties of Hibiscus sabdariffa Linn. This study was designed to investigate the effects of H. sabdariffa UKMR-2 variety on sperm functioning of streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were allotted into four groups, namely control group (C), H. sabdariffa extract (HSE) group, diabetes group (D) and diabetes plus HSE group (D+HSE). HSE (100 mg/ kg/body weight) was administered orally for 28 consecutive days. After 28-days of supplementation, the rats were sacrificed to obtain epididymal sperm. Administration of HSE significantly lowered the level of fasting blood glucose and increased plasma insulin level in D+HSE group as compared to D group (p<0.05). Sperm quality in the D+HSE group was improved with significantly higher sperm concentrations (p<0.05) and sperm motility (p<0.001) as well as lower percentage of sperm abnormality (p<0.05) as compared to the diabetic group. Plasma follicle-stimulating hormone (FSH) level was significantly elevated (p<0.05) in D+HSE group than in D group while no significant alteration in plasma testosterone and luteinizing hormone (LH) level were seen between groups. In conclusion, this study suggested that H. sabdariffa UKMR-2 variety has a potential protective role against diabetes-induced sperm damage. PMID:27847454

  6. Protective role of Hibiscus sabdariffa calyx extract against streptozotocin induced sperm damage in diabetic rats.

    PubMed

    Idris, Muhd Hanis Md; Budin, Siti Balkis; Osman, Mohamad; Mohamed, Jamaludin

    2012-01-01

    Diabetes mellitus contributes to male sexual dysfunction and infertility by modulating oxidative damage. To date, a number of studies have demonstrated antioxidant properties of Hibiscus sabdariffa Linn. This study was designed to investigate the effects of H. sabdariffa UKMR-2 variety on sperm functioning of streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were allotted into four groups, namely control group (C), H. sabdariffa extract (HSE) group, diabetes group (D) and diabetes plus HSE group (D+HSE). HSE (100 mg/ kg/body weight) was administered orally for 28 consecutive days. After 28-days of supplementation, the rats were sacrificed to obtain epididymal sperm. Administration of HSE significantly lowered the level of fasting blood glucose and increased plasma insulin level in D+HSE group as compared to D group (p<0.05). Sperm quality in the D+HSE group was improved with significantly higher sperm concentrations (p<0.05) and sperm motility (p<0.001) as well as lower percentage of sperm abnormality (p<0.05) as compared to the diabetic group. Plasma follicle-stimulating hormone (FSH) level was significantly elevated (p<0.05) in D+HSE group than in D group while no significant alteration in plasma testosterone and luteinizing hormone (LH) level were seen between groups. In conclusion, this study suggested that H. sabdariffa UKMR-2 variety has a potential protective role against diabetes-induced sperm damage.

  7. Immunomodulatory effects of thalidomide analogs on LPS-induced plasma and hepatic cytokines in the rat.

    PubMed

    Fernández-Martínez, Eduardo; Morales-Ríos, Martha S; Pérez-Alvarez, Víctor; Muriel, Pablo

    2004-10-01

    Thalidomide has shown to inhibit, selectively and mainly the cytokine tumor necrosis factor-alpha (TNF-alpha), thus, thalidomide has inhibitory consequences on other cytokines; this is ascribed as an immunomodulatory effect. Novel thalidomide analogs are reported with immunomodulatory activity. The aim of this work was to synthesize some of these analogs and to assess them as immunomodulatory agents in an acute model of LPS-induced septic challenge in rat. Animal groups received orally twice a day vehicle carboxymethylcellulose (0.9%), or thalidomide in suspension (100mg/kg), or analogs in an equimolar dose. Two hours after last dose, rats were injected with saline (NaCl, 0.9%, i.p.) or LPS (5mg/kg, i.p.). Groups were sacrificed 2h after injection and samples of blood and liver were obtained. TNF-alpha, interleukin-6, -1beta, and -10 (IL-6, IL-1beta, IL-10) were quantified by enzyme linked immunosorbent assay (ELISA) and studied in plasma and liver. After 2h of LPS-induction, different patterns of measured cytokines were observed with thalidomide analogs administration evidencing their immunomodulatory effects. Interestingly, some analogs decreased significantly plasma and hepatic levels of LPS-induced proinflammatory TNF-alpha and others increased plasma concentration of anti-inflammatory IL-10. Thalidomide analogs also showed slight effects on the remaining proinflammatory cytokines. Differences among immunomodulatory effects of analogs can be related to potency, mechanism of action, and half lives. Thalidomide analogs could be used as a pharmacological tool and in therapeutics in the future.

  8. Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery.

    PubMed

    Knock, Greg A; Shaifta, Yasin; Snetkov, Vladimir A; Vowles, Benjamin; Drndarski, Svetlana; Ward, Jeremy P T; Aaronson, Philip I

    2008-02-01

    We investigated the role of src family kinases (srcFK) in agonist-mediated Ca2+-sensitization in pulmonary artery and whether this involves interaction with the rho/rho-kinase pathway. Intra-pulmonary arteries (IPAs) and cultured pulmonary artery smooth muscle cells (PASMC) were obtained from rat. Expression of srcFK was determined at the mRNA and protein levels. Ca2+-sensitization was induced by prostaglandin F(2 alpha) (PGF(2 alpha)) in alpha-toxin-permeabilized IPAs. Phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of myosin light-chain-20 (MLC20) and translocation of rho-kinase in response to PGF(2 alpha) were also determined. Nine srcFK were expressed at the mRNA level, including src, fyn, and yes, and PGF(2 alpha) enhanced phosphorylation of three srcFK proteins at tyr-416. In alpha-toxin-permeabilized IPAs, PGF(2 alpha) enhanced the Ca2+-induced contraction (pCa 6.9) approximately three-fold. This enhancement was inhibited by the srcFK blockers SU6656 and PP2 and by the rho-kinase inhibitor Y27632. Y27632, but not SU6656 or PP2, also inhibited the underlying pCa 6.9 contraction. PGF(2 alpha) enhanced phosphorylation of MYPT-1 at thr-697 and thr-855 and of MLC20 at ser-19. This enhancement, but not the underlying basal phosphorylation, was inhibited by SU6656. Y27632 suppressed both basal and PGF(2 alpha)-mediated phosphorylation. The effects of SU6656 and Y27632, on both contraction and MYPT-1 and MLC20 phosphorylation, were not additive. PGF(2 alpha) triggered translocation of rho-kinase in PASMC, and this was inhibited by SU6656. srcFK are activated by PGF(2 alpha) in the rat pulmonary artery and may contribute to Ca2+-sensitization and contraction via rho-kinase translocation and phosphorylation of MYPT-1.

  9. Anti-fertility effects of different fractions of Anethum graveolens L. extracts on female rats.

    PubMed

    Malihezaman, Monsefi; Mojaba, Masoudi; Elham, Hosseini; Farnaz, Gramifar; Ramin, Miri

    2012-01-01

    Our previous studies showed the effects of aqueous and ethanol extracts of Anethum graveolens L. (dill) on female infertility. In the present study we investigated whether different fractions of this herb extract can cause infertility in rats. Female rats were divided into the control groups, the groups receiving either a low (0.5 g/kg)) or a high dose (5g/kg) of water, N-butanol, chloroform and ether fractions of the aqueous plant extract, and the groups receiving either a low (0.045 g/kg) or a high dose (0.45 g/kg) of the same fractions of ethanol extract. The mentioned doses were gavaged in 1mL for 10 days. Vaginal smears were prepared daily. Estradiol and progesterone levels were measured. The left oviduct and ovary were removed, their tissue subsequently being prepared in form of histology slides and stained using haematoxylin-eosin and Masson's trichrome. Female rats assigned to each group were mated with males; after that, crown-rump lengths and weights of newborn rats were measured. Results showed that each fraction produced some changes such as hormonal level reduction (chloroform fraction), diestrus phase prolongation and infertility (water fraction), and increase in pregnancy duration (chloroform and ether fractions). We concluded that each fraction comprises only some of the mentioned components and therefore recommended the usage of crude extract, especially the aqueous one, in case infertility aims to be induced.

  10. Treatment with geraniol ameliorates methionine-choline-deficient diet-induced non-alcoholic steatohepatitis in rats.

    PubMed

    Chen, Jun; Fan, Xiaoxia; Zhou, Lin; Gao, Xiaogang

    2016-07-01

    Non-alcoholic steatohepatitis (NASH) is one of the most common causes of chronic liver disease and is considered to be a causative factor of cryptogenic cirrhosis and hepatocellular carcinoma. The aim of this work was to investigate whether treatment with geraniol (a monoterpene) attenuated NASH induced by methionine-choline-deficient (MCD) diet in rats. Rats were fed with MCD diet to induce NASH and treated with geraniol (200 mg/kg/day) for 10 weeks. Treatment with geraniol reduced histological scores, fibrosis, and apoptosis in livers, lowered activities of alanine aminotransferase and aspartate aminotransferase in serum, and attenuated hepatic fat accumulation in rats fed with MCD diet. Treatment with geraniol preserved hepatic mitochondrial function, evidenced by reduced mitochondrial reactive oxygen species formation, enhanced adenosine triphosphate formation and membrane integrity, restored mitochondrial electron transport chain enzyme activity, and increased mitochondrial DNA content in rats fed with MCD diet. Treatment with geraniol reduced uncoupling protein 2 protein expression, and enhanced protein expression of prohibitin, mRNA expression of peroxisome proliferator-activated receptor α, and activity of mitochondrial carnitine palmitoyl transferase-I in livers of rats fed with MCD diet. Treatment with geraniol abated oxidative stress, evidenced by reduced malondialdehyde and 3-nitrotyrosine formation, enhanced activity of glutathione S-epoxide transferase, and down-regulated expression of inducible nitric oxide synthase and cytochrome P450 2E1 in livers of rats fed with MCD diet. Treatment with geraniol reduced myeloperoxidase activity and protein expression of tumor necrosis factor alpha and IL-6 in livers of rats fed with MCD diet. Treatment with geraniol attenuated MCD-induced NASH in rats. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  11. Age-related changes in neocortical high-voltage spindles and alpha EEG power during quiet waking in rats.

    PubMed

    Moyanova, Slavianka G; Kirov, Roumen K; Kortenska, Lidia V

    2002-04-01

    Age-related changes in neocortical high-voltage spindle (HVS) and in electroencephalographic (EEG) alpha power were examined in young (3.0 to 4.6 months), middle-aged (10.2 to 13.8 months), and old (21.5 to 24.0 months) male Wistar rats during quiet waking. Whereas the duration of quiet waking stage did not change as a function of age, a significant increase in HVS amount and EEG alpha peak power was observed in the middle-aged rats with only a tendency for a further enhancement in the old animals. An additional analysis showed that the elevation of alpha power is associated with age rather than with HVS activity.

  12. Regulation of expression of hyperalgesic priming by estrogen receptor alpha in the rat

    PubMed Central

    Ferrari, Luiz F.; Araldi, Dionéia; Levine, Jon D.

    2017-01-01

    Hyperalgesic priming, a sexually dimorphic model of transition to chronic pain, is expressed as prolongation of prostaglandin E2 (PGE2)-induced hyperalgesia by the activation of an additional pathway including an autocrine mechanism at the plasma membrane. The autocrine mechanism involves the transport of cAMP to the extracellular space, and its conversion to AMP and adenosine, by ecto-5′phosphodiesterase and ecto-5′nucleotidase, respectively. The end product, adenosine, activates A1 receptors, producing delayed onset prolongation of PGE2 hyperalgesia. We tested the hypothesis that the previously reported, estrogen-dependent, sexual dimorphism observed in the induction of priming is present in the mechanisms involved in its expression, as a regulatory effect on ecto-5′nucleotidase by estrogen receptor alpha (EsRα), in female rats. In the primed paw AMP hyperalgesia was dependent on conversion to adenosine, being prevented by ecto-5′nucleotidase inhibitor AMPCP and A1 receptor antagonist DPCPX. To investigate an interaction between EsRα and ecto-5′nucleotidase, we treated primed female rats with ODN antisense or mismatch against EsRα mRNA. While in rats treated with antisense AMP-induced hyperalgesia was abolished, the A1 receptor agonist N6-cyclopentiladenosine (CPA) still produced hyperalgesia. Thus, EsRα interacts with this autocrine pathway at the level of ecto-5′nucleotidase. These results demonstrate a sexually dimorphic mechanism for the expression of priming. Perspective This study presents evidence of an estrogen-dependent mechanism of expression of chronic pain in females, supporting the suggestion that differential targets must be considered when establishing protocols for the treatment of painful conditions in males and females. PMID:28089711

  13. Lipoic acid prevents suppression of connective tissue proliferation in the rat liver induced by n-3 PUFAs. A pilot study.

    PubMed

    Arend, A; Zilmer, M; Vihalemm, T; Selstam, G; Sepp, E

    2000-01-01

    As previously shown, dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) suppress connective tissue proliferation in the rat liver wound concurrent with an elevated level of lipid peroxidation. The present study was undertaken to investigate the influence of alpha-lipoic acid (LA), a natural anti-oxidant, on these effects of n-3 PUFAs. Rats were fed with a commercial pellet diet (control group) or with diets enriched with 10% of sunflower oil (n-6 group) or 10% of fish oil (n-3 group) for 8 weeks followed by addition of LA to the same diets for 10 days. Then a liver thermic wound was induced and the administration of LA was continued for 6 days. The proliferation of the connective tissue, the level of lipid peroxidation and their peroxidizability and the content of prostaglandins E2 and F2alpha were measured in the liver wounds. LA prevented the suppression of connective tissue proliferation in the healing wound induced by n-3 PUFAs, avoided the increase in peroxidation of lipids, reduced peroxidizability of lipids and modulated the decrease in PGE2 and PGF2alpha. The results indicate that dietary LA may prevent the suppression of liver wound healing induced by n-3 PUFAs.

  14. Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis

    PubMed Central

    Rato, L.; Alves, M. G.; Dias, T. R.; Cavaco, J. E.; Oliveira, Pedro F.

    2015-01-01

    Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by 1H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters. PMID:26064993

  15. Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis.

    PubMed

    Rato, L; Alves, M G; Dias, T R; Cavaco, J E; Oliveira, Pedro F

    2015-01-01

    Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by (1)H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters.

  16. Urokinase plasminogen activator mRNA is induced by IL-1alpha and TNF-alpha in in vitro acantholysis.

    PubMed

    Feliciani, Claudio; Toto, Paola; Wang, Binghe; Sauder, Daniel N; Amerio, Pierluigi; Tulli, Antonio

    2003-08-01

    The role of urokinase type plasminogen activator (uPA) has been well documented in the pathogenesis of pemphigus vulgaris (PV). Activation of plasminogen into active serine protease plasmin initiates extracellular proteolysis leading to acantholysis but the mechanisms underlying this process are not clearly understood. We have previously shown that keratinocyte derived cytokines IL-1alpha and TNF-alpha are involved in PV-induced acantholysis. In the present study we sought to examine whether keratinocyte-derived IL-1alpha and TNF-alpha are correlated with uPA induction in keratinocytes during acantholysis. Normal human keratinocytes were incubated with diluted PV serum. mRNAs for IL-1alpha, TNF-alpha and uPA were examined with RT-PCR at various time points and acantholysis was measured. IL-1alpha, TNF-alpha and uPA mRNAs were all induced in keratinocytes following PV serum stimulation; IL-1alpha/TNF-alpha mRNAs' expression was earlier than the expression of uPA mRNA. To further examine the role of IL-1alpha, TNF-alpha and uPA in acantholysis, we performed antibody blocking studies. Anti-IL-1alpha, anti-TNF-alpha and anti-uPA antibodies suppressed acantholysis by 76%, 80% and 90%, respectively. In addition, anti-IL-1alpha and anti-TNF-alpha antibodies inhibited uPA mRNA induction, whereas anti-uPA antibodies did not alter IL-1alpha/TNF-alpha mRNAs' expression. Our results confirm the role of uPA in acantholysis and suggest an involvement of IL-1alpha/TNF-alpha in uPA induction.

  17. Chemoprevention of rat prostate carcinogenesis by dietary 16alpha-fluoro-5-androsten-17-one (fluasterone), a minimally androgenic analog of dehydroepiandrosterone.

    PubMed

    McCormick, David L; Johnson, William D; Kozub, Nicole M; Rao, K V N; Lubet, Ronald A; Steele, Vernon E; Bosland, Maarten C

    2007-02-01

    Dehydroepiandrosterone (DHEA) is a potent inhibitor of prostate carcinogenesis in rats. However, concerns related to the possible androgenicity of DHEA may preclude its use for chemoprevention of human prostate cancer. Studies were performed to compare the androgenicity of DHEA and a fluorinated DHEA analog, 16alpha-fluoro-5-androsten-17-one (fluasterone), and to determine the chemopreventive activity of fluasterone in the rat prostate. Comparisons of accessory sex gland weight and histology in gonadectomized male rats demonstrated that fluasterone is less androgenic than is DHEA. Fluasterone conferred significant protection against prostate carcinogenesis induced in Wistar-Unilever rats by a sequential regimen of N-methyl-N-nitrosourea+testosterone. Chronic administration of fluasterone at levels of 2000 and 1000 mg/kg diet reduced the incidence of adenocarcinoma in the dorsolateral/anterior prostate from 64% in dietary controls to 28 and 31%, respectively. Other than a dose-related suppression of body weight gain, chronic exposure to fluasterone induced no clinical evidence of toxicity; suppression of body weight gain may be either a pharmacological effect or a minimally toxic effect of the compound. These data demonstrate that a minimally androgenic analog of DHEA protects against prostate carcinogenesis induced in rats by a chemical carcinogen + androgen. The reduced androgenicity of fluasterone may obviate toxicities associated with the androgenicity of the parent compound. On this basis, fluasterone merits consideration for evaluation in clinical trials for prostate cancer prevention. The chemopreventive activity of a non-androgenic DHEA analog suggests that at least a portion of the chemopreventive activity of DHEA in the rat prostate is unrelated to hormonal effects.

  18. Dietary medium-chain triglycerides prevent chemically induced experimental colitis in rats.

    PubMed

    Kono, Hiroshi; Fujii, Hideki; Ishii, Kenichi; Hosomura, Naohiro; Ogiku, Masahito

    2010-03-01

    The effects of dietary medium-chain triglycerides (MCTs) on experimental colitis induced by 2,4,6-trinitrobenzene sulphonic acid (TNBS) were investigated in rats. Male Wistar rats were given an intracolonic injection of TNBS and were then fed liquid diets containing MCTs or corn oil (AIN93) as controls. Serum and tissue samples were collected 1 week after TNBS enema. The severity of colitis was evaluated pathologically, and tissue myeloperoxidase (MPO) activity was measured. Furthermore, messenger RNA (mRNA) and protein levels for inflammatory cytokines and a chemokine were assessed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. In another set of experiments, the protein expression of Toll-like receptor (TLR)-4 in the colon was measured 1 week after feeding of liquid diets. To investigate the effects of MCTs on macrophages, RAW246.7 macrophages were incubated with media containing albumin conjugated with MCT or linoleic acid, which is the major component of corn oil. Then, the production of tumor necrosis factor-alpha (TNF-alpha) was measured. Dietary MCTs blunted significantly the protein levels of TLR-4 in the colon. Furthermore, the expression of TLR-4 was significantly blunted in RAW264.7 cells incubated with MCTs compared with cells incubated with linoleic acid. Induction of interleukin 1beta (IL-1beta), TNF-alpha, and macrophage inflammatory protein-2 (MIP-2) in the colon was attenuated by dietary MCT. Furthermore, MPO activities in the colonic tissue were significantly blunted in animals fed the MCT diets compared with those fed the control diets. As a result, dietary MCTs improved chemically induced colitis significantly. MCTs most likely are useful for the therapy of inflammatory bowel disease as an anti-inflammatory immunomodulating nutrient. Copyright 2010 Mosby, Inc. All rights reserved.

  19. The effects of interferon-alpha/beta in a model of rat heart transplantation

    NASA Technical Reports Server (NTRS)

    Slater, A. D.; Klein, J. B.; Sonnenfeld, G.; Ogden, L. L. 2nd; Gray, L. A. Jr

    1992-01-01

    Interferons have multiple immunologic effects. One such effect is the activation of expression of cell surface antigens. Interferon alpha/beta enhance expression of class I but not class II histocompatibility antigens. Contradictory information has been published regarding the effect of interferon-alpha/beta administration in patients with kidney transplantation. In a model of rat heart transplantation we demonstrated that administration of interferon-alpha/beta accelerated rejection in a dose-dependent fashion in the absence of maintenance cyclosporine. Animals treated with maintenance cyclosporine had evidence of increased rejection at 20 days that was resolved completely at 45 days with cyclosporine alone.

  20. The development of novel inhibitors of tumor necrosis factor-alpha production based on substituted [5,5]-bicyclic pyrozolones

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Laufersweiler, Matthew; Brugel, Todd; Clark, Michael

    Novel substituted [5,5]-bicyclic pyrzazolones are presented as inhibitors of tumor necrosis factor-{alpha} (TNF-{alpha}) production. Many of these compounds show low nanomolar activity against lipopolysaccaride (LPS)-induced TNF-{alpha} production in THP-1 cells. This class of molecules was co-crystallized with mutated p38, and several analogs showed good oral bioavailability in the rat. Oral activity of these compounds in the rat iodoacetate model for osteoarthritis is discussed.

  1. gamma-tocopherol, but not alpha-tocopherol, potently inhibits neointimal formation induced by vascular injury in insulin resistant rats.

    PubMed

    Takahashi, Katsuaki; Komaru, Tatsuya; Takeda, Satoru; Takeda, Morihiko; Koshida, Ryoji; Nakayama, Masaharu; Kokusho, Yasunori; Kawakami, Yuki; Yamaguchi, Nobuhiro; Miyazawa, Teruo; Shimokawa, Hiroaki; Shirato, Kunio

    2006-09-01

    Insulin resistance may enhance the neointima formation via increased oxidative stress. However, clinical trials investigating the benefit of antioxidant therapy with alpha-tocopherol showed negative results. Recent studies showed that chemical characteristics of gamma-tocopherol are distinct from those of alpha-tocopherol. We hypothesized that gamma-tocopherol is superior to alpha-tocopherol in preventing the neointima growth after arterial injury in insulin resistance. Male rats were fed with standard chow or a high fructose diet for induction of insulin resistance. Thereafter, the left carotid artery was injured with a balloon catheter. After 2 weeks, the carotid arteries were harvested and histomorphometrically analyzed. The neointima-media ratio of the injured artery was significantly greater in insulin resistance group (n=8, 1.33+/-0.12) than in normal group (n=10, 0.76+/-0.11, p<0.01). gamma-Tocopherol (100 mg/kg/day) reduced the ratio (n=5, 0.55+/-0.21, p<0.01 vs. insulin resistance group), while alpha-tocopherol was without effect (n=7, 1.08+/-0.14). The quantification of plasma phosphatidylcholine hydroperoxide, an indicator of systemic oxidative stress, and dihydroethidium fluorescence staining of the carotid artery, an indicator of the local superoxide production, showed that oxidative stress in the systemic circulation and local arterial tissue was increased in insulin resistance. Both tocopherols decreased plasma phosphatidylcholine hydroperoxide, but failed to suppress the superoxide production in the carotid arteries. Increased 3-nitrotyrosine in neointima by insulin resistance was greatly reduced only by gamma-tocopherol. In conclusion, gamma-tocopherol, but not alpha-tocopherol, reduces the neointima proliferation in insulin resistance, independently of its effects on superoxide production. The beneficial effect may be related with its inhibitory effects on nitrosative stress.

  2. Protection against cyanide-induced convulsions with alpha-ketoglutarate.

    PubMed

    Yamamoto, H

    1990-04-30

    Protection against convulsions induced by cyanide was observed after treatment with alpha-ketoglutarate, either alone or in combination with sodium thiosulfate, a classical antagonist for cyanide intoxication. However, sodium thiosulfate alone did not protect against cyanide (30 mg/kg)-induced convulsions. gamma-Aminobutyric acid (GABA) levels in brain were decreased by 31% in KCN-treated mice exhibiting convulsions. The combined administration of alpha-ketoglutarate and sodium thiosulfate completely abolished the decrease of GABA levels induced by cyanide. Furthermore, sodium thiosulfate alone also completely abolished the decrease of GABA levels. These results suggest that the depletion of brain GABA levels may not directly contribute to the development of convulsions induced by cyanide. On the other hand, cyanide increased calcium levels by 32% in brain crude mitochondrial fractions in mice with convulsions. The increased calcium levels were completely abolished by the combined administration of alpha-ketoglutarate and sodium thiosulfate, but not affected by sodium thiosulfate alone. These findings support the hypothesis proposed by Johnson et al. (Toxicol. Appl. Pharmacol., 84 (1986) 464) and Robinson et al. (Toxicology, 35 (1985) 59) that calcium may play an important role in mediating cyanide neurotoxicity.

  3. Tumor necrosis factor-{alpha} enhances IL-15-induced natural killer cell differentiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Jiwon; Lee, Suk Hyung; Korea University of Science and Technology, Yusong, Daejeon 305-333

    2009-09-04

    The differentiation of natural killer (NK) cells is regulated by various factors including soluble growth factors and transcription factors. Here, we have demonstrated that tumor necrosis factor-{alpha} (TNF-{alpha}) is a positive regulator of NK cell differentiation. TNF-{alpha} augmented the IL-15-induced expression of NK1.1 and CD122 in mature NK cells, and TNF-{alpha} alone also induced NK cell maturation as well as IL-15. TNF-{alpha} also increased IFN-{gamma} production in NK cells in the presence of IL-15. Meanwhile, mRNA expression of several transcription factors, including T-bet and GATA-3, was increased by the addition of TNF-{alpha} and IL-15. In addition, TNF-{alpha} increased nuclear factor-kappamore » B (NF-{kappa}B) activity in NK cells and inhibition of NF-{kappa}B impeded TNF-{alpha}-enhanced NK cell maturation. Overall, these data suggest that TNF-{alpha} significantly increased IL-15-driven NK cell differentiation by increasing the expression of transcription factors that play crucial roles in NK cell maturation and inducing the NF-{kappa}B activity.« less

  4. An investigation into the selectivity of a novel series of benzoquinolizines for alpha 2-adrenoceptors in vivo.

    PubMed Central

    Paciorek, P. M.; Pierce, V.; Shepperson, N. B.; Waterfall, J. F.

    1984-01-01

    The potencies and selectivities of a novel series of benzoquinolizines for the alpha 2-adrenoceptor have been investigated in the rat in comparison with yohimbine and indoramin. Peripheral postjunctional alpha 2- and alpha 1-adrenoceptor blockade was measured as the reversal of B-HT 933 and methoxamine-induced pressor responses, respectively, in the pithed rat. Peripheral prejunctional alpha 2-adrenoceptor blockade was measured as the reversal of B-HT 933-induced inhibition of an electrically evoked tachycardia in the pithed rat. Central alpha 2-adrenoceptor blockade was measured as a reversal of the hypotension induced in anaesthetized rats by central (i.c.v.) administration of clonidine. Wy 25309, Wy 26392, Wy 26703 and yohimbine (0.3-3 mg kg-1 i.v.) evoked dose-dependent shifts to the right of the dose-response curves to B-HT 933 whilst having minimal effects on the methoxamine dose-response curve. The selectivity for alpha 2-adrenoceptors increased with the dose of antagonist administered. In general, the order of selectivity was Wy 25309 greater than Wy 26392 greater than Wy 26703 greater than yohimbine. Indoramin (1 mg kg-1 i.v.) shifted the methoxamine pressor dose-response curve to the right without affecting the B-HT 933 dose-response curves, confirming its selective alpha 1-antagonist activity. Peripheral administration of all three benzoquinolizines (1-100 micrograms kg-1 i.v.) led to a dose-dependent reversal of the hypotension evoked by central administration of clonidine (500 ng i.c.v.). The reversal was incomplete, higher doses causing a further decrease in blood pressure. (ABSTRACT TRUNCATED AT 250 WORDS) PMID:6329385

  5. Preventive and therapeutic anti-inflammatory effects of systemic and topical thalidomide on endotoxin-induced uveitis in rats.

    PubMed

    Rodrigues, Gustavo Büchele; Passos, Giselle Fazzioni; Di Giunta, Gabriella; Figueiredo, Cláudia Pinto; Rodrigues, Eduardo Büchele; Grumman, Astor; Medeiros, Rodrigo; Calixto, João B

    2007-03-01

    The present study examined the outcomes of systemic or topical treatment with thalidomide, a compound that possesses anti-inflammatory, immunomodulatory and anti-angiogenic properties, in rats subjected to endotoxin-induced uveitis (EIU). The effects of thalidomide were evaluated on endotoxin-induced leucocyte and protein infiltration and also on the production of interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha in rat aqueous humour (AqH). Moreover, the actions of thalidomide were assessed on the cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein expression in retinal tissue. EIU was produced by a hindpaw injection of lipopolysaccharide (LPS), in male Wistar rats. Thalidomide (5, 25 and 50 mg/kg) was administered orally 1 h before LPS injection. In another set of experiments, to evaluate the therapeutic efficacy, 5% thalidomide was applied topically to both eyes at 6, 12 and 18 h after LPS administration. The oral pre-treatment with thalidomide decreased, in a dose-dependent manner, the number of inflammatory cells, the protein concentration, and the levels of IL-1beta and TNF-alpha in the AqH. Similar results were found in the AqH of rats that received a topical application of thalidomide. Furthermore, oral (50 mg/kg) and local (5%) thalidomide treatment also reduced expression of the pro-inflammatory proteins COX-2 and iNOS in the posterior segment of the eye. Thalidomide exhibited marked preventive and curative ocular effects in EIU in rats, a property that might be associated with its ability to inhibit the production of inflammatory cytokines and the expression of COX-2 and iNOS. This assembly of data provides additional molecular and functional insights into beneficial effects of thalidomide as an agent for the management of ocular inflammation.

  6. Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat

    PubMed Central

    Chen, Huaguo; Xu, Yongfu; Wang, Jianzhong; Zhao, Wei; Ruan, Huihui

    2015-01-01

    Baicalin belongs to glucuronic acid glycosides and after hydrolysisbaicalein and glucuronic acid come into being. It has such effects as clearing heat and removing toxicity, anti-inflammation, choleresis, bringing high blood pressure down, diuresis, anti-allergic reaction and so on. In this study, we investigated whether baicalin ameliorates isoproterenol-induced acute myocardial infarction and its mechanism. Rat model of acute myocardial infarction was induced by isoproterenol. Casein kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), cardiac troponin T (cTnT) and infarct size measurement were used to measure the protective effect of baicalin on isoproterenol-induced acute myocardial infarction. iNOS protein expression in rat was analyzed using western blot analysis. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), malondialdehyde (MDA) and superoxide dismutase (SOD) and caspase-3 activation levels were explored using commercial ELISA kits. In the acute myocardial infarction experiment, baicalin effectively ameliorates the level of CK, CK-MB, LDH and cTnT, reduced infarct size in acute myocardial infarction rat model. Meanwhile, treatment with baicalin effectively decreased the iNOS protein expression, inflammatory factors and oxidative stresses in a rat model of acute myocardial infarction. However, baicalin emerged that anti-apoptosis activity and suppressed the activation of caspase-3 in a rat model of acute myocardial infarction. The data suggest that the protective effect of baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat. PMID:26617721

  7. Isoflavone genistein inhibits estrogen-induced chloride and bicarbonate secretory mechanisms in the uterus in rats.

    PubMed

    Chinigarzadeh, Asma; Karim, Kamarulzaman; Muniandy, Sekaran; Salleh, Naguib

    2017-04-01

    We hypothesized that genistein could affect the chloride (Cl - ) and bicarbonate (HCO 3 - ) secretory mechanisms in uterus. Ovariectomized female rats were given estradiol or estradiol plus progesterone with 25, 50, or 100 mg/kg/day genistein. Following completion of the treatment, uterine fluid Cl - and HCO 3 - concentrations were determined by in vivo uterine perfusion. Uteri were subjected for molecular biological analysis (Western blot, qPCR, and immunohistochemistry) to detect levels of expression of Cystic Fibrosis transmembrane regulator (CFTR), Cl - /HCO 3 - exchanger (SLC26a6), Na + /HCO 3 - cotransporter (SLC4a4), and estrogen receptor (ER)-α and β. Coadministration of genistein resulted in decrease in Cl - and HCO 3 - concentrations and expression of CFTR, SLC26a6, SLC4a4, and ER-α and ER-β in the uteri of estradiol-treated rats. In estradiol plus progesterone-treated rats, a significant increase in the above parameters were observed following high-dose genistein treatment except for the SLC24a4 level. In conclusion, genistein-induced changes in the uterus could affect the reproductive processes that might result in infertility. © 2016 Wiley Periodicals, Inc.

  8. Beneficial effect of garlic on D-galactosamine and lipopolysaccharide-induced acute hepatic failure in male albino rats.

    PubMed

    Abdel-Salam, Bahaa K A; Sayed, Abd-Alla A A

    2012-01-01

    Activation of the pro-inflammatory and anti-inflammatory cytokine cascade, including tumour necrosis factor (TNF)-alpha and interleukin (IL)-4, is considered to play an important role in severe liver injury. Kupffer cells, resident macrophages of the liver, activated with lipopolysaccharide (LPS) release pro-inflammatory cytokine. D-Galactosamine (D-GalN), a hepatocyte-specific inhibitor of RNA synthesis, is known to sensitise animals to the lethal effects of LPS. In the present study we seek to reverse some altered parameters, immunological and histopathological, to normal values of rats pre-treated with garlic. Acute hepatic failure was induced in male albino rats by the intraperitoneal injection of 500 mg D-GalN and 50 μg LPS/kg body weight. Expression levels of TNF-α and IL-4 were detected by ELISA. Leukocytes proliferation was carried out by differential count. For histopathology, liver sections were stained with haematoxylin and eosin. Data were analysed by SPSS program version 13.0. The data showed significant increase in the numbers of granulocytes, but with significant decreases in lymphocyte and monocytes proliferation and the TNF-alpha and IL-4 levels in D-GalN/LPS-induced group. Garlic pre-treatment of liver-injured rats induced significant amelioration in the numbers of monocytes and lymphocytes, with significant increase in granulocytes numbers, TNF-α level and IL-4 level. Results of this study revealed that garlic could afford a significant protection in the alleviation of D-GalN/LPS-induced hepatocellular injury. Copyright © 2011 SEICAP. Published by Elsevier Espana. All rights reserved.

  9. Alpha-particle-induced cancer in humans

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mays, C.W.

    Updated information is given on alpha-particle-induced cancer in persons internally exposed to 222Rn progeny, Thorotrast, long-lived 226Ra and 228Ra, and short-lived 224Ra. The lung cancer risk to persons breathing 222Rn progeny in the indoor air of offices, schools, and homes is of increasing concern. About half of the recent deaths among the German Thorotrast patients have been from liver cancer. Animal studies indicate that the liver cancer risk from Thorotrast is mainly from its radioactivity and that the risk coefficient for the Thorotrast patients can be used provisionally for other alpha emitters in the human liver. Six skeletal cancers havemore » occurred in persons with average skeletal doses between 0.85 and 11.8 Gy from 226Ra and 228Ra. In the low-dose German 224Ra patients, two skeletal sarcomas have occurred at about 0.7 Gy compared to about six cases predicted by results from 224Ra patients at higher doses. The minimal appearance time for radiation-induced bone sarcomas in humans is about 4 y. Following brief irradiation, the vast majority of induced bone sarcomas are expressed by about 30 y. Recent evidence against the practical threshold hypothesis is given. With the downward revision of neutron doses to the atomic-bomb survivors, the follow-up of persons exposed to alpha particles may be the best opportunity to evaluate directly the effects of high LET radiation on humans. 90 references.« less

  10. Alpha particle-induced soft errors in microelectronic devices. I

    NASA Astrophysics Data System (ADS)

    Redman, D. J.; Sega, R. M.; Joseph, R.

    1980-03-01

    The article provides a tutorial review and trend assessment of the problem of alpha particle-induced soft errors in VLSI memories. Attention is given to an analysis of the design evolution of modern ICs, and the characteristics of alpha particles and their origin in IC packaging are reviewed. Finally, the process of an alpha particle penetrating an IC is examined.

  11. Beneficial effects of enalapril on chlorhexidine digluconate-induced liver peritoneal fibrosis in rats.

    PubMed

    Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Ke, Chen-Yen; Lin, Nien-Tsung; Hsu, Bang-Gee

    2011-08-31

    Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of enalapril on chlorhexidine digluconate-induced liver PF by decreasing transforming growth factor-β1 (TGF-β1) production in rats. PF was induced in Sprague-Dawley rats by daily administration of 0.5 ml 0.1% chlorhexidine digluconate in normal saline via PD tube for one week. Rats received daily intravenous injections of low dose enalapril (1 mg/kg), or high dose enalapril (2.5 mg/kg), for one week. After 7 days, conventional 4.25% Dianeal (30 ml) was administered via a PD catheter with a dwell time of 4 h and assessment of peritoneal function. At the end of dialysis, the rats were sacrificed and liver peritoneum was harvested for microscopic examination and immunohistochemistry. There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D₄/P₄(urea) level was reduced, the D₄/D₀ glucose level, serum and the dialysate TGF-β1 level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-β1, alpha-smooth muscle actin (α-SMA), fibronectin, collagen and vascular endothelial growth factor (VEGF) were elevated in the PF group compared with the vehicle group. High dose of enalapril decreased the serum and dialysate TGF-β1 levels, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-β1, α-SMA, fibronectin, collagen and VEGF-positive cells in the liver peritoneum. Low dose of enalapril did not protect against chlorhexidine digluconate-induced PF in the rat. Enalapril protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-β1 production.

  12. Cardioprotective effect of vitamin D2 on isoproterenol-induced myocardial infarction in diabetic rats.

    PubMed

    El Agaty, Sahar M

    2018-03-08

    To assess the effect of vitamin D 2 and to elucidate the underlying mechanisms on acute myocardial injury induced by isoproterenol (ISO) in diabetic rats. Rats were divided into control rats, diabetic rats (DM), diabetic rats received ISO (DM-ISO), and diabetic rats pretreated with vitamin D 2 and received ISO (DM-D 2 -ISO). Vitamin D 2 pretreatment significantly decreased fasting glucose and myocardial malondialdehyde, associated with increased insulin, myocardial glutathione and superoxide dismutase in DM-D 2 -ISO versus DM-ISO. The serum triglycerides, total cholesterol, and LDL were significantly decreased, along with increased HDL and adiponectin. Poly-ADP ribose polymerase, cyclooxygenase-2, tumour necrosis factor alpha, interleukin-6, caspase-3, BAX, and p53 were significantly downregulated in myocardium of DM-D 2 -ISO versus DM-ISO. Histological studies showed diminished inflammatory cells infiltration in myocardium of DM-D 2 -ISO versus DM-ISO. Vitamin D 2 ameliorates hyperglycaemia, dyslipidaemia, redox imbalance, inflammatory and apoptotic processes, protecting the myocardium of diabetic rats against acute myocardial infarction.

  13. [Vitamin E activity of some alpha-tocopherol derivatives and their effect on the ubiquinone level in rat liver in vitro].

    PubMed

    Donchenko, G V; Kovalenko, V N; Zolotashko, O M; Makovetskiĭ, V P; Basalkevich, E D; Sivachek, T E; Svishchuk, A A; Khalmuradov, A G

    1979-01-01

    An addition of alpha-tocopherol (I) and its synthetic derivatives (alpha-tocopheryl quinone (II), its short-chained analog (III), alpha-tocopherol lactone (IV), and short-chained alpha-tocopheryl acetate (V)) to the homogenized liver of vitamin E deficient rats resulted in a significant increase of ubiquinone after 2 hour incubation. Activity of the above derivatives (II-V) was not associated directly with their transformation into I or with a noticeable increase of the I content. There is a certain correlation between the chemical structure and the level of vitamin E activity of alpha-tocopherol derivatives that led to an increase in the ubiquinone content and prevented the decrease of tissue respiration and termination of pregnancy in rats.

  14. Inhibitory effects of atropine and hexamethonium on the angiotensin II-induced contractions of rat anococcygeus smooth muscles.

    PubMed

    de Godoy, Márcio Augusto Fressatto; Accorsi-Mendonça, Daniela; de Oliveira, Ana Maria

    2003-02-01

    We have evaluated the interaction between angiotensin II (Ang II) and the cholinergic transmission in anococcygeus smooth muscles isolated from rats treated (sympathectomised group) or not (vehicle group) with reserpine and alpha-methyl-p-tyrosine. For this, we contracted the tissues with Ang II in the presence and absence of atropine and hexamethonium. Ang II induced concentration-dependent contractions, which did not undergo temporal changes in tissues isolated from both groups of rats. In the vehicle group, Ang II induced more potent contractions than in the sympathectomised group. In the sympathectomised rat group, atropine inhibited the contractions induced by Ang II in a concentration-dependent fashion with no decrease in E(max). Additionally, hexamethonium inhibited the contraction induced by Ang II in a concentration-dependent fashion with a decrease in E(max). Association of atropine and hexamethonium produced Ang II-induced curves with rightward shifts from the control curve with a decrease in E(max). Incubation with N(G)-nitro-L-arginine methyl ester (L-NAME) reversed the effects of atropine and hexamethonium association. Conversely, in the vehicle group of rats, atropine and hexamethonium did not produce any significant effect. However, in the presence of yohimbine, atropine shifted the Ang II-induced curves to the right of the control curve with no E(max) decrease. Results suggest that there is a positive interaction between Ang II and cholinergic transmission in the rat anococcygeus smooth muscle mediated by angiotensin receptors located on pre-ganglionic cells.

  15. Glutathione regulation of redox-sensitive signals in tumor necrosis factor-{alpha}-induced vascular endothelial dysfunction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tsou, T.-C.; Yeh, S.C.; Tsai, F.-Y.

    2007-06-01

    We investigated the regulatory role of glutathione in tumor necrosis factor-alpha (TNF-{alpha})-induced vascular endothelial dysfunction as evaluated by using vascular endothelial adhesion molecule expression and monocyte-endothelial monolayer binding. Since TNF-{alpha} induces various biological effects on vascular cells, TNF-{alpha} dosage could be a determinant factor directing vascular cells into different biological fates. Based on the adhesion molecule expression patterns responding to different TNF-{alpha} concentrations, we adopted the lower TNF-{alpha} (0.2 ng/ml) to rule out the possible involvement of other TNF-{alpha}-induced biological effects. Inhibition of glutathione synthesis by L-buthionine-(S,R)-sulfoximine (BSO) resulted in down-regulations of the TNF-{alpha}-induced adhesion molecule expression and monocyte-endothelial monolayermore » binding. BSO attenuated the TNF-{alpha}-induced nuclear factor-kappaB (NF-{kappa}B) activation, however, with no detectable effect on AP-1 and its related mitogen-activated protein kinases (MAPKs). Deletion of an AP-1 binding site in intercellular adhesion molecule-1 (ICAM-1) promoter totally abolished its constitutive promoter activity and its responsiveness to TNF-{alpha}. Inhibition of ERK, JNK, or NF-{kappa}B attenuates TNF-{alpha}-induced ICAM-1 promoter activation and monocyte-endothelial monolayer binding. Our study indicates that TNF-{alpha} induces adhesion molecule expression and monocyte-endothelial monolayer binding mainly via activation of NF-{kappa}B in a glutathione-sensitive manner. We also demonstrated that intracellular glutathione does not modulate the activation of MAPKs and/or their downstream AP-1 induced by lower TNF-{alpha}. Although AP-1 activation by the lower TNF-{alpha} was not detected in our systems, we could not rule out the possible involvement of transiently activated MAPKs/AP-1 in the regulation of TNF-{alpha}-induced adhesion molecule expression.« less

  16. Epidemiology of infertility: social problems of the infertile couples.

    PubMed

    Araoye, Margaret O

    2003-06-01

    Infertility is of public health importance in Nigeria and many other developing nations because of its high prevalence and especially due to its serious social implications. A review of the epidemiology of infertility in Nigeria and other parts of Sub-Saharan Africa is presented and socio-cultural issues including the social impact on couples are discussed. The major cause of infertility in Africa is infection--STDs, post-abortal and puerperal sepsis. Beliefs about causes, and failure of orthodox methods of treatment have led many couples to seek solution from traditional doctors and faith healers without success. Infertility causes marital disharmony, which often leads to divorce. Women are often blamed for the infertility and men engage in polygyny in an attempt to have children. The couple can also suffer stress from the management of the infertility. Adoption is not popular and assisted reproduction has medico-legal implications. Preventive measures are suggested, including counselling at every stage of the management.

  17. Differences in cholinergic responses from outer hair cells of rat and guinea pig.

    PubMed

    Chen, C; LeBlanc, C; Bobbin, R P

    1996-09-01

    A cholinergic receptor on outer hair cells (OHC) in guinea pig cochlea induces a K+ current when it is activated by acetylcholine and suberyldicholine but not by nicotine or muscarine (Bobbin, 1995). This unusual receptor may contain an alpha 9-subunit. However, the pharmacology of the alpha 9-subunit cloned from rat and expressed in Xenopus oocytes does not completely match that obtained for the ACh receptor in guinea pig OHCs. The response to 1,1-dimethyl-4-phenylpiperazinium (DMPP) is large in guinea pig OHCs and small in oocytes containing receptors of the alpha 9-subunit. Therefore, we compared the effects of cholinergic receptor agonists in rat and guinea pig OHCs using the whole-cell variant of the patch-clamp technique. ACh caused the largest outward K+ current in OHCs from both rat and guinea pig. Carbachol- and suberyldicholine-induced responses were similar in magnitude in OHCs of rat and guinea pig. However, DMPP produced a small response in OHCs from rat and a large response in OHCs from guinea pig. At a concentration of 100 microM, muscarine, oxotremorine M, nicotine and cytisine induced little response in guinea pig OHCs and none in rat OHCs. Results suggest that the ACh receptor on rat OHCs is similar to the alpha 9-subunit-containing receptor expressed in oocytes but different from the ACh receptor on guinea pig OHCs.

  18. Synthesis of DNA in oestrogen-induced pituitary tumurs in rats: effect of bromocriptine.

    PubMed

    Kalbermann, L E; Machiavelli, G A; De Nicola, A F; Weissenberg, L S; Burdman, J A

    1980-11-01

    Bromocriptine increased the concentration of prolactin in oestrogen-induced tumours of the rat pituitary gland. Prolactinaemia was significantly reduced and at the same time there was a considerable decrease in the weight of the tumour, in the incorporation of tritiated thymidine into DNA and in the activity of DNA polymerase alpha. The results suggested that the intracellular content of prolactin controls cell proliferation in this experimental tumour. A hypothalamic disorder is proposed as the primary cause of these tumours.

  19. On the Mechanism of Serotonin-Induced Dipsogenesis in the Rat

    NASA Technical Reports Server (NTRS)

    Kikta, Dianne C.; Barney, Christopher C.; Threatte, Rose M.; Fregly, Melvin J.; Rowland, Neil E.; Greenleaf, John E.

    1983-01-01

    Subcutaneous administration of 1-5-hydroxytryptophan (5-HTP), the precursor of serotonin, to female rats induces copious drinking accompanied by activation of the renin-angiotensin system. Neither a reduction in blood pressure nor body temperature accompanied administration of 5-HTP. The objective of the present study was to determine whether serotonin-induced dipsogenesis, like that of 5-HTP, is mediated via the renin-angiotensin system. Serotonin (2 mg/kg, SC)-induced drinking was inhibited by the dopaminergic antagonist, haloperidol (150 /micro g/kg, IP), which also inhibits angiotensin II-induced drinking, Both captopril (35 mg/kg, IP), an angiotensin converting enzyme inhibitor, and propranolol (6 micro g/kg, IP), a beta-adrenergic antagonist, blocked serotonin-induced dipsogenesis. The alpha(sub a),-adrenergic agonist, clonidine (6.25 micro g/kg, SC), which suppresses renin release from the kidney, attenuated serotonin-induced water intake. The dipsogenic responses to submaximal concentrations of both serotonin (1 mg/kg, SC) and isoproterenol (8 micro g/kg, SC) were additive rather than interactive suggesting that similar pathways mediate both responses. The serotonergic receptor antagonist, methysergide (3 mg/kg, IP), inhibited serotonin-induced drinking but had no effect on isoproterenol (25micro g/kg, SC)-induced dipsogenesis. However, neither serotonin (2 mg/kg, SC) nor isoproterenol (25 micro g/kg, SC)-induced drinking was inhibited by cinansefin (25 micro g/kg, IP). These data indicate that serotonin induces drinking in rats via the renin-angiotensin system. However, the results of the studies using methysergide suggest that scrotonin appears to act at a point prior to activation of beta-adrenoceptors in the pathway leading to release of renin from the kidneys.

  20. Interleukin-10 to tumor necrosis factor-alpha ratio is a predictive biomarker in nonalcoholic fatty liver disease: interleukin-10 to tumor necrosis factor-alpha ratio in steatohepatitis.

    PubMed

    Hashem, Reem M; Mahmoud, Mona F; El-Moselhy, Mohamed A; Soliman, Hala M

    2008-10-01

    Fatty liver disease is commonly associated with diabetes mellitus (DM). Insulin resistance (IR) as an investigative biomarker is only concerned with fatty liver that results from DM type 2 associated with metabolic syndrome. Irrespective of IR, DM is generally characterized by overproduction of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), whereas action of the latter is modulated by the anti-inflammatory cytokine interleukin-10 (IL-10). The aim of this study was to investigate the efficacy of using TNF-alpha alone or IL-10/TNF-alpha ratio compared to IR, as a promising biomarker for fatty liver assessment in DM. Furthermore, we hypothesized that using garlic as an immunomodulator may decrease TNF-alpha and increase IL-10 production to improve steatohepatitis. DM was induced metabolically by a high-fat diet to bring about IR, or chemically by alloxan, producing insulin deficiency, in male albino rats. Garlic powder was supplemented (15 mg/kg per day) for 3 weeks. Fatty liver was depicted histologically and biochemically (aspartic aminotransferase, alanine aminotransferase, HOMA-IR, TNF-alpha, IL-10, IL-10/TNF-alpha ratio). We found that, in contrast to obese rats, garlic decreased IL-10/TNF-alpha ratio, despite decreasing TNF-alpha in alloxan diabetic rats in agreement with the histology, which revealed more prominent improvement in the obese group. Moreover, the effect of garlic was not linked to improvement of IR in obese rats. We conclude that IL-10/TNF-alpha ratio may be considered as a convenient biomarker for investigation of fatty liver of different grades, apart from being associated with IR, and immunomodulation of this ratio in favor of increasing it may exert significant improvement.

  1. Selective blockade by nicergoline of vascular responses elicited by stimulation of alpha 1A-adrenoceptor subtype in the rat.

    PubMed

    Alvarez-Guerra, M; Bertholom, N; Garay, R P

    1999-01-01

    The alpha 1-adrenergic blocking activity of nicergoline was re-examined in rats, with a particular emphasis on alpha 1-adrenoceptor subtypes. In pithed rats, nicergoline and prazosin infused at a single small dose (0.5 microgram/kg/min i.v.) produced a substantial and identical shift to the right of the control dose pressor response curve to the specific alpha 1-agonist cirazoline (ED50 = 4.0 +/- 0.1, 4.0 +/- 0.1 and 0.9 +/- 0.01 microgram/kg i.v. for nicergoline, prazosin and vehicle respectively). In the isolated perfused mesenteric vascular bed, nicergoline strongly inhibited the pressor responses elicited by cirazoline, with approximately 40-fold higher potency (pA2 = 11.1 +/- 0.3) than prazosin (pA2 = 9.5 +/- 0.3). Conversely, nicergoline was 20-fold less potent than prazosin to antagonize the contractile effects of cirazoline in isolated endothelium-denuded aorta (pA2 = 8.6 +/- 0.2 and 9.9 +/- 0.2 for nicergoline and prazosin respectively). Pretreatment of mesenteric vascular beds with chloroethylclonidine did not significantly modify nicergoline antagonistic potency (pA2 = 10.6 +/- 0.2). Nicergoline displaced [3H]-prazosin bound to rat forebrain membranes pretreated with chloroethylclonidine (pKi = 9.9 +/- 0.2) at concentrations 60-fold lower than in rat liver membranes (pKi = 8.1 +/- 0.2). Finally, of the nicergoline metabolites studied, lumilysergol acted as a modest alpha 1 antagonist (bromonicotinic acid was devoid of alpha 1 antagonist activity). In conclusion, nicergoline is a potent and selective alpha 1A-adrenoceptor subtype antagonist, an alpha 1-adrenoceptor subtype which is mainly represented in resistance arteries.

