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Sample records for aged rats treated

  1. Voluntary Exercise Impairs Initial Delayed Spatial Alternation Performance in Estradiol Treated Ovariectomized Middle-Aged Rats

    PubMed Central

    Neese, Steven L.; Korol, Donna L.; Schantz, Susan L.

    2013-01-01

    Estrogens differentially modulate behavior in the adult female rodent. Voluntary exercise can also impact behavior, often reversing age associated decrements in memory processes. Our research group has published a series of papers reporting a deficit in the acquisition of an operant working memory task, delayed spatial alternation (DSA), following 17β-estradiol treatment to middle-aged ovariectomized (OVX) rats. The current study examined if voluntary exercise could attenuate the 17β-estradiol induced deficits on DSA performance. OVX 12-month old Long- Evans rats were implanted with a Silastic capsule containing 17β-estradiol (10% in cholesterol: low physiological range) or with a blank capsule. A subset of the 17β-estradiol and OVX untreated rats were given free access to a running wheel in their home cage. All rats were tested for 40 sessions on the DSA task. Surprisingly, we found running wheel access to impair initial acquisition of the DSA task in 17β-estradiol treated rats, an effect not seen in OVX untreated rats given running wheel access. This deficit was driven by an increase in perseverative responding on a lever no longer associated with reinforcement. We also report for the first time a 17β-estradiol induced impairment on the DSA task following a long intertrial delay (18-sec), an effect revealed following more extended testing than in our previous studies (15 additional sessions). Overall, running wheel access increased initial error rate on the DSA task in 17β-estradiol treated middle-aged OVX rats, and failed to prevent the 17β-estradiol induced deficits in performance of the operant DSA task in later testing sessions. PMID:24013039

  2. Growth response of weanling rats to heated, aged, fractionated, and chemically treated yogurts.

    PubMed

    Hargrove, R E; Alford, J A

    1980-07-01

    Significance of viable cultures in yogurt at time of ingestion on rate of growth of weaning rats was determined. Fresh yogurts were compared with those in which cultures were treated with heat, hydrogen peroxide, and ethylene oxide. They also were aged and freeze-dried. Fractions of yogurt prepared by ultrafiltration were recombined to determine which fraction gave the highest rate of gain in weight. Cultures were inactivated and growth in rats was depressed when yogurt was heated at 60 C and above for 2 min. Hydrogen peroxide reduced the viable yogurt count and rate of gain but not feed consumption. Yogurts treated with ethylene oxide were toxic. Aging did not effect culture viability or feed efficiency, but growth response was reduced. Fractionation of yogurt into components of high and low molecular weight and recombinations with control milk fractions indicated that the growth stimulant remained in the component of high molecular weight.

  3. Superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the heart of hypergravity-treated and aging rats

    NASA Astrophysics Data System (ADS)

    Utko, Natalie

    2005-08-01

    Activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GP), and glutathione reductase (GR) were determined in the heart of young and old control and hypergravity (HG) treated male Wistar rats. Relatively small and insignificant changes were observed when comparing enzyme activities in the heart of young and old control rats, whereas HG induced significant decline of SOD and GP in the group of old rats and GR in young animals. Statistically highly significant positive correlation found for SOD and downstream acting catalase in young (r=0.72; P<0.00001) and old rats (r=0,86; P<0.00001) was preserved in HG- treated young animals as well (r=0.66; P<0.02), assuming that SOD-catalase pair could remain functionally related in both aging and HG. However, three-dimensional (3D) non- linear plotting and cluster analysis revealed significant alterations in enzyme relations in the heart of both aging and HG-treated animals.

  4. Aged garlic extract ameliorates immunotoxicity, hematotoxicity and impaired burn-healing in malathion- and carbaryl-treated male albino rats.

    PubMed

    Ramadan, Gamal; El-Beih, Nadia M; Ahmed, Rehab S A

    2017-03-01

    Malathion and carbaryl are the most widely used organophosphate and carbamate insecticides, respectively, especially in developing countries; they pose a potential health hazard for both humans and animals. Here, we evaluated the protective effects of an odorless (free from allicin) Kyolic aged garlic extract (AGE, containing 0.1% S-allylcysteine; 200 mg/kg body weight) on the toxicity induced by 0.1 LD50 of malathion (89.5 mg/kg body weight) and/or carbaryl (33.9 mg/kg body weight) in male Wistar rats. Doses were orally administered to animals for four consecutive weeks. The present study showed that AGE completely modulated most adverse effects induced by malathion and/or carbaryl in rats including the normocytic normochromic anemia, immunosuppression, and the delay in the skin-burning healing process through normalizing the count of blood cells (erythrocytes, leucocytes and platelets), hemoglobin content, hematocrit value, blood glucose-6-phosphodehydrogenase activity, weights and cellularity of lymphoid organs, serum γ-globulin concentration, and the delayed type of hypersensitivity response to the control values, and accelerating the inflammatory and proliferative phases of burn-healing. In addition, AGE completely modulated the decrease in serum reduced glutathione (GSH) concentration and the increase in clotting time in malathion alone and carbaryl alone treated rats. Moreover, AGE induced a significant increase (P < 0.001) in serum GSH concentration (above the normal value) and accelerating burn-healing process in healthy rats. In conclusion, AGE was effective in modulating most adverse effects induced in rats by malathion and carbaryl, and hence may be useful as a dietary adjunct for alleviating the toxicity in highly vulnerable people to insecticides intoxication. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 789-798, 2017.