  2. Acute effects of pentobarbital, thiopental and urethane on lung oedema induced by alpha-naphthythiourea (ANTU).

    PubMed

    Sipahi, Emine; Ustün, Hüseyin; Niyazi Ayoglu, Ferruh

    2002-03-01

    This study was designed to investigate the possible participation of urethane, pentobarbital sodium and thiopental sodium anaesthesia in the lung oedema induced by alpha-naphthylthiourea (ANTU), which is a well known noxious chemical agent in the lung. ANTU when injected intraperitoneally (i.p.) into rats (10 mg x kg (-1) i.p.) produced lung oedema as indicated by an increase in lung weight/body weight (LW/BW) ratio and pleural effusion (PE) reaching a maximum within 4 h. Administration of urethane prior to ANTU, at doses of 100 and 200mg(100g)(-1), elicited a significant and dose-dependent inhibition in LW/BW ratio and PE. Thiopental sodium at doses of 25, 50 mg x kg (-1), also produced a significant and dose-dependent inhibition of both parameters. Prior i.p. injection of pentobarbital sodium at a dose of 40 mg x kg (-1) elicited a significant inhibition in both parameters. These results suggest that i.p. urethane, thiopental sodium and pentobarbital sodium pretreatment have a prophylactic effect on ANTU-induced lung injury in rats. The possible role of the anaesthetics in lung oedema induced by ANTU and the possible underlying mechanisms are discussed. Copyright 2002 Elsevier Science Ltd.

  3. Reishi mushroom Ganoderma lucidum Modulates IgA production and alpha-defensin expression in the rat small intestine.

    PubMed

    Kubota, Atsuhito; Kobayashi, Masaki; Sarashina, Sota; Takeno, Reiko; Okamoto, Keisuke; Narumi, Katsuya; Furugen, Ayako; Suzuki, Yuji; Takahashi, Natsuko; Iseki, Ken

    2018-03-25

    Immunoglobulin A (IgA) secretion and alpha-defensins play a role in the innate immune system to protect against infection. Ganoderma lucidum (W.Curt.: Fr.) P. Karst. (Reishi) is a well-known mushroom in traditional Chinese medicine. This study aimed to determine the effects of Reishi on IgA secretion from Peyer's patch (PP) cells and alpha-defensin-5 (RD-5) and RD-6 expression in the rat small intestine. The rats received an oral injection of 0.5-5mg/kg of Reishi powder (1mL/kg) by sonde. All animals were euthanized 24h after Reishi administration. We examined RD-5, RD-6, and Toll-like receptor (TLR) 4 mRNA levels in the jejunum, ileum, and in Peyer's patches (PP) through quantitative real-time PCR analysis. IgA secretion from PP was measured through enzyme-linked immunosorbent assay of the supernatant after primary culture. Reishi increased IgA secretion in the presence of lipopolysaccharide (LPS) and increased TLR4 mRNA levels, but had no effect on the viability of PP cells. Moreover, Reishi increased RD-5, RD-6, and TLR4 mRNA levels significantly in the ileum in a concentration-dependent manner. Reishi can induce IgA secretion and increase the mRNA levels of RD-5 and RD-6 in the rat small intestine, through a TLR4-dependent pathway. The present results indicate that Reishi might reduce the risk of intestinal infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Lipoic acid suppresses portal endotoxemia-induced steatohepatitis and pancreatic inflammation in rats

    PubMed Central

    Tian, Yu-Feng; He, Chih-Tsueng; Chen, Yu-Ting; Hsieh, Po-Shiuan

    2013-01-01

    AIM: To examine the effect of α-lipoic acid (LA) on mild portal endotoxemia-induced steatohepatitis and associated pancreatic abnormalities in fructose-fed rats. METHODS: Rats were randomly assigned into two groups with a regular or 60% fructose-enriched diet for 8 wk. After fructose feeding for 4 wk, rats were further divided into four subgroups: with intraportal saline (FPV), with intraportal saline plus administration of LA (FPV + LA), with lipopolysaccharide (LPS) infusion (FPLPS), and with LPS infusion plus administration of LA (FPLPS + LA). Rats were treated with LPS using intraportal infusion while LA was administered orally. Metabolite levels, superoxide levels, inflammatory markers, malondialdehyde content, glutathione content and toll-like receptor 4 (TLR4) gene expression were all measured using standard biochemical techniques. Pancreatic insulin secretion was evaluated by a hyperglycemic clamp technique. Histology of liver and pancreas tissues were evaluated using hematoxylin and eosin staining and immunohistochemistry. RESULTS: Fructose-induced elevation in plasma C-reactive protein, amylase, superoxide, white blood cell count as well as in hepatic and pancreatic contents of malondialdehyde, tumor necrosis factor alpha and interleukin-6 were increased in animals treated with LPS and reversed with LA administration. The augmented hepatic gene expression of TLR4 in fructose-fed rats was further increased in those with intraportal LPS infusion, which was partially reversed by LA administration. Pathological examination showed inflammatory changes and leukocyte infiltration in hepatic and pancreatic islets of animals treated with LPS but were rarely observed in those with LA treatment. In addition to affects on the liver, impaired pancreatic insulin secretion seen in fructose-fed rats was deteriorated in with LPS treatment and partially reversed with LA administration. CONCLUSION: These data suggest LA could significantly suppress mild portal

  5. Mechanism of alpha-lipoic acid in attenuating kanamycin-induced ototoxicity☆

    PubMed Central

    Wang, Aimei; Hou, Ning; Bao, Dongyan; Liu, Shuangyue; Xu, Tao

    2012-01-01

    In view of the theory that alpha-lipoic acid effectively prevents cochlear cells from injury caused by various factors such as cisplatin and noise, this study examined whether alpha-lipoic acid can prevent kanamycin-induced ototoxicity. To this end, healthy BALB/c mice were injected subcutaneously with alpha-lipoic acid and kanamycin for 14 days. Auditory brainstem response test showed that increased auditory brainstem response threshold shifts caused by kanamycin were significantly inhibited. Immunohistochemical staining and western blot analysis showed that the expression of phosphorylated p38 mitogen-activated protein kinase and phosphorylated c-Jun N-terminal kinase in mouse cochlea was significantly decreased. The experimental findings suggest that phosphorylated p38 and phosphorylated c-Jun N-terminal kinase mediated kanamycin-induced ototoxic injury in BALB/c mice. Alpha-lipoic acid effectively attenuated kanamycin ototoxicity by inhibiting the kanamycin-induced high expression of phosphorylated p38 and phosphorylated c-Jun N-terminal kinase. PMID:25317129

  6. Catabolism of 6-ketoprostaglandin F1alpha by the rat kidney cortex.

    PubMed

    Pace-Asciak, C R; Domazet, Z; Carrara, M

    1977-05-25

    Homogenates of the rat kidney cortex converted 5,8,9,11,12,14,15-hepta-tritiated 6-ketoprostaglandin F 1alpha into one major product identified by gas chromatography-mass spectrometry of the methoxime-methyl ester trimethylsilyl ether derivative as 6,15-diketo-9,11-dihydroxyprost-13-enoic acid. The sequence of derivatisation i.e. methoximation prior to methylation, was crucial as methylation of 15-keto catabolites of the E, F and 6-keto-F series affords degradation products. The corresponding 15-keto-13,14-dihydro catabolite was formed in much smaller quantities. Time course studies indicated that 6-keto-prostaglandin F1alpha was catabolised at a slower rate (about 2-5 fold) than prostaglandin F1alpha. The catabolic activity was blocked by NADH.

  7. Stress and Infertility

    MedlinePlus

    ... Home FAQs Frequently Asked Questions Quick Facts About Infertility FAQs About Infertility FAQs About the Psychological Component of Infertility FAQs About Cloning and Stem Cell Research SART's ...

  8. Smoking and Infertility

    MedlinePlus

    ... Home FAQs Frequently Asked Questions Quick Facts About Infertility FAQs About Infertility FAQs About the Psychological Component of Infertility FAQs About Cloning and Stem Cell Research SART's ...

  9. The contributions of adrenal hormones, hemodynamic factors, and the endotoxin-related stress reaction to stable prostaglandin analog-induced peripheral lymphopenia and neutrophilia.

    PubMed

    Ulich, T R; Keys, M; Ni, R X; del Castillo, J; Dakay, E B

    1988-01-01

    Stable prostaglandin analogs are known to induce lymphopenia and neutrophilia in a dose-dependent fashion after subcutaneous injection in rats. The purpose of the present investigation is to determine whether the prostaglandin-induced changes in circulating leukocytes might be secondary to hypotension with the ensuing release of adrenal hormones. The adrenal medullary catecholamine epinephrine was found to induce neutrophilia in both intact and adrenalectomized rats, and the glucocorticosteroid analog dexamethasone induced a profound lymphopenia in rats as reported by previous investigators. A stable analog of PGF2 alpha (15-S-15-methyl PGF2 alpha; M-PGF2 alpha) at the dose of 1 mg/kg induced marked systemic hypotension 1 h after injection, with lymphopenia and neutrophilia 6 h after injection. The non-prostanoid hypotensive agent captopril, at a dose of 63 mg/kg, induced a hypotension of similar magnitude and kinetics to that induced by prostaglandin. Captopril also induced lymphopenia and neutrophilia at 6 h, although the neutrophilia was of lesser magnitude than that induced by prostaglandins. The prostaglandin-induced lymphopenia was found to be mediated, at least in part, by the hypotension-induced release of adrenal hormones, as evidenced by the abrogation of lymphopenia in prostaglandin-treated adrenalectomized rats. Captopril-treated adrenalectomized rats, however, did develop a significant lymphopenia, suggesting that hypotension can result in lymphopenia even in adrenalectomized rats. The M-PGF2 alpha-induced neutrophilia in adrenalectomized rats, by comparison to captopril-induced neutrophilia in adrenalectomized rats, was greater than the neutrophilia expected as the result of hypotension alone. Indeed, the M-PGF2 alpha-induced neutrophilia in adrenalectomized rats was greater than the captopril-induced neutrophilia in sham-adrenalectomized rats. Thus, a portion of the neutrophilia induced by M-PGF2 alpha in intact rats may be mediated through adrenal

  10. Human parasitic protozoan infection to infertility: a systematic review.

    PubMed

    Shiadeh, Malihe Nourollahpour; Niyyati, Maryam; Fallahi, Shirzad; Rostami, Ali

    2016-02-01

    Protozoan parasitic diseases are endemic in many countries worldwide, especially in developing countries, where infertility is a major burden. It has been reported that such infections may cause infertility through impairment in male and female reproductive systems. We searched Medline, PubMed, and Scopus databases and Google scholar to identify the potentially relevant studies on protozoan parasitic infections and their implications in human and animal model infertility. Literature described that some of the protozoan parasites such as Trichomonas vaginalis may cause deformities of the genital tract, cervical neoplasia, and tubal and atypical pelvic inflammations in women and also non-gonoccocal urethritis, asthenozoospermia, and teratozoospermia in men. Toxopalasma gondii could cause endometritis, impaired folliculogenesis, ovarian and uterine atrophy, adrenal hypertrophy, vasculitis, and cessation of estrus cycling in female and also decrease in semen quality, concentration, and motility in male. Trypanosoma cruzi inhibits cell division in embryos and impairs normal implantation and development of placenta. Decrease in gestation rate, infection of hormone-producing glands, parasite invasion of the placenta, and overproduction of inflammatory cytokines in the oviducts and uterine horns are other possible mechanisms induced by Trypanosoma cruzi to infertility. Plasmodium spp. and Trypanosoma brucei spp. cause damage in pituitary gland, hormonal disorders, and decreased semen quality. Entamoeba histolytica infection leads to pelvic pain, salpingitis, tubo-ovarian abscess, and genital ulcers. Cutaneous and visceral leishmaniasis can induce genital lesion, testicular amyloidosis, inflammation of epididymis, prostatitis, and sperm abnormality in human and animals. In addition, some epidemiological studies have reported that rates of protozoan infections in infertile patients are higher than healthy controls. The current review indicates that protozoan parasitic

  11. Cloning, expression, and mapping of allergenic determinants of alphaS1-casein, a major cow's milk allergen.

    PubMed

    Schulmeister, Ulrike; Hochwallner, Heidrun; Swoboda, Ines; Focke-Tejkl, Margarete; Geller, Beate; Nystrand, Mats; Härlin, Annika; Thalhamer, Josef; Scheiblhofer, Sandra; Keller, Walter; Niggemann, Bodo; Quirce, Santiago; Ebner, Christoph; Mari, Adriano; Pauli, Gabrielle; Herz, Udo; Valenta, Rudolf; Spitzauer, Susanne

    2009-06-01

    Milk is one of the first components introduced into human diet. It also represents one of the first allergen sources, which induces IgE-mediated allergies in childhood ranging from gastrointestinal, skin, and respiratory manifestations to severe life-threatening manifestations, such as anaphylaxis. Here we isolated a cDNA coding for a major cow's milk allergen, alphaS1-casein, from a bovine mammary gland cDNA library with allergic patients' IgE Abs. Recombinant alphaS1-casein was expressed in Escherichia coli, purified, and characterized by circular dichroism as a folded protein. IgE epitopes of alphaS1-casein were determined with recombinant fragments and synthetic peptides spanning the alphaS1-casein sequence using microarrayed components and sera from 66 cow's milk-sensitized patients. The allergenic activity of ralphaS1-casein and the alphaS1-casein-derived peptides was determined using rat basophil leukemia cells transfected with human FcepsilonRI, which had been loaded with the patients' serum IgE. Our results demonstrate that ralphaS1-casein as well as alphaS1-casein-derived peptides exhibit IgE reactivity, but mainly the intact ralphaS1-casein induced strong basophil degranulation. These results suggest that primarily intact alphaS1-casein or larger IgE-reactive portions thereof are responsible for IgE-mediated symptoms of food allergy. Recombinant alphaS1-casein as well as alphaS1-casein-derived peptides may be used in clinical studies to further explore pathomechanisms of food allergy as well as for the development of new diagnostic and therapeutic strategies for milk allergy.

  12. Decreased enzyme activity and contents of hepatic branched-chain alpha-keto acid dehydrogenase complex subunits in a rat model for type 2 diabetes mellitus.

    PubMed

    Bajotto, Gustavo; Murakami, Taro; Nagasaki, Masaru; Sato, Yuzo; Shimomura, Yoshiharu

    2009-10-01

    The mitochondrial branched-chain alpha-keto acid dehydrogenase complex (BCKDC) is responsible for the committed step in branched-chain amino acid catabolism. In the present study, we examined BCKDC regulation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats both before (8 weeks of age) and after (25 weeks of age) the onset of type 2 diabetes mellitus. Long-Evans Tokushima Otsuka (LETO) rats were used as controls. Plasma branched-chain amino acid and branched-chain alpha-keto acid concentrations were significantly increased in young and middle-aged OLETF rats. Although the hepatic complex was nearly 100% active in all animals, total BCKDC activity and protein abundance of E1alpha, E1beta, and E2 subunits were markedly lower in OLETF than in LETO rats at 8 and 25 weeks of age. In addition, hepatic BCKDC activity and protein amounts were significantly decreased in LETO rats aged 25 weeks than in LETO rats aged 8 weeks. In skeletal muscle, E1beta and E2 proteins were significantly reduced, whereas E1alpha tended to increase in OLETF rats. Taken together, these results suggest that (1) whole-body branched-chain alpha-keto acid oxidation capacity is extremely reduced in OLETF rats independently of diabetes development, (2) the aging process decreases BCKDC activity and protein abundance in the liver of normal rats, and (3) differential posttranscriptional regulation for the subunits of BCKDC may exist in skeletal muscle.

  13. Salacia oblonga root improves postprandial hyperlipidemia and hepatic steatosis in Zucker diabetic fatty rats: Activation of PPAR-{alpha}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hsun-Wei Huang, Tom; Peng Gang; Qian Li, George

    Salacia oblonga (SO) root is an Ayurvedic medicine with anti-diabetic and anti-obese properties. Peroxisome proliferator-activated receptor (PPAR)-{alpha}, a nuclear receptor, plays an important role in maintaining the homeostasis of lipid metabolism. Here, we demonstrate that chronic oral administration of the water extract from the root of SO to Zucker diabetic fatty (ZDF) rats, a genetic model of type 2 diabetes and obesity, lowered plasma triglyceride and total cholesterol (TC) levels, increased plasma high-density lipoprotein levels and reduced the liver contents of triglyceride, non-esterified fatty acids (NEFA) and the ratio of fatty droplets to total tissue. By contrast, the extract hadmore » no effect on plasma triglyceride and TC levels in fasted ZDF rats. After olive oil administration to ZDF the extract also inhibited the increase in plasma triglyceride levels. These results suggest that SO extract improves postprandial hyperlipidemia and hepatic steatosis in ZDF rats. Additionally, SO treatment enhanced hepatic expression of PPAR-{alpha} mRNA and protein, and carnitine palmitoyltransferase-1 and acyl-CoA oxidase mRNAs in ZDF rats. In vitro, SO extract and its main component mangiferin activated PPAR-{alpha} luciferase activity in human embryonic kidney 293 cells and lipoprotein lipase mRNA expression and enzyme activity in THP-1 differentiated macrophages; these effects were completely suppressed by a selective PPAR-{alpha} antagonist MK-886. The findings from both in vivo and in vitro suggest that SO extract functions as a PPAR-{alpha} activator, providing a potential mechanism for improvement of postprandial hyperlipidemia and hepatic steatosis in diabetes and obesity.« less

  14. Neurotransmitter alteration in a testosterone propionate-induced polycystic ovarian syndrome rat model.

    PubMed

    Chaudhari, Nirja K; Nampoothiri, Laxmipriya P

    2017-02-01

    Polycystic ovarian syndrome (PCOS), one of the leading causes of infertility seen in women, is characterized by anovulation and hyperandrogenism, resulting in ovarian dysfunction. In addition, associations of several metabolic complications like insulin resistance, obesity, dyslipidemia and psychological co-morbidities are well known in PCOS. One of the major factors influencing mood and the emotional state of mind is neurotransmitters. Also, these neurotransmitters are very crucial for GnRH release. Hence, the current study investigates the status of neurotransmitters in PCOS. A PCOS rat model was developed using testosterone. Twenty-one-day-old rats were subcutaneously injected with 10 mg/kg body weight of testosterone propionate (TP) for 35 days. The animals were validated for PCOS characteristics by monitoring estrus cyclicity, serum testosterone and estradiol levels and by histological examination of ovarian sections. Neurotransmitter estimation was carried out using fluorometric and spectrophotometric methods. TP-treated animals demonstrated increased serum testosterone levels with unaltered estradiol content, disturbed estrus cyclicity and many peripheral cysts in the ovary compared to control rats mimicking human PCOS. Norepinephrine (NE), dopamine, serotonin, γ-amino butyric acid (GABA) and epinephrine levels were significantly low in TP-induced PCOS rats compared to control ones, whereas the activity of acetylcholinesterase in the PCOS brain was markedly elevated. Neurotransmitter alteration could be one of the reasons for disturbed gonadotropin-releasing hormone (GnRH) release, consequently directing the ovarian dysfunction in PCOS. Also, decrease in neurotransmitters, mainly NE, serotonin and dopamine (DA) attributes to mood disorders like depression and anxiety in PCOS.

  15. Effect of chromium niacinate and chromium picolinate supplementation on lipid peroxidation, TNF-alpha, IL-6, CRP, glycated hemoglobin, triglycerides, and cholesterol levels in blood of streptozotocin-treated diabetic rats.

    PubMed

    Jain, Sushil K; Rains, Justin L; Croad, Jennifer L

    2007-10-15

    Chromium (Cr(3+)) supplementation facilitates normal protein, fat, and carbohydrate metabolism, and is widely used by the public in many countries. This study examined the effect of chromium niacinate (Cr-N) or chromium picolinate (Cr-P) supplementation on lipid peroxidation (LP), TNF-alpha, IL-6, C-reactive protein (CRP), glycosylated hemoglobin (HbA(1)), cholesterol, and triglycerides (TG) in diabetic rats. Diabetes (D) was induced in Sprague-Dawley rats by streptozotocin (STZ) (ip, 65 mg/kg BW). Control buffer, Cr-N, or Cr-P (400 microg Cr/kg BW) was administered by gavages daily for 7 weeks. Blood was collected by heart puncture using light anesthesia. Diabetes caused a significant increase in blood levels of TNF-alpha, IL-6, glucose, HbA(1), cholesterol, TG, and LP. Compared with D, Cr-N supplementation lowered the blood levels of TNF-alpha (P=0.04), IL-6 (P=0.02), CRP (P=0.02), LP (P=0.01), HbA(1) (P=0.02), TG (P=0.04), and cholesterol (P=0.04). Compared with D, Cr-P supplementation showed a decrease in TNF-alpha (P=0.02), IL-6 (P=0.02), and LP (P=0.01). Chromium niacinate lowers blood levels of proinflammatory cytokines (TNF-alpha, IL-6, CRP), oxidative stress, and lipids levels in diabetic rats, and appears to be a more effective form of Cr(3+) supplementation. This study suggests that Cr(3+) supplementation can lower the risk of vascular inflammation in diabetes.

  16. Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Valstar, Dingena L.; Schijf, Marcel A.; Nijkamp, Frans P.

    2006-02-15

    Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs.more » On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did not affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-{alpha} levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later.« less

  17. alpha(2)-adrenoceptor antagonist properties of OPC-28326, a novel selective peripheral vasodilator.

    PubMed

    Orito, K; Kishi, M; Imaizumi, T; Nakazawa, T; Hashimoto, A; Mori, T; Kambe, T

    2001-10-01

    1. Antagonistic properties of OPC-28326 ([4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl)] piperidine hydrochloride monohydrate), a selective peripheral vasodilator, were investigated by analysing the data from functional studies in various tissues from the rat and binding studies of the drug to alpha(2)-adrenoceptor subtypes. 2. Using a human recombinant receptor and rat kidney cortex, we found that OPC-28326 displays affinities to alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptors with K(i) values of 2040, 285, and 55 nM, respectively. The K(i) values of yohimbine for alpha(2A)-, alpha(2B)-, and alpha(2C)-adrenoceptors were 3.0, 2.0 and 11.0 nM, respectively. 3. B-HT 920, an alpha(2)-adrenoceptor agonist, produced a pressor response via peripheral postsynaptic alpha(2)-adrenoceptor stimulation (thought to be an alpha(2B)-subtype) in a reserpine-pretreated pithed rat preparation. OPC-28326 (3 - 30 mg kg(-1), i.v.) and yohimbine (0.3 - 3 mg kg(-1), i.v.) caused dose-dependent rightward shift in the pressor dose-response curve induced by B-HT 920. The apparent pA(2) values were 1.55 (0.87 - 2.75, 95% confidence interval) and 0.11 (0.06 - 0.21) mg kg(-1), respectively. The potency of OPC-28326 was about 14 times less than that of yohimbine. 4. Clonidine inhibited the tension developed by electrical stimulation, of the rat vas deferens, by its peripheral presynaptic alpha(2A/D)-adrenoceptor action. OPC-28326 (1 - 100 microM) and yohimbine (10 - 1000 nM) caused a rightward shift in the concentration-response curve of clonidine. The pA(2) values were 5.73 (5.54 - 5.91) and 7.92 (7.84 - 8.01), respectively, providing evidence for a potency of OPC-28326 of about 155 times less than that of yohimbine. 5. Mydriasis was induced by brimonidine via stimulation of central alpha(2A/D)-adrenoceptors in anaesthetized rats. Intravenous OPC-28326 had no effect on this action, even at a very high dose of 10 mg kg(-1) i.v., while yohimbine (0.1 - 0.3 mg kg(-1

  18. Inhibitory effects of clotrimazole on TNF-alpha-induced adhesion molecule expression and angiogenesis.

    PubMed

    Thapa, Dinesh; Lee, Jong Suk; Park, Min-A; Cho, Mi-Yeon; Park, Young-Joon; Choi, Han Gon; Jeong, Tae Cheon; Kim, Jung-Ae

    2009-04-01

    Cell adhesion molecules play a pivotal role in chronic inflammation and pathological angiogenesis. In the present study, we investigated the inhibitory effects of clotrimazole (CLT) on tumor necrosis factor (TNF)-alpha-induced changes in adhesion molecule expression. CLT dose-dependently inhibited monocyte chemoattractant protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) expressions in TNF-alpha-stimulated HT29 colonic epithelial cells. This inhibitory action of CLT correlated with a significant reduction in TNF-alpha-induced adhesion of monocytes to HT29 cells, which was comparable to the inhibitory effects of anti-ICAM-1 and VCAM-1 monoclonal antibodies on monocyte-epithelial adhesion. These inhibitory actions of CLT were, at least in part, attributable to the inhibition of redox sensitive NF-kappaB activation, as CLT inhibited TNF-alpha-induced ROS generation as well as NF-kappaB nuclear translocation and activation in HT29 cells. Furthermore, the inhibition of TNF-alpha-induced monocyte adhesion was also mimicked by the specific NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC). Inflammatory mediators including TNF-alpha have known to promote angiogenesis, which in turn further contributes to inflammatory pathology. Therefore, we additionally evaluated whether CLT modulates TNF-alpha-induced angiogenesis using in vivo chick chorioallantoic membrane (CAM) assay. The CAM assay showed that CLT dose-dependently attenuated TNF-alpha-induced angiogenesis, and the effect was correlated with decreased inflammation of the CAM tissue. In conclusion, our results suggest that CLT can inhibit TNF-alpha-triggered expression of adhesion molecules, ICAM-1 and VCAM-1, and angiogenesis during inflammation.

  19. Differential regulation of the cell cycle by alpha1-adrenergic receptor subtypes.

    PubMed

    Gonzalez-Cabrera, Pedro J; Shi, Ting; Yun, June; McCune, Dan F; Rorabaugh, Boyd R; Perez, Dianne M

    2004-11-01

    Alpha(1)-Adrenergic receptors have been implicated in growth-promoting pathways. A microarray study of individual alpha(1)-adrenergic receptor subtypes (alpha(1A), alpha(1B), and alpha(1D)) expressed in Rat-1 fibroblasts revealed that epinephrine altered the transcription of several cell cycle regulatory genes in a direction consistent with the alpha(1A)- and alpha(1D)-adrenergic receptors mediating G(1)-S cell cycle arrest and the alpha(1B-)mediating cell-cycle progression. A time course indicated that in alpha(1A) cells, epinephrine stimulated a G(1)-S arrest, which began after 8 h of stimulation and maximized at 16 h, at which point was completely blocked with cycloheximide. The alpha(1B)-adrenergic receptor profile also showed unchecked cell cycle progression, even under low serum conditions and induced foci formation. The G(1)-S arrest induced by alpha(1A)- and alpha(1D)-adrenergic receptors was associated with decreased cyclin-dependent kinase-6 and cyclin E-associated kinase activities and increased expression of the cyclin-dependent kinase inhibitor p27(Kip1), all of which were blocked by prazosin. There were no differences in kinase activities and/or expression of p27(Kip1) in epinephrine alpha(1B)-AR fibroblasts, although the microarray did indicate differences in p27(Kip1) RNA levels. Cell counts proved the antimitotic effect of epinephrine in alpha(1A) and alpha(1D) cells and indicated that alpha(1B)-adrenergic receptor subtype expression was sufficient to cause proliferation of Rat-1 fibroblasts independent of agonist stimulation. Analysis in transfected PC12 cells also confirmed the alpha(1A)- and alpha(1B)-adrenergic receptor effect. The alpha(1B)-subtype native to DDT1-MF2 cells, a smooth muscle cell line, caused progression of the cell cycle. These results indicate that the alpha(1A)- and alpha(1D)-adrenergic receptors mediate G(1)-S cell-cycle arrest, whereas alpha(1B)-adrenergic receptor expression causes a cell cycle progression and may induce

  20. Dopamine-regulated adrenocorticotropic hormone secretion in lactating rats: functional plasticity of melanotropes.

    PubMed

    Oláh, Márk; Fehér, Pálma; Ihm, Zsófia; Bácskay, Ildikó; Kiss, Timea; Freeman, Marc E; Nagy, Gyorgy M; Vecsernyés, Miklós

    2009-01-01

    Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and beta-lipotropin in corticotropes of the anterior lobe, and to alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D(2) type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence alpha-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E(2))-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in alpha-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by alpha-methyl-p-tyrosine (alphaMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma alpha-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E(2) animals. In lactating mothers, BRC was able to block ACTH responses induced by both alphaMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is

  1. The organic solute transporters alpha and beta are induced by hypoxia in human hepatocytes

    PubMed Central

    Schaffner, Carlos A; Mwinyi, Jessica; Gai, Zhibo; Thasler, Wolfgang E; Eloranta, Jyrki J; Kullak-Ublick, Gerd A

    2015-01-01

    Background & Aims The organic solute transporters alpha and beta (OSTα-OSTβ) form a heterodimeric transporter located at the basolateral membrane of intestinal epithelial cells and hepatocytes. Liver injury caused by ischaemia-reperfusion, cancer, inflammation or cholestasis can induce a state of hypoxia in hepatocytes. Here, we studied the effect of hypoxia on the expression of OSTα-OSTβ. Methods OSTα-OSTβ expression was measured in Huh7 cells and primary human hepatocytes (PHH) exposed to chenodeoxycholic acid (CDCA), hypoxia or both. OSTα-OSTβ promoter activity was analysed in luciferase reporter gene assays. Binding of hypoxia-inducible factor-1 alpha (HIF-1α) to the OSTα-OSTβ gene promoters was studied in electrophoretic mobility shift assays (EMSA). Results Expression of OSTα and OSTβ increased in PHH under conditions of hypoxia. Exposure of Huh7 cells or PHH to CDCA (50 μM) enhanced the effect of hypoxia on OSTα mRNA levels. In luciferase assays and EMSA, the inducing effect of low oxygen could be assigned to HIF-1α, which binds to hypoxia responsive elements (HRE) in the OSTα and OSTβ gene promoters. Site-directed mutagenesis of either the predicted HRE or the bile acid responsive FXR binding site abolished inducibility of the OSTα promoter, indicating that both elements need to be intact for induction by hypoxia and CDCA. In a rat model of chronic renal failure, the known increase in hepatic OSTα expression was associated with an increase in HIF-1α protein levels. Conclusion OSTα-OSTβ expression is induced by hypoxia. FXR and HIF-1α bind in close proximity to the OSTα gene promoter and produce synergistic effects on OSTα expression. PMID:24703425

  2. Difference in luteal and placental P450(17) alpha: substrate preference and hormonal regulation in the rat.

    PubMed

    Eckstein, B; Khan, I; Gibori, G

    1987-12-01

    The purpose of this study was to assess the substrate specificity of P450(17) alpha in both the corpus luteum and placenta of pregnant rats, and to analyse the site at which LH/human chorionic gonadotrophin (hCG) regulates the activities of this enzyme. To distinguish the substrate preference, placentas and corpora lutea were obtained from rats on day 15 of pregnancy. Tissues were homogenized and the 10,000 g supernatants incubated in the presence of equimolar concentrations of [14C]progesterone and [3H]17 alpha-hydroxyprogesterone as substrate with either NADH or NADPH as cofactors for 2, 8, 16 and 24 min. The labelling pattern of both 17 alpha-hydroxyprogesterone and testosterone indicated that the corpus luteum produced testosterone preferentially from progesterone, whereas the placenta principally used 17 alpha-hydroxyprogesterone and synthesized six times as much testosterone from 17 alpha-hydroxyprogesterone than from progesterone. Addition of either NADPH or NADH as cofactors had no effect on substrate preference. The products of the two enzymatic activities were identified by recrystallization to constant 14C/3H ratios. The ratio of 14C/3H in testosterone produced by the corpus luteum was 16-fold higher than in that produced by the placenta. To explore which of the two activities of P450(17) alpha is regulated by the gonadotrophin, rats were treated with either 1.5 IU hCG or vehicle between days 13 and 15 of pregnancy. Hydroxylase and lyase activities were determined on day 15 after incubation for 2, 8, 16 or 24 min in the presence of either NADH or NADPH. Administration of hCG significantly inhibited NADH-dependent 17 alpha-hydroxylase in the placenta at each time-point studied.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Low-level laser therapy (LLLT) attenuates RhoA mRNA expression in the rat bronchi smooth muscle exposed to tumor necrosis factor-alpha.

    PubMed

    de Lima, Flávia Mafra; Bjordal, Jan M; Albertini, Regiane; Santos, Fábio V; Aimbire, Flavio

    2010-09-01

    Low-level laser therapy (LLLT) has been found to produce anti-inflammatory effects in a variety of disorders. Bronchial smooth muscle (BSM) hyperreactivity is associated with increased Ca+2 sensitivity and increased RhoA mRNA expression. In the current study, we investigated if LLLT could reduce BSM contraction force and RhoA mRNA expression in tumor necrosis factor-alpha (TNF-alpha)-induced BSM hyperreactivity. In the study, 112 male Wistar rats were divided randomly into 16 groups, and BSM was harvested and suspended in TNF-alpha baths for 6 and 24 h, respectively. Irradiation with LLLT was performed with a wavelength of 660 nm for 42 s with a dose of 1.3 J/cm2. This LLLT dose was administered once in the 6-h group and twice in the 24-h group. LLLT significantly decreased contraction force in BSM at 6 h (TNF-alpha + LLLT: 11.65+/-1.10 g/100 mg of tissue) (F=3115) and at 24 h (TNF-alpha+ LLLT: 14.15+/-1.1 g/100 mg of tissue) (F=3245, p<0.05) after TNF-alpha, respectively, when compared to vehicle-bathed groups (control). LLLT also significantly decreased the expression of RhoA mRNA in BSM segments at 6 h (1.22+/-0.20) (F=2820, p<0.05) and 24 h (2.13+/-0.20) (F=3324, p<0.05) when compared to BSM segments incubated with TNF-alpha without LLLT irradiation. We conclude that LLLT administered with this protocol, reduces RhoA mRNA expression and BSM contraction force in TNF-alpha-induced BSM hyperreactivity.

  4. Responsiveness of intestinal epithelial cell turnover to TGF-alpha after bowel resection in a rat is correlated with EGF receptor expression along the villus-crypt axis.

    PubMed

    Sukhotnik, Igor; Mogilner, Jorge G; Shaoul, Ron; Karry, Rahel; Lieber, Michael; Suss-Toby, Edith; Ure, Benno M; Coran, Arnold G

    2008-01-01

    Recent evidence suggests that transforming growth factor alpha (TGF-alpha) enhances enterocyte proliferation and stimulates intestinal adaptation after massive bowel resection. In the present study, we evaluated the effects of TGF-alpha on enterocyte turnover and correlated it with epidermal-growth factor (EGF) receptor expression along the villus-crypt axis in a rat model of short bowel syndrome (SBS). Male rats were divided into three groups, sham rats underwent bowel transection (group A); SBS rats underwent a 75% bowel resection (group B); and SBS/TGF-alpha rats underwent bowel resection and were treated with TGF-alpha (75 microg/kg) (group C) from the seventh postoperative day. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Villus tips, lateral villi and crypts were separated using laser capture microdissection. EGF receptor expression for each compartment was assessed by quantitative real-time PCR (Taqman). Statistical analysis was performed using one-way ANOVA test, with P < 0.05 considered statistically significant. Treatment with TGF-alpha resulted in a significant increase in all parameters of intestinal adaptation. EGF receptor expression in crypts significantly increased in SBS rats (vs sham rats) (0.035 +/- 0.013 vs 0.010 +/- 0.002 Log ng Total RNA/18 s) and was accompanied by a significant increase in enterocyte proliferation (169 +/- 8 vs 138 +/- 5 BrdU positive cells/per 10 crypts, P < 0.05) and decreased apoptosis following TGF-alpha administration (group C). A significant decrease in EGF receptor expression at the tip of the villus (0.005 +/- 0.002 vs 0.029 +/- 0.014 Log ng Total RNA/18 s) and in the lateral villus (0.003 +/- 0.001 vs 0.028 +/- 0.006 Log ng Total RNA/18 s) in SBS (group B) rats (vs sham, group A) was accompanied by increased cell apoptosis in these compartments following treatment with TGF-alpha (group C). In a rat model of SBS, TGF-alpha increased enterocyte proliferation

  5. IL-23 induces human osteoclastogenesis via IL-17 in vitro, and anti-IL-23 antibody attenuates collagen-induced arthritis in rats

    PubMed Central

    Yago, Toru; Nanke, Yuki; Kawamoto, Manabu; Furuya, Takefumi; Kobashigawa, Tsuyoshi; Kamatani, Naoyuki; Kotake, Shigeru

    2007-01-01

    This study demonstrates that IL-23 stimulates the differentiation of human osteoclasts from peripheral blood mononuclear cells (PBMC). Furthermore, in vivo blockade of endogenous IL-23 activity by treatment with anti-IL-23 antibody attenuates collagen-induced arthritis in rats by preventing both inflammation and bone destruction. IL-23 induced human osteoclastogenesis in cultures of PBMC in the absence of osteoblasts or exogenous soluble-receptor activator of NF-kappaB ligand (RANKL). This IL-23-induced osteoclastogenesis was inhibited by osteoprotegerin, anti-IL-17 antibody, and etanercept, suggesting that RANKL, IL-17, and TNF-alpha are involved. In addition, we found the ratio of production levels of IL-17 to those of IFN-gamma from activated human T cells was elevated at 1 to 10 ng/ml IL-23. The inductive effect of IL-17 and the inhibitory effect of IFN-gamma on osteoclastogenesis indicate that the balance of these two cytokines is particularly important. We also demonstrated that IL-23 administered at a later stage significantly reduced paw volume in rats with collagen-induced arthritis, in a dose-dependent manner. Furthermore, anti-IL-23 antibody reduced synovial tissue inflammation and bone destruction in these rats. These findings suggest that IL-23 is important in human osteoclastogenesis and that neutralizing IL-23 after onset of collagen-induced arthritis has therapeutic potential. Thus, controlling IL-23 production and function could be a strategy for preventing inflammation and bone destruction in patients with rheumatoid arthritis. PMID:17888176

  6. IL-23 induces human osteoclastogenesis via IL-17 in vitro, and anti-IL-23 antibody attenuates collagen-induced arthritis in rats.

    PubMed

    Yago, Toru; Nanke, Yuki; Kawamoto, Manabu; Furuya, Takefumi; Kobashigawa, Tsuyoshi; Kamatani, Naoyuki; Kotake, Shigeru

    2007-01-01

    This study demonstrates that IL-23 stimulates the differentiation of human osteoclasts from peripheral blood mononuclear cells (PBMC). Furthermore, in vivo blockade of endogenous IL-23 activity by treatment with anti-IL-23 antibody attenuates collagen-induced arthritis in rats by preventing both inflammation and bone destruction. IL-23 induced human osteoclastogenesis in cultures of PBMC in the absence of osteoblasts or exogenous soluble-receptor activator of NF-kappaB ligand (RANKL). This IL-23-induced osteoclastogenesis was inhibited by osteoprotegerin, anti-IL-17 antibody, and etanercept, suggesting that RANKL, IL-17, and TNF-alpha are involved. In addition, we found the ratio of production levels of IL-17 to those of IFN-gamma from activated human T cells was elevated at 1 to 10 ng/ml IL-23. The inductive effect of IL-17 and the inhibitory effect of IFN-gamma on osteoclastogenesis indicate that the balance of these two cytokines is particularly important. We also demonstrated that IL-23 administered at a later stage significantly reduced paw volume in rats with collagen-induced arthritis, in a dose-dependent manner. Furthermore, anti-IL-23 antibody reduced synovial tissue inflammation and bone destruction in these rats. These findings suggest that IL-23 is important in human osteoclastogenesis and that neutralizing IL-23 after onset of collagen-induced arthritis has therapeutic potential. Thus, controlling IL-23 production and function could be a strategy for preventing inflammation and bone destruction in patients with rheumatoid arthritis.

  7. Effects of Alpha-Lipoic Acid on Oxidative Stress and Kinin Receptor Expression in Obese Zucker Diabetic Fatty Rats.

    PubMed

    Midaoui, Adil El; Talbot, Sébastien; Lahjouji, Karim; Dias, Jenny Pena; Fantus, I George; Couture, Réjean

    2015-06-01

    To investigate the impact of alpha-lipoic acid on superoxide anion production and NADPH oxidase activity as well as on the expression of kinin B1 and B2 receptors in key organs of obese Zucker Diabetic Fatty rats. Superoxide anion production was measured by lucigenin chemiluminescence. Kinin B1 and B2 receptors expression was measured at protein and mRNA levels by western blot and qRT-PCR in key organs of Zucker Diabetic Fatty and Zucker lean control rats treated for a period of 6 weeks with a standard diet or a diet containing the antioxidant α-lipoic acid (1 g/kg). Superoxide anion production and NADPH oxidase activity were significantly enhanced in aorta and adipose tissue of Zucker Diabetic Fatty rats. Kinin B1 and B2 receptors expression levels were also significantly increased in the liver and the gastrocnemius muscle of Zucker Diabetic Fatty rats. Expression of both receptors was not altered in the pancreas of Zucker Diabetic Fatty rats and was undetectable in white retroperitoneal adipose tissue. Alpha-lipoic acid prevented the rise in NADPH oxidase activity in aorta and epididymal adipose tissue of Zucker Diabetic Fatty rats and the upregulation of kinin B1 receptor in liver and gastrocnemius muscle and that of kinin B2 receptor in the liver. Alpha-lipoic acid treatment was found to prevent the final body weight increase without affecting significantly hyperglycemia, hyperinsulinemia and insulin resistance index in Zucker Diabetic Fatty rats. Findings support the hypothesis that oxidative stress is implicated in the induction of kinin B1 receptor in Zucker Diabetic Fatty rats. The ability of α-lipoic acid to blunt the body weight gain appears to be mediated in part by preventing NADPH oxidase activity rise in adipose tissue and reversing the hepatic upregulation of kinin B1 receptor in Zucker Diabetic Fatty rats.

  8. Leptin potentiates Prevotella intermedia lipopolysaccharide-induced production of TNF-alpha in monocyte-derived macrophages.

    PubMed

    Kim, Sung-Jo

    2010-06-01

    In addition to regulating body weight, leptin is also recognized for its role in the regulation of immune function and inflammation. The purpose of this study was to investigate the effect of leptin on Prevotella (P.) intermedia lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production in differentiated THP-1 cells, a human monocytic cell line. LPS from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. The amount of TNF-alpha and interleukin-8 secreted into the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). TNF-alpha and Ob-R mRNA expression levels were determined by semi-quantitative reverse transcription-polymerase chain reaction analysis. Leptin enhanced P. intermedia LPS-induced TNF-alpha production in a dose-dependent manner. Leptin modulated P. intermedia LPS-induced TNF-alpha expression predominantly at the transcriptional level. Effect of leptin on P. intermedia LPS-induced TNF-alpha production was not mediated by the leptin receptor. The ability of leptin to enhance P. intermedia LPS-induced TNF-alpha production may be important in the establishment of chronic lesion accompanied by osseous tissue destruction observed in inflammatory periodontal disease.

  9. Kenaf seed supercritical fluid extract reduces aberrant crypt foci formation in azoxymethane-induced rats.

    PubMed

    Ghafar, Siti Aisyah Abd; Yazan, Latifah Saiful; Tahir, Paridah Md; Ismail, Maznah

    2012-03-01

    Kenaf (Hibiscus cannabinus) a plant of the family Malvaceae, is a valuable fiber plant native to India and Africa. Kenaf seeds contain alpha-linolenic acid, phytosterol such as β-sitosterol, vitamin E and other antioxidants with chemopreventive properties. In the present study we examined the hypothesis that kenaf seed 'supercritical fluid extract' (SFE) extract could suppress the early colon carcinogenesis in vivo by virtue of its bioactive compounds. To accomplish this goal, 60 male rats were randomly assigned to 5 groups which were (1) negative control group [not induced with azoxymethane (AOM)]; (2) positive control group (induced with AOM but received no treatment); (3) group treated with 500 mg/kg kenaf seed SFE extract; (4) group treated with 1000 mg/kg kenaf seed SFE extract; (5) group treated with 1500 mg/kg kenaf seed SFE extract. At 7 weeks of age, all rats except the negative control group received 15 mg/kg of AOM injection subcutaneously once a week for 2 weeks. Rats were euthanized at 13 weeks of the experiment. Number of ACF (mean±SD) ranged from 84.4±4.43 to 179.5±12.78 in group 2, 3, 4, 5. ACF reductions compared with the untreated group were 45.3, 51.4 and 53.1% in rats fed with 500, 1000 and 1500 mg/kg body weight, respectively. There were no significant differences in weight gain among groups. Our finding indicates that kenaf seed SFE extract reduced AOM-induced ACF in Sprague-Dawley male rats. Copyright © 2010 Elsevier GmbH. All rights reserved.

  10. Development and Validation of Attitude toward Gestational Surrogacy Scale in Iranian Infertile Couples.

    PubMed

    Rahimi Kian, Fatemeh; Zandi, Afsaneh; Omani Samani, Reza; Maroufizadeh, Saman; Mehran, Abbas

    2016-01-01

    Surrogacy is one of the most challenging infertility treatments engaging ethical, psychological and social issues. Attitudes survey plays an important role to disclosure variant aspects of surrogacy, to help meeting legislative gaps and ambiguities, and to convert controversial dimensions surrounding surrogacy to a normative concept that eliminates stigma. The aim of this study is to develop a comprehensive scale for gestational surrogacy attitudes. Development process of gestational surrogacy attitudes scale (GSAS) performed based on a descriptive cross-sectional study and included a rich data pool gathered from literature reviews, a qualitative pilot study on 15 infertile couples (n=30), use of expert advisory panel (EAP) consisting of 20 members, as well as use of content validity through qualitative and quantitative study by the means of content validity ratio (CVR) and content validity index (CVI). Also internal consistence using Cronbach's alpha and test-retest reliability using intracalss correlation coefficient (ICC) were evaluated. Application of GSAS was tested in a cross-sectional study that was conducted on 200 infertile couples (n=400) at Royan Institute, Tehran, Iran, during 2014. Final version of GSAS had 30 items within five subscales including "acceptance of surrogacy", "Surrogacy and public attitudes", "Child born through surrogacy", "Surrogate mother", and "Intentional attitude and surrogacy future attempt". Content validity was represented with values of CVR=0.73 and CVI =0.98. Cronbach's alpha value was 0.91 for the overall scale, while ICC value due to test-retest responses was 0.89. Acceptable level of competency and capability of GSAS is significantly indicated; therefore, it seems to be an appropriate tool for the evaluation of gestational surrogacy attitudes in Iranian infertile couples.

  11. Estrogen-Induced Developmental Disorders of the Rat Penis Involve Both Estrogen Receptor (ESR)- and Androgen Receptor (AR)-Mediated Pathways1

    PubMed Central

    Goyal, H.O.; Braden, T.D.; Williams, C.S.; Williams, J.W.

    2009-01-01

    This study tested the hypothesis that the estrogen receptor (ESR) pathway, androgen receptor (AR) pathway, or both mediate estrogen-induced developmental penile disorders. Rat pups received diethylstilbestrol (DES), with or without the ESR antagonist ICI 182,780 (ICI) or the AR agonist dihydrotestosterone (DHT) or testosterone (T), from Postnatal Days 1 to 6. Testicular T concentration, penile morphology and morphometry, and/or fertility was determined at age 7, 28, or 150 days. DES treatment alone caused 90% reduction in the neonatal intratesticular T surge; this reduction was prevented by ICI coadministration, but not by DHT or T coadministration. Unlike the T surge, coadministration of ICI and coadministration of DHT or T mitigated penile deformities and loss of fertility. Generally, ICI, DHT, or T treatment alone did not alter penile morphology; however, fertility was 20% that of controls in ICI-treated rats vs. 70%–90% in DHT- or T-treated rats. The lower fertility in the rats treated with ICI alone could be due to altered sexual behavior, as these males did not deposit vaginal plugs. In conclusion, observations that both an ESR antagonist and AR agonists prevent penile deformities and infertility suggest that both pathways are involved in estrogen-induced penile disorders. Observations that coadministration of ICI, but not DHT or T, prevents the DES-induced reduction in the neonatal T surge suggest that, although ICI exerts its mitigating effect both at the level of Leydig cells and penile stromal cells, DHT and T do so only at the level of stromal cells. PMID:19420389

  12. Effect of pregnant mare's serum gonadotrophin on the activities of delta 4-5 alpha-reductase, aromatase, and other enzymes in the ovaries of immature rats.

    PubMed

    Suzuki, K; Kawakura, K; Tamaoki, B I

    1978-05-01

    After incubation of progesterone, 17 alpha-hydroxyprogesterone, androstenedione, and testostrone with an ovarian preparation (supernatant fluid at 10,000 x g) of immature rats (21-23 days of age) in the presence of NADPH, 3 alpha- and 3 beta-hydroxy-5 alpha-reduced steroids were obtained as the major metabolites. Among the enzyme activities relevant to the metabolism, delta 4-5 alpha-reductase and 3 beta-hydroxysteroid dehydrogenase were intracellularly localized to the microsomal fraction (10,000--105,000 x g), and 3 alpha-hydroxysteroid dehydrogenase was detected exclusively in the cytosol fraction (supernatant fluid at 105,000 x g). Within 2 days after a single injection of pregnant mare's serum gonadotrophin (10 IU/rat) to 21-day-old female rats, the following occurred: 1) an enhancement of 17 alpha-hydroxylase and C-17-C-20 lyase activities; 2) a suppression of delta 4-5 alpha-reductase activity; and 3) an increase in aromatizing activity. From the above-mentioned results, it was concluded that the increased secretion of estrogen from ovaries of immature rats stimulated by pregnant mare's serum gonadotrophin administration was caused by a modification of the ovarian enzyme activities relevant to estrogen production.

  13. Anti-fibrotic effects of thalidomide on hepatic stellate cells and dimethylnitrosamine-intoxicated rats.

    PubMed

    Chong, Lee-Won; Hsu, Yi-Chao; Chiu, Yung-Tsung; Yang, Kuo-Ching; Huang, Yi-Tsau

    2006-05-01

    Tumor necrosis factor-alpha (TNF-alpha) plays a central role in cellular necrosis, apoptosis, organ failure, tissue damage, inflammation and fibrosis. These processes, occurring in liver injury, may lead to cirrhosis. Thalidomide, alpha-N-phthalidoglutarimide, (C(13)H(10)N(2))(4), has been shown to have immunomodulatory and anti-inflammatory properties, possibly mediated through its anti-TNF-alpha effect. In this study, we investigated the in vitro and in vivo effects of thalidomide on hepatic fibrosis. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with transforming growth factor-beta1 (TGF-beta1) or TNF-alpha. The inhibitory effects of thalidomide on the NFkappaB signaling cascade and fibrosis markers including alpha-smooth muscle actin (alpha-SMA) and collagen, were assessed. An in vivo therapeutic study was conducted in dimethylnitrosamine (DMN)-treated rats, which were randomly assigned to 1 of 4 groups: vehicle (0.7% carboxyl methyl cellulose, CMC), thalidomide (40 mg/kg), thalidomide (200 mg/kg), or silymarin (50 mg/kg), each given by gavage twice daily for 3 weeks starting after 1 week of DMN administration. Thalidomide (100-800 nM) concentration-dependently inhibited NFkappaB transcriptional activity induced by TNF-alpha, including IKKalpha expression and IkappaBalpha phosphorylation in HSC-T6 cells. In addition, thalidomide also suppressed TGF-beta1-induced alpha-SMA expression and collagen deposition in HSC-T6 cells. Fibrosis scores of livers from DMN-treated rats receiving high dose of thalidomide (0.89 +/- 0.20) were significantly reduced in comparison with those of DMN-treated rats receiving vehicle (1.56 +/- 0.18). Hepatic collagen contents of DMN rats were also significantly reduced by either thalidomide or silymarin treatment. Immunohistochemical double staining results showed that alpha-SMA- and NFkappaB-positive cells were decreased in the livers from DMN rats receiving either thalidomide or silymarin treatment. In addition

  14. Icilin-evoked behavioral stimulation is attenuated by alpha2-adrenoceptor activation

    PubMed Central

    Kim, Jae; Cowan, Alan; Lisek, Renata; Raymondi, Natalie; Rosenthal, Aaron; Hirsch, Daniel D.; Rawls, Scott M.

    2011-01-01

    Icilin is a transient receptor potential cation channel subfamily M (TRPM8) agonist that produces behavioral activation in rats and mice. Its hallmark overt pharmacological effect is wet-dog shakes (WDS) in rats. The vigorous shaking associated with icilin is dependent on NMDA receptor activation and nitric oxide production, but little else is known about the biological systems that modulate the behavioral phenomenon. The present study investigated the hypothesis that alpha2-adrenoceptor activation inhibits icilin-induced WDS. Rats injected with icilin (0.5, 1, 2.5, 5 mg/kg, i.p.) displayed dose-related WDS that were inhibited by pretreatment with a fixed dose of clonidine (0.15 mg/kg, s.c.). Shaking behavior caused by a fixed dose (2.5 mg/kg) of icilin was also inhibited in a dose-related manner by clonidine pretreatment (0.03–0.15 mg/kg, s.c.) and reduced by clonidine posttreatment (0.15 mg/kg, s.c.). Pretreatment with a peripherally restricted alpha2-adrenoceptor agonist, ST91 (0.075, 0.15 mg/kg), also decreased the incidence of shaking elicited by 2.5 mg/kg of icilin. Pretreatment with yohimbine (2 mg/kg, i.p.) enhanced the shaking induced by a low dose of icilin (0.5 mg/kg). The imidazoline site agonists, agmatine (150 mg/kg, i.p.) and 2-BFI (7 mg/kg, i.p.), did not affect icilin-evoked shaking. These results suggest that alpha2-adrenoceptor activation inhibits shaking induced by icilin and that increases in peripheral, as well as central, alpha2-adrenoceptor signaling oppose the behavioral stimulant effect of icilin. PMID:21315691

  15. Infertility and the provision of infertility medical services in developing countries

    PubMed Central

    Ombelet, Willem; Cooke, Ian; Dyer, Silke; Serour, Gamal; Devroey, Paul

    2008-01-01

    BACKGROUND Worldwide more than 70 million couples suffer from infertility, the majority being residents of developing countries. Negative consequences of childlessness are experienced to a greater degree in developing countries when compared with Western societies. Bilateral tubal occlusion due to sexually transmitted diseases and pregnancy-related infections is the most common cause of infertility in developing countries, a condition that is potentially treatable with assisted reproductive technologies (ART). New reproductive technologies are either unavailable or very costly in developing countries. This review provides a comprehensive survey of all important papers on the issue of infertility in developing countries. METHODS Medline, PubMed, Excerpta Medica and EMBASE searches identified relevant papers published between 1978 and 2007 and the keywords used were the combinations of ‘affordable, assisted reproduction, ART, developing countries, health services, infertility, IVF, simplified methods, traditional health care'. RESULTS The exact prevalence of infertility in developing countries is unknown due to a lack of registration and well-performed studies. On the other hand, the implementation of appropriate infertility treatment is currently not a main goal for most international non-profit organizations. Keystones in the successful implementation of infertility care in low-resource settings include simplification of diagnostic and ART procedures, minimizing the complication rate of interventions, providing training-courses for health-care workers and incorporating infertility treatment into sexual and reproductive health-care programmes. CONCLUSIONS Although recognizing the importance of education and prevention, we believe that for the reasons of social justice, infertility treatment in developing countries requires greater attention at National and International levels. PMID:18820005

  16. The effects of SB 216469, an antagonist which discriminates between the alpha 1A-adrenoceptor and the human prostatic alpha 1-adrenoceptor.

    PubMed Central

    Chess-Williams, R.; Chapple, C. R.; Verfurth, F.; Noble, A. J.; Couldwell, C. J.; Michel, M. C.

    1996-01-01

    1. The affinity of the alpha 1-adrenoceptor antagonist SB 216469 (also known as REC 15/2739) has been determined at native and cloned alpha 1-adrenoceptor subtypes by radioligand binding and at functional alpha 1-adrenoceptor subtypes in isolated tissues. 2. In radioligand binding studies with [3H]-prazosin, SB 216469 had a high affinity at the alpha 1A-adrenoceptors of the rat cerebral cortex and kidney (9.5-9.8) but a lower affinity at the alpha 1B-adrenoceptors of the rat spleen and liver (7.7-8.2). 3. At cloned rat alpha 1-adrenoceptor subtypes transiently expressed in COS-1 cells and also at cloned human alpha 1-adrenoceptor subtypes stably transfected in Rat-1 cells, SB 216469 exhibited a high affinity at the alpha 1a-adrenoceptors (9.6-10.4) with a significantly lower affinity at the alpha 1b-adrenoceptor (8.0-8.4) and an intermediate affinity at the alpha 1d-adrenoceptor (8.7-9.2). 4. At functional alpha 1-adrenoceptors, SB 216469 had a similar pharmacological profile, with a high affinity at the alpha 1A-adrenoceptors of the rat vas deferens and anococcygeus muscle (pA2 = 9.5-10.0), a low affinity at the alpha 1B-adrenoceptors of the rat spleen (6.7) and guinea-pig aorta (8.0), and an intermediate affinity at the alpha 1D-adrenoceptors of the rat aorta (8.8). 5. Several recent studies have concluded that the alpha 1-adrenoceptor present in the human prostate has the pharmacological characteristics of the alpha 1A-adrenoceptor subtype. However, the affinity of SB 216469 at human prostatic alpha 1-adrenoceptors (pA2 = 8.1) determined in isolated tissue strips, was significantly lower than the values obtained at either the cloned alpha 1a-adrenoceptors (human, rat, bovine) or the native alpha 1A-adrenoceptors in radioligand binding and functional studies in the rat. 6. Our results with SB 216469, therefore, suggest that the alpha 1-adrenoceptor mediating contractile responses of the human prostate has properties which distinguish it from the cloned alpha 1a

  17. The inhibitory effect of dexamethasone on platelet-derived growth factor-induced vascular smooth muscle cell migration through up-regulating PGC-1{alpha} expression

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu, Wei; Department of cardiology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin 150081; Guo, Ting

    2011-05-01

    Dexamethasone has been shown to inhibit vascular smooth muscle cell (VSMC) migration, which is required for preventing restenosis. However, the mechanism underlying effect of dexamethasone remains unknown. We have previously demonstrated that peroxisome proliferator-activated receptor gamma (PPAR{gamma}) coactivator-1 alpha (PGC-1{alpha}) can inhibit VSMC migration and proliferation. Here, we investigated the role of PGC-1{alpha} in dexamethasone-reduced VSMC migration and explored the possible mechanism. We first examined PGC-1{alpha} expression in cultured rat aortic VSMCs. The results revealed that incubation of VSMCs with dexamethasone could significantly elevate PGC-1{alpha} mRNA expression. In contrast, platelet-derived growth factor (PDGF) decreased PGC-1{alpha} expression while stimulating VSMC migration.more » Mechanistic study showed that suppression of PGC-1{alpha} by small interfering RNA strongly abrogated the inhibitory effect of dexamethasone on VSMC migration, whereas overexpression of PGC-1{alpha} had the opposite effect. Furthermore, an analysis of MAPK signal pathways showed that dexamethasone inhibited ERK and p38 MAPK phosphorylation in VSMCs. Overexpression of PGC-1{alpha} decreased both basal and PDGF-induced p38 MAPK phosphorylation, but it had no effect on ERK phosphorylation. Finally, inhibition of PPAR{gamma} activation by a PPAR{gamma} antagonist GW9662 abolished the suppressive effects of PGC-1{alpha} on p38 MAPK phosphorylation and VSMC migration. These effects of PGC-1{alpha} were enhanced by a PPAR{gamma} agonist troglitazone. Collectively, our data indicated for the first time that one of the anti-migrated mechanisms of dexamethasone is due to the induction of PGC-1{alpha} expression. PGC-1{alpha} suppresses PDGF-induced VSMC migration through PPAR{gamma} coactivation and, consequently, p38 MAPK inhibition.« less

  18. Effect of infliximab and tocilizumab on fructose-induced hyperinsulinemia and hypertension in rats.

    PubMed

    Abdelrahman, Aly M; Al Suleimani, Yousuf M; Ashique, Mohammed; Manoj, Priyadarsini; Ali, Badreldin H

    2018-05-29

    Fructose administration can induce hypertension, insulin resistance and hypertriglyceridemia. Here, we investigated the possible protective effect of infliximab (IFX), a tumor necrosis factor alpha (TNF-α) inhibitor, or tocilizumab (TOC), an interleukin-6 (IL6) inhibitor, on fructose-induced increase in blood pressure, insulin resistance and hyperlipidemia in rats. The animals were fed a 60% fructose diet in the absence or presence of IFX (5 mg/kg, i.p., once weekly) or TOC (8 mg/kg, i.p., once every two weeks). Fructose significantly increased blood pressure, heart rate and homeostatic model assessment of insulin resistance (HOMA-IR). Fructose also significantly raised the concentrations of fasting plasma insulin, triglycerides, total cholesterol, uric acid, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), malondialdhyde (MDA) and nitric oxide. Fructose also significantly decreased plasma superoxide dismutase (SOD) and catalase activities. In addition, fructose significantly increased aortic endothelin and nitric oxide concentrations. Both IFX and TOC attenuated the fructose-induced increase in blood pressure, insulin resistance, and the concentrations of uric acid, MDA and IL-6. TOC significantly reduced fructose-induced increase in triglycerides and cholesterol. In addition, IFX increased plasma SOD and catalase activities. Our results showed that both IFX and TOC were partially successful in reversing fructose - induced changes. Copyright © 2018. Published by Elsevier Masson SAS.

  19. Involvement of Mst1 in tumor necrosis factor-{alpha}-induced apoptosis of endothelial cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ohtsubo, Hideki; Ichiki, Toshihiro; Imayama, Ikuyo

    2008-03-07

    Mammalian sterile 20-kinase 1 (Mst1), a member of the sterile-20 family protein kinase, plays an important role in the induction of apoptosis. However, little is know about the physiological activator of Mst1 and the role of Mst1 in endothelial cells (ECs). We examined whether Mst1 is involved in the tumor necrosis factor (TNF)-{alpha}-induced apoptosis of ECs. Western blot analysis revealed that TNF-{alpha} induced activation of caspase 3 and Mst1 in a time- and dose-dependent manner. TNF-{alpha}-induced Mst1 activation is almost completely prevented by pretreatment with Z-DEVD-FMK, a caspase 3 inhibitor. Nuclear staining with Hoechst 33258 and fluorescence-activated cell sorting ofmore » propidium iodide-stained cells showed that TNF-{alpha} induced apoptosis of EC. Diphenyleneiodonium, an inhibitor of NADPH oxidase, and N-acetylcysteine, a potent antioxidant, also inhibited TNF-{alpha}-induced activation of Mst1 and caspase 3, as well as apoptosis. Knockdown of Mst1 expression by short interfering RNA attenuated TNF-{alpha}-induced apoptosis but not cleavage of caspase 3. These results suggest that Mst1 plays an important role in the induction of TNF-{alpha}-induced apoptosis of EC. However, positive feedback mechanism between Mst1 and caspase 3, which was shown in the previous studies, was not observed. Inhibition of Mst1 function may be beneficial for maintaining the endothelial integrity and inhibition of atherogenesis.« less

  20. Sexual dysfunction and male infertility.

    PubMed

    Lotti, Francesco; Maggi, Mario

    2018-05-01

    Infertility affects up to 12% of all men, and sexual dysfunction occurs frequently in men of reproductive age, causing infertility in some instances. In infertile men, hypoactive sexual desire and lack of sexual satisfaction are the most prevalent types of sexual dysfunction, ranging from 8.9% to 68.7%. Erectile dysfunction and/or premature ejaculation, evaluated with validated tools, have a prevalence of one in six infertile men, and orgasmic dysfunction has a prevalence of one in ten infertile men. In addition, infertile men can experience a heavy psychological burden. Infertility and its associated psychological concerns can underlie sexual dysfunction. Furthermore, general health perturbations can lead to male infertility and/or sexual dysfunction. Erectile dysfunction and male infertility are considered proxies for general health, the former underlying cardiovascular disorders and the latter cancerous and noncancerous conditions. The concept that erectile dysfunction in infertile men might be an early marker of poor general health is emerging. Finally, medications used for general health problems can cause sperm abnormalities and sexual dysfunction. The treatment of some causes of male infertility might improve semen quality and reverse infertility-related sexual dysfunction. In infertile men, an investigation of sexual, general, and psychological health status is advisable to improve reproductive problems and general health.

  1. Male infertility, azoozpermia and cryptozoospermia incidence among three infertility clinics in Turkey

    PubMed Central

    Keskin, İlknur; Kutlu, Pelin; Delikara, Nuri; Atvar, Özhan; Öztürk, Metin İ.

    2018-01-01

    Objective Semen parameters are directly correlated with the infertility of the male. Incidence rates of male factor infertility, azoospermia and cryptozoospermia differ according to many factors such as geographic region, age, occupation and body weight. The aim of the present study is to determine the incidence of male factor infertility, azoospermia and cryptozoospermia among patients who have been admitted to three separate infertility clinics in Turkey for infertility investigation and analyze the outcomes of these patients. Material and methods A total of 9733 men, who have been admitted to 3 infertility clinics in Turkey due to infertility between March 2011 and October 2016, were included in the study. Male infertility, azoozpermia and cryptozoospermia incidence were calculated according to WHO criteria. Results Male factor infertility was determined in 3114 (32%) of the patients including cases with azoospermia and cryptozoospermia. Azoospermia cases were observed in 570 (5.85%) and cryptozoospermia in 850 (8.73%) men. Azoospermic, and cryptozoospermic patients constitute 18.3%, and 27.2% of the male infertility cases. Sperm retrieval rates in diagnostic or oocyte pick-up plus testicular sperm extraction groups were found to be comparable (16.39%, and 41.3%, respectively). Conclusion The data obtained may help to estimate the number of in vitro fertilization cycles and testicular sperm extraction cases, to determine social security policies, and reproductive potential, and in the light of these data to establish social insurance policies. These data will help patients to decide on treatment alternatives, and guide the urologists about the issue. PMID:29511578

  2. Effects of insulin, dexamethasone and cytokines on {alpha}{sub 1}-acid glycoprotein gene expression in primary cultures of normal rat hepatocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Barraud, B.; Balavoine, S.; Feldmann, G.

    1996-04-01

    While the effects of insulin, dexamethasone and cytokines on {alpha}{sub 1}-acid glycoprotein gene expression have been investigated in various hepatoma cell lines, the individual and combined effects of these components on the expression of this gene have been rarely studied in cultured normal rat hepatocytes. In this cell model, we have shown that mRNA levels of {alpha}{sub 1}-acid glycoprotein were not decreased at least during the first 24 h of culture under basal conditions. During these short-term cultures, the expression of {alpha}{sub 1}-acid glycoprotein in normal hepatocytes showed a high degree of responsiveness to dexamethasone alone (20-fold increase) and tomore » dexamethasone associated with various cytokines (interleukin-1{beta}, interleukin-6 and tumor necrosis factor {alpha}) with a 40 to 100-fold increase depending on the cytokine. Insulin alone did not modify {alpha}{sub 1}-acid glycoprotein mRNA; however, this hormone exerted a positive effect (about 50% increase) in the presence of dexamethasone or dexamethasone with cytokines. These results indicate that the regulation of {alpha}{sub 1}-acid glycoprotein in cultured normal rat hepatocytes presents major differences when compared to reported observations in rat hepatoma cell lines. 49 refs., 2 figs., 2 tabs.« less

  3. Estrogen induces rapid decrease in dendritic thorns of CA3 pyramidal neurons in adult male rat hippocampus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tsurugizawa, Tomokazu; Core Research for Evolutional Science and Technology Project of Japan Science and Technology Agency, Graduate School of Arts and Sciences, University of Tokyo at Komaba, 3-8-1 Meguro, Tokyo 153; Mukai, Hideo

    2005-12-02

    Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. Here we demonstrated the rapid effect of estradiol on the density of thorns of thorny excrescences, by imaging Lucifer Yellow-injected CA3 neurons in adult male rat hippocampal slices. The application of 1 nM estradiol induced rapid decrease in the density of thorns on pyramidal neurons within 2 h. The estradiol-mediated decrease in the density of thorns was blocked by CNQX (AMPA receptor antagonist) and PD98059 (MAP kinase inhibitor), but notmore » by MK-801 (NMDA receptor antagonist). ER{alpha} agonist PPT induced the same suppressive effect as that induced by estradiol on the density of thorns, but ER{beta} agonist DPN did not affect the density of thorns. Note that a 1 nM estradiol treatment did not affect the density of spines in the stratum radiatum and stratum oriens. A search for synaptic ER{alpha} was performed using purified RC-19 antibody. The localization of ER{alpha} (67 kDa) in the CA3 mossy fiber terminals and thorns was demonstrated using immunogold electron microscopy. These results imply that estradiol drives the signaling pathway including ER{alpha} and MAP kinase.« less

  4. Endotoxin-induced mortality in rats is reduced by nitrones

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hamburger, S.A.; McCay, P.B.

    The goal of these investigations was to determine if nitrone spin-trapping agents can alter mortality associated with endotoxemia in the rat. Reactive free radicals attack nitrone spin-trapping agents forming relatively reactive, persistent free radical spin adducts. We administered 85 mM (10 ml/kg) of alpha-phenyl N-tert-butyl nitrone (PBN), alpha-4-pyridyl-N-oxide N-tert-butyl nitrone (4-POBN), 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), or vehicle (saline i.p.) 30 min before endotoxin (25 mg/kg i.p.) or vehicle to Sprague-Dawley (SD) or Holtzman virus-free (HVF) rats (n = 10-17/group). All vehicle-treated rats receiving endotoxin were dead by 1 day. At 7 days, 83% of PBN-treated SD, 42% of PBN- or POBN-treated HVF,more » and 25% of DMPO-treated HVF rats were alive. The difference in survival of PBN-treated animals between strains may reflect the higher susceptibility of HVF rats to endotoxin. The observed reduction in mortality may be related to the well-established capacity of spin-trapping agents to capture reactive free radicals that may be generated in target tissues in response to endotoxin, and that would otherwise react with cell components and produce tissue injury.« less

  5. Comparison of Sperm Parameters in Patients with Infertility Induced by Genital Infection versus Varicocele

    PubMed Central

    Pajovic, Bogdan; Dimitrovski, Antonio; Radojevic, Nemanja; Vukovic, Marko

    2015-01-01

    Background: Male infertility is a common and complex problem and, despite much research in this field, the major cause of infertility unfortunately remains unknown. Genital infection and varicocele are important causes of infertility. Aims: To compare the influence of genital infection and varicocele individually on male infertility based on semen analysis. Study Design: Cross-sectional study. Methods: The study included 120 infertile patients divided into two groups according to the presence of genital infection or varicocele. The first group included 60 examinees with proven genital infection, but without varicocele formation. The second included 60 patients with varicocele, regardless of the varicocele grade, but without genital infection. The fertile parameters were compared and an assessment was performed on the impact on quality of spermatogenesis due to infection and varicocele. Results: There is a statistically significant difference regarding abnormal forms of spermatozoids (45.94±9.79 vs. 25.27±6.54) and progressive motility (8.15±1.24 vs. 24.95±7.2), between two groups of patients. However, acidity of ejaculates, minimum sperm concentration, total spermatozoid motility and ejaculate volume showed no statistically significant difference. Conclusion: The study showed a stronger negative influence of genital infection on fertile parameters over varicocele. The significance of our study is the lack of contemporary researches comparing varicocele and genital infection influence on male infertility individually. PMID:26185712

  6. Comparison of Sperm Parameters in Patients with Infertility Induced by Genital Infection versus Varicocele.

    PubMed

    Pajovic, Bogdan; Dimitrovski, Antonio; Radojevic, Nemanja; Vukovic, Marko

    2015-07-01

    Male infertility is a common and complex problem and, despite much research in this field, the major cause of infertility unfortunately remains unknown. Genital infection and varicocele are important causes of infertility. To compare the influence of genital infection and varicocele individually on male infertility based on semen analysis. Cross-sectional study. The study included 120 infertile patients divided into two groups according to the presence of genital infection or varicocele. The first group included 60 examinees with proven genital infection, but without varicocele formation. The second included 60 patients with varicocele, regardless of the varicocele grade, but without genital infection. The fertile parameters were compared and an assessment was performed on the impact on quality of spermatogenesis due to infection and varicocele. There is a statistically significant difference regarding abnormal forms of spermatozoids (45.94±9.79 vs. 25.27±6.54) and progressive motility (8.15±1.24 vs. 24.95±7.2), between two groups of patients. However, acidity of ejaculates, minimum sperm concentration, total spermatozoid motility and ejaculate volume showed no statistically significant difference. The study showed a stronger negative influence of genital infection on fertile parameters over varicocele. The significance of our study is the lack of contemporary researches comparing varicocele and genital infection influence on male infertility individually.

  7. Myocardial and vascular adrenergic alterations in a rat model of endotoxin shock: reversal by an anti-tumor necrosis factor-alpha monoclonal antibody.

    PubMed

    Boillot, A; Massol, J; Maupoil, V; Grelier, R; Bernard, B; Capellier, G; Berthelot, A; Barale, F

    1997-03-01

    a) To investigate responsiveness to exogenous catecholamines in rat endotoxin shock by studying both myocardial and vascular functional parameters, and to determine the relationship of these parameters with other relevant biological parameters of the adrenergic pathway, such as myocardial beta-adrenergic receptors and cyclic adenosine monophosphate (cAMP); b) to investigate the role of tumor necrosis factor (TNF)-alpha via prophylactic anti-TNF-alpha monoclonal antibody administration. Experimental, comparative hospital. Laboratory in a university hospital. Male Sprague-Dawley rats, weighing 280 to 340 g. Intravenous injection of Escherichia coli endotoxin (5 mg/100 g) in the first group; injection of the same dose of endotoxin preceded by 2 mg/100 g of anti-TNF-alpha monoclonal antibody in the second group; injection of saline in the third (control) group. TNF-alpha concentration was measured before and during the first 3 hrs in all three groups. Myocardial and vascular functional parameters were obtained, respectively, from Langendorff perfused hearts and isolated aortic rings. Adrenergic biochemical parameters (catecholamines, density and affinity of beta-receptors, and isoproterenol-stimulated myocardial cAMP) were determined 3 hrs after injections in the three groups. After endotoxin injection, serum TNF-alpha concentrations peaked at 60 mins (2496 +/- 412 pg/mL) and returned slowly to control values at 3 hrs; serum TNF-alpha concentrations remained under the limit of detection in the other two groups. When compared with the control group, plasma concentrations of epinephrine and norepinephrine were significantly (p < .05) increased. Baseline values for differential left ventricular pressure and coronary flow were significantly (p < .001, p < .01, respectively) reduced in the endotoxin group; heart rate remained unchanged. In the endotoxin and control groups, isoproterenol induced a similar increase in differential left ventricular pressure and in heart rate

  8. Evaluation of the protective effect of pentoxifylline on carrageenan-induced chronic non-bacterial prostatitis in rats.

    PubMed

    Hajighorbani, Mahboobeh; Ahmadi-Hamedani, Mahmood; Shahab, Elaheh; Hayati, Farzad; Kafshdoozan, Khatereh; Keramati, Keivan; Amini, Amin Hossein

    2017-06-01

    Chronic non-bacterial prostatitis (CNP) is the most common type of prostatitis and oxidative stress (OS) was shown to be highly elevated in prostatitis patients. This study aimed to investigate the protective effect of pentoxifylline (PTX) on CNP induced by carrageenan in rats. Male adult Wistar rats (n = 30) were divided into control, CNP and three treatment groups (n = 6) including CNP + cernilton and CNP + PTX groups. CNP was induced by single intraprostatic injection of 1% carrageenan (100 µl). Rats in treatment groups received orally cernilton 100 mg/kg and PTX at 50 and 100 mg/kg 1 week after CNP induction for 21 days. Prostatic index (PI), prostatic specific antigen (PSA), tumor-necrosis factor alpha (TNF-α), serum lipid peroxidation (MDA), blood urea nitrogen, creatinine and histopathological changes were compared between groups. There were significant increase of PI, serum levels of PSA, TNF-α and MDA in CNP group at 29 day. In treatment groups, significant reduction in PI, serum levels of PSA, TNF-α, MDA and creatinine was observed especially in rats treated with dose of 50 mg/kg of PTX. In CNP group, histopathological changes of the prostate such as leucocyte infiltration, large involutions and projection into the lumen and reducing the volume of the lumen were observed as well. Whereas PTX, especially at dose of 50 mg/kg, could improve the above-mentioned changes remarkably in CNP treated rats. For the first time, our findings indicated that PTX improved CNP induced by carrageenan in rats.

  9. Sestrin2 Induced by Hypoxia Inducible Factor 1 alpha protects the Blood-Brain Barrier via Inhibiting VEGF after Severe Hypoxic-Ischemic Injury in Neonatal Rats

    PubMed Central

    Shi, Xudan; Doycheva, Desislava Met; Xu, Liang; Tang, Jiping; Yan, Min; Zhang, John H

    2016-01-01

    Objective Hypoxic ischemic (HI) encephalopathy remains the leading cause of perinatal brain injury resulting in long term disabilities. Stabilization of blood brain barrier (BBB) after HI is an important target, therefore, in this study we aim to determine the role of sestrin2, a stress inducible protein which is elevated after various insults, on BBB stabilization after moderate and severe HI injury. Methods Rat pups underwent common carotid artery ligation followed by either 150 min (severe model) or 100 min (moderate model) of hypoxia. 1h post HI, rats were intranasally administered with recombinant human sestrin2 (rh-sestrin2) and sacrificed for infarct area, brain water content, righting reflex and geotaxis reflex. Sestrin2 was silenced using siRNA and an activator/inhibitor of hypoxia inducible factor1α (HIF1α) were used to examine their roles on BBB permeability. Results Rats subjected to severe HI exhibited larger infarct area and higher sestrin2 expression compared to rats in the moderate HI group. rh-sestrin2 attenuated brain infarct and edema, while silencing sestrin2 reversed these protective effects after severe HI. HIF1α induced sestrin2 activation in severe HI but not in moderate HI groups. A HIF1a agonist was shown to increase permeability of the BBB via vascular endothelial growth factor (VEGF) after moderate HI. However, after severe HI, HIF1α activated both VEGF and sestrin2. But HIF1α dependent sestrin2 activation was the predominant pathway after severe HI which inhibited VEGF and attenuated BBB permeability. Conclusions rh-sestrin2 attenuated BBB permeability via upregulation of endogenous sestrin2 which was induced by HIF1α after severe HI. However, HIF1α’s effects as a prodeath or prosurvival signal were influenced by the severity of HI injury. PMID:27425892

  10. Antinociceptive and antiallodynic effects of Momordica charantia L. in tibial and sural nerve transection-induced neuropathic pain in rats.

    PubMed

    Jain, Vivek; Pareek, Ashutosh; Paliwal, Nishant; Ratan, Yashumati; Jaggi, Amteshwar Singh; Singh, Nirmal

    2014-02-01

    This study was designed to investigate the ameliorative potential of Momordica charantia L. (MC) in tibial and sural nerve transection (TST)-induced neuropathic pain in rats. TST was performed by sectioning tibial and sural nerve portions (2 mm) of the sciatic nerve, and leaving the common peroneal nerve intact. Acetone drop, pin-prick, hot plate, paint-brush, and walking track tests were performed to assess cold allodynia, mechanical and heat hyperalgesia, and dynamic mechanical allodynia and tibial functional index, respectively. The levels of tumour necrosis factor (TNF)-alpha and thio-barbituric acid reactive substances (TBARS) were measured in the sciatic nerve as an index of inflammation and oxidative stress. MC (all doses, orally, once daily) was administered to the rats for 24 consecutive days. TST led to significant development of cold allodynia, mechanical and heat hyperalgesia, dynamic mechanical allodynia, and functional deficit in walking along with rise in the levels of TBARS and TNF-alpha. Administration of MC (200, 400, and 800 mg/kg) significantly attenuated TST-induced behavioural and biochemical changes. Furthermore, pretreatment of BADGE (120 mg/kg, intraperitoneally) abolished the protective effect of MC in TST-induced neuropathic pain. Collectively, it is speculated that PPAR-gamma agonistic activity, anti-inflammatory, and antioxidative potential is critical for antinociceptive effect of MC in neuropathic pain.

  11. Ovarian Drilling for Infertility

    MedlinePlus

    ... Home FAQs Frequently Asked Questions Quick Facts About Infertility FAQs About Infertility FAQs About the Psychological Component of Infertility FAQs About Cloning and Stem Cell Research SART's ...

  12. Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin.

    PubMed

    Liu, Yan-Li; Lin, Hai-Ming; Zou, Rong; Wu, Jun-Chao; Han, Rong; Raymond, Laurence N; Reid, Paul F; Qin, Zheng-Hong

    2009-02-01

    Cobratoxin (CTX), the long-chain alpha-neurotoxin from Thailand cobra venom, has been demonstrated to have analgesic action in rodent pain models. The present study evaluated the anti-inflammatory and anti-nociceptive effects of CTX on adjuvant arthritis (AA) in rats. Arthritis was induced by injection of complete Freund's adjuvant (CFA) in rats. Paw swelling and hyperalgesia of AA rats were measured at various times after CFA administration. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-2 (IL-2) and interleukin-10 (IL-10) levels in serum were determined with ELISA. Histopathological changes in synoviocytes were examined under a microscope. Involvement of the cholinergic system in the effects of CTX was examined by pretreatment of animals with the alpha(7) nicotinic receptor (alpha(7)-nAChR) antagonist methyllycaconitine (MLA). CFA induced marked paw swelling and reduced thresholds of mechanical and cold-induced paw withdrawal. The levels of TNF-alpha, IL-1 and IL-2 in the serum of AA rats were increased, whereas the level of IL-10 was decreased. Histopathological examination of synoviocytes showed pronounced inflammation and accumulation of collagen. The administration of CTX (17.0 microg/kg, ip) significantly reduced paw swelling and mechanical and thermal hyperalgesia. CTX also reduced the production of TNF-alpha, IL-1, and IL-2 but increased the production of IL-10 and altered pathohistological changes. The analgesic and anti-inflammatory efficacy of CTX was significantly reduced by MLA (3 mg/kg, sc). These results indicate that CTX has a beneficial effect on CFA-induced arthritis by modulating the production of inflammatory cytokines. alpha(7)-nAChR appears to mediate the anti-nociceptive and anti-inflammatory actions of CTX.

  13. Omentin inhibits TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via ERK/NF-{kappa}B pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhong, Xia, E-mail: zhongxia1977@126.com; Li, Xiaonan; Liu, Fuli

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Black-Right-Pointing-Pointer Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-{alpha} in HUVECs. Black-Right-Pointing-Pointer Omentin inhibits TNF-{alpha}-induced ERK and NF-{kappa}B activation in HUVECs. Black-Right-Pointing-Pointer Omentin supreeses TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 via ERK/NF-{kappa}B pathway. -- Abstract: In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-{alpha} (TNF-{alpha}) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibitedmore » TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-{alpha}-activated signal pathway of nuclear factor-{kappa}B (NF-{kappa}B) by preventing NF-{kappa}B inhibitory protein (I{kappa}B{alpha}) degradation and NF-{kappa}B/DNA binding activity. Omentin pretreatment significantly inhibited TNF-{alpha}-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-{alpha}-induced NF-{kappa}B activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-{alpha}. These results suggest that omentin may inhibit TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-{kappa}B pathway.« less

  14. Suppression of glutamate-induced excitotoxicity by 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride in rat glial cultures.

    PubMed

    Kim, Eun-A; Hahn, Hoh-Gyu; Kim, Key-Sun; Kim, Tae Ue; Choi, Soo Young; Cho, Sung-Woo

    2010-07-01

    We have screened new drugs with a view to developing effective drugs against glutamate-induced excitotoxicity. In the present work, we show effects of a new drug, 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride against glutamate-induced excitotoxicity in primary rat glial cultures. Pretreatment of glial cells with 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride for 2 h significantly protected glial cells against glutamate-induced excitotoxicity in a time- and dose-dependent manner with an optimum concentration of 100 microM. The drug significantly reduced production of proinflammatory cytokines, tumor necrosis factor-alpha, and interlukin-1beta in glutamate-induced excitotoxicity. The drug also prevented glutamate-induced intracellular Ca2+ influx and reduced the subsequent overproduction of nitric oxide and reactive oxygen species. Furthermore, the drug preserved the mitochondrial potential and inhibited the overproduction of cytochrome c. In addition, the drug effectively attenuated the protein level changes of beta-catenin and glycogen synthase kinase-3beta. These results suggest that 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride effectively protected primary cultures of rat glial cells against glutamate-induced excitotoxicity.

  15. Alpha-driven magnetohydrodynamics (MHD) and MHD-induced alpha loss in the Tokamak Fusion Test Reactor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chang, Z.; Nazikian, R.; Fu, G.Y.

    1997-02-01

    Alpha-driven toroidal Alfven eigenmodes (TAEs) are observed as predicted by theory in the post neutral beam phase in high central q (safety factor) deuterium-tritium (D-T) plasmas in the Tokamak Fusion Test Reactor (TFTR). The mode location, poloidal structure and the importance of q profile for TAE instability are discussed. So far no alpha particle loss due to these modes was detected due to the small mode amplitude. However, alpha loss induced by kinetic ballooning modes (KBMs) was observed in high confinement D-T discharges. Particle orbit simulation demonstrates that the wave-particle resonant interaction can explain the observed correlation between the increasemore » in alpha loss and appearance of multiple high-n (n {ge} 6, n is the toroidal mode number) modes.« less

  16. Regulation of valine and. alpha. -ketoisocaproate metabolism in rat kidney mitochondria

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miller, R.H.; Harper, A.E.

    1988-10-01

    Activities of branched-chain amino acid (BCAA) aminotransferase (BCAT) and {alpha}-keto acid dehydrogenase (BCKD) were assayed in mitochondria isolated from kidneys of rats. Rates of transamination of valine and oxidation of keto acids {alpha}-ketoisocaproate (KIC) or {alpha}-ketoisovalerate (KIV) were estimated using radioactive tracers of the appropriate substrate from amounts of {sup 14}C-labeled products formed. Because of the high mitochondrial BCAT activity, an amino acceptor for BCAT, {alpha}-ketoglutarate ({alpha}-KG) or KIC, was added to the assay medium when valine was the substrate. Rates of valine transamination and subsequent oxidation of the KIV formed were determined with 0.5 mM {alpha}-KG as the aminomore » acceptor; these rates were 5- to 50-fold those without added {alpha}-KG. Rates of CO{sub 2} evolution from valine also increased when KIC was present; however, with KIC concentrations above 0.2 mM, rates of CO{sub 2} evolution from valine declined although rates of transamination continued to rise. When 0.05 mM KIC was added to the assay medium, oxidation of KIC was suppressed by inclusion of valine or glutamate in the medium. When valine was present KIC was not oxidized preferentially, presumably because it was also serving as an amino acceptor for BCAT. These results indicate that as the supply of amino acceptor, {alpha}-KG or KIC, is increased in mitochondria not only is the rate of valine transamination stimulated but also the rate of oxidation of the KIV formed from valine. Thus the rate of oxidation of BCAA can be controlled by factors that influence the rate and direction of BCAA transamination and, thereby, the supply of substrate for BCKD.« less

  17. Development and Validation of Attitude toward Gestational Surrogacy Scale in Iranian Infertile Couples

    PubMed Central

    Rahimi Kian, Fatemeh; Zandi, Afsaneh; Omani Samani, Reza; Maroufizadeh, Saman; Mehran, Abbas

    2016-01-01

    Background Surrogacy is one of the most challenging infertility treatments engaging ethical, psychological and social issues. Attitudes survey plays an important role to disclosure variant aspects of surrogacy, to help meeting legislative gaps and ambiguities, and to convert controversial dimensions surrounding surrogacy to a normative concept that eliminates stigma. The aim of this study is to develop a comprehensive scale for gestational surrogacy attitudes. Materials and Methods Development process of gestational surrogacy attitudes scale (GSAS) performed based on a descriptive cross-sectional study and included a rich data pool gathered from literature reviews, a qualitative pilot study on 15 infertile couples (n=30), use of expert advisory panel (EAP) consisting of 20 members, as well as use of content validity through qualitative and quantitative study by the means of content validity ratio (CVR) and content validity index (CVI). Also internal consistence using Cronbach’s alpha and test-retest reliability using intracalss correlation coefficient (ICC) were evaluated. Application of GSAS was tested in a cross-sectional study that was conducted on 200 infertile couples (n=400) at Royan Institute, Tehran, Iran, during 2014. Results Final version of GSAS had 30 items within five subscales including "acceptance of surrogacy", "Surrogacy and public attitudes", "Child born through surrogacy", "Surrogate mother", and "Intentional attitude and surrogacy future attempt". Content validity was represented with values of CVR=0.73 and CVI =0.98. Cronbach’s alpha value was 0.91 for the overall scale, while ICC value due to test-retest responses was 0.89. Conclusion Acceptable level of competency and capability of GSAS is significantly indicated; therefore, it seems to be an appropriate tool for the evaluation of gestational surrogacy attitudes in Iranian infertile couples. PMID:27123208

  18. Lipid peroxide, alpha-tocopherol and retinoid levels in plasma and liver of rats fed diets containing beta-carotene and 13-cis-retinoic acid.

    PubMed

    Alam, S Q; Alam, B S

    1983-12-01

    The effect of feeding large amounts of beta-carotene and 13-cis-retinoic acid (RA) on plasma and liver levels of alpha-tocopherol, lipid peroxides and retinoids was studied. Groups of young male rats were fed semipurified diets supplemented with 0, 100 mg/kg beta-carotene, 20 and 100 mg/kg 13-cis-RA. After feeding the various diets for 11 weeks, rats were killed and the concentrations of lipid peroxides, alpha-tocopherol, and retinoids were measured in blood plasma and liver. Peroxide levels were increased and alpha-tocopherol levels were decreased in plasma as well as liver of rats fed diets containing 13-cis-RA; this effect seems to be dose dependent, beta-Carotene had no significant effect on either of the above parameters. There was a decrease in the liver and plasma concentrations of retinol in rats fed 13-cis-RA; the levels of RA were generally higher in these two groups. The results suggest that the mechanism whereby 13-cis-RA increases the tissue peroxide levels may be related to its ability to decrease alpha-tocopherol levels.

  19. The C-terminal region of alpha-crystallin: involvement in protection against heat-induced denaturation

    NASA Technical Reports Server (NTRS)

    Takemoto, L.; Emmons, T.; Horwitz, J.; Spooner, B. S. (Principal Investigator)

    1993-01-01

    Recent studies have demonstrated that the alpha-crystallins can protect other proteins against heat-induced denaturation and aggregation. To determine the possible involvement of the C-terminal region in this activity, the alpha-crystallins were subjected to limited tryptic digestion, and the amount of cleavage from the N-terminal and C-terminal regions of the alpha-A and alpha-B crystallin chains was assessed using antisera specific for these regions. Limited tryptic digestion resulted in cleavage only from the C-terminal region of alpha-A crystallin. This trypsin-treated alpha-A crystallin preparation showed a decreased ability to protect proteins from heat-induced aggregation using an in vitro assay. Together, these results demonstrate that the C-terminal region of alpha-A crystallin is important for its ability to protect against heat-induced aggregation, which is consistent with the hypothesis that post-translational changes that are known to occur at the C-terminal region may have significant effects on the ability of alpha-A crystallin to protect against protein denaturation in vivo.

  20. Bladder pain induced by prolonged peripheral alpha 1A adrenoceptor stimulation involves the enhancement of transient receptor potential vanilloid 1 activity and an increase of urothelial adenosine triphosphate release.

    PubMed

    Matos, R; Cordeiro, J M; Coelho, A; Ferreira, S; Silva, C; Igawa, Y; Cruz, F; Charrua, A

    2016-12-01

    Pathophysiological mechanisms of chronic visceral pain (CVP) are unknown. This study explores the association between the sympathetic system and bladder nociceptors activity by testing the effect of a prolonged adrenergic stimulation on transient receptor potential vanilloid 1 (TRPV1) activity and on urothelial adenosine triphosphate (ATP) release. Female Wistar rats received saline, phenylephrine (PHE), PHE + silodosin, PHE + naftopidil or PHE + prazosin. TRPV1 knockout and wild-type mice received saline or PHE. Visceral pain behaviour tests were performed before and after treatment. Cystometry was performed, during saline and capsaicin infusion. Fos immunoreactivity was assessed in L6 spinal cord segment. Human urothelial ATP release induced by mechanical and thermal stimulation was evaluated. Subcutaneous, but not intrathecal, PHE administration induced pain, which was reversed by silodosin, a selective alpha 1A adrenoceptor antagonist, but not by naftopidil, a relatively selective antagonist for alpha 1D adrenoceptor. Silodosin also reversed PHE-induced bladder hyperactivity and L6 spinal cord Fos expression. Thus, in subsequent experiments, only silodosin was used. Wild-type, but not TRPV1 knockout, mice exhibited phenylephrine-induced pain. Capsaicin induced a greater increase in voiding contractions in PHE-treated rats than in control animals, and silodosin reversed this effect. When treated with PHE, ATP release from human urothelial cells was enhanced either by mechanical stimulation or by lowering the thermal threshold of urothelial TRPV1, which becomes abnormally responsive at body temperature. This study suggests that the activation of peripheral alpha 1A adrenoceptors induces CVP, probably through its interaction with TRPV1 and ATP release. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  1. DNA-binding activity of TNF-{alpha} inducing protein from Helicobacter pylori

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kuzuhara, T.; Suganuma, M.; Oka, K.

    2007-11-03

    Tumor necrosis factor-{alpha} (TNF-{alpha}) inducing protein (Tip{alpha}) is a carcinogenic factor secreted from Helicobacter pylori (H. pylori), mediated through both enhanced expression of TNF-{alpha} and chemokine genes and activation of nuclear factor-{kappa}B. Since Tip{alpha} enters gastric cancer cells, the Tip{alpha} binding molecules in the cells should be investigated. The direct DNA-binding activity of Tip{alpha} was observed by pull down assay using single- and double-stranded genomic DNA cellulose. The surface plasmon resonance assay, indicating an association between Tip{alpha} and DNA, revealed that the affinity of Tip{alpha} for (dGdC)10 is 2400 times stronger than that of del-Tip{alpha}, an inactive Tip{alpha}. This suggestsmore » a strong correlation between DNA-binding activity and carcinogenic activity of Tip{alpha}. And the DNA-binding activity of Tip{alpha} was first demonstrated with a molecule secreted from H. pylori.« less

  2. alpha-Adrenoceptor and opioid receptor modulation of clonidine-induced antinociception.

    PubMed Central

    Sierralta, F.; Naquira, D.; Pinardi, G.; Miranda, H. F.

    1996-01-01

    1. The antinociceptive action of clonidine (Clon) and the interactions with alpha 1, alpha 2 adrenoceptor and opioid receptor antagonists was evaluated in mice by use of chemical algesiometric test (acetic acid writhing test). 2. Clon produced a dose-dependent antinociceptive action and the ED50 for intracerebroventricular (i.c.v.) was lower than for intraperitoneal (i.p.) administration (1 ng kg-1 vs 300 ng kg-1). The parallelism of the dose-response curves indicates activation of a common receptor subtype. 3. Systemic administration of prazosin and terazosin displayed antinociceptive activity. Pretreatment with prazosin produced a dual action: i.c.v. Clon effect did not change, and i.p. Clon effect was enhanced. Yohimbine i.c.v. or i.p. did not induce antinonciception, but antagonized Clon-induced activity. These results suggest that alpha 1- and alpha 2-adrenoceptors, either located at the pre- and/or post-synaptic level, are involved in the control of spinal antinociception. 4. Naloxone (NX) and naltrexone (NTX) induced antinociceptive effects at low doses (microgram kg-1 range) and a lower antinociceptive effect at higher doses (mg kg-1 range). Low doses of NX or NTX antagonized Clon antinociception, possibly in relation to a preferential mu opioid receptor antagonism. In contrast, high doses of NX or NTX increased the antinociceptive activity of Clon, which could be due to an enhanced inhibition of the release of substance P. 5. The results obtained in the present work suggest the involvement of alpha 1-, alpha 2-adrenoceptor and opioid receptors in the modulation of the antinociceptive activity of clonidine, which seems to be exerted either at spinal and/or supraspinal level. PMID:8894177

  3. alpha-Adrenoceptor and opioid receptor modulation of clonidine-induced antinociception.

    PubMed

    Sierralta, F; Naquira, D; Pinardi, G; Miranda, H F

    1996-10-01

    1. The antinociceptive action of clonidine (Clon) and the interactions with alpha 1, alpha 2 adrenoceptor and opioid receptor antagonists was evaluated in mice by use of chemical algesiometric test (acetic acid writhing test). 2. Clon produced a dose-dependent antinociceptive action and the ED50 for intracerebroventricular (i.c.v.) was lower than for intraperitoneal (i.p.) administration (1 ng kg-1 vs 300 ng kg-1). The parallelism of the dose-response curves indicates activation of a common receptor subtype. 3. Systemic administration of prazosin and terazosin displayed antinociceptive activity. Pretreatment with prazosin produced a dual action: i.c.v. Clon effect did not change, and i.p. Clon effect was enhanced. Yohimbine i.c.v. or i.p. did not induce antinonciception, but antagonized Clon-induced activity. These results suggest that alpha 1- and alpha 2-adrenoceptors, either located at the pre- and/or post-synaptic level, are involved in the control of spinal antinociception. 4. Naloxone (NX) and naltrexone (NTX) induced antinociceptive effects at low doses (microgram kg-1 range) and a lower antinociceptive effect at higher doses (mg kg-1 range). Low doses of NX or NTX antagonized Clon antinociception, possibly in relation to a preferential mu opioid receptor antagonism. In contrast, high doses of NX or NTX increased the antinociceptive activity of Clon, which could be due to an enhanced inhibition of the release of substance P. 5. The results obtained in the present work suggest the involvement of alpha 1-, alpha 2-adrenoceptor and opioid receptors in the modulation of the antinociceptive activity of clonidine, which seems to be exerted either at spinal and/or supraspinal level.

  4. Oral administration of Saccharomyces boulardii ameliorates carbon tetrachloride-induced liver fibrosis in rats via reducing intestinal permeability and modulating gut microbial composition.

    PubMed

    Li, Ming; Zhu, Lin; Xie, Ao; Yuan, Jieli

    2015-02-01

    To investigate the effects of orally administrated Saccharomyces boulardii (S. boulardii) on the progress of carbon tetrachloride (CCl4)-induced liver fibrosis, 34 male Wistar rats were randomly divided into four experimental groups including the control group (n = 8), the cirrhotic group (n = 10), the preventive group (n = 8), and the treatment group (n = 8). Results showed that the liver expression levels of collagen, type I, alpha 1 (Col1A1), alpha smooth muscle actin (αSMA), transforming growth factor beta (TGF-β) and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) increased significantly in cirrhotic rats compared with control and decreased by S. boulardii administration. Treatment of S. boulardii also attenuated the increased endotoxin levels and pro-inflammatory cytokines in CCl4-treated rats. And, these were associated with the changes of intestinal permeability and fecal microbial composition. Our study suggested that oral administration of S. boulardii can promote the liver function of CCl4-treated rats, and the preventive treatment of this probiotic yeast may decelerate the progress of liver fibrosis.

  5. Spectral measurements of alpha-induced radioluminescence in various gases

    NASA Astrophysics Data System (ADS)

    Brett, Jaclyn; Koehler, Katrina E.; Bischak, Michael; Famiano, Michael; Jenkins, Jared; Klankowski, Levi; Niraula, Prashantamani; Pancella, Paul; Lakis, Rollin

    2017-12-01

    Radioluminescent emission in Ar, N2, O2, and dry air at P = 1 atm was observed induced by 5 MeV α particles. The wavelength range with a single detector spanned 250-1100 nm, extending the range well into the UV and IR bands with a single detector. Measured spectral lines for alpha-induced luminescence were corrected for detector transmission and intensities compared to previous work. The exploration of multiple gases over a wide frequency range opens the door to security and remote sensing applications, where different environments are routinely encountered. This work provides spectra that can be used in guiding future filter development focusing on remote alpha detection.

  6. Red algae (Gelidium amansii) reduces adiposity via activation of lipolysis in rats with diabetes induced by streptozotocin-nicotinamide.

    PubMed

    Yang, Tsung-Han; Yao, Hsien-Tsung; Chiang, Meng-Tsan

    2015-12-01

    Gelidium amansii (GA) is an edible red algae that is distributed mainly in northeastern Taiwan. This study was designed to investigate the effects of GA on plasma glucose, lipids, and adipocytokines in rats with streptozotocin-nicotinamide-induced diabetes. Rats were divided into four groups: (1) rats without diabetes fed a high-fat diet (control group); (2) rats with diabetes fed a high-fat diet; (3) rats with diabetes fed a high-fat diet with thiazolidinedione in the diet; and (4) rats with diabetes fed a high-fat diet and GA. The experimental diet and drinking water were available ad libitum for 11 weeks. After the 11-week feeding study, plasma glucose, triglyceride, and cholesterol concentrations were lower in rats with diabetes fed the GA diet than in animals with diabetes fed the control diet. In addition, cholesterol and triglyceride excretion were significantly higher in rats with diabetes fed the GA diet. Moreover, GA feeding induced lipolysis in both paraepididymal and perirenal adipose tissues. Adipose tissue (paraepididymal and perirenal) weight and triglyceride contents were lower after GA treatment. Plasma adipocytokines including tumor necrosis factor-alpha, interleukin-6, and plasminogen activator inhibitor-1 were reduced by GA feeding in rats with diabetes. The results of the current study suggest that GA feeding may regulate plasma glucose and lipid levels and prevent adipose tissue accumulation in rats with diabetes. Copyright © 2015. Published by Elsevier B.V.

  7. Lower genital tract infections in infertile Nigerian women compared with controls.

    PubMed

    Okonofua, F E; Ako-Nai, K A; Dighitoghi, M D

    1995-06-01

    To investigate the possibility that infertile Nigerian women have a higher rate of cervical colonisation with pathogenic and facultative organisms than fertile controls. The prevalence of common microorganisms in the vagina and endocervical canals of infertile women was compared with that of pregnant controls. The Obafemi Awolowo University Hospital Maternity Centre. 92 infertile women were compared with 86 pregnant controls. rates of isolation of Neisseria gonorrhoeae, Candida albicans, Trichomonas vaginalis and other facultative organisms in cases and controls. The rate of isolation of Neisseria gonorrheae was 17.4% among infertile women compared with 10.5% in the group of pregnant women (p > 0.05). There was no significant difference between the groups in the rate of isolation of Candida albicans, Trichomonas vaginalis and other facultative organisms. High rates of isolation of microorganisms were observed in both groups. However, women with secondary infertility had higher rate of carriage of Neisseria gonorrheae, Candida albicans and Staphylococcus aureus as compared with women with primary infertility. Nearly 15% of infertile women had previous episodes of pelvic inflammatory disease and 26% had had induced abortions. A positive history of vaginal discharge was a poor predictor of vagina and endocervical carriage of microorganisms. High rates of pathogenic organisms exist in the lower genital tract of infertile women and controls. Women with secondary infertility are more likely to have pathogenic organisms than women with primary infertility. A policy of routinely screening women for lower genital tract infections should be pursued in this population because of the high rate of infection.

  8. Adverse cutaneous reactions induced by TNF-alpha antagonist therapy.

    PubMed

    Borrás-Blasco, Joaquín; Navarro-Ruiz, Andrés; Borrás, Consuelo; Casterá, Elvira

    2009-11-01

    To review adverse cutaneous drug reactions induced by tumor necrosis factor alpha (TNF-alpha) antagonist therapy. A literature search was performed using PubMed (1996-March 2009), EMBASE, and selected MEDLINE Ovid bibliography searches. All language clinical trial data, case reports, letters, and review articles identified from the data sources were used. Since the introduction of TNF-alpha antagonist, the incidence of adverse cutaneous drug reactions has increased significantly. A wide range of different skin lesions might occur during TNF-alpha antagonist treatment. New onset or exacerbation of psoriasis has been reported in patients treated with TNF-alpha antagonists for a variety of rheumatologic conditions. TNF-alpha antagonist therapy has been associated with a lupus-like syndrome; most of these case reports occurred in patients receiving either etanercept or infliximab. Serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely with the use of TNF-alpha antagonists. As the use of TNF-alpha antagonists continues to increase, the diagnosis and management of cutaneous side effects will become an increasingly important challenge. In patients receiving TNF-alpha antagonist treatment, skin disease should be considered, and clinicians need to be aware of the adverse reactions of these drugs.

  9. Aberrant expression and hormonal regulation of Galectin-3 in endometriosis women with infertility.

    PubMed

    Yang, H; Yin, J; Ficarrotta, K; Hsu, S H; Zhang, W; Cheng, C

    2016-07-01

    To investigate the role and potential molecular mechanism of Galectin-3 (Gal-3) in the etiology of endometriosis-associated infertility. We detected Gal-3 expression in eutopic endometrium from women with endometriosis-associated infertility and healthy women without endometriosis or infertility. We then evaluated Gal-3 expression in endometrial glandular epithelial cells (EECs) and endometrial stromal cells (ESCs) and investigated its response to hormone stimulation in EECs and ESCs from both groups of women. Results of real-time PCR and western blot analysis showed Gal-3 expression in both proliferative and secretory stages of the menstrual cycle decreased significantly in women with endometriosis-associated infertility compared to healthy women. The changes in expression of Gal-3 were more dramatic in EECs than ESCs. Moreover, estrogen (E2) and progesterone (P4) induced Gal-3 expression in EECs of healthy groups, and P4 was more significant than E2 and combined E2 and P4 (E2P4). However, in the endometriosis group, P4 failed to induce a similar increase in Gal-3 expression. Our results suggest that aberrant expression of Gal-3 might contribute to infertility in patients with endometriosis due to progesterone resistance.

  10. Vitamin E and Hippophea rhamnoides L. extract reduce nicotine-induced oxidative stress in rat heart.

    PubMed

    Gumustekin, Kenan; Taysi, Seyithan; Alp, Hamit Hakan; Aktas, Omer; Oztasan, Nuray; Akcay, Fatih; Suleyman, Halis; Akar, Sedat; Dane, Senol; Gul, Mustafa

    2010-06-01

    The effects of vitamin E and Hippophea rhamnoides L. extract (HRe-1) on nicotine-induced oxidative stress in rat heart were investigated. There were eight rats per group and supplementation period was 3 weeks. The groups were: nicotine [0.5 mg kg(-1)day(-1), intraperitoneal (i.p.)]; nicotine plus vitamin E [75 mg kg(-1)day(-1), intragastric (i.g.)]; nicotine plus HRe-1 (250 mg kg(-1)day(-1), i.g.); and the control group (receiving only vehicles). Nicotine increased the malondialdehyde level, which was prevented by both vitamin E and HRe-1. Glutathione peroxidase (GPx) activity in nicotine plus vitamin E supplemented group was higher than the others. Glutathione S-transferase (GST) activity in nicotine plus HRe-1 supplemented group was increased compared with the control group. Catalase activity was higher in nicotine group compared with others. GPx activity in nicotine plus vitamin E supplemented group was elevated compared with the others. Total and non-enzymatic superoxide scavenger activities in nicotine plus vitamin E supplemented group were lower than nicotine plus HRe-1 supplemented group. Superoxide dismutase (SOD) activity was higher in nicotine plus HRe-1 supplemented group compared with others. Glutathione reductase activity and nitric oxide level were not affected. Increased SOD and GST activities might have taken part in the prevention of nicotine-induced oxidative stress in HRe-1 supplemented group in rat heart. Flavonols such as quercetin, and isorahmnetin, tocopherols such as alpha-tocopherol and beta-tocopherol and carotenoids such as alpha-carotene and beta-carotene, reported to be present in H. rhamnoides L. extracts may be responsible for the antioxidant effects of this plant extract. 2010 John Wiley & Sons, Ltd.

  11. Intervention effect and dose-dependent response of tanreqing injection on airway inflammation in lipopolysaccharide-induced rats.

    PubMed

    Dong, Shoujin; Zhong, Yunqing; Yang, Kun; Xiong, Xiaoling; Mao, Bing

    2013-08-01

    To assess the effect of Tanreqing injection on airway inflammation in rats. A rat model of airway inflammation was generated with lipopolysaccharide (LPS). Tanreqing injection was given by intratracheal instillation, and bronchoalveolar lavage fluid (BALF) from the right lung was collected. BALF total cell and neutrophil counts were then determined. In addition, BALF levels of inflammatory cytokines interleukin-13, cytokine-induced neutrophil chemoat-tractant-1, and tumor necrosis factor-alpha were measured using enzyme linked immunosorbent assay. The middle lobe of the right lung was stained with hematoxylin-eosin and histological changes examined. LPS increased airway inflammation, decreased BALF inflammatory cell count, inflammatory cytokine levels, and suppressed leukocyte influx of the lung. The LPS-induced airway inflammation peaked at 24 h, decreased beginning at 48 h, and had decreased markedly by 96 h. Tanreqing injection contains anti-inflammatory properties, and inhibits airway inflammation in a dose-dependent manner.

  12. Gastroprotective effect of garlic in indomethacin induced gastric ulcer in rats.

    PubMed

    El-Ashmawy, Nahla E; Khedr, Eman G; El-Bahrawy, Hoda A; Selim, Hend M

    2016-01-01

    Garlic, in its natural plant state, has a great history in ancient medicine as a remedy for many diseases. In our study, the gastroprotective effect of aged garlic extract (AGE) and the possible underlying mechanisms were investigated in an experimental model of indomethacin-induced gastric ulcer. Male Wistar rats were divided into four groups: (normal control, n = 20), ulcer control (indomethacin group, n = 20), (omeprazole group, n = 30) and (garlic group, n = 20). Each dose of garlic and omeprazole was given to rats orally daily for 10 consecutive days before induction of ulcer by indomethacin. Indomethacin was given as a single oral dose (100 mg/kg). Four hours later after indomethacin treatment, the rats were sacrificed and gastric tissue was obtained for histopathological examination, calculation of ulcer index and measurement of oxidative stress markers as well as gastroprotective mediators. The results showed that indomethacin induced gastric ulcer (ulcer index = 2900), was associated with a significant increase of tumor necrosis factor-alpha and malondialdehyde, and significant decrease of the gastroprotective mediators prostaglandin E2, glutathione (GSH) and nitric oxide (NO) compared with normal control. Pretreatment with AGE produced comparable results with those obtained in the omeprazole group; the preventive index in the AGE group was 83.4% compared with 94.5% in the omeprazole group. The prophylactic role of AGE in indomethacin-induced ulcer was, in part, mediated by decreasing oxidative stress and increasing gastric level of PGE2, GSH, and NO. AGE corrected the histopathological abnormalities in gastric tissue and proved a promising gastroprotective role in gastric ulcer. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Expression of hypoxia-induced factor-1 alpha in early-stage and in metastatic oral squamous cell carcinoma.

    PubMed

    Ribeiro, Maisa; Teixeira, Sarah R; Azevedo, Monarko N; Fraga, Ailton C; Gontijo, Antônio Pm; Vêncio, Eneida F

    2017-04-01

    To investigate hypoxia-induced factor-1 alpha expression in distinct oral squamous cell carcinoma subtypes and topographies and correlate with clinicopathological data. Hypoxia-induced factor-1 alpha expression was assessed by immunohistochemistry in 93 cases of OSCC. Clinical and histopathological data were reviewed from medical records. Hypoxia-induced factor-1 alpha status was distinct according to tumor location, subtype and topography affect. In superficial oral squamous cell carcinomas, most tumor cells overexpressed hypoxia-induced factor-1 alpha, whereas hypoxia-induced factor-1 alpha was restricted to the intratumoral region in conventional squamous cell carcinomas. All basaloid squamous cell carcinomas exhibited downregulation of hypoxia-induced factor-1 alpha. Interestingly, metastatic lymph nodes (91.7%, p = 0.001) and the intratumoral regions of corresponding primary tumors (58.3%, p = 0.142) showed hypoxia-induced factor-1 alpha-positive tumor cells. Overall survival was poor in patients with metastatic lymph nodes. Hypoxia-induced factor-1 alpha has distinct expression patterns in different oral squamous cell carcinoma subtypes and topographies, suggesting that low oxygen tension promotes the growth pattern of superficial and conventional squamous cell carcinoma, but not basaloid squamous cell carcinoma. Indeed, a hypoxic environment may facilitate regional metastasis, making it a useful diagnostic and prognostic marker in primary tumors.

  14. Red Palm Oil Attenuates Lead Acetate Induced Testicular Damage in Adult Male Sprague-Dawley Rats.

    PubMed

    Jegede, A I; Offor, U; Azu, O O; Akinloye, O

    2015-01-01

    To study the protective effect of Red Palm Oil (RPO) on testicular damage induced by administration of lead acetate on male Sprague-Dawley rats, 28 rats divided into four groups of 7 animals each were used. They were administered orally with RPO (1 mL and 2 mL) and lead acetate (i.p.) 6 mg/kg body weight/day, respectively. Treatment was conducted for 8 weeks, and 24 hrs after the last treatment the rats were sacrificed using cervical dislocation. Sperms collected from epididymis were used for seminal fluid analyses; while the testes sample was used for ROS and oxidative enzyme activities assessment. Statistical analysis was carried out using GraphPad Prism 5.02 statistical analysis package. Administration of lead acetate increased generation of reactive oxygen species (ROS) significantly (p < 0.05) as evidenced by the elevated value of H2O2 and LPO and decreased GSH level. Also there was reduced epididymal sperm count, poor grade of sperm motility, and lower percentage of normal sperm morphology significantly. Coadministration with RPO, however, has a protective effect against lead toxicity by decreasing H2O2 production, increased GSH level, and increased sperm qualities especially. This shows that RPO has a potential to attenuate the toxic effect of lead on testicular cells preventing possible resultant male infertility.

  15. Adolescent Alcohol Exposure-Induced Changes in Alpha-Melanocyte Stimulating Hormone and Neuropeptide Y Pathways via Histone Acetylation in the Brain During Adulthood.

    PubMed

    Kokare, Dadasaheb M; Kyzar, Evan J; Zhang, Huaibo; Sakharkar, Amul J; Pandey, Subhash C

    2017-09-01

    Adolescent intermittent ethanol exposure causes long-lasting alterations in brain epigenetic mechanisms. Melanocortin and neuropeptide Y signaling interact and are affected by ethanol exposure in the brain. Here, the persistent effects of adolescent intermittent ethanol on alpha-melanocyte stimulating hormone, melanocortin 4 receptor, and neuropeptide Y expression and their regulation by histone acetylation mechanisms were investigated in adulthood. Male rats were exposed to adolescent intermittent ethanol (2 g/kg, i.p.) or volume-matched adolescent intermittent saline from postnatal days 28 to 41 and allowed to grow to postnatal day 92. Anxiety-like behaviors were measured by the elevated plus-maze test. Brain regions from adult rats were used to examine changes in alpha-melanocyte stimulating hormone, melanocortin 4 receptor, and neuropeptide Y expression and the histone acetylation status of their promoters. Adolescent intermittent ethanol-exposed adult rats displayed anxiety-like behaviors and showed increased pro-opiomelanocortin mRNA levels in the hypothalamus and increased melanocortin 4 receptor mRNA levels in both the amygdala and hypothalamus compared with adolescent intermittent saline-exposed adult rats. The alpha-Melanocyte stimulating hormone and melanocortin 4 receptor protein levels were increased in the central and medial nucleus of the amygdala, paraventricular nucleus, and arcuate nucleus of the hypothalamus in adolescent intermittent ethanol-exposed compared with adolescent intermittent saline-exposed adult rats. Neuropeptide Y protein levels were decreased in the central and medial nucleus of the amygdala of adolescent intermittent ethanol-exposed compared with adolescent intermittent saline-exposed adult rats. Histone H3K9/14 acetylation was decreased in the neuropeptide Y promoter in the amygdala but increased in the melanocortin 4 receptor gene promoter in the amygdala and the melanocortin 4 receptor and pro-opiomelanocortin promoters in the

  16. [Infection and infertility].

    PubMed

    Pilatz, A; Boecker, M; Schuppe, H-C; Diemer, Th; Wagenlehner, F

    2016-07-01

    Infections in the urogenital tract are accepted causes of male infertility. Epidemiologic data indicate 6-10 % of all males undergoing andrological work-up for infertility having an infectious etiology. This review gives a comprehensive overview on the most important urogenital tract infections (prostatitis, epididymitis, orchitis, male accessory gland infection-MAGI) and the impact on fertility. In males suffering infertility, evidence is also presented regarding an infectious etiology.

  17. Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat.

    PubMed

    Arakaki, Xianghong; McCleary, Paige; Techy, Matthew; Chiang, Jiarong; Kuo, Linus; Fonteh, Alfred N; Armstrong, Brian; Levy, Dan; Harrington, Michael G

    2013-03-14

    Cerebrospinal fluid (CSF) sodium concentration increases during migraine attacks, and both CSF and vitreous humor sodium increase in the rat migraine model. The Na,K-ATPase is a probable source of these sodium fluxes. Since Na,K-ATPase isoforms have different locations and physiological roles, our objective was to establish which alpha isoforms are present at sites where sodium homeostasis is disrupted. Specific Na,K-ATPase alpha isoforms were identified in rat tissues by immunohistochemistry at the blood-CSF barrier at the choroid plexus, at the blood-CSF-trigeminal barrier at the meninges, at the blood-retina barrier, and at the blood-aqueous barrier at the ciliary body. Calcitonin gene-related peptide (CGRP), occludin, or von Willibrand factor (vWF) were co-localized with Na,K-ATPase to identify trigeminal nociceptor fibers, tight junctions, and capillary endothelial cells respectively. The Na,K-ATPase alpha-2 isoform is located on capillaries and intensely at nociceptive trigeminal nerve fibers at the meningeal blood-CSF-trigeminal barrier. Alpha-1 and -3 are lightly expressed on the trigeminal nerve fibers but not at capillaries. Alpha-2 is expressed at the blood-retina barriers and, with alpha-1, at the ciliary body blood aqueous barrier. Intense apical membrane alpha-1 was associated with moderate cytoplasmic alpha-2 expression at the choroid plexus blood-CSF barrier. Na,K-ATPase alpha isoforms are present at the meningeal, choroid plexus, and retinal barriers. Alpha-2 predominates at the capillary endothelial cells in the meninges and retinal ganglion cell layer.

  18. Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat

    PubMed Central

    2013-01-01

    Background Cerebrospinal fluid (CSF) sodium concentration increases during migraine attacks, and both CSF and vitreous humor sodium increase in the rat migraine model. The Na,K-ATPase is a probable source of these sodium fluxes. Since Na,K-ATPase isoforms have different locations and physiological roles, our objective was to establish which alpha isoforms are present at sites where sodium homeostasis is disrupted. Methods Specific Na,K-ATPase alpha isoforms were identified in rat tissues by immunohistochemistry at the blood-CSF barrier at the choroid plexus, at the blood-CSF-trigeminal barrier at the meninges, at the blood-retina barrier, and at the blood-aqueous barrier at the ciliary body. Calcitonin gene-related peptide (CGRP), occludin, or von Willibrand factor (vWF) were co-localized with Na,K-ATPase to identify trigeminal nociceptor fibers, tight junctions, and capillary endothelial cells respectively. Results The Na,K-ATPase alpha-2 isoform is located on capillaries and intensely at nociceptive trigeminal nerve fibers at the meningeal blood-CSF-trigeminal barrier. Alpha-1 and −3 are lightly expressed on the trigeminal nerve fibers but not at capillaries. Alpha-2 is expressed at the blood-retina barriers and, with alpha-1, at the ciliary body blood aqueous barrier. Intense apical membrane alpha-1 was associated with moderate cytoplasmic alpha-2 expression at the choroid plexus blood-CSF barrier. Conclusion Na,K-ATPase alpha isoforms are present at the meningeal, choroid plexus, and retinal barriers. Alpha-2 predominates at the capillary endothelial cells in the meninges and retinal ganglion cell layer. PMID:23497725

  19. Protective effects of sea cucumber (Holothuria atra) extract on testicular dysfunction induced by immune suppressant drugs in Wistar rats.

    PubMed

    Saad, D Y; Soliman, M M; Mohamed, A A; Youssef, G B

    2018-04-23

    The current study was aimed to evaluate the protective effect of Holothurian atra (HA) extract; naturally occurring marine resource, against methotrexate (MTX) induced testicular dysfunction. Mature rats received either MTX (20 mg/kg, intraperitoneally) or saline on the 7th day of experiment al design. Seven days prior and after MTX-injection, rats received HA at dose of 300 mg/kg intragastrically (HA + MTX group; HA group alone). Serum was extracted and testicular tissues were examined for the changes in serum biochemistry (liver & kidney biomarkers, testicular hormones and antioxidants), molecular and histopthological alterations using RT-PCR and immunohistochemistry. MTX-injected rats induced alteration in all testicular parameters. Prior administration of HA ameliorated the MTX-induced oxidative stress. HA administration normalised MTX-induced decrease in serum levels of interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), reproductive hormones (FSH, LH and testosterone) and antioxidants GST, SOD and catalase. MTX-injected rats down-regulated mRNA expression of GST, SOD, steroidogenesis associated genes, IFN-γ, Bcl2 and NFKB. MTX up-regulated BAX expression and caspase 9 immunoreactivity that were ameliorated in HA + MTX group. Collectively, HA ameliorated and restored all altered genes. In conclusion, HA is a promising supplement that is helpful in protection against testicular cytotoxicity and dysfunction induced by methotrexate. © 2018 Blackwell Verlag GmbH.

  20. TNF-alpha antagonist induced lupus on three different agents.

    PubMed

    Mudduluru, Bindu Madhavi; Shah, Shalin; Shamah, Steven; Swaminath, Arun

    2017-03-01

    Tumor necrosis factor alpha (TNF alpha) antagonists are biologic agents used in the management of inflammatory conditions such as rheumatoid arthritis, seronegative spondyloarthropathies and inflammatory bowel disease. These agents have been recently shown to cause a syndrome called anti-TNF induced lupus (ATIL), a rare condition which has similar clinical manifestations to idiopathic systemic lupus erythematosus (SLE). Given that extra-intestinal manifestations of inflammatory bowel disease include arthritis, it can be difficult to separate arthritis due to underlying disease from drug-induced arthritis. We present a case of a 28-year-old female with Crohn's disease, who developed disabling arthritis as a clinical manifestation of ATIL following treatment with three anti-TNF agents, namely infliximab, adalimumab and certolizumab.

  1. Spectral Measurements of Alpha-induced Radioluminescence in Various Gases

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brett, Jaclyn; Koehler, Katrina Elizabeth; Bischak, Michael

    Radioluminescent emission in Ar, N 2, O 2, and dry air at P=1 atm was observed induced by 5 MeV α particles. The wavelength range with a single detector spanned 250–1100 nm, extending the range well into the UV and IR bands with a single detector. Measured spectral lines for alpha-induced luminescence were corrected for detector transmission and intensities compared to previous work. The exploration of multiple gases over a wide frequency range opens the door to security and remote sensing applications, where different environments are routinely encountered. Finally, this work provides spectra that can be used in guiding futuremore » filter development focusing on remote alpha detection.« less

  2. Spectral Measurements of Alpha-induced Radioluminescence in Various Gases

    DOE PAGES

    Brett, Jaclyn; Koehler, Katrina Elizabeth; Bischak, Michael; ...

    2017-09-06

    Radioluminescent emission in Ar, N 2, O 2, and dry air at P=1 atm was observed induced by 5 MeV α particles. The wavelength range with a single detector spanned 250–1100 nm, extending the range well into the UV and IR bands with a single detector. Measured spectral lines for alpha-induced luminescence were corrected for detector transmission and intensities compared to previous work. The exploration of multiple gases over a wide frequency range opens the door to security and remote sensing applications, where different environments are routinely encountered. Finally, this work provides spectra that can be used in guiding futuremore » filter development focusing on remote alpha detection.« less

  3. Vitamin C attenuation of the development of type I diabetes mellitus by interferon-alpha.

    PubMed

    al-Zuhair, H; Mohamed, H E

    1998-07-01

    Interferon alpha (IFN-alpha) inhibits insulin release and may be cytotoxic to pancreatic islets. Increased free radical activity may be implicated in the cytotoxic action of IFN-alpha and development of diabetes mellitus. Therefore we measured markers of free radical activity (lipid peroxides and the non-peroxide-conjugated diene isomer of linoleic acid [PL-9,11-LA']) along with some pancreatic variables in male albino rats treated with IFN-alpha, as well as the possible protective effect of two antioxidants, vitamin C and mannitol. Compared to untreated rats, it was shown that IFN-alpha induced an increase in plasma glucose. Pancreatic and serum insulin, as well as serum C-peptide, were increased after 1 week, then their levels were reduced after 2 weeks. Plasma lipids peroxides and (PL-9,11-LA') were markedly elevated, while linoleic acid was reduced. These changes in the studied parameters were attributed, in part, to the superoxide and free radical generation during IFN-alpha treatment. Plasma glucagon was increased after 2 weeks. Administration of vitamin C along with IFN-alpha succeeded in modulating most of the altered parameters affected during IFN-alpha. The hyperglycaemic effect of IFN-alpha was greatly ameliorated and the negative effect on pancreatic and serum insulin and serum C-peptide were nearly abolished. The elevated levels of lipid peroxide and (PL-9,11-LA') and the reduction in linoleic acid being normalised. The only persistent effect was the increase in plasma glucagon. Concurrent administration of mannitol with IFN-alpha caused no changes in the parameters studied compared to that induced by treatment with IFN-alpha alone.

  4. Neuroendocrine mechanisms of development of experimental hyperandrogen-induced anovulation.

    PubMed

    Reznikov, A G; Sinitsyn, P V; Tarasenko, L V; Polyakova, L I

    2003-10-01

    An experimental model of hyperandrogen-induced anovulatory infertility (s.c. implantation of Silastic capsules containing testosterone into adult female rats) was used to study morphological, hormonal, and biochemical measures characterizing the state of the hypothalamo-hypophyseal-ovarian system. Impairments in functional androgen metabolism in the hypothalamus were seen, with decreases in the Luliberin sensitivity of the hypophysis, changes in the structure of estral cycles, and morphological changes in the ovaries; these findings are evidence for neuroendocrine disturbances in the control of ovulation. Flutamide, an experimental antiandrogen, led to partial normalization of the hormonal, biochemical, and morphological characteristics, as well as to recovery of fertility in females with anovulatory infertility.

  5. Anti-inflammatory effect of resveratrol on TNF-{alpha}-induced MCP-1 expression in adipocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhu Jian; Key Laboratory of Human Functional Genomics of Jiangsu Province, School of Basic Medical Science, Jiangsu Province Diabetes Center, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029; Yong Wei

    2008-05-02

    Chronic low-grade inflammation characterized by adipose tissue macrophage accumulation and abnormal cytokine production is a key feature of obesity and type 2 diabetes. Adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, induced by cytokines, has been shown to play an essential role in the early events during macrophage infiltration into adipose tissue. In this study we investigated the effects of resveratrol upon both tumor necrosis factor (TNF)-{alpha}-induced MCP-1 gene expression and its underlying signaling pathways in 3T3-L1 adipoctyes. Resveratrol was found to inhibit TNF-{alpha}-induced MCP-1 secretion and gene transcription, as well as promoter activity, which based on down-regulation of TNF-{alpha}-induced MCP-1 transcription. Nuclearmore » factor (NF)-{kappa}B was determined to play a major role in the TNF-{alpha}-induced MCP-1 expression. Further analysis showed that resveratrol inhibited DNA binding activity of the NF-{kappa}B complex and subsequently suppressed NF-{kappa}B transcriptional activity in TNF-{alpha}-stimulated cells. Finally, the inhibition of MCP-1 may represent a novel mechanism of resveratrol in preventing obesity-related pathologies.« less

  6. Boric acid inhibits LPS-induced TNF-alpha formation through a thiol-dependent mechanism in THP-1 cells.

    PubMed

    Cao, Jun; Jiang, Liping; Zhang, Xiaomei; Yao, Xiaofeng; Geng, Chengyan; Xue, Xiangxin; Zhong, Laifu

    2008-01-01

    Oxidative stress plays an important role during inflammatory diseases and antioxidant administration to diminish oxidative stress may arrest inflammatory processes. Boron has been implicated to modulate certain inflammatory mediators and regulate inflammatory processes. Here we investigated the role of the tripeptide glutathione (GSH) in modulating the effects of boric acid (BA) on lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) formation in THP-1 monocytes. Interestingly, we found that BA had no significant effects on both TNF-alpha production and intracellular GSH contents, whereas it could inhibit LPS-induced TNF-alpha formation and ameliorated the d,l-buthionine-S,R-sulfoximine (BSO)-induced GSH depletion. Twenty-four hour incubation with BSO induced a decrease of the intracellular GSH and an increase of TNF-alpha. Treatment with N-acetyl-l-cysteine (NAC) did not significantly increase intracellular content of GSH but significantly reduced the secretion of TNF-alpha. BSO-pretreatment for 24h enhanced the LPS-induced secretion and mRNA expression of TNF-alpha further. BA inhibited LPS-stimulated TNF-alpha formation was also seen after GSH depletion by BSO. These results indicate that BA may have anti-inflammatory effect in the LPS-stimulated inflammation and the effect of BA on TNF-alpha secretion may be induced via a thiol-dependent mechanism.

  7. Attenuation of the cyproterone acetate-induced testicular hypofunction by a novel nutraceutical lycopene: a genomic approach.

    PubMed

    Tripathy, A; Ghosh, A; Dey, A; Pakhira, B P; Ghosh, D

    2017-10-01

    This study was designed to explore the cyproterone acetate (CPA)-induced andrological hypofunction and its correction by oral administration of lycopene. In this concern, spermatogenic, biochemical, histological and genomic profiles were studied. Cyproterone acetate administration for 1 month helped to develop infertile model rats. A significant recovery was noted in sperm motility, sperm count, sperm viability, hypo-osmotic swelling tail-coiled spermatozoa; activities of testicular ∆ 5 , 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, catalase (CAT) and superoxide dismutase (SOD); and levels of conjugated diene (CD), malondialdehyde (MDA), testicular cholesterol and serum testosterone after the administration of lycopene at 1.5 mg/0.5 ml Tween-80/100 g body weight/day for last 1 month to infertile model rats. Simultaneously, qRT-PCR study of Bax, Bcl-2, caspase-3, ∆ 5 , 3β-HSD and 17β-HSD genes in testicular tissue showed a significant rectification towards the control in CPA-pre-treated cum CPA-lycopene-cotreated rats. Side-by-side histological and histometric studies showed a significant correction in qualitative analysis of spermatogenesis and seminiferous tubular diameter (STD) in CPA-pre-treated cum CPA-lycopene-cotreated rats. Lycopene showed outstanding efficacy in the management of CPA-induced testicular hypofunction with special reference to correction in oxidative stress-induced testicular apoptosis at genomic level. © 2016 Blackwell Verlag GmbH.

  8. PPAR-alpha agonist treatment increases trefoil factor family-3 expression and attenuates apoptosis in the liver tissue of bile duct-ligated rats.

    PubMed

    Karakan, Tarkan; Kerem, Mustafa; Cindoruk, Mehmet; Engin, Doruk; Alper, Murat; Akın, Okan

    2013-01-01

    Peroxisome proliferators-activated receptor alpha activation modulates cholesterol metabolism and suppresses bile acid synthesis. The trefoil factor family comprises mucin-associated proteins that increase the viscosity of mucins and help protect epithelial linings from insults. We evaluated the effect of short-term administration of fenofibrate, a peroxisome proliferators activated receptor alpha agonist, on trefoil factor family-3 expression, degree of apoptosis, generation of free radicals, and levels of proinflammatory cytokines in the liver tissue of bile duct-ligated rats. Forty male Wistar rats were randomly divided into four groups: 1 = sham operated, 2 = bile duct ligation, 3 = bile duct-ligated + vehicle (gum Arabic), and 4 = bile duct-ligated + fenofibrate (100 mg/kg/day). All rats were sacrificed on the 7 th day after obtaining blood samples and liver tissue. Liver function tests, tumor necrosis factor-alpha and interleukin 1 beta in serum, and trefoil factor family-3 mRNA expression, degree of apoptosis (TUNEL) and tissue malondialdehyde (malondialdehyde, end-product of lipid peroxidation by reactive oxygen species) in liver tissue were evaluated. Fenofibrate administration significantly reduced serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and tumor necrosis factor-alpha and interleukin-1β levels. Apoptosis and malondialdehyde were significantly reduced in the fenofibrate group. Trefoil factor family-3 expression increased with fenofibrate treatment in bile duct-ligated rats. The peroxisome proliferators-activated receptor alpha agonist fenofibrate significantly increased trefoil factor family-3 expression and decreased apoptosis and lipid peroxidation in the liver and attenuated serum levels of proinflammatory cytokines in bile duct-ligated rats. Further studies are needed to determine the protective role of fenofibrate in human cholestatic disorders.

  9. Anthocyanins Reversed D-Galactose-Induced Oxidative Stress and Neuroinflammation Mediated Cognitive Impairment in Adult Rats.

    PubMed

    Rehman, Shafiq Ur; Shah, Shahid Ali; Ali, Tahir; Chung, Jong Il; Kim, Myeong Ok

    2017-01-01

    Aging is a major factor involved in neurological impairments, decreased anti-oxidant activities, and enhanced neuroinflammation. D-galactose (D-gal) has been considered an artificial aging model which induces oxidative stress and inflammatory response resulting in memory and synaptic dysfunction. Dietary supplementation exerts valuable effects against oxidative stress and neuroinflammation. Polyphenolic flavonoids, such as anthocyanins, have been reported as an anti-inflammatory and anti-oxidant agents against various neurodegenerative diseases. Recently, our group reported anthocyanin neuroprotection of the developing rat brain against ethanol-induced oxidative stress and neurodegenaration and ethanol-induced neuronal apoptosis via GABA B1 receptor intracellular signaling in prenatal rat hippocampus. Here, we examined the protective effect of anthocyanin neuroprotection against D-gal-induced oxidative and inflammatory response in the hippocampus and cortex regions and explore the potential mechanism of its action. Our results indicated that anthocyanins treatment significantly improved behavioral performance of D-gal-treated rats in Morris water maze and Y-maze tests. One of the potential mechanisms of this action was decreased expression of the receptor for advance glycation end product, reduced level of reactive oxygen species (ROS) and lipid peroxidation as well as markers of the Alzheimer's disease. Furthermore, the results also indicated that anthocyanins inhibited activated astrocytes and neuroinflammation via suppression of various inflammatory markers including p-NF- K B, inducible nitric oxide synthase (iNOS), and tumor necrosis factor-alpha (TNF-α) in the hippocampus and cortex regions of D-gal-treated rats brain. Moreover, anthocyanins abrogated neuroapoptosis via C-jun N-terminal kinase (p-JNK) suppression and improved deregulated synaptic proteins including synaptophysin, synaptosomal-associated protein (SNAP)-23, SNAP-25, and phosphorylated CREB

  10. Ginger and alpha lipoic acid ameliorate age-related ultrastructural changes in rat liver.

    PubMed

    Mahmoud, Y I; Hegazy, H G

    2016-01-01

    Because of the important role that oxidative stress is thought to play in the aging process, antioxidants could be candidates for preventing its related pathologies. We investigated the ameliorative effects of two antioxidant supplements, ginger and alpha lipoic acid (ALA), on hepatic ultrastructural alterations in old rats. Livers of young (4 months) and old (24 months) Wistar rats were studied using transmission electron microscopy. Livers of old rats showed sinusoidal collapse and congestion, endothelial thickening and defenestration, and inconsistent perisinusoidal extracellular matrix deposition. Aged hepatocytes were characterized by hypertrophy, cytoplasmic vacuolization and a significant increase in the volume densities of the nuclei, mitochondria and dense bodies. Lipofuscin accumulation and decreased microvilli in bile canaliculi and space of Disse also were observed. The adverse alterations were ameliorated significantly by both ginger and ALA supplementation; ALA was more effective than ginger. Ginger and ALA appear to be promising anti-aging agents based on their amelioration of ultrastructural alterations in livers of old rats.

  11. An immunocapture/scintillation proximity analysis of G alpha q/11 activation by native serotonin (5-HT)2A receptors in rat cortex: blockade by clozapine and mirtazapine.

    PubMed

    Mannoury La Cour, C; Chaput, C; Touzard, M; Millan, M J

    2009-02-01

    Though transduction mechanisms recruited by heterologously expressed 5-HT(2A) receptors have been extensively studied, their interaction with specific subtypes of G-protein remains to be directly evaluated in cerebral tissue. Herein, as shown by an immunocapture/scintillation proximity analysis, 5-HT, the prototypical 5-HT(2A) agonist, DOI, and Ro60,0175 all enhanced [(35)S]GTPgammaS binding to G alpha q/11 in rat cortex with pEC(50) values of 6.22, 7.24 and 6.35, respectively. No activation of G o or G s/olf was seen at equivalent concentrations of DOI. Stimulation of G alpha q/11 by 5-HT (30 microM) and DOI (30 microM) was abolished by the selective 5-HT(2A) vs. 5-HT(2C)/5-HT(2B) antagonists, ketanserin (pK(B) values of 9.11 and 8.88, respectively) and MDL100,907 (9.82 and 9.68). By contrast, 5-HT-induced [(35)S]GTPgammaS binding to G alpha q/11 was only weakly inhibited by the preferential 5-HT(2C) receptor antagonists, RS102,221 (6.94) and SB242,084 (7.39), and the preferential 5-HT(2B) receptor antagonist, LY266,097 (6.66). The antipsychotic, clozapine, which had marked affinity for 5-HT(2A) receptors, blocked the recruitment of G alpha q/11 by 5-HT and DOI with pK(B) values of 8.54 and 8.14, respectively. Its actions were mimicked by the "atypical" antidepressant and 5-HT(2A) receptor antagonist, mirtazapine, which likewise blocked 5-HT and DOI-induced G alpha q/11 protein activation with pK(B) values of 7.90 and 7.76, respectively. In conclusion, by use of an immunocapture/scintillation proximity strategy, this study shows that native 5-HT(2A) receptors in rat frontal cortex specifically recruit G alpha q/11 and that this action is blocked by clozapine and mirtazapine. Quantification of 5-HT(2A) receptor-mediated G alpha q/11 activation in frontal cortex should prove instructive in characterizing the actions of diverse classes of psychotropic agent. 2008 Wiley-Liss, Inc.

  12. Effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits in the hippocampus of streptozotocin-induced type 1 diabetes mellitus rats.

    PubMed

    Zhang, Songyun; Li, Hongyan; Zhang, Lihui; Li, Jie; Wang, Ruiying; Wang, Mian

    2017-02-15

    Increasing evidence demonstrates an association between diabetes and hippocampal neuron damage. This study aimed to determine the effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits (GCLM and GCLC) in the hippocampus of streptozotocin-induced type 1 diabetes mellitus (T1DM) rats. At 12weeks after streptozotocin injection, T1DM rats were randomly divided into 4 groups (n=15 each group) to receive no treatment (T1DM), saline (T1DM+saline), alpha-lipoic acid (T1DM+alpha-lipoic acid), and troxerutin (T1DM+troxerutin), respectively, for 6weeks. Meanwhile, 10 control animals (NC group) were assessed in parallel. Learning performance was evaluated by the Morris water maze. After treatment, hippocampi were collected for pathological examination by hematoxylin and eosin (H&E) staining. Next, hippocampal superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and glutathione (GSH) levels were assessed. Finally, glutamate cysteine ligase catalytic (GCLC) and glutamate cysteine ligase modifier (GCLM) subunit mRNA and protein levels were quantified by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. Compared with T1DM and T1DM+saline groups, escape latency was overtly reduced in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. Significantly increased GCLM and GCLC mRNA levels, GCLC protein amounts, SOD activity, and GSH levels, and reduced MDA amounts were observed in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. In T1DM and T1DM+saline groups, H&E staining showed less pyramidal cells in the hippocampus, with disorganized layers, karyopyknosis, decreased endochylema, and cavitation, effects relieved in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. Troxerutin alleviates oxidative stress and promotes learning in streptozotocin-induced T1DM rats, a process involving GCLC expression. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Interactions of xylazine and detomidine with alpha2-adrenoceptors in brain tissue from cattle, swine and rats.

    PubMed

    Törneke, K; Bergström, U; Neil, A

    2003-06-01

    Xylazine is an alpha2-adrenoceptor agonist sedative with a much higher interspecies variability in effect than detomidine, another alpha2-agonist used in veterinary practice. In the present study, we have used radioligand binding in brain tissue to investigate if the high species variation in sensitivity to xylazine could be explained in terms of receptor interactions. Species known to be more (cattle) or less (swine and rats) sensitive to xylazine were used. There was no variation in the density or the subtype pattern of the alpha2-adrenoceptors that could explain the species variation recorded in vivo, as a homogenous population of the alpha2A/D-subtype (200-300 fmol/mg protein) was found in all species. The species differences in the affinities of xylazine and detomidine were minor and similar for the two drugs. The only parameter investigated where a significant species difference was found for xylazine but not for detomidine was the slope of the inhibition binding curve when the G-protein coupling was diminished. For xylazine this slope was considerably lower than unity (i.e. 0.77 +/- 0.075) using cattle preparations compared with 0.92 +/- 0.037 (mean +/- SE) and 0.90 +/- 0.028, respectively for swine and rats, while for detomidine this parameter was close to unity in all species (cattle, swine, rat). This finding indicates that the species variation in effect for xylazine could be due to differences at the G-protein level or further down-stream in the effect cascade.

  14. Chlorinated Phospholipids and Fatty Acids: (Patho)physiological Relevance, Potential Toxicity, and Analysis of Lipid Chlorohydrins

    PubMed Central

    2016-01-01

    Chlorinated phospholipids are formed by the reaction of hypochlorous acid (HOCl), generated by the enzyme myeloperoxidase under inflammatory conditions, and the unsaturated fatty acyl residues or the head group. In the first case the generated chlorohydrins are both proinflammatory and cytotoxic, thus having a significant impact on the structures of biomembranes. The latter case leads to chloramines, the properties of which are by far less well understood. Since HOCl is also widely used as a disinfecting and antibacterial agent in medicinal, industrial, and domestic applications, it may represent an additional source of danger in the case of abuse or mishandling. This review discusses the reaction behavior of in vivo generated HOCl and biomolecules like DNA, proteins, and carbohydrates but will focus on phospholipids. Not only the beneficial and pathological (toxic) effects of chlorinated lipids but also the importance of these chlorinated species is discussed. Some selected cleavage products of (chlorinated) phospholipids and plasmalogens such as lysophospholipids, (chlorinated) free fatty acids and α-chloro fatty aldehydes, which are all well known to massively contribute to inflammatory diseases associated with oxidative stress, will be also discussed. Finally, common analytical methods to study these compounds will be reviewed with focus on mass spectrometric techniques. PMID:28090245

  15. Valsartan decreases TGF-β1 production and protects against chlorhexidine digluconate-induced liver peritoneal fibrosis in rats.

    PubMed

    Subeq, Yi-Maun; Ke, Chen-Yen; Lin, Nien-Tsung; Lee, Chung-Jen; Chiu, Yi-Han; Hsu, Bang-Gee

    2011-02-01

    Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of valsartan on chlorhexidine digluconate-induced PF by decreasing TGF-β1 production in rats. PF was induced in Sprague-Dawley rats by daily administration of 0.5 ml 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis (PD) tube for 1 week. Rats received daily intravenous injections of low dose valsartan (1 mg/kg) or high dose valsartan (3 mg/kg) for 1 week. After 7 days, conventional 4.25% Dianeal (30 ml) was administered via a PD catheter with a dwell time of 4 h and assessed of peritoneal function. At the end of dialysis, rats were sacrificed and the liver peritoneum was harvested for microscopically and immunohistochemistry. There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D₄/P(4Urea) level was reduced, the D₄/D₀ glucose level, serum and dialysate transforming growth factor-β1 (TGF-β1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-β1, alpha-smooth muscle actin (α-SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF) were elevated in the PF group compared with the vehicle group. High dose of valsartan decreased the serum and dialysate TGF-β1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-β1, α-SMA, fibronectin, collagen, and VEGF-positive cells in liver peritoneum. The low dose of valsartan did not protect against chlorhexidine digluconate-induced PF in rat. Valsartan protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-β1 production. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Induction of tumor necrosis factor alpha by the group- and type-specific polysaccharides from type III group B streptococci.

    PubMed Central

    Mancuso, G; Tomasello, F; von Hunolstein, C; Orefici, G; Teti, G

    1994-01-01

    Previous studies suggested that circulating tumor necrosis factor alpha (TNF-alpha) may have a pathophysiologic role in experimental neonatal sepsis induced by group B streptococci (GBS). This study was undertaken to investigate the ability of the type III and group-specific polysaccharides of GBS to induce TNF-alpha production and TNF-alpha-dependent lethality in neonatal rats. The cytokine was detected in plasma samples by the L929 cytotoxicity assay. Intracardiac injections of either polysaccharide induced dose-dependent, transient elevations in plasma TNF-alpha levels that returned to baseline values after 5 h. The group-specific antigen induced significantly higher mean peak TNF-alpha levels than the type III antigen (125 +/- 47 versus 44 +/- 15 U/ml with 70 mg/kg of body weight). Glycogen (70 mg/kg), used as a negative control, did not induce TNF-alpha. The lipopolysaccharide-neutralizing agent polymyxin B did not decrease TNF-alpha levels induced by either polysaccharide, ruling out contamination with endotoxin as a possible cause of TNF-alpha induction. Fifty percent lethal doses of the type III and group-specific antigens given as intracardiac injections were 105 and 16 mg/kg, respectively. Salmonella endotoxin, used as a positive control, had a 50% lethal dose of 0.1 mg/kg. The lethal activities of GBS polysaccharides, as well as endotoxin, were completely prevented by pretreatment of neonatal rats with the respective specific antibodies or anti-murine TNF-alpha serum. To assess the relative importance of the type-specific substance in TNF-alpha induction by whole bacteria, two unrelated GBS transposon mutants devoid of only the type-specific capsular polysaccharide (COH1-13 and COH31-15) were employed. Each of the heat-killed unencapsulated mutants was able to produce plasma TNF-alpha level elevations or TNF-alpha-dependent lethality but was significantly less efficient in these activities than the corresponding encapsulated wild-type strain. These data

  17. Tolazoline decreases survival time during microwave-induced lethal heat stress in anesthetized rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jauchem, J.R.; Chang, K.S.; Frei, M.R.

    1996-03-01

    Effects of {alpha}-adrenergic antagonists have been studied during environmental heating but not during microwave-induced heating. Tolazoline may exert some of its effects via {alpha}-adrenergic blockade. In the present study, ketamine-anesthetized Sprague-Dawley rats were exposed to 2450-MHz microwaves at an average power density of 60 mW/cm{sup 2} (whole-body specific absorption rate of approximately 14 W/kg) until lethal temperatures were attained. The effects of tolazoline (10 mg/kg body weight) on physiological responses (including changes in body temperature, heart rate, blood pressure, and respiratory rate) were examined. Survival time was significantly shorter in the tolazoline group than in saline-treated animals. In general, heartmore » rate and blood pressure responses were similar to those that occur during environmental heat stress. Heart rate, however, was significantly elevated in animals that received tolazoline, both before and during terminal microwave exposure. It is possible that changes associated with the elevated heart rate (e.g., less cardiac filling) in tolazoline-treated animals resulted in greater susceptibility to microwave-induced heating and the lower survival time. 47 refs., 3 figs., 2 tabs.« less

  18. FcepsilonRI-alpha siRNA inhibits the antigen-induced activation of mast cells.

    PubMed

    Safaralizadeh, Reza; Soheili, Zahra-Soheila; Deezagi, Abdolkhaleg; Pourpak, Zahra; Samiei, Shahram; Moin, Mostafa

    2009-12-01

    FcepsilonRI, The high affinity receptor for IgE plays a critical role in triggering the allergic reactions. It is responsible for inducing mast cell degranulation and deliberation of allergy mediators when it is aggregated by allergen and IgE complexes. FcepsilonRI on the mast cells consists of three subunits; alpha chain directly binds IgE, beta chain and dimmer of gamma chains together mediate intracellular signaling. Cross-linking of IgE-bound FcepsilonRI on the surface of mast cells and basophils by the multivalent antigen induces release of chemical mediators. The present in vitro study was designed to investigate the effect of synthetic FcepsilonRI-alpha siRNA on the antigen-induced activation of MC/9 cells. MC/9 cells which are murine mast cells were transfected by FcepsilonRI-alpha siRNA and negative control siRNA. After 6 h, anti-DNP (Dinitrophenyl) IgE was used for the cells sensitization. Then the cells were challenged with Dinitrophenyl-Human Serum Albumin (DNP-HSA) for mast cell degranulation induction before collection of supernatants. The amount of mRNA and protein expression was measured by Real Time PCR and western blot analysis, respectively. Determination of the expression rate of FcepsilonRI-alpha on cell surface was achieved by flow cytometry. ELISA and spectrophotometry methods were used subsequently for measuring the effects of FcepsilonRI-alpha siRNA on antigen-induced histamine and beta-hexosaminidase release. FcepsilonRI-alpha siRNA treated cells showed significant decrease in FcepsilonRI-alpha mRNA and protein expression in comparison to control cells. FcepsilonRI-mediated mast cell release of beta-hexosaminidase and histamine were also inhibited. In this study it was shown that FcepsilonRI-alpha siRNA could suppress FcepsilonRI-alpha expression and inhibited degranulation and histamine release in antigen-stimulated MC/9 cells. In conclusion, knock-down of FcepsilonRI-alpha by siRNA could be a promising method for inhibition of the mast

  19. Overexpression of cellular repressor of E1A-stimulated genes inhibits TNF-{alpha}-induced apoptosis via NF-{kappa}B in mesenchymal stem cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Peng, Cheng-Fei; Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang; Han, Ya-Ling, E-mail: hanyaling53@gmail.com

    2011-03-25

    Research highlights: {yields} CREG protected MSCs from tumor necrosis factor-{alpha} (TNF-{alpha}) induced apoptosis. {yields} CREG inhibits the phosphorylation of I{kappa}B{alpha} and prevents the activation of NF-{kappa}B. {yields} CREG inhibits NF-{kappa}B nuclear translocation and pro-apoptosis protein transcription. {yields} CREG anti-apoptotic effect involves inhibition of the death receptor pathway. {yields} p53 is downregulated by CREG via NF-{kappa}B pathway under TNF-{alpha} stimulation. -- Abstract: Bone marrow-derived mesenchymal stem cells (MSCs) show great potential for therapeutic repair after myocardial infarction. However, poor viability of transplanted MSCs in the ischemic heart has limited their use. Cellular repressor of E1A-stimulated genes (CREG) has been identified asmore » a potent inhibitor of apoptosis. This study therefore aimed to determine if rat bone marrow MSCs transfected with CREG-were able to effectively resist apoptosis induced by inflammatory mediators, and to demonstrate the mechanism of CREG action. Apoptosis was determined by flow cytometric and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assays. The pathways mediating these apoptotic effects were investigated by Western blotting. Overexpression of CREG markedly protected MSCs from tumor necrosis factor-{alpha} (TNF-{alpha}) induced apoptosis by 50% after 10 h, through inhibition of the death-receptor-mediated apoptotic pathway, leading to attenuation of caspase-8 and caspase-3. Moreover, CREG resisted the serine phosphorylation of I{kappa}B{alpha} and prevented the nuclear translocation of the transcription factor nuclear factor-{kappa}B (NF-{kappa}B) under TNF-{alpha} stimulation. Treatment of cells with the NF-{kappa}B inhibitor pyrrolidine dithiocarbamate (PDTC) significantly increased the transcription of pro-apoptosis proteins (p53 and Fas) by NF-{kappa}B, and attenuated the anti-apoptotic effects of CREG on MSCs. The results of this

  20. Effects of muscarinic receptor agonists and antagonists on alpha 2-adrenoceptors in rat brain.

    PubMed

    Hollingsworth, P J; Smith, C B

    1989-09-13

    The specific binding of [3H]clonidine to alpha 2-adrenoceptors on neural membranes isolated from six brain areas was determined with rats treated for various periods of time with the muscarinic agonists, oxotremorine or pilocarpine, or with the muscarinic antagonists atropine, atropine methyl nitrate, scopolamine and scopolamine methyl bromide. Administration of pilocarpine, 10 mg/kg, twice daily i.p. for 1 and 14 days increased markedly the number of alpha 2-adrenoceptors on neural membranes from all six brain areas. In contrast, oxotremorine, 0.3 mg/kg, twice daily i.p., for 7 days decreased the number of alpha 2-adrenoceptors on membranes from all brain areas except the brainstem and caudate nucleus. Both atropine and scopolamine increased the density of alpha 2-adrenoceptors in specific brain areas. Neither atropine methyl nitrate nor scopolamine methyl bromide had an appreciable effect upon the specific binding of [3H]clonidine to neural membranes from most brain areas.

  1. Teucrium polium reversed the MCD diet-induced liver injury in rats.

    PubMed

    Amini, Rahim; Yazdanparast, Razieh; Aghazadeh, Safiyeh; Ghaffari, Seyed H

    2011-09-01

    In the present study, we evaluated the ability of Teucrium polium ethyl acetate fraction, with high antioxidant activity, in the treatment of nonalcoholic steatohepatitis (NASH) in rats and its possible effect on factors involved in pathogenesis of the disease. To induce NASH, a methionine and choline deficient (MCD) diet was given to N-Mary rats for 8 weeks. After NASH development, MCD-fed rats were divided into 2 groups: NASH group that received MCD diet and NASH + T group which was fed MCD diet plus ethyl acetate fraction of T. polium orally for 3 weeks. Histopathological evaluations revealed that treatment with the extract has abated the severity of NASH among the MCD-fed rats. In addition, the fraction reduced the elevated levels of hepatic tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) gene expression and also the elevated level of malondialdehyde (MDA). In addition, the extract increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and enhanced the level of hepatic glutathione (GSH). Moreover, the fraction treatments lowered caspase-3 level and the phosphorylated form of C-Jun N-terminal kinase (JNK) and augmented the phosphorylated level of extracellular regulated kinase1/2 (ERK1/2). These results indicate that the ethyl acetate fraction of T. poium effectively reversed NASH, mainly due to its strong antioxidant and anti-inflammatory properties.

  2. Remote Associates Test and Alpha Brain Waves

    ERIC Educational Resources Information Center

    Haarmann, Henk J.; George, Timothy; Smaliy, Alexei; Dien, Joseph

    2012-01-01

    Previous studies found that performance on the remote associates test (RAT) improves after a period of incubation and that increased alpha brain waves over the right posterior brain predict the emergence of RAT insight solutions. We report an experiment that tested whether increased alpha brain waves during incubation improve RAT performance.…

  3. Seminal Corynebacterium strains in infertile men with and without leucocytospermia.

    PubMed

    Mashaly, M; Masallat, D T; Elkholy, A A; Abdel-Hamid, I A; Mostafa, T

    2016-04-01

    This study aimed to identify seminal Corynebacterium strains in infertile men with and without leucocytospermia. Semen samples from 60 infertile men were allocated into two equal groups: semen samples with leucocytospermia and semen samples without leucocytospermia. Semen culture for Corynebacterium species was carried out on Columbia agar medium confirmed by Gram-stained film and biochemical tests followed by analytical profile index biotyping and antibiotic susceptibility. Bacterial isolates were detected in 20/60 semen cultures (33.3%) as Corynebacteria, Staphylococci, Alpha haemolytic streptococci and E. coli. In all, 12/60 (20%) had Corynebacterium positive semen culture, whereas C. seminal was the major isolated species followed by C. amycolatum, C. jekium and C. urealyticum. There was nonsignificant difference between patients with/without Corynebacterium positive culture regarding sperm concentration and normal sperm morphology; however, in positive cultures sperm motility was significantly lower compared with negative cultures. Antimicrobial sensitivity among Corynebacteria strains was highest for vancomycin, rifampicin then imipenem, ampicillin + sulbactam, ciprofloxacin. It is concluded that positive semen cultures for different Corynebacteria species were demonstrated in infertile men, whereas Corynebacterium seminale was the most common isolated species. Vancomycin, rifampicin then imipenem and ampicillin + sulbactam are recommended as sensitive antibiotics. © 2015 Blackwell Verlag GmbH.

  4. Laparoscopic evaluation of female factors in infertility.

    PubMed

    Aziz, Nousheen

    2010-10-01

    To find out different causes of female infertility with diagnostic laparoscopy and their comparative frequency in primary and secondary infertility. A case series. Department of Obstetric and Gynaecology, Liaquat University Hospital (LUH), Hyderabad, rom January 2006 to December 2007. All infertile women underwent diagnostic laparoscopy for primary and secondary infertility during the study period were included. Couples who had not lived together for at least 12 months, and those with male factor infertility were excluded. Data were collected on a proforma, and analysed on SPSS package for windows version 10. Frequencies were calculated for laparoscopic findings regarding primary and secondary infertility. Fifty infertile women underwent laparoscopy during the study period, 32 (64%) had primary infertility while 18 (36%) secondary infertility. Eight (25.0%) patients with primary and 2 (11.1%) patients with secondary infertility had no visible abnormality. The common finding was tubal blockage in 7 (21.9%) and 6 (33.3%) cases of primary and secondary infertility respectively. Five (15.6%) cases of primary infertility were detected as polycystic ovaries (PCO) which was not found in cases of secondary infertility. Endometriosis was found in 4 (12.5%) cases with primary infertility and 2 (11.1%) cases with secondary infertility. Pelvic inflammatory disease (PID) was found in 1 (3.1%) and 2 (16.7%) cases of primary and secondary infertility respectively. Peritubal and periovarian adhesions were detected in 2 (6.3%) cases with primary infertility and 4 (22.2%) cases with secondary infertility. Fibriod was found in 2 (6.3%) and 1 (5.6%) cases of primary and secondary infertility respectively. Ovarian cyst detected in 2 (6.3%) cases with primary infertility while none was found in cases of secondary infertility. Most common causes responsible for infertility were tubal occlusion, endometriosis, peritubal and periovarian adhesions. Ovarian causes were seen in primary

  5. Copper induces vasorelaxation and antagonizes noradrenaline-induced vasoconstriction in rat mesenteric artery.

    PubMed

    Wang, Yu-Chun; Hu, Chao-Wei; Liu, Ming-Yu; Jiang, Hong-Chao; Huo, Rong; Dong, De-Li

    2013-01-01

    Copper is an essential trace element for normal cellular function and contributes to critical physiological or pathological processes. The aim of the study was to investigate the effects of copper on vascular tone of rat mesenteric artery and compare the effects of copper on noradrenaline (NA) and high K(+) induced vasoconstriction. The rat mesenteric arteries were isolated and the vessel tone was measured by using multi wire myograph system in vitro. Blood pressure of carotid artery in rabbits was measured by using physiological data acquisition and analysis system in vivo. Copper dose-dependently blunted NA-induced vasoconstriction of rat mesenteric artery. Copper-induced vasorelaxation was inhibited when the vessels were pretreated with NG-nitro-L-arginine methyl ester (L-NAME). Copper did not blunt high K(+)-induced vasoconstriction. Copper preincubation inhibited NA-evoked vasoconstriction and the inhibition was not affected by the presence of L-NAME. Copper preincubation showed no effect on high K(+)-evoked vasoconstriction. Copper chelator diethyldithiocarbamate trihydrate (DTC) antagonized the vasoactivity induced by copper in rat mesenteric artery. In vivo experiments showed that copper injection (iv) significantly decreased blood pressure of rabbits and NA or DTC injection (iv) did not rescue the copper-induced hypotension and animal death. Copper blunted NA but not high K(+)-induced vasoconstriction of rat mesenteric artery. The acute effect of copper on NA-induced vasoconstriction was depended on nitric oxide (NO), but the effect of copper pretreatment on NA-induced vasoconstriction was independed on NO, suggesting that copper affected NA-induced vasoconstriction by two distinct mechanisms. © 2013 S. Karger AG, Basel.

  6. A novel water-soluble vitamin E derivative protects against aspirin-induced gastric mucosal injury in rats.

    PubMed

    Isozaki, Yutaka; Yoshida, Norimasa; Ichikawa, Hiroshi; Kuroda, Masaaki; Kokura, Satoshi; Naito, Yuji; Okanoue, Takeshi; Yoshikawa, Toshikazu

    2005-12-01

    Oxygen radical-mediated lipid peroxidation and neutrophil activation may be involved in the development of gastric mucosal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs). Vitamin E is one of the lipid-soluble antioxidants and is generally considered to protect against lipid peroxidation of the cell membrane and to scavenge singlet oxygen and superoxide anion radicals. Our object was to investigate the antioxidative effects of water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetra-methylchroman-6-ol (TMG), on aspirin-induced gastric mucosal injury in rats. Gastric injury was induced by intragastric administration of aspirin and 0.15 N HCl in male Sprague-Dawley rats. TMG dissolved in physiological saline was injected intraperitoneally 0.5 h before the aspirin administration. The intragastric administration of acidified aspirin induced hyperemia and hemorragic erosions in rat stomach. The increase in total area of gastric erosions was reduced by pretreatment with TMG in a dose-dependent manner. The increases of thiobarbituric acid-reactive substances (TBA-RS) and myeloperoxidase (MPO) activity 3 h after aspirin administration were significantly inhibited by pretreatment with TMG. The gastric concentration of cytokine-induced neutrophil chemoattractants-1 (CINC-1) increased after aspirin administration, and the increase was also inhibited by pretreatment with TMG. These results suggest that TMG is effective for the treatment of aspirin-induced gastric injury. This anti-inflammatory effect of TMG seems to be related to impairment of lipid peroxidation, neutrophil function and cytokine production in gastric mucosa.

  7. N-acetylcysteine attenuates TNF-alpha-induced human vascular endothelial cell apoptosis and restores eNOS expression.

    PubMed

    Xia, Zhengyuan; Liu, Min; Wu, Yong; Sharma, Vijay; Luo, Tao; Ouyang, Jingping; McNeill, John H

    2006-11-21

    The circulatory inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is increased in pathological conditions, such as diabetes, which initiate or exacerbate vascular endothelial injury. Both nitric oxide (NO) and reactive oxygen species may play a dual role (i.e., inhibiting or promoting) in TNF-alpha-induced endothelial cell apoptosis. We investigated the effects of the antioxidant N-acetylcysteine on TNF-alpha-induced apoptosis in human vascular endothelial cell (cell line ECV304) apoptosis, NO production and lipid peroxidation. Cultured vascular endothelial cell (ECV304) were either not treated (control), or treated with TNF-alpha (40 ng/ml) alone or TNF-alpha in the presence of N-acetylcysteine at 30 mmol/l or 1 mmol/l, respectively, for 24 h. Cell viability was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was assessed by flow cytometry. TNF-alpha-induced endothelial cell apoptosis was associated with increased inducible NO synthase but reduced endothelial NO synthase (eNOS) protein expression. NO production and the levels of the lipid peroxidation product malondialdehyde were concomitantly increased. Treatment with NAC at 30 mmol/l restored eNOS expression and further increased NO production as compared to TNF-alpha alone, resulting in improved cell viability and reduced apoptosis. This was accompanied by increased superoxide dismutase activity, increased glutathione peroxidase production and reduced malondialdehyde levels. N-acetylcysteine at 1 mmol/l, however, did not have significant effects on TNF-alpha-induced endothelial cell apoptosis and cell viability despite it slightly enhanced glutathione peroxidase production. N-acetylcysteine attenuation of TNF-alpha-induced human vascular endothelial cell apoptosis is associated with the restoration of eNOS expression.

  8. Endometriosis-related infertility: ovarian endometrioma per se is not associated with presentation for infertility.

    PubMed

    Santulli, P; Lamau, M C; Marcellin, L; Gayet, V; Marzouk, P; Borghese, B; Lafay Pillet, Marie-Christine; Chapron, C

    2016-08-01

    Is there an association between the endometriosis phenotype and presentation with infertility? In a population of operated patients with histologically proven endometriosis, ovarian endometrioma (OMA) per se is not associated with an increased risk of presentation with infertility, while previous surgery for endometriosis was identified as a risk factor for infertility. The increased prevalence of endometriosis among subfertile women indicates that endometriosis impairs reproduction for reasons that are not completely understood. This was an observational, cross-sectional study using data prospectively collected in all non-pregnant patients aged between 18 and 42 years, who were surgically explored for benign gynaecological conditions at our institution between January 2004 and March 2013. For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery. Surgery was performed in 2208 patients, of which 2066 signed their informed consent. Of the 1059 women with a visual diagnosis of endometriosis, 870 had histologically proven endometriosis and complete treatment for their endometriotic lesions, including 307 who presented with infertility. Univariate analysis and multiple logistic regression analysis were performed to determine factors associated with infertility. The following variables were identified as risk factors for endometriosis-related infertility: age >32 years (odds ratio [OR] = 1.9; 95% confidence interval [CI]: 1.4-2.4), previous surgery for endometriosis (OR = 1.9; 95% CI: 1.3-2.2), as well as peritoneal superficial endometriosis (OR = 3.1; 95% CI: 1.9-4.9); Conversely, previous pregnancy was associated with a lower rate of infertility (OR = 0.7; 95% CI: 0.6-0.9 and OR = 0.6; 95% CI: 0.4-0.9, respectively). OMA is not selected as a significant risk factor for infertility. The selection of our study population was based on a surgical diagnosis. We cannot exclude

  9. Dapoxetine attenuates testosterone-induced prostatic hyperplasia in rats by the regulation of inflammatory and apoptotic proteins

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sayed, Rabab H., E-mail: rabab.sayed@pharma.cu.edu

    Serotonin level plays a role in suppressing the pathological findings of benign prostatic hyperplasia (BPH). Thus a new selective serotonin reuptake inhibitor, dapoxetine was used to test its ability to ameliorate the pathological changes in the rat prostate. A dose response curve was constructed between the dose of dapoxetine and prostate weight as well as relative prostate weight, then a 5 mg/kg dose was used as a representative dose for dapoxetine administration. Rats were divided into four groups; the control group that received the vehicle; the BPH-induced group received daily s.c injection of 3 mg/kg testosterone propionate dissolved in olivemore » oil for four weeks; BPH-induced group treated with finasteride 5 mg/kg/day p.o and BPH-induced group treated with dapoxetine 5 mg/kg/day p.o. Injection of testosterone increased prostate weight and relative prostate weight which were both returned back to the normal value after treatment with dapoxetine as well as finasteride. Testosterone also upregulated androgen receptor (AR) and proliferating cell nuclear antigen gene expression. Furthermore, testosterone injection elevated cyclooxygenase-II (COX II), inducible nitric oxide synthase (iNOS), B-cell lymphoma-2 (Bcl2) expression and tumor necrosis factor alpha content and reduced caspase-3 activity, Bcl-2-associated X protein (Bax) expression and Bax/Bcl2 ratio. Dapoxetine and finasteride administration reverted most of the changes made by testosterone injection. In conclusion, the current study provides an evidence for the protective effects of dapoxetine against testosterone-induced BPH in rats. This can be attributed, at least in part, to decreasing AR expression, and the anti-proliferative, anti-inflammatory and pro-apoptotic activities of dapoxetine in BPH. - Highlights: • Dapoxetine attenuates testosterone-induced prostatic hyperplasia in rats. • Dapoxetine decreased androgen receptor gene expression in rat prostate. • Dapoxetine possess anti

  10. Midluteal immunoreactive alpha-inhibin serum concentrations as markers of luteal phase deficiency.

    PubMed

    Balasch, J; Creus, M; Fábregues, F; Casamitjana, R; Ordi, J; Vanrell, J A

    1996-12-01

    The present prospective clinical study was undertaken to determine the usefulness of midluteal phase serum immunoreactive alpha-inhibin concentrations as markers of luteal phase deficiency and whether they are better indicators of biopsy confirmed luteal phase defect than serum progesterone. Consecutive patients (n = 138) with regular menstrual cycles attending our Infertility Clinic (experimental group) and 15 fertile women who were requesting contraception and had regular menstrual patterns (control group) were included. In all women (patients and controls), basal body temperature, midluteal serum concentrations of oestradiol, prolactin, progesterone and immunoreactive alpha-inhibin, and premenstrual endometrial biopsy were used in the same cycle to assess luteal function. Out-of-phase secretory endometria were detected in 15 of the 138 patients. Thus, hormonal concentrations were compared between the following three groups of women: group 1 (n = 15), infertile patients with defective secretory endometria; group 2 (n = 123), infertile patients with normal secretory endometria; and controls (n = 15), fertile women with normal secretory endometria. Midluteal serum concentrations of progesterone, immunoreactive alpha-inhibin, oestradiol, and prolactin of the two groups studied were similar to those of the control group of fertile women. Our results indicate that midluteal serum inhibin determination does not accurately reflect histological maturation of the endometrium and it is not a better indicator of endometrial luteal phase deficiency than midluteal serum progesterone concentration.

  11. Danshensu-mediated protective effect against hepatic fibrosis induced by carbon tetrachloride in rats.

    PubMed

    Qu, W; Huang, H; Li, K; Qin, C

    2014-12-01

    The culprit of hepatic fibrosis (HF) is linked to suprathreshold deposition of collagen. Thus, collagen reduction by improved metabolism contributes to HF management. In this study, we aimed to investigate the hepatoprotective effects of Danshensu (DSS) against carbon tetrachloride (CCl4)-induced HF rats. The results showed that DSS-administrated rats resulted in decreasing in hepatosomatic indexes, and lowering serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Meanwhile, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were increased, while the content of malonaldehyde (MDA) was lessened in liver tissue of DSS administration group. In addition, the pro-fibrotic markers of hydroxyproline (Hyp), type III procollagen (PCIII) and hyaluronic acid (HA) contents were decreased. Histopathological examination confirmed that the hepatotoxicity in CCl4-injured rats was alleviated following the DSS administration. Furthermore, intrahepatic protein expressions of alpha-smooth muscle actin (α-SMA), phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) were effectively down-regulated, respectively. Overall, this work demonstrates that DSS played the protective effect against CCl4-induced cytotoxicity in liver tissue, which the probable mechanism is associated with attenuation of lipid peroxidation, collagen accumulation and enhancement of anti-oxidative defense capability, as well as regulation of intrahepatic JAK/STAT pathway for maintaining collagenic homoeostasis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Therapeutic Potential of Date Palm Pollen for Testicular Dysfunction Induced by Thyroid Disorders in Male Rats.

    PubMed

    El-Kashlan, Akram M; Nooh, Mohammed M; Hassan, Wafaa A; Rizk, Sherine M

    2015-01-01

    Hyper- or hypothyroidism can impair testicular function leading to infertility. The present study was designed to examine the protective effect of date palm pollen (DPP) extract on thyroid disorder-induced testicular dysfunction. Rats were divided into six groups. Group I was normal control. Group II received oral DPP extract (150 mg kg(-1)), group III (hyperthyroid group) received intraperitoneal injection of L-thyroxine (L-T4, 300 μg kg(-1); i.p.), group IV received L-T4 plus DPP extract, group V (hypothyroid group) received propylthiouracil (PTU, 10 mg kg(-1); i.p.) and group VI received PTU plus DPP extract. All treatments were given every day for 56 days. L-T4 or PTU lowered genital sex organs weight, sperm count and motility, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone (T), testicular function markers and activities of testicular 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD). Moreover, L-T4 or PTU increased estradiol (E2) serum level, testicular oxidative stress, DNA damage and apoptotic markers. Morphometric and histopathologic studies backed these observations. Treatment with DPP extract prevented LT4- or PTU induced changes. In addition, supplementation of DPP extract to normal rats augmented sperm count and motility, serum levels of LH, T and E2 paralleled with increased activities of 3β-HSD and 17β-HSD as well as testicular antioxidant status. These results provide evidence that DPP extract may have potential protective effects on testicular dysfunction induced by altered thyroid hormones.

  13. Therapeutic Potential of Date Palm Pollen for Testicular Dysfunction Induced by Thyroid Disorders in Male Rats

    PubMed Central

    El-Kashlan, Akram M.; Nooh, Mohammed M.; Hassan, Wafaa A.; Rizk, Sherine M.

    2015-01-01

    Hyper- or hypothyroidism can impair testicular function leading to infertility. The present study was designed to examine the protective effect of date palm pollen (DPP) extract on thyroid disorder-induced testicular dysfunction. Rats were divided into six groups. Group I was normal control. Group II received oral DPP extract (150 mg kg-1), group III (hyperthyroid group) received intraperitoneal injection of L-thyroxine (L-T4, 300μg kg-1; i.p.), group IV received L-T4 plus DPP extract, group V (hypothyroid group) received propylthiouracil (PTU, 10 mg kg-1; i.p.) and group VI received PTU plus DPP extract. All treatments were given every day for 56 days. L-T4 or PTU lowered genital sex organs weight, sperm count and motility, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone (T), testicular function markers and activities of testicular 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD). Moreover, L-T4 or PTU increased estradiol (E2) serum level, testicular oxidative stress, DNA damage and apoptotic markers. Morphometric and histopathologic studies backed these observations. Treatment with DPP extract prevented LT4- or PTU induced changes. In addition, supplementation of DPP extract to normal rats augmented sperm count and motility, serum levels of LH, T and E2 paralleled with increased activities of 3β-HSD and 17β-HSD as well as testicular antioxidant status. These results provide evidence that DPP extract may have potential protective effects on testicular dysfunction induced by altered thyroid hormones. PMID:26425844

  14. Amelioration of nandrolone decanoate-induced testicular and sperm toxicity in rats by taurine: Effects on steroidogenesis, redox and inflammatory cascades, and intrinsic apoptotic pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ahmed, Maha A.E., E-mail: mahapharm@yahoo.com

    The wide abuse of the anabolic steroid nandrolone decanoate by athletes and adolescents for enhancement of sporting performance and physical appearance may be associated with testicular toxicity and infertility. On the other hand, taurine; a free β-amino acid with remarkable antioxidant activity, is used in taurine-enriched beverages to boost the muscular power of athletes. Therefore, the purpose of this study was to investigate the mechanisms of the possible protective effects of taurine on nandrolone decanoate-induced testicular and sperm toxicity in rats. To achieve this aim, male Wistar rats were randomly distributed into four groups and administered either vehicle, nandrolone decanoatemore » (10 mg/kg/week, I.M.), taurine (100 mg/kg/day, p.o.) or combination of taurine and nandrolone decanoate, for 8 successive weeks. Results of the present study showed that taurine reversed nandrolone decanoate-induced perturbations in sperm characteristics, normalized serum testosterone level, and restored the activities of the key steroidogenic enzymes; 3β-HSD, and 17β-HSD. Moreover, taurine prevented nandrolone decanoate-induced testicular toxicity and DNA damage by virtue of its antioxidant, anti-inflammatory, and anti-apoptotic effects. This was evidenced by taurine-induced modulation of testicular LDH-x activity, redox markers (MDA, NO, GSH contents, and SOD activity), inflammatory indices (TNF-α, ICAM-1 levels, and MMP-9 gene expression), intrinsic apoptotic pathway (cytochrome c gene expression and caspase-3 content), and oxidative DNA damage markers (8-OHdG level and comet assay). In conclusion, at the biochemical and histological levels, taurine attenuated nandrolone decanoate-induced poor sperm quality and testicular toxicity in rats. - Highlights: • Nandrolone decanoate (ND) disrupts sperm profile and steroidogenesis in rats. • ND upregulates gene expression of inflammatory and apoptotic markers. • Taurine normalizes sperm profile and serum

  15. Hormonal regulation of the alpha-ketoglutarate dehydrogenase complex in the isolated perfused rat liver.

    PubMed

    Rashed, H M; Waller, F M; Patel, T B

    1988-04-25

    The metabolic flux through the alpha-ketoglutarate dehydrogenase reaction in perfused livers was monitored by measuring the rate of 14CO2 production from [1-14C]alpha-ketoglutarate. The rates of 14CO2 production and glucose production from [1-14C]alpha-ketoglutarate were increased with increasing perfusate alpha-ketoglutarate concentrations. Vasopressin, angiotensin II, and the alpha 1-adrenergic agonist phenylephrine stimulated transiently by 2.5-fold the metabolic flux through the alpha-ketoglutarate dehydrogenase reaction in the presence and absence of Ca2+ in the perfusion medium. High concentrations of glucagon (1 x 10(-8) M) and 8-p-chlorophenylthio-cAMP (100 microM) (data not shown) also stimulated transiently the metabolic flux through the alpha-ketoglutarate dehydrogenase reaction. However, lower glucagon concentrations (1 x 10(-9) M) stimulated the rate of 14CO2 production from [1-14C]alpha-ketoglutarate only under conditions optimized to fix the cellular oxidation-reduction state at an intermediate level, when glucagon (1 x 10(-9) M)-mediated elevation of cAMP content was greater than that observed under highly oxidizing and reducing conditions. These data indicate that agonists which increase cytosolic free Ca2+ levels stimulate the metabolic flux through the alpha-ketoglutarate dehydrogenase complex. Furthermore, the data presented here demonstrate for the first time that physiological glucagon concentrations stimulate the metabolic flux through the alpha-ketoglutarate dehydrogenase reaction only under conditions known to be optimal for glucagon-mediated Ca2+ mobilization in the isolated perfused rat liver.

  16. In vitro inhibition activity of polyphenol-rich extracts from Syzygium aromaticum (L.) Merr. & Perry (Clove) buds against carbohydrate hydrolyzing enzymes linked to type 2 diabetes and Fe2+-induced lipid peroxidation in rat pancreas

    PubMed Central

    Adefegha, Stephen Adeniyi; Oboh, Ganiyu

    2012-01-01

    Objective To investigate and compare the inhibitory properties of free and bound phenolic extracts of clove bud against carbohydrate hydrolyzing enzymes (alpha-amylase & alpha-glucosidase) and Fe2+-induced lipid peroxidation in rat pancreas in vitro. Methods The free phenolics were extracted with 80% (v/v) acetone, while bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate. Then, the interaction of the extracts with alpha-amylase and alpha-glucosidase was subsequently assessed. Thereafter, the total phenolic contents and antioxidant activities of the extracts were determined. Results The result revealed that both extracts inhibited alpha-amylase and alpha-glucosidase in a dose-dependent manner. However, the alpha-glucosidase inhibitory activity of the extracts were significantly (P<0.05) higher than their alpha-amylase inhibitory activity. The free phenolics (31.67 mg/g) and flavonoid (17.28 mg/g) contents were significantly (P<0.05) higher than bound phenolic (23.52 mg/g) and flavonoid (13.70 mg/g) contents. Both extracts also exhibited high antioxidant activities as typified by their high reducing power, 1,1 diphenyl-2- picrylhydrazyl (DPPH) and 2, 2-azinobis-3-ethylbenzo-thiazoline-6-sulfonate (ABTS) radical scavenging abilities, as well as inhibition of Fe2+-induced lipid peroxidation in rat pancreas in vitro. Conclusions This study provides a biochemical rationale by which clove elicits therapeutic effect on type 2 diabetes. PMID:23569846

  17. In vitro inhibition activity of polyphenol-rich extracts from Syzygium aromaticum (L.) Merr. & Perry (Clove) buds against carbohydrate hydrolyzing enzymes linked to type 2 diabetes and Fe(2+)-induced lipid peroxidation in rat pancreas.

    PubMed

    Adefegha, Stephen Adeniyi; Oboh, Ganiyu

    2012-10-01

    To investigate and compare the inhibitory properties of free and bound phenolic extracts of clove bud against carbohydrate hydrolyzing enzymes (alpha-amylase & alpha-glucosidase) and Fe(2+)-induced lipid peroxidation in rat pancreas in vitro. The free phenolics were extracted with 80% (v/v) acetone, while bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate. Then, the interaction of the extracts with alpha-amylase and alpha-glucosidase was subsequently assessed. Thereafter, the total phenolic contents and antioxidant activities of the extracts were determined. The result revealed that both extracts inhibited alpha-amylase and alpha-glucosidase in a dose-dependent manner. However, the alpha-glucosidase inhibitory activity of the extracts were significantly (P<0.05) higher than their alpha-amylase inhibitory activity. The free phenolics (31.67 mg/g) and flavonoid (17.28 mg/g) contents were significantly (P<0.05) higher than bound phenolic (23.52 mg/g) and flavonoid (13.70 mg/g) contents. Both extracts also exhibited high antioxidant activities as typified by their high reducing power, 1,1 diphenyl-2- picrylhydrazyl (DPPH) and 2, 2-azinobis-3-ethylbenzo-thiazoline-6-sulfonate (ABTS) radical scavenging abilities, as well as inhibition of Fe(2+)-induced lipid peroxidation in rat pancreas in vitro. This study provides a biochemical rationale by which clove elicits therapeutic effect on type 2 diabetes.

  18. Expression of alpha-AR subtypes in T lymphocytes and role of the alpha-ARs in mediating modulation of T cell function.

    PubMed

    Bao, Jing-Yin; Huang, Yan; Wang, Feng; Peng, Yu-Ping; Qiu, Yi-Hua

    2007-01-01

    Previous work in our laboratory has shown that alpha-adrenoreceptors (alpha-ARs) and beta-ARs exist on lymphocytes from functional profile, and that the receptors mediate the regulation of lymphocyte function by catecholamines. In the present study, we directly examined the expression of alpha-AR subtypes, alpha(1)-AR and alpha(2)-AR mRNAs, in T lymphocytes and explored the roles of the alpha-AR subtypes and intracellular signal transduction mechanisms linked to the receptors in mediating the modulation of T lymphocyte function. T lymphocytes from mesenteric lymph nodes of rats were purified by using a nylon wool column. Reverse transcription polymerase chain reaction was used to detect the expression of alpha(1)-AR and alpha(2)-AR mRNAs in the freshly isolated T cells and the mitogen concanavalin A (Con A)-activated lymphocytes. Colorimetric methylthiazoletetrazolium assay was employed to measure lymphocyte proliferation induced by Con A. Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels in the Con A-stimulated lymphocyte culture supernatants were examined by enzyme-linked immunosorbent assay. T cells expressed both alpha(1)-AR and alpha(2)-AR mRNAs. The expression of both alpha(1)-AR and alpha(2)-AR mRNAs was significantly higher in the Con A-activated lymphocytes than in the resting lymphocytes. Phenylephrine, a selective alpha(1)-AR agonist, had no evident effect on lymphocyte proliferation nor on IFN-gamma and IL-4 production induced by Con A. However, the selective alpha(2)-AR agonist clonidine attenuated Con A-induced lymphocyte proliferation as well as IFN-gamma and IL-4 production. The inhibited lymphocyte proliferation and IFN-gamma and IL-4 production by clonidine were blocked by yohimbine, an alpha(2)-AR antagonist. Either phospholipase C inhibitor U-73122 or protein kinase C inhibitor chelerythrine partially prevented the suppressive effect of clonidine on Con A-stimulated lymphocyte proliferation and IL-4 production. T lymphocytes express

  19. Influence of Panax ginseng on Alpha-Adrenergic Receptor of Benign Prostatic Hyperplasia

    PubMed Central

    Kim, Su Kang; Chung, Joo-Ho; Lee, Byung-Cheol; Lee, Sang Won; Lee, Kang Hyo

    2014-01-01

    Purpose Benign prostatic hyperplasia (BPH) is the most common prostate problem in older men. The present study aimed to investigate the inhibitory effect of Panax ginseng C.A. Meyer (P. ginseng) on a rat model of testosterone-induced BPH. Methods The rats were divided into 3 groups (each group, n=10): control, testosterone-induced BPH (20 mg/kg, subcutaneous injection), and P. ginseng (200 mg/kg, orally) groups. After 4 weeks, all animals were sacrificed to examine the blood biochemical profiles, prostate volume, weight, histopathological changes, alpha-1D adrenergic receptor (Adra1d) mRNA expression, and epidermal growth factor receptor (EGFR) and B-cell CLL/lymphoma 2 (BCL2) protein expression. Results The group treated with P. ginseng showed significantly lesser prostate size and weight than the testosterone-induced BPH group. In addition, P. ginseng decreased the mRNA expression of Adra1d as well as the expression of EGFR and BCL2 in prostate tissue. Conclusions These results suggest that P. ginseng may inhibit the alpha-1-adrenergic receptor to suppress the development of BPH. PMID:25558416

  20. Diagnostic Testing for Female Infertility

    MedlinePlus

    ... Home FAQs Frequently Asked Questions Quick Facts About Infertility FAQs About Infertility FAQs About the Psychological Component of Infertility FAQs About Cloning and Stem Cell Research SART's ...

  1. Adult rats are more sensitive to the vascular effects induced by hyperhomocysteinemia than young rats.

    PubMed

    de Andrade, Claudia Roberta; de Campos, Glenda Andréa Déstro; Tirapelli, Carlos Renato; Laurindo, Francisco R M; Haddad, Renato; Eberlin, Marcos N; de Oliveira, Ana Maria

    2010-01-01

    We aimed to investigate the vascular effects of hyperhomocysteinemia (HHcy) on carotid arteries from young and adult rats. With this purpose young and adult rats received a solution of DL-homocysteine-thiolactone (1 g/kg body weight/day) in the drinking water for 7, 14 and 28 days. Increase on plasma homocysteine occurred in young and adult rats treated with DL-homocysteine-thiolactone in all periods. Vascular reactivity experiments using standard muscle bath procedures showed that HHcy enhanced the contractile response of endothelium-intact, carotid rings to phenylephrine in both young and adult rats. However, in young rats, the increased phenylephrine-induced contraction was observed after hyperhomocysteinemia for 14 and 28 days, whereas in adult rats this response was already apparent after 7 day treatment. HHcy impaired acetylcholine-induced relaxation in arteries from adult but not young rats. The contraction induced by phenylephrine in carotid arteries in the presence of Y-27632 was reversed to control values in arteries from young but not adult rats with hyperhomocysteinemia. HHcy did not alter the contraction induced by CaCl(2) in carotid arteries from young rats, but enhanced CaCl(2)-induced contraction in the arteries from adult rats. HHcy increased the basal levels of superoxide anion in arteries from both groups. Finally, HHcy decreased the basal levels of nitrite in arteries from adult but not young rats. The major new finding of the present work is that arteries from young rats are more resistant to vascular changes evoked by HHcy than arteries from adult rats. Also, we verified that the enhanced vascular response to phenylephrine observed in carotid arteries of DL-homocysteine thiolactone-treated rats is mediated by different mechanisms in young and adult rats. Copyright 2010. Published by Elsevier Inc.

  2. Anti-inflammatory actions of clonidine, guanfacine and B-HT 920 against various inflammagen-induced acute paw oedema in rats.

    PubMed

    Kulkarni, S K; Mehta, A K; Kunchandy, J

    1986-02-01

    Clonidine (0.1-1.0 mg/kg, i.p.) exhibited anti-inflammatory activity in carrageenan-, formalin-, 5-HT- and histamine-induced paw oedema in rats. Similarly, other two alpha 2-adrenoceptor agonists, guanfacine and B-HT 920, also displayed an anti-inflammatory action in these models. The anti-inflammatory effect of all the three alpha 2-adrenoceptor agonists was reversed by yohimbine. However, prazosin failed to block the anti-inflammatory effect of clonidine. Intracerebroventricularly administered clonidine had a delayed onset of anti-inflammatory action, starting only from 60 min post carrageenan administration. This was in contrast to the systemically administered clonidine which was effective against both phases of carrageenan-induced oedema. On the other hand, irrespective of the route of administration, i.e. peripheral or central, guanfacine and B-HT 920 were effective against the early as well as against the delayed phases of the inflammatory reaction. The studies suggest that it is not the imidazoline moiety but the activation of alpha 2-adrenoceptors which is essential for the anti-inflammatory action of these agents.

  3. Sexual function in infertile women with polycystic ovary syndrome and unexplained infertility.

    PubMed

    Diamond, Michael P; Legro, Richard S; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D; Casson, Peter A; Christman, Gregory M; Huang, Hao; Hansen, Karl R; Baker, Valerie; Usadi, Rebecca; Seungdamrong, Aimee; Bates, G Wright; Rosen, R Mitchell; Schlaff, William; Haisenleder, Daniel; Krawetz, Stephen A; Barnhart, Kurt; Trussell, J C; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

    2017-08-01

    While female sexual dysfunction is a frequent occurrence, characteristics in infertile women are not well delineated. Furthermore, the impact of infertility etiology on the characteristics in women with differing androgen levels observed in women with polycystic ovary syndrome and unexplained infertility has not been assessed. The objective of the study was to determine the characteristics of sexual dysfunction in women with polycystic ovary syndrome and unexplained infertility. A secondary data analysis was performed on 2 of Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Networks clinical trials: Pregnancy in Polycystic Ovary Syndrome Study II and Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation. Both protocols assessed female sexual function using the Female Sexual Function Inventory and the Female Sexual Distress Scale. Women with polycystic ovary syndrome had higher weight and body mass index than women with unexplained infertility (each P < .001), greater phenotypic (Ferriman-Gallwey hirsutism score, sebum score, and acne score; each P < .001), and hormonal (testosterone, free testosterone, and dehydroepiandrosterone; each P < .001) evidence of androgen excess. Sexual function scores, as assessed by the Female Sexual Function Inventory, were nearly identical. The Female Sexual Distress Scale total score was higher in women with polycystic ovary syndrome. The mean Female Sexual Function Inventory total score increased slightly as the free androgen index increased, mainly as a result of the desire subscore. This association was more pronounced in the women with unexplained infertility. Reproductive-age women with infertility associated with polycystic ovary syndrome and unexplained infertility, despite phenotypic and biochemical differences in androgenic manifestations, do not manifest clinically significant differences in sexual function. Copyright © 2017 Elsevier Inc

  4. Sexually Transmitted Diseases and Infertility

    PubMed Central

    TSEVAT, Danielle G.; WIESENFELD, Harold C.; Parks, Caitlin; PEIPERT, Jeffrey F.

    2016-01-01

    Female infertility, including tubal factor infertility, is a major public health concern worldwide. Most cases of tubal factor infertility are attributable to untreated sexually transmitted diseases that ascend along the reproductive tract and are capable of causing tubal inflammation, damage, and scarring. Evidence has consistently demonstrated the effects of Chlamydia trachomatis and Neisseria gonorrhoeae as pathogenic bacteria involved in reproductive tract morbidities including tubal factor infertility and pelvic inflammatory disease. There is limited evidence in the medical literature that other sexually transmitted organisms, including Mycoplasma genitalium, Trichomonas vaginalis, and other microorganisms within the vaginal microbiome may be important factors involved in the pathology of infertility. Further investigation into the vaginal microbiome and other potential pathogens is necessary in order to identify preventable causes of tubal factor infertility. Improved clinical screening and prevention of ascending infection may provide a solution to the persistent burden of infertility. PMID:28007229

  5. Actions of alpha2 adrenoceptor ligands at alpha2A and 5-HT1A receptors: the antagonist, atipamezole, and the agonist, dexmedetomidine, are highly selective for alpha2A adrenoceptors.

    PubMed

    Newman-Tancredi, A; Nicolas, J P; Audinot, V; Gavaudan, S; Verrièle, L; Touzard, M; Chaput, C; Richard, N; Millan, M J

    1998-08-01

    This study examined the activity of chemically diverse alpha2 adrenoceptor ligands at recombinant human (h) and native rat (r) alpha2A adrenoceptors compared with 5-HT1A receptors. First, in competition binding experiments at h alpha2A and h5-HT1A receptors expressed in CHO cells, several compounds, including the antagonists 1-(2-pyrimidinyl)piperazine (1-PP), (+/-)-idazoxan, benalfocin (SKF 86466), yohimbine and RX 821,002, displayed preference for h alpha2A versus h5-HT1A receptors of only 1.4-, 3.6-, 4-, 10- and 11-fold, respectively (based on differences in pKi values). Clonidine, brimonidine (UK 14304), the benzopyrrolidine fluparoxan and the guanidines guanfacine and guanabenz exhibited intermediate selectivity (22- to 31-fold) for h alpha2A receptors. Only the antagonist atipamezole and the agonist dexmedetomidine (DMT) displayed high preference for alpha2 adrenoceptors (1290- and 91-fold, respectively). Second, the compounds were tested for their ability to induce h5-HT1A receptor-mediated G-protein activation, as indicated by the stimulation of [35S]GTPgammaS binding. All except atipamezole and RX 821,002 exhibited agonist activity, with potencies which correlated with their affinity for h5-HT1A receptors. Relative efficacies (Emax values) were 25-35% for guanabenz, guanfacine, WB 4101 and benalfocin, 50-65% for 1-PP, (+/-)-idazoxan and clonidine, and over 70% for fluparoxan, oxymetazoline and yohimbine (relative to 5-HT = 100%). Yohimbine-induced [35S]GTPgammaS binding was inhibited by the selective 5-HT1A receptor antagonist WAY 100,635. In contrast, RX 821,002 was the only ligand which exhibited antagonist activity at h5-HT1A receptors, inhibiting 5-HT-stimulated [35S]GTPgammaS binding. Atipamezole, which exhibited negligeable affinity for 5-HT1A receptors, was inactive. Third, the affinities for r alpha2A differed considerably from the affinities for h alpha2A receptors whereas the affinities for r5-HT1A differed much less from the affinities for h5-HT

  6. Inhibition of arsenic induced-rat liver injury by grape seed exact through suppression of NADPH oxidase and TGF-{beta}/Smad activation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pan Xinjuan; Dai Yujie; Li Xing

    2011-08-01

    Chronic arsenic exposure induces oxidative damage to liver leading to liver fibrosis. We aimed to define the effect of grape seed extract (GSE), an antioxidant dietary supplement, on arsenic-induced liver injury. First, Male Sprague-Dawley rats were exposed to a low level of arsenic in drinking water (30 ppm) with or without GSE (100 mg/kg, every other day by oral gavage) for 12 months and the effect of GSE on arsenic-induced hepatotoxicity was examined. The results from this study revealed that GSE co-treatment significantly attenuated arsenic-induced low antioxidant defense, oxidative damage, proinflammatory cytokines and fibrogenic genes. Moreover, GSE reduced arsenic-stimulated Smad2/3more » phosphorylation and protein levels of NADPH oxidase subunits (Nox2, Nox4 and p47phox). Next, we explored the molecular mechanisms underlying GSE inhibition of arsenic toxicity using cultured rat hepatic stellate cells (HSCs). From the in vitro study, we found that GSE dose-dependently reduced arsenic-stimulated ROS production and NADPH oxidase activities. Both NADPH oxidases flavoprotein inhibitor DPI and Nox4 siRNA blocked arsenic-induced ROS production, whereas Nox4 overexpression suppressed the inhibitory effects of GSE on arsenic-induced ROS production and NADPH oxidase activities, as well as expression of TGF-{beta}1, type I procollagen (Coll-I) and {alpha}-smooth muscle actin ({alpha}-SMA) mRNA. We also observed that GSE dose-dependently inhibited TGF-{beta}1-induced transactivation of the TGF-{beta}-induced smad response element p3TP-Lux, and that forced expression of Smad3 attenuated the inhibitory effects of GSE on TGF-{beta}1-induced mRNA expression of Coll-I and {alpha}-SMA. Collectively, GSE could be a potential dietary therapeutic agent for arsenic-induced liver injury through suppression of NADPH oxidase and TGF-{beta}/Smad activation. - Research Highlights: > GSE attenuated arsenic-induced low antioxidant defense, oxidative damage, proinflammatory cytokines

  7. Phthalate metabolites related to infertile biomarkers and infertility in Chinese men.

    PubMed

    Liu, Liangpo; Wang, Heng; Tian, Meiping; Zhang, Jie; Panuwet, Parinya; D'Souza, Priya Esilda; Barr, Dana Boyd; Huang, Qingyu; Xia, Yankai; Shen, Heqing

    2017-12-01

    Although in vitro and in vivo laboratory studies have demonstrated androgen and anti-androgen effects on male reproduction from phthalate exposures, human studies still remain inconsistent. Therefore, a case-control study (n = 289) was conducted to evaluate the associations between phthalate exposures, male infertility risks, and changes in metabolomic biomarkers. Regional participants consisted of fertile (n = 150) and infertile (n = 139) males were recruited from Nanjing Medical University' affiliated hospitals. Seven urinary phthalate metabolites were measured using HPLC-MS/MS. Associations between levels of phthalate metabolites, infertility risks, and infertility-related biomarkers were statistically evaluated. MEHHP, one of the most abundant DEHP oxidative metabolites was significantly lower in cases than in controls (p = 0.039). When using the 1st quartile range as a reference, although statistically insignificant for odds ratios (ORs) of the 2nd, 3rd, and 4th quartiles (OR (95% CI) = 1.50 (0.34-6.48), 0.70 (0.14-3.52) and 0.42 (0.09-2.00), respectively), the MEHHP dose-dependent trend of infertility risk expressed as OR decreased significantly (p = 0.034). More interestingly, most of the phthalate metabolites, including MEHHP, were either positively associated with fertile prevention metabolic biomarkers or negatively associated with fertile hazard ones. Phthalate metabolism, along with their activated infertility-related biomarkers, may contribute to a decreased risk of male infertility at the subjects' ongoing exposure levels. Our results may be illustrated by the low-dose related androgen effect of phthalates and can improve our understanding of the controversial epidemiological results on this issue. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Primary infertility (image)

    MedlinePlus

    Primary infertility is a term used to describe a couple that has never been able to conceive a pregnancy ... to do so through unprotected intercourse. Causes of infertility include a wide range of physical as well ...

  9. Vasodilating effect of norethisterone and its 5 alpha metabolites: a novel nongenomic action.

    PubMed

    Perusquía, Mercedes; Villalón, Carlos M; Navarrete, Erika; García, Gustavo A; Pérez-Palacios, Gregorio; Lemus, Ana E

    2003-08-15

    Estrogens are generally administered in hormone replacement therapy in combination with synthetic progestins. Studies of cardiovascular risk factors in postmenopausal women have shown a variety of responses according to the molecular structure of the progestin used in hormone replacement therapy schemes. The present study sets out to determine the vasoactive effects of norethisterone and its 5alpha-dihydro (5alpha-norethisterone) and -tetrahydro (3alpha,5alpha-norethisterone and 3beta,5alpha-norethisterone) metabolites in isolated precontracted rat thoracic aorta. The addition of norethisterone and 3alpha,5alpha-norethisterone in rat aorta exhibited a potent, concentration-response inhibition of noradrenaline-induced contraction, while 5alpha- and 3beta,5alpha-norethisterone had very little, if any, vasorelaxing effect. Relaxation to norethisterone and 3alpha,5alpha-norethisterone had very rapid time-courses and it was neither affected by the absence of endothelium nor by the inhibitor of nitric oxide synthase, Nomega-nitro-L-arginine methyl ester (L-NAME). The addition of specific anti-androgen, anti-progestin and anti-estrogen compounds and protein synthesis inhibitors did not preclude the vasorelaxing effect of norethisterone and its 3alpha,5alpha-reduced metabolite. The results strongly suggest that these effects are not mediated by nuclear sex steroid hormone receptors. The overall data document a novel nongenomic endothelium-independent vasorelaxing action of a 19-nor synthetic progestin and one of its A-ring-reduced derivatives.

  10. Infliximab Modulates Cisplatin-Induced Hepatotoxicity in Rats

    PubMed Central

    Cüre, Medine Cumhur; Cüre, Erkan; Kalkan, Yıldıray; Kırbaş, Aynur; Tümkaya, Levent; Yılmaz, Arif; Türkyılmaz, Ayşegül Küçükali; Şehitoğlu, İbrahim; Yüce, Süleyman

    2016-01-01

    Background: Cisplatin (Cis) is one of the most commonly used antineoplastic drugs. It is used as chemotherapy for many solid organ malignancies such as brain, neck, male and female urogenital, vesical and pulmonary cancers. Infliximab blocks tumor necrosis factor alpha (TNF-α). Several studies have reported that infliximab ameliorates cell damage by reducing cytokine levels. Aims: We aimed to investigate whether infliximab has a preventive effect against cisplatin-induced hepatotoxicity and whether it has a synergistic effect when combined with Cis. Study Design: Animal experimentation. Methods: Male Wistar albino rats were divided in three groups as follows: Cis group, infliximab + Cis (CIN) group and the control group. Each group comprised 10 animals. Animals in the Cis group received an intraperitoneal single-dose injection of Cis (7 mg/kg). In the CIN group, a single dose of infliximab (7 mg/kg) was administered 72 h prior to the Cis injection. After 72 h, a single dose of Cis (7 mg/kg) was administered. All rats were sacrificed five days after Cis injection. Results: TNF-α levels in the Cis group were significantly higher (345.5±40.0 pg/mg protein) than those of the control (278.7±62.1 pg/mg protein, p=0.003) and CIN groups (239.0±64.2 pg/mg protein, p=0.013). The Cis group was found to have high carbonic anhydrase (CA)-II and low carbamoyl phosphate synthetase-1 (CPS-1) levels. Aspartate transaminase (AST) and alanine transaminase (ALT) levels were lower in the CIN group as compared to the Cis group. Total histological damage was greater in the Cis group as compared to the control and CIN groups. Conclusion: Cis may lead to liver damage by increasing cytokine levels. It may increase oxidative stress-induced tissue damage by increasing carbonic anhydrase II (CA-II) enzyme levels and decreasing CPS-1 enzyme levels. Infliximab decreases Cis-induced hepatic damage by blocking TNF-α and it may also protect against liver damage by regulating CPS-1 and CA

  11. Lead nitrate-induced development of hypercholesterolemia in rats: sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis.

    PubMed

    Kojima, Misaki; Masui, Toshimitsu; Nemoto, Kiyomitsu; Degawa, Masakuni

    2004-12-01

    Changes in the gene expressions of hepatic enzymes responsible for cholesterol homeostasis were examined during the process of lead nitrate (LN)-induced development of hypercholesterolemia in male rats. Total cholesterol levels in the liver and serum were significantly increased at 3-72 h and 12-72 h, respectively, after LN-treatment (100 micromol/kg, i.v.). Despite the development of hypercholesterolemia, the genes for hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and other enzymes (FPPS, farnesyl diphosphate synthase; SQS, squalene synthase; CYP51, lanosterol 14alpha-demethylase) responsible for cholesterol biosynthesis were activated at 3-24 h and 12-18 h, respectively. On the other hand, the gene expression of cholesterol 7alpha-hydroxylase (CYP7A1), a catabolic enzyme of cholesterol, was remarkably suppressed at 3-72 h. The gene expression levels of cytokines interleukin-1beta (IL-1beta) and TNF-alpha, which activate the HMGR gene and suppress the CYP7A1 gene, were significantly increased at 1-3 h and 3-24 h, respectively. Furthermore, gene activation of SREBP-2, a gene activator of several cholesterogenic enzymes, occurred before the gene activations of FPPS, SQS and CYP51. This is the first report demonstrating sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis in LN-treated male rats. The mechanisms for the altered-gene expressions of hepatic enzymes in LN-treated rats are discussed.

  12. Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats.

    PubMed

    Oakes, Nicholas D; Thalén, Pia; Hultstrand, Therese; Jacinto, Severina; Camejo, Germán; Wallin, Boel; Ljung, Bengt

    2005-10-01

    Insulin resistance, impaired glucose tolerance, high circulating levels of free fatty acids (FFA), and postprandial hyperlipidemia are associated with the metabolic syndrome, which has been linked to increased risk of cardiovascular disease. We studied the metabolic responses to an oral glucose/triglyceride (TG) (1.7/2.0 g/kg lean body mass) load in three groups of conscious 7-h fasted Zucker rats: lean healthy controls, obese insulin-resistant/dyslipidemic controls, and obese rats treated with the dual peroxisome proliferator-activated receptor alpha/gamma agonist, tesaglitazar, 3 mumol.kg(-1).day(-1) for 4 wk. Untreated obese Zucker rats displayed marked insulin resistance, as well as glucose and lipid intolerance in response to the glucose/TG load. The 2-h postload area under the curve values were greater for glucose (+19%), insulin (+849%), FFA (+53%), and TG (+413%) compared with untreated lean controls. Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance. Fasting FFA were not affected, but postprandial FFA suppression was restored to levels seen in lean controls. Mechanisms of tesaglitazar-induced lowering of plasma TG were studied separately using the Triton WR1339 method. In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls. In conclusion, the glucose/lipid tolerance test in obese Zucker rats appears to be a useful model of the metabolic syndrome that can be used to evaluate therapeutic effects on impaired postprandial glucose and lipid metabolism. The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model.

  13. Stimulation of nicotinic acetylcholine alpha7 receptors rescue schizophrenia-like cognitive impairments in rats.

    PubMed

    Potasiewicz, Agnieszka; Nikiforuk, Agnieszka; Hołuj, Małgorzata; Popik, Piotr

    2017-02-01

    Alpha7 nicotinic acetylcholine receptor (α7 nAChR) dysfunction plays an important role in schizophrenia. Positive allosteric modulators of α7 nAChR have emerged as a promising therapeutic approach to manage cognitive deficits that are inadequately treated in schizophrenic patients. The aim of the present study was to evaluate the ability of type I (CCMI) and type II (PNU120596) α7 nAChR positive allosteric modulators to counteract MK-801-induced cognitive and sensorimotor gating deficits. The activity of these compounds was compared with the action of the α7 nAChR agonist A582941. CCMI, PNU120596 and A582941 reversed the sensorimotor gating impairment evoked by MK-801 based on the prepulse inhibition of the startle response. Additionally, no MK-801-evoked working memory deficits were observed with α7 nAChR ligand pretreatment as assessed in a discrete paired-trial delayed alternation task. However, these compounds did not affect the rats' attentional performances in the five-choice serial reaction time test. The α7 nAChR agents demonstrated a beneficial effect on sensorimotor gating and some aspects of cognition tested in a rat model of schizophrenia. Therefore, these results support the use of α7 nAChR positive allosteric modulators as a potential treatment strategy in schizophrenia.

  14. Functional characterization of mongoose nicotinic acetylcholine receptor alpha-subunit: resistance to alpha-bungarotoxin and high sensitivity to acetylcholine.

    PubMed

    Asher, O; Lupu-Meiri, M; Jensen, B S; Paperna, T; Fuchs, S; Oron, Y

    1998-07-24

    The mongoose is resistant to snake neurotoxins. The mongoose muscle nicotinic acetylcholine receptor (AChR) alpha-subunit contains a number of mutations in the ligand-binding domain and exhibits poor binding of alpha-bungarotoxin (alpha-BTX). We characterized the functional properties of a hybrid (alpha-mongoose/beta gamma delta-rat) AChR. Hybrid AChRs, expressed in Xenopus oocytes, respond to acetylcholine with depolarizing current, the mean maximal amplitude of which was greater than that mediated by the rat AChR. The IC50 of alpha-BTX to the hybrid AChR was 200-fold greater than that of the rat, suggesting much lower affinity for the toxin. Hybrid AChRs exhibited an apparent higher rate of desensitization and higher affinity for ACh (EC50 1.3 vs. 23.3 microM for the rat AChR). Hence, changes in the ligand-binding domain of AChR not only affect the binding properties of the receptor, but also result in marked changes in the characteristics of the current.

  15. Anti-Inflammatory and Osteoprotective Effects of Cannabinoid-2 Receptor Agonist HU-308 in a Rat Model of Lipopolysaccharide-Induced Periodontitis.

    PubMed

    Ossola, Cesar A; Surkin, Pablo N; Mohn, Claudia E; Elverdin, Juan C; Fernández-Solari, Javier

    2016-06-01

    Anti-inflammatory and immunologic properties of cannabinoids have been reported in several tissues. Expression of cannabinoid receptor Type 2 was reported in osteoblasts and osteoclasts, suggesting a key role in bone metabolism. The aim of this study is to assess the effect of treatment with cannabinoid-2 receptor agonist HU-308 in the oral health of rats subjected to lipopolysaccharide (LPS)-induced periodontitis. Twenty-four rats were distributed in four groups (six rats per group): 1) control rats; 2) sham rats; 3) rats submitted to experimental periodontitis (LPS); and 4) rats submitted to experimental periodontitis and treated with HU-308 (LPS+HU). In groups LPS and LPS+HU, periodontitis was induced by LPS (1 mg/mL) injected into the gingival tissue (GT) of maxillary and mandibular first molars and into the interdental space between the first and second molars, 3 days per week for 6 weeks. In group LPS+HU, HU-308 (500 ng/mL) was applied topically to the GT daily. Alveolar bone loss resulting from LPS-induced periodontitis was significantly attenuated with HU-308 treatment (LPS+HU), measured by macroscopic and histologic examination. Treatment also reduced gingival production of inflammatory mediators augmented in LPS-injected rats, such as: 1) inducible nitric oxide (iNOS) activity (LPS: 90.18 ± 36.51 pmol/minute/mg protein versus LPS+HU: 16.37 ± 4.73 pmol/minute/mg protein; P <0.05); 2) tumor necrosis factor alpha (LPS: 185.70 ± 25.63 pg/mg protein versus LPS+HU: 95.89 ± 17.47 pg/mg protein; P <0.05); and 3) prostaglandin E2 (PGE2) (LPS: 159.20 ± 38.70 pg/mg wet weight versus LPS+HU: 71.25 ± 17.75 pg/mg wet weight; P <0.05). Additionally, HU-308 treatment prevented the inhibitory effect of LPS-induced periodontitis on the salivary secretory response to pilocarpine. Moreover, iNOS activity and PGE2 content, which were increased by LPS-induced periodontitis in the submandibular gland, returned to control values after HU-308 treatment. This study

  16. Nicotinic acetylcholine receptor alpha5 subunits modulate oxotremorine-induced salivation and tremor.

    PubMed

    Wang, Ningshan; Orr-Urtreger, Avi; Chapman, Joab; Rabinowitz, Ruth; Korczyn, Amos D

    2004-07-15

    Neuronal nicotinic acetylcholine receptors (nAChRs) are composed of 12 subunits (alpha2-alpha10 and beta2-beta4). alpha5 Subunits, expressed throughout the central nervous system (CNS) and the autonomic nervous system (ANS), possess unique pharmacological properties. The effects of oxotremorine (OXO) on autonomic functions and tremor were examined in mice lacking alpha5 nAChR subunits (alpha5-/-) and compared with those in wild-type (WT) control mice. The alpha5-/- mice showed significantly increased salivation and tremor responses to OXO. The hypothermia, bradycardia and defecation induced by OXO were of similar magnitudes in the two mouse strains. The enhanced OXO effects in alpha5-/- mice indicate inhibitory effects of alpha5 subunits in autonomic ganglia, and support the participation of these subunits in cholinergic transmission in autonomic ganglia.

  17. Air puff-induced 22-kHz calls in F344 rats.

    PubMed

    Inagaki, Hideaki; Sato, Jun

    2016-03-01

    Air puff-induced ultrasonic vocalizations in adult rats, termed "22-kHz calls," have been applied as a useful animal model to develop psychoneurological and psychopharmacological studies focusing on human aversive affective disorders. To date, all previous studies on air puff-induced 22-kHz calls have used outbred rats. Furthermore, newly developed gene targeting technologies, which are essential for further advancement of biomedical experiments using air puff-induced 22-kHz calls, have enabled the production of genetically modified rats using inbred rat strains. Therefore, we considered it necessary to assess air puff-induced 22-kHz calls in inbred rats. In this study, we assessed differences in air puff-induced 22-kHz calls between inbred F344 rats and outbred Wistar rats. Male F344 rats displayed similar total (summed) duration of air puff-induced 22 kHz vocalizations to that of male Wistar rats, however, Wistar rats emitted fewer calls of longer duration, while F344 rats emitted higher number of vocalizations of shorter duration. Additionally, female F344 rats emitted fewer air puff-induced 22-kHz calls than did males, thus confirming the existence of a sex difference that was previously reported for outbred Wistar rats. The results of this study could confirm the reliability of air puff stimulus for induction of a similar amount of emissions of 22-kHz calls in different rat strains, enabling the use of air puff-induced 22-kHz calls in inbred F344 rats and derived genetically modified animals in future studies concerning human aversive affective disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Effects of lipoic Acid on acrylamide induced testicular damage.

    PubMed

    Lebda, Mohamed; Gad, Shereen; Gaafar, Hossam

    2014-06-01

    Acrylamide is very toxic to various organs and associated with significant increase of oxidative stress and depletion of antioxidants. Alpha-lipoic acid enhances cellular antioxidant defense capacity, thereby protecting cells from oxidative stress. This study aimed to evaluate the protective role of alpha-lipoic acid on the oxidative damage induced by acrylamide in testicular and epididymal tissues. Forty adult male rats were divided into four groups (10 rats each). Control group; acrylamide treated group administered acrylamide 0.05% (w/v) in drinking water for 21 days; alpha-lipoic acid group received basal diet supplemented with 1% alpha-lipoic acid and forth group was exposed to acrylamide and treated with alpha-lipoic acid at the same doses and treatment regimen mentioned before. The administration of acrylamide resulted in significant elevation in testicular and epididymal malondialdehyde level (MDA) and significant reduction in the level of reduced glutathione (GSH) and the activities of glutathione-S-transferase (GST), glutathione peroxidase (GPX) and glutathione reductase (GR). Also, acrylamide significantly reduced serum total testosterone and progesterone but increased estradiol (E2) levels. Treatment with alpha-lipoic acid prior to acrylamide induced protective effects and attenuated these biochemical changes. Alpha-lipoic acid has been shown to possess antioxidant properties offering promising efficacy against oxidative stress induced by acrylamide administration.

  19. [Mental disorders and female infertility].

    PubMed

    Schweiger, U; Wischmann, T; Strowitzki, T

    2012-11-01

    Approximately 5-10% of women in the reproductive years are affected by infertility which is associated with depression, anxiety and disturbed eating behavior. Part of this association can be explained by the emotional stress resulting from infertility. As mental disorders, such as depressive disorder or eating disorders are also prospectively associated with infertility, a bidirectional relationship is assumed. A special relationship exists between mental disorders and the main causes of ovulatory infertility, hypothalamic amenorrhea and polycystic ovary disease. The results of pilot studies support the assumption that psychotherapy may constitute an important component of the treatment of infertility.

  20. New insights on the modulatory roles of metformin or alpha-lipoic acid versus their combination in dextran sulfate sodium-induced chronic colitis in rats.

    PubMed

    Samman, Fatma S; Elaidy, Samah M; Essawy, Soha S; Hassan, Mohammad S

    2017-11-24

    Dextran sulfate sodium (DSS)-induced colitis is the most widely used model that resembles ulcerative colitis (UC) in human with challenging chronic mechanistic oxidative stress-inflammatory/immunological cascades. In models of acute colitis, reduction of oxidative stress and inflammatory burdens beside manipulation of many transcriptional factors were achieved by metformin or alpha-lipoic acid (α-LA). Currently, in vivo DSS-induced chronic colitis was conducted and the possible therapeutic roles of metformin and/or α-LA were explored. Chronic UC was induced by adding 5% DSS orally in drinking water for 7 days followed by 3% DSS in drinking water for 14 days in adult male albino Wistar rats. Intraperitoneal administration of α-LA (25 mg/kg, twice/day) and/or metformin (100 mg/kg/day) were set at day 7 of DSS administration and continued for 14 days. Body weights, survival rates, disease activity index (DAI), colonic oxidative stress markers, tumor necrosis factor (TNF)-α levels, colonic nuclear factor-kappa-B (NF-κB) immunohistochemical expression, and the colonic histopathological changes were observed. Metformin or/and α-LA attenuated the severity of the DSS-induced colitis through improving the reductions in body weights, the DAI, the colonic oxidative stress markers, TNF-α, and NF-κB levels, and the morphological mucosal damage scores. Significant synergetic therapeutic effects were observed with combined therapeutic regimens. Therapeutically, metformin and α-LA could be administered in chronic colitis. The combination of currently used pharmaceutics with natural and synthetic potent antioxidant compounds will become a therapeutic strategy of choice for UC to improve the quality of life if sufficient clinical trials are available. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  1. The effect of varenicline on the development and expression of nicotine-induced behavioral sensitization and cross-sensitization in rats.

    PubMed

    Goutier, Wouter; Kloeze, Margreet B; McCreary, Andrew C

    2015-03-01

    The present study focused on the evaluation of behavioral sensitization and cross-sensitization induced by nicotine and varenicline in rats. Furthermore, it examined the influence of varenicline, a partial alpha4beta2 nicotinic receptor agonist, on nicotine-induced sensitization. To assess the development of behavioral sensitization, rats were chronically treated with vehicle, varenicline (0.03-3.0 mg/kg), nicotine (0.4 mg/kg) or combinations for 5 days and locomotor activity was measured. The expression of sensitization was assessed following a withdrawal period (17-26 days). The present results confirmed previous data showing the development and expression of nicotine-induced sensitization of locomotor activity in the rat. Varenicline did not induce sensitization on its own. When varenicline and nicotine were repeatedly administered sequentially, varenicline blocked the development and expression of nicotine-induced sensitization. Acute varenicline blocked the expression of nicotine-induced sensitization in a dose-dependent manner. Acute varenicline did not significantly increase locomotor activity, nor did it attenuate nicotine-induced sensitization. However, varenicline did cross-sensitize to the effects of nicotine, and vice versa. The present study showed that varenicline produced a dose-dependent bidirectional cross-sensitization with nicotine. Taken together, these findings provide pre-clinical evidence that varenicline is able to attenuate the effects of nicotine, yet simultaneously 'substitutes' for the effects of nicotine in the rat. Longitudinal studies would be needed to see if similar effects are seen in the clinical setting, and whether such effects contribute to the actions of varenicline as a smoking cessation aid. © 2013 Society for the Study of Addiction.

  2. ALPHA-CHLOROHYDRIN INDUCED CHANGES IN SPERM ATP LEVELS AND MOTILITY IN THE RAT: ASSOCIATION WITH DIMINISHED IN VITRO FERTILIZATION. (R825351)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  3. Hematologic interactions of endotoxin, tumor necrosis factor alpha (TNF alpha), interleukin 1, and adrenal hormones and the hematologic effects of TNF alpha in Corynebacterium parvum-primed rats.

    PubMed

    Ulich, T R; del Castillo, J; Ni, R X; Bikhazi, N

    1989-06-01

    Endotoxin reduces the release among other cytokines of tumor necrosis factor (TNF) and interleukin 1 (IL-1) and causes peripheral lymphopenia and a dose-response-dependent initial neutropenia followed by a monophasic neutrophilia. TNF alone induces lymphopenia and an initial neutropenia followed by a biphasic neutrophilia. IL-1 alone induces lymphopenia and a monophasic neutrophilia. TNF-plus-IL-1 caused a greater lymphopenia than either monokine alone, suggesting that both monokines contribute to LPS-induced lymphopenia. TNF-plus-IL-1 induced neutropenia similar in magnitude to that induced by TNF alone and induced a neutrophilia significantly greater than that induced by either monokine alone, suggesting that LPS-induced neutropenia is caused by TNF, while LPS-induced neutrophilia is due to the combined effects of TNF and II-1. TNF and IL-1 were administered together with LPS to simulate the in vivo condition of endogenous monokine release during gram-negative bacteremia. TNF combined with LPS increased both the duration and magnitude of LPS-induced lymphopenia, LPS-induced neutropenia, and LPS-induced neutrophilia. TNF-plus-LPS treated rats at 2 hours after injection exhibited a striking 93% decrease in bone marrow neutrophils even though no peripheral neutrophilia was yet apparent, suggesting that the subsequent neutrophilia was due to demargination and recirculation of neutrophils sequestered in the peripheral vasculature immediately after their release from the bone marrow. Epinephrine, which causes neutrophilia by demargination but not by release of marrow neutrophils, reversed the initial neutropenia in TNF-plus-LPS-treated rats and increased the neutrophilia. IL-1 combined with LPS increased LPS-induced neutrophilia, suggesting that endogenous IL-1 also contributed to LPS-induced neutrophilia. Corynebacterium parvum-primed rats with hyperplasia of the monocyte-macrophage system and treated with TNF differed from naive rats treated with TNF in that the

  4. Antioxidant status in experimental peritonitis: effects of alpha tocopherol and taurolin.

    PubMed

    Konukoglu, D; Iynem, H; Ziylan, E

    1999-03-01

    The role of oxidative stress and antioxidant defences in inflammation-induced organ injury is not clearly understood. We determined the effects of Escherichia coli (E. coli) peritonitis in rats on peritoneum lipid peroxidation and antioxidant defences. Tissue malondialdehyde (MDA) levels were measured to determine the free radical-induced lipid peroxidation in peritonitis. Tissue glutathione (GSH) levels, and activities of GSH-peroxidase, GSH-reductase and superoxide dismutase were examined to show antioxidant status. We also examined the effects of alpha-tocopherol (20 mg kg-1 body weight) as antioxidant and taurolin (200 mg kg-1 body weight) as chemotherapeutic agents on the oxidant stress and antioxidant defence. The treatment agents and E. coli were administrated intraperitoneally. Animals were killed at 2 h after the onset symptoms and then the peritoneum were obtained. Untreated rats with peritonitis had significantly higher MDA levels and significantly lower antioxidant activity than that of the control animals. Treatment of alpha-tocopherol and taurolin decreased the antioxidant activity and improved the antioxidant status. Pretreatment with alpha-tocopherol for 3 days prior to the induction of peritonitis (IP) and administration of taurolin at the time of the IP were more effective than treatment with alpha-tocopherol at the time of the IP and pretreatment of taurolin, respectively. These results are consistent with the idea that an oxidant/antioxidant imbalance is involved in animal peritonitis. Uses of alpha-tocopherol and taurolin in peritonitis were effective in decreasing the oxidative stress of tissue during peritonitis. Copyright 1999 The Italian Pharmacological Society.

  5. Alterations in Vasoreactivity of Femoral Artery Induced by Hindlimb Unweighting are Related to the Changes of Contractile Protein in Rats

    NASA Technical Reports Server (NTRS)

    Ma, Jin; Ren, Xinling; Meng, Qinjun; Zhang, Lifan; Purdy, Ralph E.

    2005-01-01

    Responses of endothelium removed femoral arterial rings to vasoactive compounds were examined in vitro, and the expression of Myosin and Actin of femoral artery were observed by Western Blotting and Immunohistochemistry in hndlimb unweighting rats and control rats. The results showed that contractile responses of femoral arterial rings evoked by Phenylephrine, Endothelin-1, Vasopressin, KCl, Ca(2+) and Ca(2+) ionophore A23187 were decreased in hindlimb unweighting rats as compared with that of controls. But vasoddatory responses induced by SNPand cGMP were not different between groups. No significant differences have been found in expressions of Calponin, Myosin, Actin, and the ratio of MHC SM1/SM2 between the two groups, but expression of alpha-SM-Actin decreased in hindlimb unweighting rats. The data indicated that the diminished contractile responsiveness probably result from altered contractile apparatus, especially the contractile proteins.

  6. Protective effect of alpha glucosyl hesperidin (G-hesperidin) on chronic vanadium induced testicular toxicity and sperm nuclear DNA damage in male Sprague Dawley rats.

    PubMed

    Vijaya Bharathi, B; Jaya Prakash, G; Krishna, K M; Ravi Krishna, C H; Sivanarayana, T; Madan, K; Rama Raju, G A; Annapurna, A

    2015-06-01

    The study was conducted to evaluate the vanadium-induced testicular toxicity and its effect on sperm parameters, sperm nuclear DNA damage and histological alterations in Sprague Dawley rats and to assess the protective effect of G-hesperidin against this damage. Treatment of rats with vanadium at a dose of 1 mg kg bw(-1) for 90 days resulted in significant reduction in serum testosterone levels, sperm count and motility. Further, a parallel increase in abnormal sperm morphology and adverse histopathological changes in testis was also associated with vanadium administration when compared to normal control. Moreover, sperm chromatin dispersion assay revealed that vanadium induces sperm nuclear DNA fragmentation. A marked increase in testicular malondialdehyde levels and decreased activity of antioxidant enzymes such as superoxide dismutase and catalase indicates vanadium-induced oxidative stress. Co-administration of G-hesperidin at a dose of 25 and 50 mg kg bw(-1) significantly attenuated the sperm parameters and histological changes by restoring the antioxidant levels in rat testis. These results suggested that vanadium exposure caused reduced bioavailability of androgens to the tissue and increased free radical formation, thereby causing structural and functional changes in spermatozoa. G-hesperidin exhibited antioxidant effect by protecting the rat testis against vanadium-induced oxidative damage, further ensures antioxidant potential of bioflavonoids. © 2014 Blackwell Verlag GmbH.

  7. Possible involvement of dopamine D-1 and D-2 receptors in diazepam-induced hyperphagia in rats.

    PubMed

    Naruse, T; Amano, H; Koizumi, Y

    1991-01-01

    Possible involvement of dopamine receptors in diazepam-induced (1 mg/kg, subcutaneous (sc] hyperphagia was studied in nondeprived rats. Pretreatment with the selective D-1 antagonist, SCH23390 (0.03 mg/kg, sc) inhibited diazepam-induced hyperphagia. In addition, pretreatment with the preferential D-2 antagonists, haloperidol (0.1 to 0.3 mg/kg, sc) and clebopride (0.1 to 0.3 mg/kg, sc) inhibited diazepam-induced hyperphagia in a dose-dependent manner. Pretreatment with co-administration of SCH23390 (0.1 mg/kg, sc) and clebopride (0.03 mg/kg, sc) completely inhibited this hyperphagia. The selective D-2 antagonist, sulpiride (40 mg/kg, sc) and the peripheral D-2 antagonist, domperidone (10 mg/kg, sc) did not affect diazepam-induced hyperphagia. However, sulpiride (10 micrograms, icv) or domperidone (2 micrograms, icv) administered centrally inhibited this hyperphagia. The highest dose of haloperidol (0.3 mg/kg, sc) or clebopride (0.3 mg/kg, sc) and higher doses of SCH23390 (0.01 and 0.03 mg/kg, sc) or SCH23390/clebopride (0.01/0.03 and 0.01/0.1 mg/kg, sc) tended to decrease spontaneous feeding in non-deprived rats. In addition, the highest dose of haloperidol, clebopride or SCH23390/clebopride inhibited spontaneous feeding in deprived rats. Interestingly, diazepam-induced hyperphagia was inhibited significantly by doses of haloperidol (0.1 mg/kg, sc), clebopride (0.1 mg/kg, sc) and SCH23390/clebopride (0.003/0.03 and 0.003/0.1 mg/kg, sc) which did not affect spontaneous feeding in non-deprived or deprived rats. Pretreatment with alpha-methyl-p-tyrosine (40 mg/kg, IP x 2, 6 and 2 h prior to diazepam administration) failed to inhibit this hyperphagia. Furthermore, pretreatment with a large dose of haloperidol (5 mg/kg, sc, 4 days before diazepam administration) augmented the sub-hyperphagic effect to diazepam (0.5 mg/kg, sc). Thus, these findings suggest that hyperphagia to diazepam is mediated in part by both dopamine D-1 and D-2 receptors in non-deprived rats.

  8. Hydrotubation in the management of female infertility: outcome in low resource settings.

    PubMed

    Adesiyun, A G; Cole, B; Ogwuche, P

    2009-01-01

    To determine the outcome of therapeutic hydrotubation (tubal flushing) in patients with tubal infertility and unexplained infertility. Prospective non-randomised observational study. Alba hospital, a five bed multidisciplinary private hospital in Kaduna city, Nigeria. Infertile women with tubal and unexplained infertility. Two hundred and fifty seven patients that had therapeutic hydrotubation over 7.5 years were analysed. The age range was 21 to 44 years with mean of 34.5 years. Secondary infertility was found in 209 (81.3%) patients and primary infertility in 166 (64.6%) patients. Of the 257 patients, 134 (52.1%) had had induced abortion. Indications for hydrotubation were bilateral perifimbrial adhesion (incomplete tubal occlusion) 47.9%, bilateral fimbrial end occlusion 24.9%, bilateral cornual blockage 16% and unexplained infertility in 11.3% of cases. One hundred and nine conceptions were recorded in this study and the overall conception rate was 42.4%. Likewise, percentage ratio of conception in these 154 patients with evidence of post-hydrotubation tubal patency was 70.8%. Pregnancy outcome of the 109 conceptions are term pregnancy 84.4%, preterm pregnancy 9.2%, miscarriage 4.6% and ectopic pregnancy in 1.8% of the conceptions. Recorded complications were pelvic pain in 177 (68.9%) patients and vaginal bleeding in 63 (24.5%) patients. With good case selection, therapeutic hydrotubation may be beneficial in resource poor countries, especially in patients with incomplete tubal occlusion (bilateral perifimbrial adhesions) and as part of treatment for unexplained infertility.

  9. Anti-endotoxic shock effects of cyproheptadine in rats.

    PubMed

    Wang, Lizan; Zhang, Qingzhu; Hu, Xiuzhou; Lun, Ning; Wang, Baosheng; Zhu, Fanhe

    2002-03-01

    To investigate the antagonistic effect and mechanism of the effect of cyproheptadine (Cyp) on endotoxic shock in rats. Endotoxic shock was produced in rats by i.v. injection of lipopolysaccharides (LPS) (5 mg/kg). Tumor necrosis factor (TNF(alpha)) mRNA expression was assessed by Northern blot. Plasma TNF(alpha) content was measured by radioimmunoassay. Plasma superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured. The intracellular free calcium concentration ([Ca(2+)](i)) in single endothelial cells was determined by laser scanning confocal microscopy (LSCM). Cyp 5 mg/kg injected immediately after i.v. LPS raised the mean arterial blood pressure (MABP) of shocked rats and improved their 24 h survival rate. Meanwhile, Cyp markedly decreased TNF(alpha) mRNA levels in rat liver (18 +/- 10 vs. LPS + saline 38 +/- 10, P < 0.01) as well as plasma TNF(alpha) content [(7.8 +/- 2.4) microg/L vs. LPS + saline (21.5 +/- 3.2) microg/L, P < 0.01)]. It enhanced plasma SOD activity [(1037.2 +/- 112.8) NU/L vs LPS + saline (615.4 +/- 92.6) NU/L, P < 0.01], reduced the MDA content [(5.2 +/- 1.1) micromol/L vs. LPS + saline (9.8 +/- 1.5) micromol/L, P < 0.01], and inhibited TNF(alpha)-induced [Ca(2+)](i) elevation. Cyp exerts an anti-endotoxic shock effect by inhibiting TNF(alpha) gene expression, enhancing SOD activity, reducing lipid peroxidation, and preventing [Ca(2+)](i) overload.

  10. Protein intake and ovulatory infertility.

    PubMed

    Chavarro, Jorge E; Rich-Edwards, Janet W; Rosner, Bernard A; Willett, Walter C

    2008-02-01

    The objective of the study was to evaluate whether intake of protein from animal and vegetable origin is associated with ovulatory infertility. A total of 18,555 married women without a history of infertility were followed up as they attempted a pregnancy or became pregnant during an 8 year period. Dietary assessments were related to the incidence of ovulatory infertility. During follow-up, 438 women reported ovulatory infertility. The multivariate-adjusted relative risk (RR) (95% confidence interval [CI]; P for trend) of ovulatory infertility comparing the highest to the lowest quintile of animal protein intake was 1.39 (1.01 to 1.90; 0.03). The corresponding RR (95% CI; P for trend) for vegetable protein intake was 0.78 (0.54 to 1.12; 0.07). Furthermore, consuming 5% of total energy intake as vegetable protein rather than as animal protein was associated with a more than 50% lower risk of ovulatory infertility (P =.007). Replacing animal sources of protein with vegetable sources of protein may reduce ovulatory infertility risk.

  11. Over-expression of C/EBP-{alpha} induces apoptosis in cultured rat hepatic stellate cells depending on p53 and peroxisome proliferator-activated receptor-{gamma}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang Xueqing; Huang Guangcun; Mei Shuang

    2009-03-06

    Hepatic stellate cells (HSCs) play a key role in the pathogenesis of hepatic fibrosis. In our previous studies, CCAAT enhancer binding protein-{alpha} (C/EBP-{alpha}) has been shown to be involved in the activation of HSCs and to have a repression effect on hepatic fibrosis in vivo. However, the mechanisms are largely unknown. In this study, we show that the infection of adenovirus vector expressing C/EBP-{alpha} gene (Ad-C/EBP-{alpha}) could induce HSCs apoptosis in a dose- and time-dependent manner by Annexin V/PI staining, caspase-3 activation assay, and flow cytometry. Also, over-expression of C/EBP-{alpha} resulted in the up-regulation of peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) andmore » P53, while P53 expression was regulated by PPAR-{gamma}. In addition, Fas, FasL, DR4, DR5, and TRAIL were studied. The results indicated that the death receptor pathway was mainly involved and regulated by PPAR-{gamma} and p53 in the process of apoptosis triggered by C/EBP-{alpha} in HSCs.« less

  12. Monoamine uptake inhibitors block alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation.

    PubMed

    Long, Cheng; Chen, Mei-Fang; Sarwinski, Susan J; Chen, Po-Yi; Si, Minliang; Hoffer, Barry J; Evans, M Steven; Lee, Tony J F

    2006-07-01

    We have proposed that activation of cerebral perivascular sympathetic alpha7-nicotinic acetylcholine receptors (alpha7-nAChRs) by nicotinic agonists releases norepinephrine, which then acts on parasympathetic nitrergic nerves, resulting in release of nitric oxide and vasodilation. Using patch-clamp electrophysiology, immunohistochemistry, and in vitro tissue bath myography, we tested this axo-axonal interaction hypothesis further by examining whether blocking norepinephrine reuptake enhanced alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation. The results indicated that choline- and nicotine-induced alpha7-nAChR-mediated nitrergic neurogenic relaxation in endothelium-denuded isolated porcine basilar artery rings was enhanced by desipramine and imipramine at lower concentrations (0.03-0.1 microM) but inhibited at higher concentrations (0.3-10 microM). In cultured superior cervical ganglion (SCG) neurons of the pig and rat, choline (0.1-30 mM)-evoked inward currents were reversibly blocked by 1-30 microM mecamylamine, 1-30 microM methyllycaconitine, 10-300 nM alpha-bungarotoxin, and 0.1-10 microM desipramine and imipramine, providing electrophysiological evidence for the presence of similar functional alpha7-nAChRs in cerebral perivascular sympathetic neurons of pigs and rats. In alpha7-nAChR-expressing Xenopus oocytes, choline-elicited inward currents were attenuated by alpha-bungarotoxin, imipramine, and desipramine. These monoamine uptake inhibitors appeared to directly block the alpha7-nAChR, resulting in diminished nicotinic agonist-induced cerebral nitrergic vasodilation. The enhanced nitrergic vasodilation by lower concentrations of monoamine uptake inhibitors is likely due to a greater effect on monoamine uptake than on alpha7-nAChR blockade. These results further support the hypothesis of axo-axonal interaction in nitrergic regulation of cerebral vascular tone.

  13. Stable, inducible thermoacidophilic alpha-amylase from Bacillus acidocaldarius.

    PubMed Central

    Buonocore, V; Caporale, C; De Rosa, M; Gambacorta, A

    1976-01-01

    Bacillus acidocaldarius Agnano 101 produces an inducible thermoacidophilic alpha-amylase. The enzyme production occurs during the stationary phase of growth in the presence of compounds with alpha-1,4-glucosidic linkages. The enzymatic activity is both present in the culture medium and associated with the cells; the enzymes purified from both sources show identical molecular and catalytic properties. The purified amylase has a single polypeptide chain of molecular weight 68,000 and behaves like an alpha-amylase with affinity constants for starch and related substances of 0.8 to 0.9 mg/ml. The pH and temperature optima for activity are 3.5 and 75degreesC, respectively. The amylase is stable at acidic pH (below 4.5). Its thermal stability is strictly dependent upon protein concentration; the half-life at 60degreesC of the amylase in a 70-mug/ml solution is about 5 days. PMID:10276

  14. Infertility diagnosis has a significant impact on the transcriptome of developing blastocysts.

    PubMed

    McCallie, Blair R; Parks, Jason C; Griffin, Darren K; Schoolcraft, William B; Katz-Jaffe, Mandy G

    2017-08-01

    unexplained infertility displayed transcription alterations related to various disease states, which included mechanistic target of rapamycin (mTOR) and adipocytokine signaling. RT-qPCR validation confirmed differential gene expression for the following genes: BCL2 like 10 (BCL2L10), heat shock protein family A member 1A (HSPA1A), heat shock protein family A member 1B (HSPA1B), activating transcription factor 3 (ATF3), fibroblast growth factor 9 (FGF9), left-right determination factor 1 (LEFTY1), left-right determination factor 2 (LEFTY2), growth differentiation factor 15 (GDF15), inhibin beta A subunit (INHBA), adherins junctions associated protein 1 (AJAP1), cadherin 9 (CDH9) and laminin subunit alpha 4 (LAMA4) (P < 0.05; >2-fold). Not available due to participant privacy. Blastocyst samples for microarray analysis required pooling. While this allows for an overall average in each infertility etiology group and can reduce noise from sample-to-sample variation, it cannot give a detailed analysis of each blastocyst within the group. Underlying patient infertility diagnosis has an impact on the blastocyst transcriptome, modifying gene expression associated with developmental competence and implantation potential. No conflict of interest or outside funding provided. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email:journals.permissions@oup.com

  15. Cardiac Nitric Oxide Synthases and Na⁺/K⁺-ATPase in the Rat Model of Polycystic Ovary Syndrome Induced by Dihydrotestosterone.

    PubMed

    Tepavčević, S; Milutinović, D V; Macut, D; Stanišić, J; Nikolić, M; Božić-Antić, I; Rodaljević, S; Bjekić-Macut, J; Matić, G; Korićanac, G

    2015-05-01

    Nitric oxide synthases (NOSs) and Na(+)/K(+)-ATPase are enzymes essential for regular functioning of the heart. Since both enzymes are under insulin and androgen regulation and since insulin action and androgen level were disturbed in polycystic ovary syndrome (PCOS), we hypothesized that cardiac nitric oxide (NO) production and sodium/potassium transport would be deteriorated in PCOS. To test our hypothesis we introduced animal model of PCOS based on dihydrotestosterone (DHT) treatment of female Wistar rats and analyzed protein expression, phosphorylation or subcellular localization of endothelial NOS (eNOS), inducible NOS (iNOS) and alpha subunits of Na(+)/K(+)-ATPase in the heart. Obtained results indicate that DHT treatment significantly decreased cardiac eNOS protein level and activating phosphorylation at serine 1,177, while inhibitory phosphorylation at threonine 495 was increased. In contrast to expression of eNOS, iNOS protein level in the heart of DHT-treated rats was significantly elevated. Furthermore, cardiac protein level of alpha 1 subunit of the ATPase, as well as its plasma membrane content, were decreased in rats with PCOS. In line with this, alpha 2 subunit protein level in fraction of plasma membranes was also significantly below control level. In conclusion, DHT treatment impaired effectiveness of NOSs and Na(+)/K(+)-ATPase in the female rat heart. Regarding the importance of NO production and sodium/potassium transport in the cardiac contraction and blood flow regulation, it implicates strong consequences of PCOS for heart functioning. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Ginseng essence, a medicinal and edible herbal formulation, ameliorates carbon tetrachloride-induced oxidative stress and liver injury in rats.

    PubMed

    Lu, Kuan-Hung; Weng, Ching-Yi; Chen, Wei-Cheng; Sheen, Lee-Yan

    2017-07-01

    Ginseng essence (GE) is a formulation comprising four medicinal and edible herbs including ginseng ( Panax ginseng ), American ginseng ( Panax quinquefolius ), lotus seed ( Nelumbo nucifera ), and lily bulb ( Lilium longiflorum ). This study was aimed at investigating the hepatoprotective effect of GE against carbon tetrachloride (CCl 4 )-induced liver injury in rats. We treated Wistar rats daily with low, medium, and high [0.625 g/kg body weight (bw), 1.25 g/kg bw, and 3.125 g/kg bw, respectively] doses of GE for 9 wk. After the 1 st wk of treatment, rats were administered 20% CCl 4 (1.5 mL/kg bw) two times a week to induce liver damage until the treatment ended. Serum biochemical analysis indicated that GE ameliorated the elevation of aspartate aminotransferase and alanine aminotransferase and albumin decline in CCl 4 -treated rats. Moreover, CCl 4 -induced accumulation of hepatic total cholesterol and triglyceride was inhibited. The hepatoprotective effects of GE involved enhancing the hepatic antioxidant defense system including glutathione, glutathione peroxidase, glutathione reductase, glutathione S -transferase, superoxide dismutase, and catalase. In addition, histological analysis using hematoxylin and eosin and Masson's trichrome staining showed that GE inhibited CCl 4 -induced hepatic inflammation and fibrosis. Furthermore, immunohistochemical staining of alpha-smooth muscle actin indicated that CCl 4 -triggered activation of hepatic stellate cells was reduced. These findings demonstrate that GE improves CCl 4 -induced liver inflammation and fibrosis by attenuating oxidative stress. Therefore, GE could be a promising hepatoprotective herbal formulation for future development of phytotherapy.

  17. Involvement of serotoninergic 5-HT1A/2A, alpha-adrenergic and dopaminergic D1 receptors in St. John's wort-induced prepulse inhibition deficit: a possible role of hyperforin.

    PubMed

    Tadros, Mariane G; Mohamed, Mohamed R; Youssef, Amal M; Sabry, Gilane M; Sabry, Nagwa A; Khalifa, Amani E

    2009-05-16

    Prepulse inhibition (PPI) of acoustic startle response is a valuable paradigm for sensorimotor gating processes. Previous research showed that acute administration of St. John's wort extract (500 mg/kg, p.o.) to rats caused significant disruption of PPI while elevating monoamines levels in some brain areas. The cause-effect relationship between extract-induced PPI disruption and augmented monoaminergic transmission was studied using different serotoninergic, adrenergic and dopaminergic antagonists. The effects of hypericin and hyperforin, as the main active constituents of the extract, on PPI response were also tested. PPI disruption was prevented after blocking the serotoninergic 5-HT1A and 5-HT2A, alpha-adrenergic and dopaminergic D1 receptors. Results also demonstrated a significant PPI deficit after acute treatment of rats with hyperforin, and not hypericin. In some conditions manifesting disrupted PPI response, apoptosis coexists. Electrophoresis of DNA isolated from brains of hyperforin-treated animals revealed absence of any abnormal DNA fragmentation patterns. It is concluded that serotoninergic 5-HT1A and 5-HT2A, alpha-adrenergic and dopaminergic D1 receptors are involved in the disruptive effect of St. John's wort extract on PPI response in rats. We can also conclude that hyperforin, and not hypericin, is one of the active ingredients responsible for St. John's wort-induced PPI disruption with no relation to apoptotic processes.

  18. Does pharmaconutrition with L-arginine and/or alpha-tocopherol improve the gut barrier in bile duct ligated rats?

    PubMed

    Tuncyurek, P; Sari, M; Firat, O; Mutaf, I; Gulter, C; Tunger, A; Yuce, G; Yilmaz, M; Makay, O; Dayangac, M; Ersin, S

    2006-01-01

    Nitric oxide supplementation and antioxidant therapy modulate gut barrier function, but the relationships between enhanced nitric oxide production, antioxidant administration, and biliary obstruction remain unclear. We evaluated the role of nitric oxide and alpha-tocopherol supplementation in bile duct ligated rats. Fifty male Wistar albino rats underwent sham operation (group I; control animals) or bile duct ligation (groups II, III, IV, and V). The ligation groups received the following regimens: standard pellet diet (group II), pellet diet plus intramuscularly administered alpha-tocopherol (group III), and L-arginine-enriched pellet diet without (group IV) or with (group V) alpha-tocopherol. Nitric oxide, malondialdehyde, and alpha-tocopherol concentrations were assessed at the end of 3 weeks. Liver and intestinal samples were scored histologically. Mesenteric lymph node and liver cultures were assessed for bacterial translocation. The liver malondialdehyde concentration was highest in group III. The nitric oxide content in the liver was higher in groups III and V, as were the blood alpha-tocopherol levels. Bacterial translocation was evident following bile duct ligation, but did not differ among the treatment groups. Intestinal histology revealed that group III had the lowest villus height, that group V had the least villus count, and that group II had the highest mucous cell count. The fibrosis scores were higher in groups IV and V. An obvious effect of alpha-tocopherol (with or without L-arginine) on the gut barrier could not be demonstrated. Moreover, the L-arginine-enriched diet promoted fibrosis in the liver. Thus, while biliary duct obstruction triggers bacterial translocation, nitric oxide and/or alpha-tocopherol supplementation did not seem to improve the gut barrier in our model. Copyright 2006 S. Karger AG, Basel.

  19. Experimentally-induced hyperthyroidism is associated with activation of the rat hypothalamic-pituitary-adrenal axis.

    PubMed

    Johnson, Elizabeth O; Kamilaris, Themis C; Calogero, Aldo E; Gold, Philip W; Chrousos, George P

    2005-07-01

    Previous studies on the effects of altered thyroid function on the secretion and metabolism of adrenocortical hormones suggest a degree of adrenocortical hyperactivity in hyperthyroidism. We have previously shown that experimentally-induced hyperthyroidism is associated with significant alterations in pituitary-adrenal responsiveness to synthetic ovine corticotropin-releasing hormone (oCRH) that are contingent upon the duration of the altered thyroid function. The purpose of this study was to assess the time-dependent effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis by in vivo stimulation of the hypothalamic CRH neuron and adrenal cortex. The functional integrity of the HPA axis was examined in vivo in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given 50 mug of thyroxine every day for 7 or 60 days. Responses to insulin-induced hypoglycemia and IL-1alpha stimulation were used to assess the hypothalamic CRH neuron. Adrenocortical reserve was assessed in response to low-dose adrenocorticotropic hormone (ACTH), following suppression of the HPA axis with dexamethasone. Adrenal and thymus tissue weight, in addition to basal plasma ACTH, corticosterone and thyroid indices were also determined. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days, cerebrospinal fluid (CSF) corticosterone levels were significantly increased. Basal plasma ACTH levels were similar to controls. Although plasma ACTH responses to hypoglycemic stress and IL-1alpha administration in both short- and long-term hyperthyroidism were normal, corticosterone responses to the ACTH release during the administration of these stimuli were significantly increased. The adrenal reserve was significantly elevated in short-term hyperthyroidsim. Long-term hyperthyroidism, however, was associated

  20. Stigma: the hidden burden of infertility.

    PubMed

    Whiteford, L M; Gonzalez, L

    1995-01-01

    Infertility is experienced by 5 million U.S. couples, some of whom perceive it a stigmatizing condition. Recent technological innovations have created a multitude of medical interventions for those infertile individuals who can financially afford them. For some infertile women, those interventions also transform infertility from a private pain to a public, prolonged crisis. Our research focuses on 25 U.S. women who sought medical treatment for infertility and describes their perception of the stigma associated with infertility. We apply a critical, feminist perspective to our analysis of the women's lived experiences within the social and medical contexts in which they occur.

  1. Identification and properties of an alpha-amylase from a strain of Eubacterium sp. isolated from the rat intestinal tract.

    PubMed

    Delahaye, E P; Foglietti, M J; Andrieux, C; Chardon-Loriaux, I; Szylit, O; Raibaud, P

    1991-01-01

    1. A bacterial amylase was isolated from the intestinal content of monoxenic rats inoculated with Eubacterium sp. B86. 2. Affinity chromatography on cross-linked starch allowed its separation from rat endogenous amylases. 3. The bacterial enzyme was characterized by its pI, molecular weight and action pattern. It behaves as a typical endo-amylase (alpha-amylase).

  2. Does rat fetal DNA induce preeclampsia in pregnant rats?

    PubMed

    Konečná, B; Borbélyová, V; Celec, P; Vlková, B

    2015-02-01

    Cell-free fetal DNA in maternal circulation is higher during preeclampsia. It is unclear whether it is the cause or the consequence of the disease. The aim of this study was to prove whether injected rat fetal DNA induces preeclampsia-like symptoms in pregnant Wistar rats. They received daily i.p. injections of water or rat fetal DNA (400 μg) from gestation day 14 to 18. Blood pressure, proteinuria, placental and fetal weight were measured at gestation day 19. Plasma DNase activity, proteinuria and creatinine clearance were assessed. There was no significant difference in any of the measured parameters. The results of this study do not confirm the hypothesis that fetal DNA might induce preeclampsia. This is in contrast to others using human fetal DNA in mice. Further studies should be focused on the effects of fetal DNA from the same species protected from DNase activity.

  3. Microbiota-based analysis reveals specific bacterial traits and a novel strategy for the diagnosis of infectious infertility

    PubMed Central

    Graspeuntner, Simon; Bohlmann, Michael K.; Gillmann, Kathrin; Speer, Runa; Kuenzel, Sven; Mark, Heike; Hoellen, Friederike; Lettau, Reinhard; Griesinger, Georg; König, Inke R.; Baines, John F.

    2018-01-01

    Tubal factor infertility (TFI) accounts for more than 30% of the cases of female infertility and mostly resides from an inflammatory process triggered by an infection. Clinical appearances largely differ, and very often infections are not recognized or remain completely asymptomatic over time. Here, we characterized the microbial pattern in females diagnosed with infectious infertility (ININF) in comparison to females with non-infectious infertility (nININF), female sex workers (FSW) and healthy controls (fertile). Females diagnosed with infectious infertility differed significantly in the seroprevalence of IgG antibodies against the C. trachomatis proteins MOMP, OMP2, CPAF and HSP60 when compared to fertile females. Microbiota analysis using 16S amplicon sequencing of cervical swabs revealed significant differences between ININF and fertile controls in the relative read count of Gardnerella (10.08% vs. 5.43%). Alpha diversity varies among groups, which are characterized by community state types including Lactobacillus-dominated communities in fertile females, an increase in diversity in all the other groups and Gardnerella-dominated communities occurring more often in ININF. While all single parameters did not allow predicting infections as the cause of infertility, including C. trachomatis IgG/IgA status together with 16S rRNA gene analysis of the ten most frequent taxa a total of 93.8% of the females were correctly classified. Further studies are needed to unravel the impact of the cervical microbiota in the pathogenesis of infectious infertility and its potential for identifying females at risk earlier in life. PMID:29315330

  4. Effect of Alpha-Particle Irradiation on Brain Glycogen in the Rat

    NASA Technical Reports Server (NTRS)

    Wolfe, L. S.; Klatzo, Igor; Miquel, Jaime; Tobias, Cornelius; Haymaker, Webb

    1962-01-01

    The studies of Klatzo, Miquel, Tobias and Haymaker (1961) have shown that one of the earliest and most sensitive indications of the effects of alpha-particle irradiation on rat bran is the appearance of glycogen granules mainly in the neuroglia of the exposed area of the brain. Periodic acid-Schiff (PAS) positive, alpha-amylase soluble granules were demonstrated within 12 hr after irradiation, preceding by approximately 36 hr the first microscopically detectable vascular permeability disturbances, as shown by the fluorescein labeled serum protein technique. These studies suggested that the injurious effects of alpha-particle energy were on cellular elements primarily, according to the physical properties and distribution of the radiation in the tissue, and that the vascular permeability disturbances played a secondary role in pathogenesis. The purpose of this study was to correlate the histochemical observations on glycogen with a quantitative assessment of the glycogen in the irradiated brain tissue. It is felt that such a study may contribute to the understanding of radiation injury at the molecular level. A practical aspect of this problem is that the information on biological radiation effects due to accelerated particles from the cyclotron source, is employed in this study, is applicable to radiation from cosmic particles both in free space and entrapped in the Van Allen belts.

  5. Splanchnic Th(2) and Th(1) cytokine redistribution in microsurgical cholestatic rats.

    PubMed

    García-Dominguez, José; Aller, María-Angeles; García, Cruz; de Vicente, Felipe; Corcuera, Maria-Teresa; Gómez-Aguado, Fernando; Alonso, María José; Vara, Elena; Arias, Jaime

    2010-08-01

    Long-term extrahepatic cholestasis in the rat induces ductular proliferation and fibrosis in the liver, portal hypertension, splenomegaly, portosystemic collateral circulation, and ascites. These splanchnic alterations could have an inflammatory pathophysiology. We measured serum levels of hepatobiliary injury markers and the acute phase proteins, alpha-1-major acid protein (alpha(1)-MAP) and alpha-1-acid glycoprotein (alpha(1)-GPA) in rats 6 wk after microsurgical extrahepatic cholestasis. We also assayed Th(1) (TNF-alpha and IL-1beta) and Th(2) (IL-4 and IL-10) cytokine levels in the liver, ileum, spleen, and mesenteric lymph complex by enzyme-linked immunosorbent assay (ELISA) techniques. Liver fibrosis was measured by Sirius red stain and by using an image system computer-assisted method and mast cell liver infiltration by Giemsa stain. The cholestatic rats showed an increase (P<0.001) in serum levels of bile acids, total and direct bilirubin, AST, ALT, AST/ALT index, gamma-GT, alkaline phosphatase, alpha(1)- MAP, alpha(1)-GPA, and LDH (P<0.05) in relation to sham-operated rats. TNF-alpha, IL-1beta, IL-4, and IL-10 increased in the ileum (P<0.01) and mesenteric lymph complex (P<0.001), and decreased in the liver (P<0.001). A marked bile proliferation associated with fibrosis (P<0.001) and mast cell infiltration was also shown in the liver of cholestatic rats. The splanchnic redistribution of cytokines, with an increase of Th(1) and Th(2) production in the small bowel and in the mesenteric lymph complex, supports the key role of inflammatory mechanisms in rats with secondary biliary fibrosis. Copyright 2010 Elsevier Inc. All rights reserved.

  6. The Effect of Lithospermum officinale, Silver Sulfadiazine and Alpha Ointments in Healing of Burn Wound Injuries in Rat.

    PubMed

    Mohtasham Amiri, Zahra; Tanideh, Nader; Seddighi, Anahita; Mokhtari, Maral; Amini, Masood; Shakouri Partovi, Alborz; Manafi, Amir; Hashemi, Seyedeh Sara; Mehrabani, Davood

    2017-09-01

    Burn is the most devastating condition in emergency medicine leading to chronic disabilities. This study aimed to compare the effect of Lithospermum officinale , silver sulfadiazine and alpha ointments on healing of burn wounds in rat. Ninety-five rats were divided into 5 groups. Group 1 just underwent burn injury, and groups 2-5 received alpha ointment, silver sulfadiazine (SSD), gel base and L. officinale extract, respectively. A hot plate was used for induction of a standard 3 rd degree burn wound. Burn wounds were macroscopically and microscopically evaluated on days 7 th , 14 th and 21 st after burn induction. A decrease in the number of inflammatory cells was noted when L. officinale and SSD were applied while the most inflammatory response was seen after administration of alpha ointment. The number of macrophages alone decreased after burn injury, while the frequency was the most when L. officinale and alpha ointment were applied. Re-epithelialization, angiogenesis and formation of granulation tissue were the best in relation to L. officinale and alpha ointment while, the worst results belonged to burn injury group and SSD regarding granulation tissue formation. Considering histological assessment, the best results were observed for scoring of inflammation, re-epithelialization, angiogenesis, formation of granulation tissue and number of macrophage when L. officinale and alpha ointment were used after burn injury. It can be concluded that topical application of L. officinale as a non-toxic, inexpensive and easy to produce herbal can lead to a rapid epithelialization and wound healing and these findings can be added to the literature on burn wound healing.

  7. Effect of chronic glomerulonephritis on the semen quality and cytokines in the semen of infertile males.

    PubMed

    Zhang, Huina; Ying, Yingfen; Chen, Yilu; Lu, Xiaosheng; Huang, Yonggang

    2017-01-01

    The effects of chronic glomerulonephritis (CGN) on semen quality and cytokine levels in the semen of infertile males remain undetermined. Fifty-eight semen samples from normal males and CGN males with and without infertility, respectively, were analyzed. Semen volume, semen pH, sperm density, percentage of forward movement of sperm, sperm activate rate, sperm survival rate, and rate of normal sperm morphology of infertility males with CGN were significantly lower than those of CGN males without infertility and normal males (P<.05). In addition, the blood urea nitrogen and serum creatinine levels and interleukin (IL)-17 and IL-18 levels in infertility males with CGN were significantly higher than those of CGN males without infertility and normal males (P<.05). CGN increased the blood urea nitrogen and serum creatinine levels, which induced abnormal expression of IL-17 and IL-18, and negatively affected male semen quality and might result in male infertility. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Infertility among kidney transplant recipients.

    PubMed

    Ghazizadeh, Shirin; Lessan-Pezeshki, Mahboob; Khatami, Mohammd R; Mahdavi-Mazdeh, Mitra; Abbasi, Mohammad R; Azmandian, Jalal; Razeghi, Effat; Seifi, Sepideh; Ahmadi, Farrokh; Maziar, Sima

    2007-03-01

    We studied 122 women with a transplanted kidney to evaluate their reproductive performance. 15 of the patients were either post-menopausal or underwent hysterectomy and 33 were unmarried. Of the 76 married reproductive age women, 10 (13.1%) were infertile. Three had male factor infertility, three had ovulatory problems and in four cases, the cause was uncertain. Six of these patients were actively treated by ovulation induction with or without IUI and two of these patients became pregnant. The remaining four patients refused treatment for infertility. We conclude that the incidence of infertility among kidney transplant recipients is similar to the general population, but they are less motivated to be treated for infertility.

  9. The effect of prolonged ethanol administration on central alpha 2-adrenoceptors sensitivity.

    PubMed

    Szmigielski, A; Szmigielska, H; Wejman, I

    1989-01-01

    The response of an endogenous inhibitor of protein kinases (type II inhibitor) to clonidine was used as an index of sensitivity of central alpha 2-adrenoceptors. Low doses of clonidine (20-50 micrograms/kg) induced an increase in type II inhibitor activity in the nucleus accumbens, hippocampus and in the anterior and posterior hypothalamus by stimulating presynaptic alpha 2-adrenoceptors. Stimulation of postsynaptic alpha 2-adrenoceptors by high doses of clonidine 0.5-1.0 mg/kg resulted in a dose-dependent decrease in type II inhibitor activity. Prolonged treatment with ethanol (5 g/kg/day po for 21 days) greatly reduced the action of high doses of clonidine in all the examined brain areas, suggesting subsensitivity of postsynaptic alpha 2-adrenoceptors lasting for at least 48 h after the last ethanol administration. A single dose of ethanol induced a short lasting subsensitivity of postsynaptic alpha 2-adrenoceptors in the anterior hypothalamus. 12 h after administration of alcohol the response of type II inhibitor to high doses of clonidine in this brain area was the same as in untreated rats.

  10. Alpha Particle Detection Using Alpha-Induced Air Radioluminescence: A Review and Future Prospects for Preliminary Radiological Characterisation for Nuclear Facilities Decommissioning

    PubMed Central

    Crompton, Anita J.; Jenkins, Alex

    2018-01-01

    The United Kingdom (UK) has a significant legacy of nuclear installations to be decommissioned over the next 100 years and a thorough characterisation is required prior to the development of a detailed decommissioning plan. Alpha radiation detection is notoriously time consuming and difficult to carry out due to the short range of alpha particles in air. Long-range detection of alpha particles is therefore highly desirable and this has been attempted through the detection of secondary effects from alpha radiation, most notably the air-radioluminescence caused by ionisation. This paper evaluates alpha induced air radioluminescence detectors developed to date and looks at their potential to develop a stand-off, alpha radiation detector which can be used in the nuclear decommissioning field in daylight conditions to detect alpha contaminated materials. PMID:29597340

  11. Alpha-adrenergic systems mediate chronic central AII hypertension in rats fed high sodium chloride diet from weaning.

    PubMed

    Camara, A K; Osborn, J L

    1999-04-16

    Hypertension is elicited by chronic, low dose intracerebroventricular (ICV) angiotensin II (AII) infusion in rats raised from weaning on relatively high sodium chloride diet (250 mEq kg(-1) food). This experimental model of hypertension is dependent upon renal innervation and associated with neurogenic sodium retention. The present study determined whether this neurogenic ICV AII hypertension is mediated by central alpha-adrenoceptors. Rats were weaned at 21 days of age and fed a 1.5% (250 mg kg(-1) food) sodium chloride diet for 10-12 weeks. At adulthood, animals were instrumented with central nervous system (CNS) lateral ventricular cannulas, femoral artery and vein catheters and housed in metabolic pens for chronic study. Low dose ICV AII infusion (20 ng min(-1)) increased mean arterial pressure (MAP) from 121 +/- 4 to 140 +/- 6 mm Hg on the day of ICV infusion. This increase in arterial pressure was associated with 3 consecutive days of decreased urinary sodium excretion. Subsequent ICV alpha-adrenoceptor blockade with phentolamine (AII + phentolamine) abolished the pressor and antinatriuretic responses to low dose chronic ICV AII infusion. Resumption of ICV AII infusion alone increased in MAP toward pre-alpha-adrenergic blockade values (133 +/- 5 mm Hg) on day 8. Following cessation of ICV AII infusion, arterial pressure and sodium excretion returned to values not significantly different from control. This model of hypertension was not dependent on circulating plasma renin activity (PRA), since PRA decreased during ICV AII infusion. These data confirm that low dose ICV AII causes hypertension and sodium retention in rats raised from weaning on moderately elevated sodium intake. We conclude that AII mediated neurogenic hypertension and antinatriuresis is elicited by stimulation of AT1 receptors on neurons which interact with noradrenergic cell bodies in cardiovascular and autonomic centers that may modulate renal sympathetic outflow via alpha-adrenoceptors.

  12. Amelioration of nandrolone decanoate-induced testicular and sperm toxicity in rats by taurine: effects on steroidogenesis, redox and inflammatory cascades, and intrinsic apoptotic pathway.

    PubMed

    Ahmed, Maha A E

    2015-02-01

    The wide abuse of the anabolic steroid nandrolone decanoate by athletes and adolescents for enhancement of sporting performance and physical appearance may be associated with testicular toxicity and infertility. On the other hand, taurine; a free β-amino acid with remarkable antioxidant activity, is used in taurine-enriched beverages to boost the muscular power of athletes. Therefore, the purpose of this study was to investigate the mechanisms of the possible protective effects of taurine on nandrolone decanoate-induced testicular and sperm toxicity in rats. To achieve this aim, male Wistar rats were randomly distributed into four groups and administered either vehicle, nandrolone decanoate (10mg/kg/week, I.M.), taurine (100mg/kg/day, p.o.) or combination of taurine and nandrolone decanoate, for 8 successive weeks. Results of the present study showed that taurine reversed nandrolone decanoate-induced perturbations in sperm characteristics, normalized serum testosterone level, and restored the activities of the key steroidogenic enzymes; 3β-HSD, and 17β-HSD. Moreover, taurine prevented nandrolone decanoate-induced testicular toxicity and DNA damage by virtue of its antioxidant, anti-inflammatory, and anti-apoptotic effects. This was evidenced by taurine-induced modulation of testicular LDH-x activity, redox markers (MDA, NO, GSH contents, and SOD activity), inflammatory indices (TNF-α, ICAM-1 levels, and MMP-9 gene expression), intrinsic apoptotic pathway (cytochrome c gene expression and caspase-3 content), and oxidative DNA damage markers (8-OHdG level and comet assay). In conclusion, at the biochemical and histological levels, taurine attenuated nandrolone decanoate-induced poor sperm quality and testicular toxicity in rats. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Effect of the lectins wheat germ agglutinin (WGA) and Ulex europaeus agglutinin (UEA-I) on the alpha-amylase secretion of rat pancreas in vitro and in vivo.

    PubMed

    Mikkat, U; Damm, I; Schröder, G; Schmidt, K; Wirth, C; Weber, H; Jonas, L

    1998-05-01

    Lectins are able to bind to cholecystokinin (CCK) receptors and other glycosylated membrane proteins. The lectins wheat germ agglutinin (WGA) and Ulex europaeus agglutinin (UEA-I) are used for affinity chromatography to isolate the highly glycosylated CCK-A receptor of pancreatic acinar cells. According to the working hypothesis that lectin binding to the CCK receptor should alter the ligand-receptor interaction, the effect of WGA and UEA-I on CCK-8-induced enzyme secretion was studied on isolated rat pancreatic acini in vitro. In vitro both lectins showed a dosage-dependent inhibition of CCK-8-induced alpha-amylase secretion of acini over 60 min. WGA showed a strong inhibitory effect on amylase secretion, approximately 40%, in vitro. UEA-I caused a smaller, but significant decrease, approximately 20%, in enzyme secretion of isolated acini. Additionally, both lectins inhibited cerulein/secretin- or cerulein-induced pancreatic secretion of rats in vivo, but not after secretin alone. The results are discussed with respect to a possible influence of both lectins on the interaction of CCK or cerulein with the CCK-A receptor.

  14. Curcumin confers neuroprotection against alcohol-induced hippocampal neurodegeneration via CREB-BDNF pathway in rats.

    PubMed

    Motaghinejad, Majid; Motevalian, Manijeh; Fatima, Sulail; Hashemi, Hajar; Gholami, Mina

    2017-03-01

    Alcohol abuse causes severe damage to the brain neurons. Studies have reported the neuroprotective effects of curcumin against alcohol-induced neurodegeneration. However, the precise mechanism of action remains unclear. Seventy rats were equally divided into 7 groups (10 rats per group). Group 1 received normal saline (0.7ml/rat) and group 2 received alcohol (2g/kg/day) for 21days. Groups 3, 4, 5 and 6 concurrently received alcohol (2g/kg/day) and curcumin (10, 20, 40 and 60mg/kg, respectively) for 21days. Animals in group 7 self- administered alcohol for 21days. Group 8 treated with curcumin (60mg/kg, i.p.) alone for 21days. Open Field Test (OFT) was used to investigate motor activity in rats. Hippocampal oxidative, antioxidative and inflammatory factors were evaluated. Furthermore, brain cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) levels were studied at gene level by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, protein expression for BDNF, CREB, phosphorylated CREB (CREB-P), Bax and Bcl-2 was determined by western blotting. Voluntary and involuntary administration of alcohol altered motor activity in OFT, and curcumin treatment inhibited this alcohol-induced motor disturbance. Also, alcohol administration augmented lipid peroxidation, mitochondrial oxidized glutathione (GSSG), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and Bax levels in isolated hippocampal tissues. Furthermore, alcohol-induced significant reduction were observed in reduced form of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and CREB, BDNF and Bcl-2 levels. Also curcumin alone did not change the behavior and biochemical and molecular parameters. Curcumin can act as a neuroprotective agent against neurodegenerative effects of alcohol abuse, probably via activation of CREB-BDNF signaling pathway

  15. High-density lipoproteins protect endothelial cells from tumor necrosis factor-alpha-induced apoptosis.

    PubMed

    Sugano, M; Tsuchida, K; Makino, N

    2000-06-16

    High-density lipoproteins (HDL) levels have been shown to be inversely correlated with coronary heart disease, but the mechanisms of the direct protective effect of HDL on endothelial cells are not fully understood. The apoptosis of endothelial cells induced by cytokines and/or oxidized low-density lipoproteins, etc. may provide a mechanistic clue to the "response-to-injury" hypothesis of atherogenesis. Here we report that HDL prevent the apoptosis of human umbilical venous endothelial cells (HUVECs) induced by tumor necrosis factor-alpha (TNF-alpha) via an inhibition of CPP32-like protease activity. The incubation of HUVECs with TNF-alpha significantly increased the CPP32-like protease activity, and induced apoptosis. Preincubation of HUVECs with HDL before incubation with TNF-alpha significantly suppressed the increase in the CPP32-like protease activity, preventing apoptosis in a concentration-dependent manner. These results suggest that HDL prevent the suicide pathway leading to apoptosis of endothelial cells by decreasing the CPP32-like protease activity and that HDL thus play a protective role against the "response-to-injury" hypothesis of atherogenesis. Copyright 2000 Academic Press.

  16. Identification of human candidate genes for male infertility by digital differential display.

    PubMed

    Olesen, C; Hansen, C; Bendsen, E; Byskov, A G; Schwinger, E; Lopez-Pajares, I; Jensen, P K; Kristoffersson, U; Schubert, R; Van Assche, E; Wahlstroem, J; Lespinasse, J; Tommerup, N

    2001-01-01

    Evidence for the importance of genetic factors in male fertility is accumulating. In the literature and the Mendelian Cytogenetics Network database, 265 cases of infertile males with balanced reciprocal translocations have been described. The candidacy for infertility of 14 testis-expressed transcripts (TETs) were examined by comparing their chromosomal mapping position to the position of balanced reciprocal translocation breakpoints found in the 265 infertile males. The 14 TETs were selected by using digital differential display (electronic subtraction) to search for apparently testis-specific transcripts in the TIGR database. The testis specificity of the 14 TETs was further examined by reverse transcription-polymerase chain reaction (RT-PCR) on adult and fetal tissues showing that four TETs (TET1 to TET4) were testis-expressed only, six TETs (TET5 to TET10) appeared to be differentially expressed and the remaining four TETs (TET11 to TET14) were ubiquitously expressed. Interestingly, the two tesis expressed-only transcripts, TET1 and TET2, mapped to chromosomal regions where seven and six translocation breakpoints have been reported in infertile males respectively. Furthermore, one ubiquitously, but predominantly testis-expressed, transcript, TET11, mapped to 1p32-33, where 13 translocation breakpoints have been found in infertile males. Interestingly, the mouse mutation, skeletal fusions with sterility, sks, maps to the syntenic region in the mouse genome. Another transcript, TET7, was the human homologue of rat Tpx-1, which functions in the specific interaction of spermatogenic cells with Sertoli cells. TPX-1 maps to 6p21 where three cases of chromosomal breakpoints in infertile males have been reported. Finally, TET8 was a novel transcript which in the fetal stage is testis-specific, but in the adult is expressed in multiple tissues, including testis. We named this novel transcript fetal and adult testis-expressed transcript (FATE).

  17. Antioxidant and antiapoptotic effects of green tea polyphenols against azathioprine-induced liver injury in rats.

    PubMed

    El-Beshbishy, Hesham A; Tork, Ola M; El-Bab, Mohamed F; Autifi, Mohamed A

    2011-04-01

    Green tea polyphenols (GTP) is considered to have protective effects against several diseases. The hepatotoxicity of azathioprine (AZA) has been reported and was found to be associated with oxidative damage. This study was conducted to evaluate the role of GTP to protect against AZA-induced liver injury in rats. AZA was administered i.p. in a single dose (50mgkg(-1)) to adult male rats. AZA-intoxicated rats were orally administered GTP (either 100mgkg(-1)day(-1) or 300mgkg(-1)day(-1), for 21 consecutive days, started 7 days prior AZA injection). AZA administration to rats resulted in significant elevation of serum transaminases (sALT and sAST), alkaline phosphatase (sALP), depletion of hepatic reduced glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx), accumulation of oxidized glutathione (GSSG), elevation of lipid peroxides (LPO) expressed as malondialdehyde (MDA), reduction of the hepatic total antioxidant activity (TAA), decrease serum total proteins and elevation of liver protein carbonyl content. Significant rises in liver tumor necrosis factor-alpha (TNF-α) and caspase-3 levels were noticed in AZA-intoxicated rats. Treatment of the AZA-intoxicated rats with GTP significantly prevented the elevations of sALT, sAST and sALP, inhibited depletion of hepatic GSH, GPx, CAT and GSSG and inhibited MDA accumulation. Furthermore, GTP had normalized serum total proteins and hepatic TAA, CAT, TNF-α and caspase-3 levels of AZA-intoxicated rats. In addition, GTP prevented the AZA-induced apoptosis and liver injury as indicated by the liver histopathological analysis. The linear regression analysis showed significant correlation in either AZA-GTP100 or AZA-GTP300 groups between TNF-α and each of serum ALT, AST, ALP and total proteins and liver TAA, GPX, CAT, GSH, GSSG, MDA and caspase-3 levels. However, liver TNF-α produced non-significant correlation with the serum total proteins in both AZA-GTP100 and AZA-GTP300 groups. In conclusion, our data indicate

  18. Glutamine and ornithine alpha-ketoglutarate supplementation on malate dehydrogenases expression in hepatectomized rats.

    PubMed

    Guimarães Filho, Artur; Cunha, Rodrigo Maranguape Silva da; Vasconcelos, Paulo Roberto Leitão de; Guimarães, Sergio Botelho

    2014-06-01

    To evaluate the relative gene expression (RGE) of cytosolic (MDH1) and mitochondrial (MDH2) malate dehydrogenases enzymes in partially hepatectomized rats after glutamine (GLN) or ornithine alpha-ketoglutarate (OKG) suplementation. One-hundred and eight male Wistar rats were randomly distributed into six groups (n=18): CCaL, GLNL and OKGL and fed calcium caseinate (CCa), GLN and OKG, 0.5 g/Kg by gavage, 30 minutes before laparotomy. CCaH, GLNH and OKGH groups were likewise fed 30 minutes before 70% partial hepatectomy. Blood and liver samples were collected three, seven and 14 days after laparotomy/hepatectomy for quantification of MDH1/MDH2 enzymes using the real-time polymerase chain reaction (PCR) methodology. Relative enzymes expression was calculated by the 2-(ΔΔC)T method using the threshold cycle (CT) value for normalization. MDH1/MDH2 RGE was not different in hepatectomized rats treated with OKG compared to rats treated with CCa. However, MDH1/MDH2 RGE was greater on days 3 (321:1/26.48:1) and 7 (2.12:1/2.48:1) while MDH2 RGE was greater on day 14 (7.79:1) in hepatectomized rats treated with GLN compared to control animals. Glutamine has beneficial effects in liver regeneration in rats by promoting an up-regulation of the MDH1 and MDH2 relative gene expression.

  19. Protective effect of bacoside A on cigarette smoking-induced brain mitochondrial dysfunction in rats.

    PubMed

    Anbarasi, Kothandapani; Vani, Ganapathy; Devi, Chennam Srinivasulu Shyamala

    2005-01-01

    Chronic exposure to cigarette smoke affects the structure and function of mitochondria, which may account for the pathogenesis of smoking-related diseases. Bacopa monniera Linn., used in traditional Indian medicine for various neurological disorders, was shown to possess mitrochondrial membrane-stabilizing properties in the rat brain during exposure to morphine. We investigated the protective effect of bacoside A, the active principle of Bacopa monniera, against mitochondrial dysfunction in rat brain induced by cigarette smoke. Male Wistar albino rats were exposed to cigarette smoke and administered bacoside A for a period of 12 weeks. The mitochondrial damage in the brain was assessed by examining the levels of lipid peroxides, cholesterol, phospholipid, cholesterol/phospholipid (C/P) ratio, and the activities of isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase, and cytochrome C oxidase. The oxidative phosphorylation (rate of succinate oxidation, respiratory control ratio and ADP/O ratio, and the levels of ATP) was evaluated for the assessment of mitochondrial functional capacity. We found significantly elevated levels of lipid peroxides, cholesterol, and C/P ratio, and decreased levels of phospholipids and mitochondrial enzymes in the rats exposed to cigarette smoke. Measurement of oxidative phosphorylation revealed a marked depletion in all the variables studied. Administration of bacoside A prevented the structural and functional impairment of mitochondria upon exposure to cigarette smoke. From the results, we suggest that chronic cigarette smoke exposure induces damage to the mitochondria and that bacoside A protects the brain from this damage by maintaining the structural and functional integrity of the mitochondrial membrane.

  20. Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Akita, Shingo; Kubota, Koji; Kobayashi, Akira, E-mail: kbys@shinshu-u.ac.jp

    Highlights: Black-Right-Pointing-Pointer BMC-derived PSCs play a role in a rat CDE diet-induced pancreatitis model. Black-Right-Pointing-Pointer BMC-derived PSCs contribute mainly to the early stage of pancreatic fibrosis. Black-Right-Pointing-Pointer BMC-derived activated PSCs can produce PDGF and TGF {beta}1. -- Abstract: Bone marrow cell (BMC)-derived myofibroblast-like cells have been reported in various organs, including the pancreas. However, the contribution of these cells to pancreatic fibrosis has not been fully discussed. The present study examined the possible involvement of pancreatic stellate cells (PSCs) originating from BMCs in the development of pancreatic fibrosis in a clinically relevant rat model of acute pancreatitis induced by amore » choline-deficient/ethionine-supplemented (CDE) diet. BMCs from female transgenic mice ubiquitously expressing green fluorescent protein (GFP) were transplanted into lethally irradiated male rats. Once chimerism was established, acute pancreatitis was induced by a CDE diet. Chronological changes in the number of PSCs originating from the donor BMCs were examined using double immunofluorescence for GFP and markers for PSCs, such as desmin and alpha smooth muscle actin ({alpha}SMA), 1, 3 and 8 weeks after the initiation of CDE feeding. We also used immunohistochemical staining to evaluate whether the PSCs from the BMCs produce growth factors, such as platelet-derived growth factor (PDGF) and transforming growth factor (TGF) {beta}1. The percentage of BMC-derived activated PSCs increased significantly, peaking after 1 week of CDE treatment (accounting for 23.3 {+-} 0.9% of the total population of activated PSCs) and then decreasing. These cells produced both PDGF and TGF{beta}1 during the early stage of pancreatic fibrosis. Our results suggest that PSCs originating from BMCs contribute mainly to the early stage of pancreatic injury, at least in part, by producing growth factors in a rat CDE diet-induced pancreatitis

  1. ALLYLISOPROPYLACETAMIDE INDUCES RAT HEPATIC ORNITHINE DECARBOXYLASE

    EPA Science Inventory

    In rat liver, allylisopropylacetamide (AIA) treatment strongly induced (25-fold) the activity of rat hepatic ornithine decarboxylase (ODC). y either the oral or the subcutaneous routes, AIA produced a long-lasting induction (30 to 4O hours) of hepatic ODC activity. hree analogs o...

  2. Anti-inflammation effects of corn silk in a rat model of carrageenin-induced pleurisy.

    PubMed

    Wang, Guang-Qiang; Xu, Tao; Bu, Xue-Mei; Liu, Bao-Yi

    2012-06-01

    Pleurisy is an inflammation of the pleural layers that surround the lungs. Despite much research into inflammatory diseases, no drugs with favorable safety profiles are available yet for their treatment. Corn silk has been used in many parts of the world for the treatment of edema, cystitis, gout, kidney stones nephritis, and prostitutes. However, no scientific reports on the anti-inflammatory effects of corn silk were so far available. To test the anti-inflammatory efficacy of corn silk extract (CSEX) in a rat model of carrageenin (Cg)-induced pleurisy, exudate formation, and cellular infiltration, tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), vascular endothelial growth factor alpha (VEGF-α), interleukin-17 (IL-17), C3 and C4 complement protein levels, adhesion molecule (ICAM-1) and inducible nitric oxide synthase (iNOS) levels, nuclear factor kappa B (NF-κB) activation, and total antioxidant activity were studied, respectively. Pretreatment with CSEX reduced Cg-induced pleurisy exudate, number of leukocytes, oxidative stress, C3 protein level, and O (2)(-) levels at the inflammatory site. Pretreatment with CSEX also inhibited TNF-α, IL-1β, VEGF-α, and IL-17A and blocked inflammation-related events (ICAM-1 and iNOS) by activation of NF-κB. Supplementation with CSEX may be a promising treatment for inflammatory diseases that involve oxidative stress.

  3. Fertility of male rats treated with 15(S)-15-methyl prostaglandin F2 alpha methyl ester-containing silastic implants.

    PubMed

    Kimball, F A; Frielink, R D; Porteus, S E

    1978-01-01

    Male Spraque-Dawley rats receiving implants of silicone rubber discs containing 1% or 2% 15(S)-15-methyl prostaglandin F2 alpha methyl ester (15-Me-PGF 2 alpha) or no prostaglandin were tested in successive breeding trials for potency and fertility. One week after implantation, discs containing 1% 15-Me-PGF2 alpha reduced potency and fertility, which returned 2 weeks after implantation. Animals receiving implants of the 2% discs were apparently impotent the 1st week following implantation; potency returned before full fertility returned 11 weeks after implantation.

  4. Potential Role of L-Arginine and Vitamin E Against Bone Loss Induced by Nano-Zinc Oxide in Rats.

    PubMed

    Abdelkarem, Hala M; Fadda, Laila H; El-Sayed, Eman M; Radwan, Omyma K

    2018-05-04

    The purpose of this study was to illustrate the effects of zinc oxide nanoparticles (ZnO-NPs) administration on bone turnover and bone resorbing agents in rats and how L-arginine (L-arg) or vitamin E (vit E) co-administrations might affect them. Fasting rats were randomly divided into four groups (n = 10): G1-normal healthy animals; G2-ZnO-NPs-exposed rats (600 mg/kg - 1/day -1 ); G3-ZnO-NPs-exposed rats co-administrated L-arg (200 mg/kg - 1/day -1 ); G4-ZnO-NPs-exposed rats co-administrated vit E (200 mg/kg - 1/day -1 ). The ingredients were orally administered daily. The body weight and food consumption of rats were recorded during the administration period and the experiment continued for three consecutive weeks. The results demonstrated that ZnO-NPs administration induced bone loss in rats as manifested by reduced activity of bone alkaline phosphatase (B-ALP) and increased level of C-terminal peptide type I collagen (CTx). The increase of inflammatory markers, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by ZnO-NPs suggests that deleterious effects of ZnO-NPs on bone turnover were, in part, due to inflammation. Confirming to this suggestion, both L-arg and vit E reduced TNF-α and IL-6 levels and consequently decreased bone resorption as indicated by reduced serum CTx level. This study proved that ZnO-NPs can induce bone turnover, which may be reduced by L-arg or vit.E co-administration, partly by anti-inflammatory mechanism.

  5. Therapeutic efficacy of osthole against dinitrobenzene sulphonic acid induced-colitis in rats.

    PubMed

    Khairy, Hanan; Saleh, Hanan; Badr, Abeer M; Marie, Mohamed-Assem S

    2018-04-01

    Several mediators were associated with the pathogenesis of inflammatory bowel disease such as oxidative stress through the production of reactive oxygen metabolites, neutrophils infiltration and release of pro-inflammatory cytokines. This study was designed to investigate the therapeutic efficacy of osthole against dinitrobenzene sulfonic acid (DNBS) induced-colitis in rats through its anti-oxidant and anti-inflammatory properties. Colitis was induced in rats by single intracolonic instillation of (250 μl DNBS-25 mg/rat). Then 4 days later, rats were received oral administration of either (osthole 50 mg/kg), (sulfasalazine 500 mg/kg) or both in combination for 7 consecutive days. Body weight, some hematological parameters, colonic malondialdehyde (MDA) and myeloperoxidase activity (MPO), antioxidant parameters, colon injury and mucosa architectures were assessed. T helper (Th1)-related cytokines [Tumor necrosis factor alpha (TNF-α) and interferon-gamma (INF-γ)], Th2-relarted cytokines (interleukin-4 [IL-4 and IL-10], and Th-17 related cytokines [IL-17] were determined by ELISA. Osthole significantly improved the loss in body weight. That was accompanied with a remarkable amelioration of the disruption of the colonic architecture as well as a significant improvement in the antioxidant defense system. A reduction in MPO and MDA was observed in flamed colon. Treatment with either osthole or combination therapy showed suppressive activities on pro-inflammatory Th2-related cytokines and upregulation of anti-inflammatory Th2-related cytokines The results of this study suggest that osthole exert beneficial therapeutic effect in experimental colitis and improved the efficacy of the synthetized drugs such as sulfasalazine. Therefore, osthole may have a valuable sound in the treatment of inflammatory bowel disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  6. Infertility: Medical and Social Choices.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Office of Technology Assessment.

    This report illustrates a range of options for Congressional action in nine principal areas of public policy related to infertility: (1) collecting data on reproductive health; (2) preventing infertility; (3) information to inform and protect consumers; (4) providing access to infertility services; (5) reproductive health of veterans; (6) transfer…

  7. Infertility as a transformational process: a framework for psychotherapeutic support of infertile women.

    PubMed

    Gonzalez, L O

    2000-09-01

    The purpose of this qualitative descriptive study was to investigate the phenomenon of infertility as experienced by infertile women. A purposive sample of 25 infertile women participated in the study. Data were extracted from taped interviews and the researcher's observational field notes. Data analysis was conducted according to the techniques described by Miles and Huberman (1994). Participant responses to interviews were categorized by examining the interview transcripts and identifying significant statements and meanings. Themes which emerged from the statements were then ascertained and cross-case comparisons were made in order to confirm or to reconsider these themes. Five key themes emerged from the data: failure to fulfill a prescribed societal norm, assault on personal identity, mourning, transformation, and restitution. The women experienced infertility as a transformational process in which they mourned their loss of reproductive function and parenting roles and struggled to make restitution for the perceived stigma and powerlessness associated with nonfulfillment of a prescribed societal norm, the exclusion from cherished societal rituals, and the deprivation of ties of descent. Findings from this study have provided a framework for increased awareness of the phenomenon of infertility and for the essential components of supportive counseling or psychotherapy, regardless of the outcome of the infertility experience.

  8. EGF receptor tyrosine kinase inhibitors diminish transforming growth factor-alpha-induced pulmonary fibrosis.

    PubMed

    Hardie, William D; Davidson, Cynthia; Ikegami, Machiko; Leikauf, George D; Le Cras, Timothy D; Prestridge, Adrienne; Whitsett, Jeffrey A; Korfhagen, Thomas R

    2008-06-01

    Transforming growth factor-alpha (TGF-alpha) is a ligand for the EGF receptor (EGFR). EGFR activation is associated with fibroproliferative processes in human lung disease and animal models of pulmonary fibrosis. We determined the effects of EGFR tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva) on the development and progression of TGF-alpha-induced pulmonary fibrosis. Using a doxycycline-regulatable transgenic mouse model of lung-specific TGF-alpha expression, we determined effects of treatment with gefitinib and erlotinib on changes in lung histology, total lung collagen, pulmonary mechanics, pulmonary hypertension, and expression of genes associated with synthesis of ECM and vascular remodeling. Induction in the lung of TGF-alpha caused progressive pulmonary fibrosis over an 8-wk period. Daily administration of gefitinib or erlotinib prevented development of fibrosis, reduced accumulation of total lung collagen, prevented weight loss, and prevented changes in pulmonary mechanics. Treatment of mice with gefitinib 4 wk after the induction of TGF-alpha prevented further increases in and partially reversed total collagen levels and changes in pulmonary mechanics and pulmonary hypertension. Increases in expression of genes associated with synthesis of ECM as well as decreases of genes associated with vascular remodeling were also prevented or partially reversed. Administration of gefitinib or erlotinib did not cause interstitial fibrosis or increases in lavage cell counts. Administration of small molecule EGFR tyrosine kinase inhibitors prevented further increases in and partially reversed pulmonary fibrosis induced directly by EGFR activation without inducing inflammatory cell influx or additional lung injury.

  9. Effects of Extract from Mangifera indica Leaf on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats

    PubMed Central

    Jiang, Yan; You, Xiao-Ying; Fu, Kong-Long; Yin, Wan-Le

    2012-01-01

    The leaves of Mangifera indica L. (Anacardiaceae) is used as a medicinal material in traditional herb medicine for a long time in India, China, and other Eastern Asian countries. Our present study investigated the therapeutic effects of the ethanol extract from Mangifera indica (EMI) in rat with monosodium urate (MSU) crystals-induced gouty arthritis. Effects of EMI (50, 100, and 200 mg/kg, p.o.) administrated for 9 days on the ankle swelling, synovial tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1β) levels were assessed in MSU crystal rat. Data from our study showed that rat with gouty arthritis induced by MSU crystal demonstrated an elevation in ankle swelling, synovial TNF-α, IL-1β mRNA, and protein levels. Oral administration of 100 and 200 mg/kg EMI for 9 days reversed the abnormalities in ankle swelling, synovial TNF-α, IL-1β mRNA, and protein levels. The results indicated that the beneficial antigouty arthritis effect of EMI may be mediated, at least in part, by inhibiting TNF-α and IL-1β expression in the synovial tissues. Our study suggests that Mangifera indica and its extract may have a considerable potential for development as an anti-gouty arthritis agent for clinical application. PMID:23304232

  10. Social stigma and familial attitudes related to infertility.

    PubMed

    Ergin, Rahime Nida; Polat, Aslıhan; Kars, Bülent; Öztekin, Deniz; Sofuoğlu, Kenan; Çalışkan, Eray

    2018-03-01

    To determine the perceived social stigma and familial attitides and perception of sexuality in infertile couples attending infertility clinics. Infertile couples attending infertility clinics between the years of 2014 and 2015 were requested to complete detailed evaluation forms including questions related to the social stigma on their infertility, their familial attitudes, and perception of sexuality. Any partner of the infertile couple accepting to enroll in the study was given the evaluation forms. Their scores related to answers and demographics, and parameters related to infertility were analyzed. A total 598 partners of infertile couples enrolled in the study, 58% represented 177 couples. Their infertility was primary in 98.3% and the duration of marriage and infertility was 9.81±5.58 and 9.76±5.53 years, respectively. The perception of social exclusion was present in 38% (p<0.001) of infertile couple, which was more significantly pronounced in female partners (p=0.013). Fifteen percent of the infertile couples thought themselves as isolated in public and losing value in public (p<0.001). However, sixty percent of infertile couples thought that they would achieve a notable place in community after having a baby (p<0.001). Infertility was accepted as a reason of divorce in only 13% of infertile couples (p<0.001). The majority of perticipnats, irrespective of sex, rejected that infertile women or men lost sexual appeal (86%; p<0.001). There is significant effect of infertility on familial attitudes and perception of sexuality of infertile couples. Unfortunately, there is significant negative social stigma on infertile couples.

  11. Thermally induced disintegration of the oligomeric structure of alphaB-crystallin mutant F28S is associated with diminished chaperone activity.

    PubMed

    Kelley, Patrick B; Abraham, Edathara C

    2003-10-01

    alphaB-crystallin, a member of the small heat-shock protein (hsp) family of proteins, is able to function as a molecular chaperone by protecting other proteins from stress-induced aggregation by recognizing and binding to partially unfolded species of damaged proteins. The present work has investigated the role of phenylalanine-28 (F28) of the 22RLFDQFF28 region of alphaB-crystallin in maintaining chaperone function and oligomeric structure under physiological condition and under thermal stress. Bovine alphaB-crystallin was cloned for the first time and the cDNA sequence revealed greater than 90% homology to that of human, rat and mouse alphaB-crystallins. F28 was mutated to a serine followed by expression of the mutant F28S and the wild-type alphaB (alphaB-wt) in E. coli and subsequent purification of the protein by size-exclusion chromatography. Secondary and tertiary structure analyses showed some structural changes in the mutant. Chaperone activity and oligomeric size of the mutant was unchanged at 37 degrees C whereas at 58 degrees C the chaperone activity was significantly decreased and the oligomeric size ranged from low molecular weight to high molecular weight showing disintegration of the oligomeric structure. The data support the idea that the participation of large oligomeric structure rather than smaller units is required to have optimal chaperone activity and the hydrophobic F28 residue is needed for maintaining the native oligomeric structure under thermal stress.

  12. Beyond the Mechanics of Infertility: Perspectives on the Social Psychology of Infertility and Involuntary Childlessness.

    ERIC Educational Resources Information Center

    Matthews, Anne Martin; Matthews, Ralph

    1986-01-01

    Examines the social and social psychological implications of infertility and involuntary childlessness. Examines the clinical and popular literature on the correlates and causes of infertility and the social psychological consequences of infertility. Suggests ways that family practitioners and researchers might overcome some of the limitations.…

  13. Enhanced homologous recombination is induced by alpha-particle radiation in somatic cells of Arabidopsis thaliana

    NASA Astrophysics Data System (ADS)

    Bian, Po; Liu, Ping; Wu, Yuejin

    Almost 9 percent of cosmic rays which strike the earth's atmosphere are alpha particles. As one of the ionizing radiations (IR), its biological effects have been widely studied. However, the plant genomic instability induced by alpha-particle radiation was not largely known. In this research, the Arabidopsis thaliana transgenic for GUS recombination substrate was used to evaluate the genomic instability induced by alpha-particle radiation (3.3MeV). The pronounced effects of systemic exposure to alpha-particle radiation on the somatic homologous recombination frequency (HRF) were found at different doses. The 10Gy dose of radiation induced the maximal HRF which was 1.9-fold higher than the control. The local radiation of alpha-particle (10Gy) on root also resulted in a 2.5-fold increase of somatic HRF in non-radiated aerial plant, indicating that the signal(s) of genomic instability was transferred to non-radiated parts and initiated their genomic instability. Concurrent treatment of seedlings of Arabidopsis thaliana with alpha-particle and DMSO(ROS scavenger) both in systemic and local radiation signifi- cantly suppressed the somatic HR, indicating that the free radicals produced by alpha-particle radiation took part in the production of signal of genomic instability rather than the signal transfer. Key words: alpha-particle radiation, somatic homologous recombination, genomic instability

  14. Chlorella vulgaris triggers apoptosis in hepatocarcinogenesis-induced rats*

    PubMed Central

    Mohd Azamai, Emey Suhana; Sulaiman, Suhaniza; Mohd Habib, Shafina Hanim; Looi, Mee Lee; Das, Srijit; Abdul Hamid, Nor Aini; Wan Ngah, Wan Zurinah; Mohd Yusof, Yasmin Anum

    2009-01-01

    Chlorella vulgaris (CV) has been reported to have antioxidant and anticancer properties. We evaluated the effect of CV on apoptotic regulator protein expression in liver cancer-induced rats. Male Wistar rats (200~250 g) were divided into eight groups: control group (normal diet), CDE group (choline deficient diet supplemented with ethionine in drinking water to induce hepatocarcinogenesis), CV groups with three different doses of CV (50, 150, and 300 mg/kg body weight), and CDE groups treated with different doses of CV (50, 150, and 300 mg/kg body weight). Rats were sacrificed at various weeks and liver tissues were embedded in paraffin blocks for immunohistochemistry studies. CV, at increasing doses, decreased the expression of anti-apoptotic protein, Bcl-2, but increased the expression of pro-apoptotic protein, caspase 8, in CDE rats, which was correlated with decreased hepatoctyes proliferation and increased apoptosis as determined by bromodeoxy-uridine (BrdU) labeling and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assay, respectively. Our study shows that CV has definite chemopreventive effect by inducing apoptosis via decreasing the expression of Bcl-2 and increasing the expression of caspase 8 in hepatocarcinogenesis-induced rats. PMID:19198018

  15. Prostatitis and male infertility.

    PubMed

    Alshahrani, Saad; McGill, John; Agarwal, Ashok

    2013-11-01

    The prostate gland plays an important role in male reproduction. Inflammation of the prostate gland (prostatitis) is a common health problem affecting many young and middle aged men. Prostatitis is considered a correctable cause of male infertility, but the pathophysiology and appropriate treatment options of prostatitis in male infertility remain unclear. This literature review will focus on current data regarding prostatitis and its impact on male infertility. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Recombinant follicle-stimulating hormone: new biotechnology for infertility.

    PubMed

    Prevost, R R

    1998-01-01

    The frequency of infertility in developed countries is approximately 8-10%. New drugs are available for assisted reproduction techniques. Two recombinant follicle-stimulating hormone (FSH) products, follitropin-beta (Follistim in the United States, Puregon in Europe) and follitropin-alpha (Gonal-F), join compounds derived through transfecting nonhuman cell lines with genetic material capable of replicating identical amino acid sequences to human compounds. The cell line used for recombinant (r)-FSH production is the Chinese hamster ovary (CHO). Previously, the only agents that showed benefit in controlled ovulatory stimulation were derived from the urine of menopausal women. Those compounds contain additional substances, such as urinary proteins and various amounts of luteininzing hormone. The amino acid sequence of r-FSH is identical to that of human FSH, but the two recombinant products exist in many different isoforms and differ from each other and from human FSH due to varied carbohydrate side chains. Due to variation in the carbohydrate side chains, follitropin-beta in solution has a higher pH than urine-derived FSH, which enhances receptor affinity and therefore is a greater inducer of folliculogenesis. Follitropin-beta does not cause endogenous production of anti-CHO or anti-FSH antibodies, and is well tolerated.

  17. Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure.

    PubMed

    Wang, Y; Mu, J J; Liu, F Q; Ren, K Y; Xiao, H Y; Yang, Z; Yuan, Z Y

    2014-02-01

    Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13(BN) rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure.

  18. Epigenetics of reproductive infertility.

    PubMed

    Das, Laxmidhar; Parbin, Sabnam; Pradhan, Nibedita; Kausar, Chahat; Patra, Samir K

    2017-06-01

    Infertility is a complex pathophysiological condition. It may caused by specific or multiple physical and physiological factors, including abnormalities in homeostasis, hormonal imbalances and genetic alterations. In recent times various studies implicated that, aberrant epigenetic mechanisms are associated with reproductive infertility. There might be transgenerational effects associated with epigenetic modifications of gametes and studies suggest the importance of alterations in epigenetic modification at early and late stages of gametogenesis. To determine the causes of infertility it is necessary to understand the altered epigenetic modifications of associated gene and mechanisms involved therein. This review is devoted to elucidate the recent mechanistic advances in regulation of genes by epigenetic modification and emphasizes their possible role related to reproductive infertility. It includes environmental, nutritional, hormonal and physiological factors and influence of internal structural architecture of chromatin nucleosomes affecting DNA and histone modifications in both male and female gametes, early embryogenesis and offspring. Finally, we would like to emphasize that research on human infertility by gene knock out of epigenetic modifiers genes must be relied upon animal models.

  19. Alpha-mangostin attenuates diabetic nephropathy in association with suppression of acid sphingomyelianse and endoplasmic reticulum stress.

    PubMed

    Liu, Tingting; Duan, Wang; Nizigiyimana, Paul; Gao, Lin; Liao, Zhouning; Xu, Boya; Liu, Lerong; Lei, Minxiang

    2018-02-05

    Diabetic nephropathy is a common complication of diabetes, but there are currently few treatment options. The aim of this study was to gain insight into the effect of alpha-mangostin on diabetic nephropathy and possible related mechanisms. Goto-Kakizaki rats were used as a diabetic model and received alpha-mangostin or desipramine treatment with normal saline as a control. Ten age-matched Sprague Dawley rats were used as normal controls and treated with normal saline. At week 12, blood glucose, albuminuria, apoptosis and renal pathologic changes were assessed. Protein levels for acid sphingomyelinase, glucose-regulated protein 78, phosphorylated PKR-like ER-resident kinase, activated transcription factor 4, CCAAT/enhancer-binding protein, homologous protein), and cleaved-caspase12 were measured. The level of acid sphingomyelinase was significantly increased, and ER stress was activated in diabetic rat kidneys when compared to the control animals. When acid sphingomyelinase was inhibited by alpha-mangostin, the expression of ER stress-related proteins was down-regulated in association with decreased levels of diabetic kidney injury. Alpha-mangostin, an acid sphingomyelinase inhibitor plays a protective role in diabetic neuropathy by relieving ER stress induced-renal cell apoptosis. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Quantitative analysis of rat brain alpha 2-receptors discriminated by [3H]clonidine and [3H]rauwolscine.

    PubMed

    Asakura, M; Tsukamoto, T; Imafuku, J; Matsui, H; Ino, M; Hasegawa, K

    1984-10-30

    Quantitative analysis of direct ligand binding of both [3H]clonidine and [3H]rauwolscine to the rat cerebral cortex alpha 2-receptors indicates the existence of two affinity states of the same receptor populations. In the presence of Mn2+, the high affinity state of [3H]clonidine binding was increased, whereas the high affinity state of [3H]rauwolscine binding was reduced. By contrast, GTP in micromolar ranges caused a decrease of the agonist high affinity state and an increase of the antagonist high affinity state. The total receptor sites and the respective separate affinities for both radioligands were approximately equal to their control values under all conditions, indicating that Mn2+ and GTP modulate the proportion of the two affinity states of the receptor. These results can be incorporated into a two-step, ternary complex model involving a guanine nucleotide binding protein (N protein) for the agonist and antagonist interaction with the alpha 2-receptor. Furthermore, the effects of GTP on the interaction of both ligands with the two affinity states can be mimicked by EDTA. It is suggested that divalent cations induce the formation of the receptor-N protein binary complex showing high affinity for agonists and low affinity for antagonists.

  1. Mycophenolic acid attenuates tumor necrosis factor-alpha-induced endothelin-1 production in human aortic endothelial cells.

    PubMed

    Yang, Won Seok; Lee, Joo Mi; Han, Nam Jeong; Kim, Yoon Ji; Chang, Jai Won; Park, Su-Kil

    2010-07-01

    Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in solid organ transplant recipients. Endothelin-1 (ET-1) is implicated in the pathogenesis of atherosclerosis and is one of the potential therapeutic targets. This study was conducted to evaluate the effect of mycophenolic acid (MPA), an immunosuppressant for the transplant recipients, on tumor necrosis factor-alpha (TNF-alpha)-induced ET-1 production in aortic endothelial cells. In cultured human aortic endothelial cells, TNF-alpha increased ET-1 through AP-1 and NF-kappaB, whereas MPA attenuated it by reducing both AP-1 and NF-kappaB DNA-binding activities. TNF-alpha increased ET-1 via c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), but not extracellular signal-regulated kinase. N-acetylcysteine that downregulated TNF-alpha-induced reactive oxygen species (ROS) inhibited JNK activation, but not p38 MAPK. N-acetylcysteine, SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated TNF-alpha-induced DNA-binding activities of both AP-1 and NF-kappaB. MPA inhibited JNK and p38 MAPK activations as well as ROS generation. N-acetylcysteine, SP600125, SB203580 and MPA had no effect on either TNF-alpha-induced IkappaBalpha degradation or p65 nuclear translocation, but attenuated p65 Ser276 phosphorylation. MPA attenuated TNF-alpha-induced ET-1 production through inhibitions of ROS-dependent JNK and ROS-independent p38 MAPK that regulated NF-kappaB as well as AP-1. These findings suggest that MPA could have an effect of amelioration of atherosclerosis. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  2. Clofibric acid induces hepatic CYP 2B1/2 via constitutive androstane receptor not via peroxisome proliferator activated receptor alpha in rat.

    PubMed

    Ibrahim, Zein Shaban; Ahmed, Mohamed Mohamed; El-Shazly, Samir Ahmed; Ishizuka, Mayumi; Fujita, Shoichi

    2014-01-01

    Peroxisome proliferator activated receptor α (PPARα) ligands, fibrates used to control hyperlipidemia. We demonstrated CYP2B induction by clofibric acid (CFA) however, the mechanism was not clear. In this study, HepG2 cells transfected with expression plasmid of mouse constitutive androstane receptor (CAR) or PPARα were treated with CFA, phenobarbital (PB) or TCPOBOP. Luciferase assays showed that CFA increased CYP2B1 transcription to the same level as PB, or TCPOBOP in HepG2 transfected with mouse CAR But failed to induce it in PPARα transfected cells. CYP2B expressions were increased with PB or CFA in Wistar female rats (having normal levels of CAR) but not in Wistar Kyoto female rats (having low levels of CAR). The induction of CYP2B by PB or CFA was comparable to nuclear CAR levels. CAR nuclear translocation was induced by CFA in both rat strains. This indicates that fibrates can activate CAR and that fibrates-insulin sensitization effect may occur through CAR, while hypolipidemic effect may operate through PPARα.

  3. Solution structure of {alpha}-conotoxin PIA, a novel antagonist of {alpha}6 subunit containing nicotinic acetylcholine receptors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chi, Seung-Wook; Lee, Si-Hyung; Kim, Do-Hyoung

    2005-12-30

    {alpha}-Conotoxin PIA is a novel nicotinic acetylcholine receptor (nAChR) antagonist isolated from Conus purpurascens that targets nAChR subtypes containing {alpha}6 and {alpha}3 subunits. {alpha}-conotoxin PIA displays 75-fold higher affinity for rat {alpha}6/{alpha}3{beta}2{beta}3 nAChRs than for rat {alpha}3{beta}2 nAChRs. We have determined the three-dimensional structure of {alpha}-conotoxin PIA by nuclear magnetic resonance spectroscopy. The {alpha}-conotoxin PIA has an '{omega}-shaped' overall topology as other {alpha}4/7 subfamily conotoxins. Yet, unlike other neuronally targeted {alpha}4/7-conotoxins, its N-terminal tail Arg{sup 1}-Asp{sup 2}-Pro{sup 3} protrudes out of its main molecular body because Asp{sup 2}-Pro{sup 3}-Cys{sup 4}-Cys{sup 5} forms a stable type I {beta}-turn. In addition, amore » kink introduced by Pro{sup 15} in the second loop of this toxin provides a distinct steric and electrostatic environment from those in {alpha}-conotoxins MII and GIC. By comparing the structure of {alpha}-conotoxin PIA with other functionally related {alpha}-conotoxins we suggest structural features in {alpha}-conotoxin PIA that may be associated with its unique receptor recognition profile.« less

  4. Is Any Press Good Press? The Impact of Media Portrayals of Infertility on Young Adults' Perceptions of Infertility.

    PubMed

    Sangster, Sarah L; Lawson, Karen L

    2015-12-01

    Infertility is an issue of current concern across North America. The Society of Obstetricians and Gynaecologists of Canada advocates for public education regarding infertility issues. Public education is supposed to be a fundamental objective of news media. However, it is uncertain whether the media are acting as good partners to the medical profession in this objective of educating the public, and young women in particular. Recent findings suggest that print news tends to present infertility using high-alarm framing strategies; however, the impact of this framing on news consumers is unknown. The purpose of this study was to understand the effects of high- versus low-alarm frames on consumers of infertility-related news. In this experiment, 131 undergraduate students were randomly assigned to read infertility-focused news articles judged to employ either high- or low-alarm framing strategies in presenting infertility. Participants subsequently completed various psychological, emotional, and knowledge measures to gauge the impact of the news exposure. The participants exposed to the high-alarm framing showed higher levels of perceived personal susceptibility to infertility, marginally higher levels of worry about infertility, and significantly lower levels of infertility-related knowledge than those exposed to the low-alarm framing. The manner in which the news media report on infertility has repercussions on how individuals think and feel about infertility. The findings of this study can inform health care providers about how the media are shaping perceptions of infertility, and can assist professional bodies interested in undertaking public education initiatives.

  5. The economic cost of infertility-related services: an examination of the Massachusetts infertility insurance mandate.

    PubMed

    Griffin, M; Panak, W F

    1998-07-01

    To examine the costs and outcomes of infertility-related services in Massachusetts during a time of expanded use of assisted reproductive technology (ART). Cost data were obtained from the Massachusetts Department of Insurance Rate-Setting Commission and 9 large group insurance plans for the period 1986-1993. Utilization and success rates of ART were examined, and the cost per live delivery with the use of ART in 1993 was estimated. The state of Massachusetts, in which access to infertility-related services has been mandated by law since 1989. The study population consisted of 8 large health maintenance organization plans and the Blue Cross/Blue Shield indemnity plan. None. Per capita infertility-related expenditures, infertility-related expenditures as a percentage of total expenditures, live deliveries per initiated ART cycle, and cost per live delivery. Expenditures for infertility services increased at a rate similar to or slower than inflation during the years 1988-1992. Increases were slowest in health maintenance organizations, probably as a result of provider arrangements. Infertility services accounted for 0.41% of total expenditures within the indemnity plan in 1993 (approximately $1.71 per contract-month). Examination of ART utilization showed no evidence of overutilization by patients with a low chance of success. The cost per live delivery with the use of ART in 1993 was $59,484. Mandated infertility coverage was associated with increased use of ART but not with excessive increases in consumer cost for infertility insurance coverage.

  6. Vascular influences of calcium supplementation and vitamin D-induced hypercalcemia in NaCl-hypertensive rats.

    PubMed

    Kähönen, Mika; Näppi, Satu; Jolma, Pasi; Hutri-Kähönen, Nina; Tolvanen, Jari-Petteri; Saha, Heikki; Koivisto, Pasi; Krogerus, Leena; Kalliovalkama, Jarkko; Pörsti, Ilkka

    2003-09-01

    This 8-week study investigated the effects of increasing dietary Ca2+ content from 1.0% to 3.0% and hypercalcemia induced by oral 1alpha-OH vitamin D3 (1OH-D3, 1.2 microg/kg), on arterial tone in NaCl-hypertensive rats. The high-Ca2+ diet completely prevented the increase in blood pressure induced by the 6.0% NaCl chow, while plasma total Ca2+ and body weight were not different from controls. The 1OH-D3 treatment moderately elevated plasma total Ca2+ and attenuated the NaCl-induced rise in blood pressure, but also impaired weight gain. The tone of isolated mesenteric arterial rings was examined at the end of study. The endothelium-independent relaxations to nitroprusside, isoproterenol, and cromakalim were impaired in NaCl-hypertension. Experiments with NG-nitro-l-arginine methyl ester and tetraethylammonium in vitro suggested that both the nitric oxide- and hyperpolarization-mediated components of endothelium-dependent relaxation to acetylcholine were reduced in NaCl-hypertensive rats. All of the impaired relaxations in NaCl hypertension were normalized by concomitant Ca2+ supplementation. The 1OH-D3 treatment did not affect vascular relaxation, but it attenuated maximal contractile responses induced by norepinephrine and KCl by more than 50%. The reduced vasoconstrictor responses could not be explained by increased apoptosis in the vessel wall, but calcification may have played a role, since moderate signs of medial or adventitial calcification were observed in the aortic preparations after the 1OH-D3 treatment. In conclusion, a high-Ca2+ diet, which did not cause hypercalcemia, normalized blood pressure and endothelium-dependent and endothelium-independent vasorelaxation in NaCl-hypertensive rats. In contrast, chronic hypercalcemia induced by 1OH-D3 was associated with moderately lowered blood pressure, possibly because of reduced vasoconstrictor responses in arterial smooth muscle.

  7. Colforsin-induced vasodilation in chronic hypoxic pulmonary hypertension in rats.

    PubMed

    Yokochi, Ayumu; Itoh, Hiroo; Maruyama, Junko; Zhang, Erquan; Jiang, Baohua; Mitani, Yoshihide; Hamada, Chikuma; Maruyama, Kazuo

    2010-06-01

    Colforsin, a water-soluble forskolin derivative, directly activates adenylate cyclase and thereby increases the 3',5'-cyclic adenosine monophosphate (cAMP) level in vascular smooth muscle cells. In this study, we investigated the vasodilatory action of colforsin on structurally remodeled pulmonary arteries from rats with pulmonary hypertension (PH). A total of 32 rats were subjected to hypobaric hypoxia (380 mmHg, 10% oxygen) for 10 days to induce chronic hypoxic PH, while 39 rats were kept in room air. Changes in isometric force were recorded in endothelium-intact (+E) and -denuded (-E) pulmonary arteries from the PH and control (non-PH) rats. Colforsin-induced vasodilation was impaired in both +E and -E arteries from PH rats compared with their respective controls. Endothelial removal did not influence colforsin-induced vasodilation in the arteries from control rats, but attenuated it in arteries from PH rats. The inhibition of nitric oxide (NO) synthase did not influence colforsin-induced vasodilation in +E arteries from controls, but attenuated it in +E arteries from PH rats, shifting its concentration-response curve closer to that of -E arteries from PH rats. Vasodilation induced by 8-bromo-cAMP (a cell-permeable cAMP analog) was also impaired in -E arteries from PH rats, but not in +E arteries from PH rats, compared with their respective controls. cAMP-mediated vasodilatory responses without beta-adrenergic receptor activation are impaired in structurally remodeled pulmonary arteries from PH rats. In these arteries, endothelial cells presumably play a compensatory role against the impaired cAMP-mediated vasodilatory response by releasing NO (and thereby attenuating the impairment). The results suggest that colforsin could be effective in the treatment of PH.

  8. The Effect of Lithospermum officinale, Silver Sulfadiazine and Alpha Ointments in Healing of Burn Wound Injuries in Rat

    PubMed Central

    Mohtasham Amiri, Zahra; Tanideh, Nader; Seddighi, Anahita; Mokhtari, Maral; Amini, Masood; Shakouri Partovi, Alborz; Manafi, Amir; Hashemi, Seyedeh Sara; Mehrabani, Davood

    2017-01-01

    BACKGROUND Burn is the most devastating condition in emergency medicine leading to chronic disabilities. This study aimed to compare the effect of Lithospermum officinale, silver sulfadiazine and alpha ointments on healing of burn wounds in rat. METHODS Ninety-five rats were divided into 5 groups. Group 1 just underwent burn injury, and groups 2-5 received alpha ointment, silver sulfadiazine (SSD), gel base and L. officinale extract, respectively. A hot plate was used for induction of a standard 3rd degree burn wound. Burn wounds were macroscopically and microscopically evaluated on days 7th, 14th and 21st after burn induction. RESULTS A decrease in the number of inflammatory cells was noted when L. officinale and SSD were applied while the most inflammatory response was seen after administration of alpha ointment. The number of macrophages alone decreased after burn injury, while the frequency was the most when L. officinale and alpha ointment were applied. Re-epithelialization, angiogenesis and formation of granulation tissue were the best in relation to L. officinale and alpha ointment while, the worst results belonged to burn injury group and SSD regarding granulation tissue formation. Considering histological assessment, the best results were observed for scoring of inflammation, re-epithelialization, angiogenesis, formation of granulation tissue and number of macrophage when L. officinale and alpha ointment were used after burn injury. CONCLUSION It can be concluded that topical application of L. officinale as a non-toxic, inexpensive and easy to produce herbal can lead to a rapid epithelialization and wound healing and these findings can be added to the literature on burn wound healing. PMID:29218280

  9. Sertoli cell specific knockdown of RAR-related orphan receptor (ROR) alpha at puberty reduces sperm count in rats.

    PubMed

    Mandal, Kamal; Sarkar, Rajesh K; Sen Sharma, Souvik; Jain, Ayushi; Majumdar, Subeer S

    2018-01-30

    Globally, there is an alarming decline in sperm count. Very often hormonal supplementation fails to restore normal sperm count. Sertoli cells (Sc) present within seminiferous tubules provide appropriate niche and factors required for the differentiation of germ cells (Gc) into mature sperm (spermatogenesis). Functionally compromised Sc may be one of the reasons for failure of hormones to facilitate normal spermatogenesis. Although role of secretory proteins and signaling molecules of Sc has been studied well, role of transcription factors regulating sperm count has not been addressed appropriately. Retinoic acid receptor-related orphan receptor (ROR)-alpha is one of such transcription factors reported in testis but its role in testicular function is not yet known. In a separate study, we found abundant ROR-alpha binding sites on promoter regions of several genes upregulated in pubertal rat Sc as compared to infant Sc. Immunostaining studies also revealed presence of ROR alpha in nucleus of pubertal Sc. We generated a transgenic knockdown rat model expressing shRNA targeted to ROR-alpha under Sc specific promoter, which is transcriptionally active only at and after puberty. ROR-alpha knockdown animals were found to have abnormal association of Sc and Gc, including Gc sloughing and restricted release of sperm. The knockdown animals displayed compromised spermatogenesis leading to significant reduction in sperm count. This is the first report describing the Sc specific role of ROR-alpha in maintaining quantitatively normal sperm output. Identification of various such molecules can generate avenues to limit or reverse an alarmingly declining sperm count witnessed globally in men. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Lithium ameliorates lipopolysaccharide-induced neurotoxicity in the cortex and hippocampus of the adult rat brain.

    PubMed

    Khan, Muhammad Sohail; Ali, Tahir; Abid, Muhammad Noman; Jo, Myeung Hoon; Khan, Amjad; Kim, Min Woo; Yoon, Gwang Ho; Cheon, Eun Woo; Rehman, Shafiq Ur; Kim, Myeong Ok

    2017-09-01

    Lithium an effective mood stabilizer, primary used in the treatment of bipolar disorders, has been reported as a protective agent in various neurological disorders. In this study, we examined the neuroprotective role of lithium chloride (LiCl) against lipopolysaccharide (LPS) in the cortex and hippocampus of the adult rat brain. We determined that LiCl -attenuated LPS-induced activated toll-like receptor 4 (TLR4) signalling and significantly reduced the nuclear factor- k B (NF- K B) translation factor and various other inflammatory mediators such as interleukin-1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α). We also analyzed that LiCl significantly abrogated activated gliosis via attenuation of specific markers for activated microglia, ionized calcium-binding adaptor molecule (Iba-1) and astrocytes, glial fibrillary acidic protein (GFAP) in both the cortex and hippocampus of the adult rat brain. Furthermore, we also observed that LiCl treatment significantly ameliorated the increase expression level of apoptotic neurodegeneration protein markers Bax/Bcl2, activated caspase-3 and poly (ADP-ribose) polymerase-1 (PARP-1) in the cortex and hippocampus regions of the LPS-treated adult rat brain. In addition, the morphological results of the fluoro-jade B (FJB) and Nissl staining showed that LiCl attenuated the neuronal degeneration in the cortex and hippocampus regions of the LPS-treated adult rat brain. Taken together, our Western blot and morphological results indicated that LiCl significantly prevents the LPS-induced neurotoxicity via attenuation of neuroinflammation and apoptotic neurodegeneration in the cortex and hippocampus of the adult rat brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Asiatic acid alleviates hemodynamic and metabolic alterations via restoring eNOS/iNOS expression, oxidative stress, and inflammation in diet-induced metabolic syndrome rats.

    PubMed

    Pakdeechote, Poungrat; Bunbupha, Sarawoot; Kukongviriyapan, Upa; Prachaney, Parichat; Khrisanapant, Wilaiwan; Kukongviriyapan, Veerapol

    2014-01-16

    Asiatic acid is a triterpenoid isolated from Centella asiatica. The present study aimed to investigate whether asiatic acid could lessen the metabolic, cardiovascular complications in rats with metabolic syndrome (MS) induced by a high-carbohydrate, high-fat (HCHF) diet. Male Sprague-Dawley rats were fed with HCHF diet with 15% fructose in drinking water for 12 weeks to induce MS. MS rats were treated with asiatic acid (10 or 20 mg/kg/day) or vehicle for a further three weeks. MS rats had an impairment of oral glucose tolerance, increases in fasting blood glucose, serum insulin, total cholesterol, triglycerides, mean arterial blood pressure, heart rate, and hindlimb vascular resistance; these were related to the augmentation of vascular superoxide anion production, plasma malondialdehyde and tumor necrosis factor-alpha (TNF-α) levels (p<0.05). Plasma nitrate and nitrite (NOx) were markedly high with upregulation of inducible nitric oxide synthase (iNOS) expression, but dowregulation of endothelial nitric oxide synthase (eNOS) expression (p<0.05). Asiatic acid significantly improved insulin sensitivity, lipid profiles, hemodynamic parameters, oxidative stress markers, plasma TNF-α, NOx, and recovered abnormality of eNOS/iNOS expressions in MS rats (p<0.05). In conclusion, asiatic acid improved metabolic, hemodynamic abnormalities in MS rats that could be associated with its antioxidant, anti-inflammatory effects and recovering regulation of eNOS/iNOS expression.

  12. ICSI Outcome in Infertile Couples with Different Causes of Infertility: A Cross-Sectional Study.

    PubMed

    Ashrafi, Mahnaz; Jahanian Sadatmahalleh, Shahideh; Akhoond, Mohammad Reza; Ghaffari, Firouzeh; Zolfaghari, Zahra

    2013-07-01

    Different success rate of Intracytoplasmic Sperm injection (ICSI) has been observed in various causes of infertility. In this study, we evaluated the relation between ICSI outcome and different causes of infertility. We also aimed to examine parameters that might predict the pregnancy success rate following ICSI. This cross sectional study included1492 infertile women referred to Infertility Center of Royan Institute between 2010 and 2011. We assigned two groups including pregnant (n=504) and non-pregnant (n=988), while all participants underwent ICSI cycles. All statistics were performed by SPSS program. Statistical Analysis was carried out using Chi-square and t test. Logistic regression was done to build a prediction model in ICSI cycles. The overall clinical pregnancy rate in our study was 33.9% (n=1492). There was a statistically significant difference in mean serum concentration on day 3 after application of luteinizing hormone (LH) between the pregnant and the non-pregnant groups (p<0.05). However, There were no significant differences between two groups in the serum concentrations on day 3 after application of the following hormones: folliclestimulating hormone (FSH), thyroid-stimulating hormone (TSH), and metoclopramidestimulated prolactin (PRL) . We found no association between different causes of infertility and clinical outcomes . The number of metaphase II (MII) oocytes, embryo transfer, number of good embryo (grade A, B, AB), total dose of gonadotropin, endometrial thickness, maternal age, number of previous cycle were statistically significant between two groups (p<0.05). Our results indicate that ICSI in an effective option in couples with different causes of infertility. These variables were integrated into a statistical model to allow the prediction for the chance of pregnancy following ICSI cycles. It is required that each infertility center gather enough information about the causes of infertility in order to provide more information and better

  13. [Impact of autosomal dominant polycystic kidney disease on the outcomes of intracytoplasmic sperm injection in infertile males].

    PubMed

    Su, Huang; Liu, Bian-jiang; Yang, Xiao-yu; Song, Ning-hong; Yin, Chang-jun; Zhang, Wei; Liu, Jia-yin

    2015-01-01

    To summarize the features and treatment of male infertility induced by autosomal dominant polycystic kidney disease (ADPKD), and compare the outcomes of intracytoplasmic sperm injection (ICSI) for infertile men with ADPKD and those with congenital bilateral absence of vas deferens (CBAVD). We retrospectively analyzed 21 cases of ADPKD-induced infertility, 15 treated by ICSI (group A), and another 164 cases of strictly matched CBAVD-induced infertility (group B). We compared the two groups in the couples' age, the number of ICSI oocytes, and the rates of fertilization, transferrable embryos, good embryos, embryos implanted, clinical pregnancy, biochemical pregnancy, early abortion, singleton and twins in the first cycle. After 28 cycles of ICSI, 10 of the 15 ADPKD-induced infertility patients achieved clinical pregnancy, including 7 cases of live birth, 1 case of spontaneous abortion, and 2 cases of pregnancy maintenance. No significant differences were observed between groups A and B in the couples' age, the wives' BMI, or the numbers of ICSI oocytes and embryos transplanted (P >0.05), nor in the rates of ICSI fertilization (72.64% vs 76.17%), transferrable embryos (51.28% vs 63.24%), quality embryos (38.46% vs 49.83%), embryo implantation (17.64% vs 38.50%), abortion (0 vs 9.23%), singleton (50% vs 81.54%) and twins (50% vs 18.46%). However, the rates of clinical pregnancy (13.33% vs 42.68%, P = 0.023 <0.05) and biochemical pregnancy (13.33% vs 39.63%, P = 0.032 <0.05) were significantly lower in group A than in B. ICSI is effective in the treatment of male infertility induced by either ADPKD or CBAVD, but the ADPKD cases have a lower success rate than the CBAVD cases in an individual cycle. The affected couples should be informed of the necessity of prenatal genetic diagnosis before embryo implantation and the inevitable vertical transmission of genetic problems to the offspring.

  14. Alpha lipoic acid (ALA) modulates expression of apoptosis associated proteins in hippocampus of rats exposed during postnatal period to sodium arsenite (NaAsO2).

    PubMed

    Dixit, Shilpi; Dhar, Pushpa; Mehra, Raj D

    2015-01-01

    The present study focused on the role of exogenous alpha lipoic acid (ALA) in amelioration of inorganic arsenic ( iAs ) induced effects on apoptosis and apoptosis associated proteins in developing rat hippocampus. NaAsO 2 (1.5/2.0 mg/kg bw) alone or along with ALA (70 mg/kg bw) was administered to rat pups (experimental groups) by intraperitoneal (i.p.) route from postnatal day (PND) 4-15. Controls received no treatment/distilled water/ALA. On PND 16, the animals were perfusion fixed and the brains were processed for paraffin embedding (CV and TUNEL staining) and cryopreservation (immunohistochemistry). The fresh brain tissue was used for Western blotting. Significant increase was observed in TUNEL positive cells and Bax (pro-apoptotic protein) expression in hippocampal sub-regions of iAs alone treated groups, whereas Bcl-2 expression was intensified in animals receiving ALA with iAs . Densitometric analysis (Western blots) revealed optimal restoration of Bax and Bcl-2 ratio in animals receiving ALA with iAs , thereby suggesting the protective role of ALA in iAs induced developmental neurotoxicity.

  15. Nicotine is neuroprotective when administered before but not after nigrostriatal damage in rats and monkeys.

    PubMed

    Huang, Luping Z; Parameswaran, Neeraja; Bordia, Tanuja; Michael McIntosh, J; Quik, Maryka

    2009-05-01

    Nicotine reduces dopaminergic deficits in parkinsonian animals when administered before nigrostriatal damage. Here we tested whether nicotine is also beneficial when given to rats and monkeys with pre-existing nigrostriatal damage. Rats were administered nicotine before and after a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle, and the results compared with those in which rats received nicotine only after lesioning. Nicotine pre-treatment attenuated behavioral deficits and lessened lesion-induced losses of the striatal dopamine transporter, and alpha6beta2* and alpha4beta2* nicotinic receptors (nAChRs). By contrast, nicotine administered 2 weeks after lesioning, when 6-hydroxydopamine-induced neurodegenerative effects are essentially complete, did not improve these same measures. Similar results were observed in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys. Nicotine did not enhance striatal markers when administered to monkeys with pre-existing nigrostriatal damage, in contrast to previous data that showed improvements when nicotine was given to monkeys before lesioning. These combined findings in two animal models suggest that nicotine is neuroprotective rather than neurorestorative against nigrostriatal damage. Receptor studies with (125)I-alpha-conotoxinMII and the alpha-conotoxinMII analog E11A were next performed to determine whether nicotine treatment pre- or post-lesioning differentially affected expression of alpha6alpha4beta2* and alpha6(nonalpha4)beta2* nAChR subtypes in striatum. The observations suggest that protection against nigrostriatal damage may be linked to striatal alpha6alpha4beta2* nAChRs.

  16. PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPAR{gamma} activation in the liver

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oishi, Katsutaka, E-mail: k-ooishi@aist.go.jp; Uchida, Daisuke; Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki

    Research highlights: {yields} PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression. {yields} Hepatic expressions of PPAR{gamma} and PCG-1{alpha} are induced by a ketogenic diet. {yields} PPAR{gamma} antagonist attenuates a ketogenic diet-induced PAI-1 expression. {yields} Ketogenic diet advances the phase of circadian clock in a PPAR{alpha}-independent manner. -- Abstract: An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD).more » To determine whether peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPAR{alpha}-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPAR{alpha}-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPAR{alpha} target genes such as Cyp4A10 and FGF21 was damped in PPAR{alpha}-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPAR{alpha}-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPAR{alpha} activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPAR{gamma} and its coactivator PCG-1{alpha} were more effectively induced in PPAR{alpha}-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPAR{gamma} antagonist, in both WT and PPAR{alpha

  17. Infertility, Psychological Distress, and Coping Strategies among Women in Mali, West Africa: A Mixed-Methods Study.

    PubMed

    Hess, Rosanna F; Ross, Ratchneewan; GilillandJr, John L

    2018-03-01

    Relatively little is known about infertility and its consequences in Mali, West Africa where the context and culture are different from those of previously studied settings. This study therefore aimed to specifically examine infertility induced psychological distress and coping strategies among women in Mali. A convergent mixed-methods design-correlational cross-sectional and qualitative descriptive-guided the study. Fifty-eight infertile Malian women participated: 52 completed the Psychological Evaluation Test specific for infertility and a question on general health status, and 26 were interviewed in-depth. Over 20% scored above the cut-off point for psychological distress, and 48% described their general health as poor. There was no significant difference between women with primary vs. secondary infertility. The study found that infertile women lived with marital tensions, criticism from relatives, and stigmatization from the community. They experienced sadness, loneliness, and social deprivation. Coping strategies included traditional and biomedical treatments, religious faith and practices, and self-isolation. Health care professionals should provide holistic care for infertile women to meet their physical, spiritual, psychological, and social needs.

  18. An epidemiologic survey on the causes of infertility in patients referred to infertility center in Fatemieh Hospital in Hamadan.

    PubMed

    Masoumi, Seyedeh Zahra; Parsa, Parisa; Darvish, Nooshin; Mokhtari, Sahar; Yavangi, Mahnaz; Roshanaei, Ghodratollah

    2015-08-01

    Infertility is considered as a major health care problem of different communities. The high prevalence of this issue doubled its importance. A significant proportion of infertility have been related to environmental conditions and also acquired risk factors. Different environmental conditions emphasized the need to study the different causes of infertility in each area. The aim of this study was to determine the frequency causes of infertility in infertile couples. In this cross sectional descriptive study 1200 infertile men and women that were referred to infertility clinic of Fatemieh Hospital during 2010 to 2011, were examined. This center is the only governmental center for infertility in Hamadan. Sampling was based on census method. Information about the patients was obtained from medical examinations and laboratory findings. To analyze the data, descriptive statistics such as frequencies and the mean were used. The prevalence of primary and secondary infertility was 69.5% and 30.5% respectively. Among the various causes of infertility women factors (88.6%) had the highest regard. In the causes of female infertility, menstrual disorders, diseases (obesity, thyroid diseases, and diabetes), ovulation dysfunction, uterine factor, fallopian tubes and cervical factor had the highest prevalence respectively. The causes of male infertility based on their frequency included semen fluid abnormalities, genetic factors, vascular abnormalities, and anti-spermatogenesis factors, respectively. Etiology pattern of infertility in our study is similar with the many other patterns that have been reported by the World Health Organization. However, frequency of menstrual disorders is much higher than other studies that require further consideration.

  19. Medical Imaging and Infertility.

    PubMed

    Peterson, Rebecca

    2016-11-01

    Infertility affects many couples, and medical imaging plays a vital role in its diagnosis and treatment. Radiologic technologists benefit from having a broad understanding of infertility risk factors and causes. This article describes the typical structure and function of the male and female reproductive systems, as well as congenital and acquired conditions that could lead to a couple's inability to conceive. Medical imaging procedures performed for infertility diagnosis are discussed, as well as common interventional options available to patients. © 2016 American Society of Radiologic Technologists.

  20. A Dyadic Approach to Infertility Stress, Marital Adjustment, and Depression on Quality of Life in Infertile Couples.

    PubMed

    Kim, Ju Hee; Shin, Hye Sook; Yun, Eun Kyoung

    2018-03-01

    This study was conducted to examine the level of infertility stress, marital adjustment, depression, and quality of life in infertile couples and assess the actor and partner effects in these areas using the actor-partner interdependence model. Cross-sectional study. Participants were 121 infertile couples. After pilot study, data were collected from November 2012 to March 2013 using the following questionnaires: the Fertility Quality of Life, Fertility Problem Inventory, Revised Dyadic Adjustment Scale, and Beck Depression Inventory. There was a gender difference in infertility stress, depression, and quality of life. Infertility stress had actor and partner effects on the quality of life. Marital adjustment had an actor effect on the quality of life for the wives. Depression had actor and partner effects on quality of life for the wives, but only an actor effect for the husbands. This study found that there were actor and partner effects of infertility stress, marital adjustment, and depression on the quality of life in infertile couples. These findings may help nurses be aware of such effects and can be used as a baseline data in the development of nursing interventions for infertile couples.

  1. The emotional-psychological consequences of infertility among infertile women seeking treatment: Results of a qualitative study

    PubMed Central

    Hasanpoor-Azghdy, Seyede Batool; Simbar, Masoumeh; Vedadhir, Abouali

    2014-01-01

    Background: Infertility is a major life event that brings about social and psychological problems. The type and rate these problems in the context of socio-cultural of different geographical areas and sex of people is different. Objective: The aim of this qualitative study was to explain the psychological consequences of infertility in Iranian infertile women seeking treatment. Materials and Methods: This qualitative study was done using qualitative content analysis on 25 women affected by primary and secondary infertility with no surviving children in 2012. They were purposefully selected with maximum sample variation from a large Fertility Health Research Center in Tehran, Iran. Data were collected using 32 semi-structured interviews and analyzed by the conventional content analysis method. Results: The findings of this study include four main themes: 1. Cognitive reactions of infertility (mental engagement; psychological turmoil). 2. Cognitive reactions to therapy process (psychological turmoil; being difficult to control in some situations; reduced self-esteem; feelings of failure). 3. Emotional-affective reactions of infertility (fear, anxiety and worry; loneliness and guilt; grief and depression; regret). 4. Emotional-affective reactions to therapy process (fear, anxiety and worry; fatigue and helplessness; grief and depression; hopelessness). Conclusion: This study revealed that Iranian infertile women seeking treatment face several psychological-emotional problems with devastating effects on the mental health and well-being of the infertile individuals and couples, while the infertility is often treated as a biomedical issue in Iranian context with less attention on the mental-emotional, social and cultural aspects. This article extracted from Ph.D. thesis. (Seyede Batool Hasanpoor-Azghady) PMID:24799871

  2. Occupational risk for male infertility: a case-control study of 218 infertile and 227 fertile men.

    PubMed

    Chia, S E; Tay, S K

    2001-11-01

    The aim of the study was to determine if certain occupations pose an increased risk for infertility (of no known cause) among a group of infertile men compared with a group of fertile men. A total of 640 consecutive men whose spouses were unable to conceive were recruited from an infertility clinic. Of these, 218 men (cases) were found to have no known cause for their infertility. A total of 227 men whose spouses were pregnant at the time of the study were recruited as controls. The Singapore Standard Occupational Classification was used to code the subjects' occupations. Semen parameters (density, total sperm counts, motility, viability, and normal morphology) in all of the cases were significantly poorer than those in the controls. The risk for infertility is associated with smoking adjusted odds ratio (OR) 2.85 and 95% confidence interval (CI) 1.91 to 4.24. Work, independently, is not a risk factor for infertility. Engineering technicians (adjusted OR, 2.75; 95% CI, 1.36 to 5.54), finance analysts (adjusted OR, 4.66; 95% CI, 1.90 to 11.40), corporate and computing managers (adjusted OR, 2.49; 95% CI, 1.04 to 5.98), and teachers (adjusted OR, 7.72; 95% CI, 1.86 to 32.10) were at a greater risk of infertility compared with "services and clerical workers." Using services and clerical workers as a reference group, certain occupations are at a higher risk for infertility. Higher work demands and possible electromagnetic field exposure could be contributory factors for infertility.

  3. Coital frequency and infertility: which male factors predict less frequent coitus among infertile couples?

    PubMed

    Perlis, Nathan; Lo, Kirk C; Grober, Ethan D; Spencer, Leia; Jarvi, Keith

    2013-08-01

    To determine the coital frequency among infertile couples and which factors are associated with less frequent coitus. Cross-sectional study. Tertiary-level male infertility clinic. A total of 1,298 infertile men. Administration of computer-based survey, semen analysis, and serum hormone evaluation. Monthly coital frequency. A total of 1,298 patients presented to clinic for infertility consultation and completed the computer-based survey. The median male age was 35 years (interquartile range [IQR] 32-39 years) and the median duration of infertility was 2 years (IQR 1-4 years) before consultation. Median monthly coital frequency was seven (IQR 5-10; range 0-40); 24% of couples were having intercourse ≤ 4 times per month. Overall, 0.6%, 2.7%, 4.8%, 5.8%, and 10.8% of the men reported having intercourse 0, 1, 2, 3, and 4 times per month, respectively. When simultaneously taking into account the influence of age, libido, erectile function, and semen volume on coital frequency, older patients had 1.05 times higher odds (per year of age) of less frequent coitus (odds ratio 1.05, 95% confidence interval 1.03-1.08). In addition, patients with better erectile function had 1.12 times higher odds (per point on Sexual Health Inventory for Men scale) of more frequent coitus (odds ratio 1.12, 95% confidence interval 1.09-1.18). Similar to the general population, most infertile couples report having coitus more than four times per month. Older male age and erectile dysfunction are independent risk factors for less frequent coitus among infertile men, which could have an impact on fertility. Coital frequency should be considered in infertility assessments. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Ameliorative effects of sildenafil and/or febuxostat on doxorubicin-induced nephrotoxicity in rats.

    PubMed

    Khames, Ali; Khalaf, Marwa M; Gad, Amany M; Abd El-Raouf, Ola M

    2017-06-15

    Sildenafil and febuxostat protect against doxorubicin-induced nephrotoxicity; however the exact mechanism remains to be elucidated. The effect of sildenafil and febuxostat on doxorubicin-induced nephrotoxicity in rats was studied. Male rats were subdivided into nine groups. The 1st group served as normal control, the 2nd group received dimethylsulfoxide 50% (DMSO), the 3rd group received doxorubicin (3.5mg/kg, i.p.), twice weekly for 3 weeks. The next 3 groups received sildenafil (5mg/kg; p.o.), febuxostat (10mg/kg; p.o.) and their combination, respectively daily for 21 days. The last 3 groups received doxorubicin in combination with sildenafil, febuxostat or their combination. Nephrotoxicity was evaluated histopathologically by light microscopy and biochemically through measuring the following parameters, Kidney function biomarkers [serum levels of urea, creatinine and uric acid], oxidative stress biomarkers [kidney contents of glutathione reduced (GSH) and malondialdehyde (MDA)], The apoptotic marker namely; caspase-3 in kidney tissue and the inflammatory mediator tumor necrosis factor alpha (TNF-α). doxorubicin-induced a significant elevation in nephrotoxicity markers, expression of caspase-3 and caused induction of inflammation and oxidative stress. Histological changes in the kidney was tubular necrosis. Sildenafil and/or febuxostat administration with doxorubicin caused a significant decrease in nephrotoxicity markers and inflammatory mediators, restoration of normal values of oxidative stress biomarkers and hampering the expression of renal caspase-3. They also ameliorate histological changes induced by doxorubicin. sildenafil and febuxostat are promising protective agents against doxorubicin-nephrotoxicity through improving biochemical, inflammatory, histopathological and immunohistochemical alterations induced by doxorubicin. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Hydrogen coadministration slows the development of COPD-like lung disease in a cigarette smoke-induced rat model.

    PubMed

    Liu, Xiaoyu; Ma, Cuiqing; Wang, Xiaoyu; Wang, Wenjing; Li, Zhu; Wang, Xiansheng; Wang, Pengyu; Sun, Wuzhuang; Xue, Baojian

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is a progressive pulmonary disease caused by harmful gases or particles. Recent studies have shown that 2% hydrogen or hydrogen water is effective in the treatment and prevention of a variety of diseases. This study investigated the beneficial effects and the possible mechanisms of different hydrogen concentrations on COPD. A rat COPD model was established through smoke exposure methods, and inhalation of different concentrations of hydrogen was used as the intervention. The daily condition of rats and the weight changes were observed; lung function and right ventricular hypertrophy index were assessed. Also, white blood cells were assessed in bronchoalveolar lavage fluid. Pathologic changes in the lung tissue were analyzed using light microscopy and electron microscopy; cardiovascular structure and pulmonary arterial pressure changes in rats were observed using ultrasonography. Tumor necrosis factor alpha, interleukin (IL)-6, IL-17, IL-23, matrix metalloproteinase-12, tissue inhibitor of metalloproteinase-1, caspase-3, caspase-8 protein, and mRNA levels in the lung tissue were determined using immunohistochemistry, Western blot, and real-time polymerase chain reaction. The results showed that hydrogen inhalation significantly reduced the number of inflammatory cells in the bronchoalveolar lavage fluid, and the mRNA and protein expression levels of tumor necrosis factor alpha, IL-6, IL-17, IL-23, matrix metalloproteinase-12, caspase-3, and caspase-8, but increased the tissue inhibitor of metalloproteinase-1 expression. Furthermore, hydrogen inhalation ameliorated lung pathology, lung function, and cardiovascular function and reduced the right ventricular hypertrophy index. Inhalation of 22% and 41.6% hydrogen showed better outcome than inhalation of 2% hydrogen. These results suggest that hydrogen inhalation slows the development of COPD-like lung disease in a cigarette smoke-induced rat model. Higher concentrations of

  6. Hydrogen coadministration slows the development of COPD-like lung disease in a cigarette smoke-induced rat model

    PubMed Central

    Liu, Xiaoyu; Ma, Cuiqing; Wang, Xiaoyu; Wang, Wenjing; Li, Zhu; Wang, Xiansheng; Wang, Pengyu; Sun, Wuzhuang; Xue, Baojian

    2017-01-01

    Background Chronic obstructive pulmonary disease (COPD) is a progressive pulmonary disease caused by harmful gases or particles. Recent studies have shown that 2% hydrogen or hydrogen water is effective in the treatment and prevention of a variety of diseases. This study investigated the beneficial effects and the possible mechanisms of different hydrogen concentrations on COPD. Methods A rat COPD model was established through smoke exposure methods, and inhalation of different concentrations of hydrogen was used as the intervention. The daily condition of rats and the weight changes were observed; lung function and right ventricular hypertrophy index were assessed. Also, white blood cells were assessed in bronchoalveolar lavage fluid. Pathologic changes in the lung tissue were analyzed using light microscopy and electron microscopy; cardiovascular structure and pulmonary arterial pressure changes in rats were observed using ultrasonography. Tumor necrosis factor alpha, interleukin (IL)-6, IL-17, IL-23, matrix metalloproteinase-12, tissue inhibitor of metalloproteinase-1, caspase-3, caspase-8 protein, and mRNA levels in the lung tissue were determined using immunohistochemistry, Western blot, and real-time polymerase chain reaction. Results The results showed that hydrogen inhalation significantly reduced the number of inflammatory cells in the bronchoalveolar lavage fluid, and the mRNA and protein expression levels of tumor necrosis factor alpha, IL-6, IL-17, IL-23, matrix metalloproteinase-12, caspase-3, and caspase-8, but increased the tissue inhibitor of metalloproteinase-1 expression. Furthermore, hydrogen inhalation ameliorated lung pathology, lung function, and cardiovascular function and reduced the right ventricular hypertrophy index. Inhalation of 22% and 41.6% hydrogen showed better outcome than inhalation of 2% hydrogen. Conclusion These results suggest that hydrogen inhalation slows the development of COPD-like lung disease in a cigarette smoke-induced

  7. Psychological and emotional concomitants of infertility diagnosis in women with diminished ovarian reserve or anatomical cause of infertility.

    PubMed

    Nicoloro-SantaBarbara, Jennifer M; Lobel, Marci; Bocca, Silvina; Stelling, James R; Pastore, Lisa M

    2017-07-01

    To examine the magnitude and predictors of emotional reactions to an infertility diagnosis in two groups of women: those with diminished ovarian reserve (DOR), and those clinically diagnosed with an anatomical cause of infertility (ACI). Cross-sectional study. Academic and private fertility clinics. Women diagnosed with DOR (n = 51) and women diagnosed with ACI (n = 51). Not applicable. Fertility Problem Inventory (infertility distress), Rosenberg Self-Esteem Scale, Health Orientation Scale (emotional reactions to receiving a diagnosis). Women with DOR had statistically significantly higher infertility distress scores than women with ACI and higher scores on subscales assessing distress from social concerns, sexual concerns, and a need for parenthood. In both groups, higher self-esteem was associated with lower infertility distress. Hierarchical multiple regression analyses revealed that for women with DOR and those with ACI lower infertility distress but not self-esteem predicted a more positive emotional reaction toward receiving a fertility diagnosis. Women diagnosed with DOR have greater infertility distress but similar self-esteem and emotional reactions to their diagnosis compared with women who have an anatomical cause of infertility. These results suggest that for both groups distress surrounding infertility itself may influence the way women respond to learning the cause of their infertility. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. Deletion of Suppressor of Cytokine Signaling 3 from Forebrain Neurons Delays Infertility and Onset of Hypothalamic Leptin Resistance in Response to a High Caloric Diet

    PubMed Central

    McEwen, Hayden J. L.; Inglis, Megan A.; Quennell, Janette H.; Grattan, David R.

    2016-01-01

    The cellular processes that cause high caloric diet (HCD)-induced infertility are poorly understood but may involve upregulation of suppressor of cytokine signaling (SOCS-3) proteins that are associated with hypothalamic leptin resistance. Deletion of SOCS-3 from brain cells is known to protect mice from diet-induced obesity, but the effects on HCD-induced infertility are unknown. We used neuron-specific SOCS3 knock-out mice to elucidate this and the effects on regional hypothalamic leptin resistance. As expected, male and female neuron-specific SOCS3 knock-out mice were protected from HCD-induced obesity. While female wild-type mice became infertile after 4 months of HCD feeding, infertility onset in knock-out females was delayed by 4 weeks. Similarly, knock-out mice had delayed leptin resistance development in the medial preoptic area and anteroventral periventricular nucleus, regions important for generation of the surge of GnRH and LH that induces ovulation. We therefore tested whether the suppressive effects of HCD on the estradiol-induced GnRH/LH surge were overcome by neuron-specific SOCS3 knock-out. Although only 20% of control HCD-mice experienced a preovulatory-like LH surge, LH surges could be induced in almost all neuron-specific SOCS3 knock-out mice on this diet. In contrast to females, HCD-fed male mice did not exhibit any fertility decline compared with low caloric diet-fed males despite their resistance to the satiety effects of leptin. These data show that deletion of SOCS3 delays the onset of leptin resistance and infertility in HCD-fed female mice, but given continued HCD feeding this state does eventually occur, presumably in response to other mechanisms inhibiting leptin signal transduction. SIGNIFICANCE STATEMENT Obesity is commonly associated with infertility in humans and other animals. Treatments for human infertility show a decreased success rate with increasing body mass index. A hallmark of obesity is an increase in circulating leptin

  9. Sulforaphane suppresses LPS-induced inflammation in primary rat microglia.

    PubMed

    Brandenburg, Lars-Ove; Kipp, Markus; Lucius, Ralph; Pufe, Thomas; Wruck, Christoph J

    2010-06-01

    The aim of this study was to investigate the signal transduction pathways involved in sulforaphane (SF) mediated inhibition of the inflammatory response to lipopolysaccharide (LPS). Additionally, we investigated the effects of SF and LPS on the activity of Nrf2. Primary rat microglia and the murine microglia cell line BV2 were used. Cells were treated with LPS with or without SF. Cell viability was measured via WST-assay. Real-time RT-PCR was performed to analyze cytokine mRNA levels. The nitric oxide (NO) release was measured in LPS-stimulated microglia. The induction of various signal transduction pathways and Nrf2 was determined by Western blotting. NF-kappaB and AP-1 activation was measured by dual luciferase assay. We showed that SF attenuates the LPS-induced increase of IL-1beta, IL-6, and TNF-alpha expression in microglia. In addition, SF significantly decreases the NO in a concentration-dependent manner. SF inhibits LPS-stimulated ERK1/2 and JNK phosphorylation and thereby inhibits the LPS-induced activation of NF-kappaB- and activator protein-1 (AP-1). Moreover, SF and LPS together are able to induce Nrf2 activation. We showed that SF, and also LPS by itself, are able to activate the cell's defence against oxidative and electrophilic stress. We conclude that SF could be a candidate agent for anti-inflammatory treatment of the central nervous system.

  10. Sexual behavior of infertile women: a qualitative study.

    PubMed

    Bokaie, Mahshid; Simbar, Masoumeh; Yassini Ardekani, Seyed Mojtaba

    2015-10-01

    Infertility makes an essential challenge to the sexual life of couples, especially infertile women. When pregnancy does not happen, infertile women think that sexual intercourse is not fruitful and sexual desire became reduce gradually. Infertile women progressively forget that their sexual relationship is also a response to their natural need. This qualitative study was conducted to explore the infertility consequences in the sexual behavior of infertile women. This was a qualitative content analysis study; and it was part of a widespread study, used a sequential mixed-method and conducted from August 2014 until February 2015. A purposeful sampling was used to recruit infertile women who had referred to Yazd Research and Clinical Center for Infertility. Data gathering techniques employed in this research included in-depth semi structured open face-to-face interviews and field notes. Credibility, transferability, confirm ability, and dependability were assessed for the rigor of the data collection. Totally, 15 infertile women and 8 key informants were interviewed. Data analysis showed four themes about impact of infertility on female sexual behavior: 1/ Impact of infertility drugs on couple sexual behavior, 2/ Impact of assisted reproductive technologies on female sexual behavior, 3/ Timed intercourse during infertility and 4/ The psychological impact of infertility on sexual behavior. Some of Iranian infertile women could cope with their problems, but some of them were very affected by infertility drugs and assisted reproductive technologies procedures. Psychosexual counseling before medical treatment could help them to have a better sexual life.

  11. Effects of simulated weightlessness on the kinase activity of MEK1 induced by bone morphogenetic protein-2 in rat osteosarcoma cells

    NASA Astrophysics Data System (ADS)

    Zhang, S.; Wang, B.; Cao, X. S.; Yang, Z.

    Objective The mRNA expression of alpha 1 chain of type I collagen COL-I alpha 1 in rat osteosarcoma ROS17 2 8 cells induced by bone morphogenetic protein-2 BMP-2 was reduced under simulated microgravity The protein kinase MEK1 of MAPK signal pathway plays an important role in the expression of COL-I alpha 1 mRNA The purpose of this study is to investigate the effects of simulated weightlessness on the activity of MEK1 induced by BMP-2 in ROS17 2 8 cells Methods ROS17 2 8 cells were cultured in 1G control and rotating clinostat simulated weightlessness for 24 h 48 h and 72 h BMP-2 500 ng ml was added into the medium 1 h before the culture ended There was a control group in which ROS17 2 8 cells were cultured in 1G condition without BMP-2 Then the total protein of cells was extracted and the expression of phosphated-ERK1 2 p-ERK1 2 protein was detected by means of Western Blotting to show the kinase activity of MEK1 Results There were no significant differences in the expression of total ERK1 2 among all groups The expression of p-ERK1 2 was unconspicuous in the control group without BMP-2 but increased significantly when BMP-2 was added P 0 01 The level of p-ERK1 2 in simulated weightlessness group was much more lower than that in 1G group in every time point P 0 01 The expression of p-ERK1 2 gradually decreased along with the time of weightlessness simulation P 0 01 Conclusions The kinase activity of MEK1 induced by BMP-2 in rat osteosarcoma cells was reduced under simulated weightlessness

  12. Deleterious effects of polynuclear aromatic hydrocarbon on blood vascular system of the rat fetus.

    PubMed

    Sanyal, Mrinal K; Li, You-Lan

    2007-10-01

    Polynuclear aromatic hydrocarbons (PAH), benzo[alpha]pyrene (B[alpha]P) and 7,12-dimethylbenz[alpha]anthracene (DMBA) are toxic environmental agents distributed widely. The relative deleterious effects of these agents on growth and blood vasculature of fetus and placental tissues of the rat were studied. Pregnant rats (Day 1 sperm positive) with implantation sites confirmed by laparotomy were treated intraperitoneally (i.p.) on Pregnancy Days 10, 12, and 14 with these agents dissolved in corn oil at cumulated total doses 50, 100, and 200 mg/kg/rat, and control with corn oil only (3-20 dams/group). Fetal growth, tissue hemorrhage, and placental pathology were evaluated by different parameters on Pregnancy Day (PD) 20 in treated and control rats. DMBA was relatively more deleterious compared to B[alpha]P indicated by increased lethality and progressive reduction of body weight of the mother with increasing doses. At 200 mg/kg/rat doses of these agents, maternal survival was 45% and 100% and body weight reduced 24% and 52% of controls, respectively. The fetal survival rates in live mothers were similar to that of controls. They induced marked fetal growth retardation and necrosis of placental tissues. B[alpha]P and DMBA produced significant toxicity to differentiating fetal blood vascular system as exhibited by rupture of blood vessels and hemorrhage, especially in the skin, cranial, and brain tissues. Maternal PAH exposure induced placental toxicity and associated adverse fetal development and hemorrhage in different parts of the fetal body, in particular, marked intradermal and cranial hemorrhage, showing that developing fetal blood vasculature is a target of PAH toxicity.

  13. alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal cortex.

    PubMed

    Livingstone, Phil D; Srinivasan, Jayaraman; Kew, James N C; Dawson, Lee A; Gotti, Cecilia; Moretti, Milena; Shoaib, Mohammed; Wonnacott, Susan

    2009-02-01

    Nicotine enhances attentional and working memory aspects of executive function in the prefrontal cortex (PFC) where dopamine plays a major role. Here, we have determined the nicotinic acetylcholine receptor (nAChR) subtypes that can modulate dopamine release in rat PFC using subtype-selective drugs. Nicotine and 5-Iodo-A-85380 (beta2* selective) elicited [(3)H]dopamine release from both PFC and striatal prisms in vitro and dopamine overflow from medial PFC in vivo. Blockade by dihydro-beta-erythroidine supports the participation of beta2* nAChRs. However, insensitivity of nicotine-evoked [(3)H]dopamine release to alpha-conotoxin-MII in PFC prisms suggests no involvement of alpha6beta2* nAChRs, in contrast to the striatum, and this distinction is supported by immunoprecipitation of nAChR subunits from these tissues. The alpha7 nAChR-selective agonists choline and Compound A also promoted dopamine release from PFC in vitro and in vivo, and their effects were enhanced by the alpha7 nAChR-selective allosteric potentiator PNU-120596 and blocked by specific antagonists. DNQX and MK801 inhibited [(3)H]dopamine release evoked by choline and PNU-120596, suggesting crosstalk between alpha7 nAChRs, glutamate and dopamine in the PFC. In vivo, systemic (but not local) administration of PNU-120596, in the absence of agonist, facilitated dopamine overflow in the medial PFC, consistent with the activation of extracortical alpha7 nAChRs by endogenous acetylcholine or choline. These data establish that both beta2* and alpha7 nAChRs can modulate dopamine release in the PFC in vitro and in vivo. Through their distinct actions on dopamine release, these nAChR subtypes could contribute to executive function, making them specific therapeutic targets for conditions such as schizophrenia and attention deficit hyperactivity disorder.

  14. Definition and epidemiology of unexplained infertility.

    PubMed

    Gelbaya, Tarek A; Potdar, Neelam; Jeve, Yadava B; Nardo, Luciano G

    2014-02-01

    The diagnosis of unexplained infertility can be made only after excluding common causes of infertility using standard fertility investigations,which include semen analysis, assessment of ovulation, and tubal patency test. These tests have been selected as they have definitive correlation with pregnancy. It is estimated that a standard fertility evaluation will fail to identify an abnormality in approximately 15% to 30% of infertile couples. The reported incidence of such unexplained infertility varies according to the age and selection criteria in the study population. We conducted a review of the literature via MEDLINE. Articles were limited to English-language, human studies published between 1950 and 2013. Since first coined more than 50 years ago, the term unexplained infertility has been a subject of debate. Although additional investigations are reported to explain or define other causes of infertility, these have high false-positive results and therefore cannot be recommended for routine clinical practice. Couples with unexplained infertility might be reassured that even after 12 months of unsuccessful attempts, 50% will conceive in the following 12 months and another 12% in the year after.

  15. Hypergravity induced prolactin surge in female rats

    NASA Technical Reports Server (NTRS)

    Megory, E.; Oyama, J.

    1985-01-01

    Acute initial exposure to hypergravity (HG) was previously found to induce prolonged diestrous in rats, which was followed by return to normal estrous cycling upon more prolonged exposure to continuous HG. Bromergocryptine was found to prevent this prolonged diestrous. In this study it is found that in female rats 20 h of 3.14 G exposure (D-1 1200 h until D-2 0800 h) can induce prolactin surge at D-2 1600 h. Shorter exposure time (8 h), or exposure during a different part of the estrous cycle (19 h: from D-1 0700 h until D-2 0200 h) could not elicit this prolactin surge. Similar exposure of male rats of HG did not alter significantly their prolactin levels. It is possible that the hypothalamus of male and female rats responds differently to stimulation by HG.

  16. Kruppel-like factor 2 inhibits hypoxia-inducible factor 1alpha expression and function in the endothelium.

    PubMed

    Kawanami, Daiji; Mahabeleshwar, Ganapati H; Lin, Zhiyong; Atkins, G Brandon; Hamik, Anne; Haldar, Saptarsi M; Maemura, Koji; Lamanna, Joseph C; Jain, Mukesh K

    2009-07-31

    Hypoxia-inducible factor 1 (HIF-1) is a central regulator of the hypoxic response in many cell types. In endothelial cells, HIF-1 induces the expression of key proangiogenic factors to promote angiogenesis. Recent studies have identified Kruppel-like factor 2 (KLF2) as a potent inhibitor of angiogenesis. However, the role of KLF2 in regulating HIF-1 expression and function has not been evaluated. KLF2 expression was induced acutely by hypoxia in endothelial cells. Adenoviral overexpression of KLF2 inhibited hypoxia-induced expression of HIF-1alpha and its target genes such as interleukin 8, angiopoietin-2, and vascular endothelial growth factor in endothelial cells. Conversely, knockdown of KLF2 increased expression of HIF-1alpha and its targets. Furthermore, KLF2 inhibited hypoxia-induced endothelial tube formation, whereas endothelial cells from mice with haploinsufficiency of KLF2 showed increased tube formation in response to hypoxia. Consistent with this ex vivo observation, KLF2 heterozygous mice showed increased microvessel density in the brain. Mechanistically, KLF2 promoted HIF-1alpha degradation in a von Hippel-Lindau protein-independent but proteasome-dependent manner. Finally, KLF2 disrupted the interaction between HIF-1alpha and its chaperone Hsp90, suggesting that KLF2 promotes degradation of HIF-1alpha by affecting its folding and maturation. These observations identify KLF2 as a novel inhibitor of HIF-1alpha expression and function. Therefore, KLF2 may be a target for modulating the angiogenic response in disease states.

  17. Attenuation by all-trans-retinoic acid of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

    PubMed

    Tatsuta, M; Iishi, H; Baba, M; Hirasawa, R; Yano, H; Sakai, N; Nakaizumi, A

    1999-02-01

    The effect of prolonged administration of all-trans-retinoic acid (RA) on sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, and the labelling and apoptotic indices and immunoreactivity of transforming growth factor (TGF) alpha in the gastric cancers was investigated in Wistar rats. After 25 weeks of carcinogen treatment, the rats were given chow pellets containing 10% sodium chloride and subcutaneous injections of RA at doses of 0.75 or 1.5 mg kg(-1) body weight every other day. In week 52, oral supplementation with sodium chloride significantly increased the incidence of gastric cancers compared with the untreated controls. Long-term administration of RA at both doses significantly reduced the incidence of gastric cancers, which was enhanced by oral administration of sodium chloride. RA at both doses significantly decreased the labelling index and TGF-alpha immunoreactivity of gastric cancers, which were enhanced by administration of sodium chloride, and significantly increased the apoptotic index of cancers, which was lowered by administration of sodium chloride. These findings suggest that RA attenuates gastric carcinogenesis, enhanced by sodium chloride, by increasing apoptosis, decreasing DNA synthesis, and reducing TGF-alpha expression in gastric cancers.

  18. Chromosomal disorders and male infertility

    PubMed Central

    Harton, Gary L; Tempest, Helen G

    2012-01-01

    Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically: chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis (PGD) in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility. PMID:22120929

  19. Chromosomal disorders and male infertility.

    PubMed

    Harton, Gary L; Tempest, Helen G

    2012-01-01

    Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically: chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis (PGD) in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.

  20. Berberine improves airway inflammation and inhibits NF-κB signaling pathway in an ovalbumin-induced rat model of asthma.

    PubMed

    Li, Zhenghao; Zheng, Jie; Zhang, Ning; Li, Chengde

    2016-12-01

    Berberine has been reported for its various activities including anti-inflammatory effects and has been used in treating many diseases. However, its effects on airway inflammation in asthma have not been investigated. This study mainly aimed to detect its effects on the airway inflammation and the nuclear factor-κB (NF-κB) signaling pathway activity in a rat model of asthma. Asthma was induced by ovalbumin (OVA) sensitization and challenge. The asthmatic rats were respectively treated with vehicle PBS or berberine (100 mg/kg or 200 mg/kg) for 28 days. The control rats were treated with PBS. Inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted and the lung inflammation was scored. Levels of NF-κB p65 (mRNA and protein), phosphorylated NF-κB p65 (p-NF-κB p65), inhibitory κB alpha (IκBα) (mRNA and protein) and phosphorylated IκBα (p-IκBα), as well as NF-κB p65 DNA-binding activity, were measured to assess the activity of NF-κB signaling pathway. Levels of the downstream inflammatory mediators of NF-κB signaling, IL-1β, IL-4, IL-5, IL-6, IL-13 and IL-17 in BALF, were measured. Besides, the serum levels of OVA-specific immunoglobulin (Ig)E were measured. Results showed that OVA increased the number of inflammatory cells in BALF, elevated lung inflammation scores, enhanced the NF-κB signaling activity and promoted the production of IgE in rats. Berberine dose-dependently reversed the alterations induced by OVA in the asthmatic rats. The findings suggested a therapeutic potential of berberine on OVA- induced airway inflammation. The ameliorative effects on the OVA-induced airway inflammation might be associated with the inhibition of the NF-κB signaling pathway.