  5. Pectinase-treated Panax ginseng extract (GINST) rescues testicular dysfunction in aged rats via redox-modulating proteins.

    PubMed

    Won, Yu-Jin; Kim, Bo-Kyung; Shin, Yong-Kyu; Jung, Seung-Hyo; Yoo, Sung-Kwang; Hwang, Seock-Yeon; Sung, Jong-Hwan; Kim, Si-Kwan

    2014-05-01

    The root of Panax ginseng improves testicular function both in humans and animals. However, the molecular mechanism by which ginseng exerts this effect has not been elucidated. Changes in protein expression in the rat testis in response to a pectinase-treated P. ginseng extract (GINST) were identified using 2-dimensional electrophoresis (2-DE) and MALDI-TOF/TOF MS. Number of sperm, Sertoli cells and germ cells, and the Sertoli Cell Index decrease in the testis of aged rats (AR) relative to young control rats (YCR). However, those parameters were completely restored in GINST-treated AR (GINST-AR). A proteomic analysis identified 14 proteins that were differentially expressed between vehicle-treated AR (V-AR) and GINST-AR. Out of these, the expression of glutathione-S-transferase (GST) mu5 and phospholipid hydroperoxide (PH) glutathione peroxidase (GPx) was significantly up-regulated in GINST-AR compared to V-AR. The activity of GPx and GST, as well as the expression of glutathione, in the testis of GINST-AR was higher than that in V-AR. The levels of lipid peroxidation (LPO) increased in AR compared with YCR, but this change was reversed by GINST-AR. These results suggest that the administration of GINST enhances testicular function by elevating GPx and GST activity, thus resulting in increased glutathione, which prevents LPO in the testis.

  6. Aging and Oxidative Stress Decrease Pineal Elongation Factor 2: In Vivo Protective Effect of Melatonin in Young Rats Treated With Cumene Hydroperoxide.

    PubMed

    Muñoz, Mario F; Argüelles, Sandro; Cano, Mercedes; Marotta, Francesco; Ayala, Antonio

    2017-01-01

    We studied the alterations of Elongation Factor 2 (eEF2) in the pineal gland of aged rats as well as the possible protective role of exogenous melatonin on these changes in young rats treated with cumene hydroperoxide (CH), a compound that promotes lipid peroxidation and inhibits protein synthesis. The study was performed using male Wistar rats of 3 (control), 12, and 24 months and 3-month-old rats treated with CH, melatonin, and CH plus melatonin. We found that pineal eEF-2 is affected by aging and CH, these changes being prevented by exogenous melatonin in the case of CH-treated rats. The proteomic studies show that many other proteins are affected by aging and oxidative stress in the pineal gland. The results suggest that one of the possible mechanisms underlying pineal gland dysfunction during aging is the effect of lipid peroxidation on eEF-2, which is a key component of protein synthesis machinery. J. Cell. Biochem. 118: 182-190, 2017. © 2016 Wiley Periodicals, Inc.

  7. Differential mechanisms of ang (1-7)-mediated vasodepressor effect in adult and aged candesartan-treated rats.

    PubMed

    Bosnyak, S; Widdop, R E; Denton, K M; Jones, E S

    2012-01-01

    Angiotensin (1-7) (Ang (1-7)) causes vasodilator effects in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) via angiotensin type 2 receptors (AT(2)R). However, the role of vascular AT(2)R in aging is not known. Therefore, we examined the effect of aging on Ang (1-7)-mediated vasodepressor effects and vascular angiotensin receptor localization in aging. Blood pressure was measured in conscious adult (~17 weeks) and aged (~19 months) normotensive rats that received drug combinations in a randomised fashion over a 4-day protocol: (i) Ang (1-7) alone, (ii) AT(1)R antagonist, candesartan, alone, (iii) Ang (1-7) and candesartan, or (iv) Ang-(1-7), candesartan, and the AT(2)R antagonist, PD123319. In a separate group of animals, the specific MasR antagonist, A779, was administered in place of PD123319. Receptor localisation was also assessed in aortic sections from adult and aged WKY rats by immunofluorescence. Ang (1-7) reduced blood pressure (~15 mmHg) in adult normotensive rats although this effect was dependant on the background dose of candesartan. This depressor effect was reversed by AT(2)R blockade. In aged rats, the depressor effect of Ang (1-7) was evident but was now inhibited by either AT(2)R blockade or MasR blockade. At the same time, AT(2)R, MasR, and ACE2 immunoreactivity was markedly elevated in aortic sections from aged animals. These results indicate that the Ang (1-7)-mediated depressor effect was preserved in aged animals. Whereas Ang (1-7) effects were mediated exclusively via stimulation of AT(2)R in adult WKY, with aging the vasodepressor effect of Ang (1-7) involved both AT(2)R and MasR.

  8. The anti-inflamm-aging and hepatoprotective effects of huperzine A in D-galactose-treated rats.

    PubMed

    Ruan, Qingwei; Liu, Fang; Gao, Zhanjuan; Kong, Deqiu; Hu, Xiaona; Shi, Dongmei; Bao, Zhijun; Yu, Zhuowei

    2013-03-01

    Oxidative stress contributes to a chronic inflammatory process referred to as "inflamm-aging". Acetylcholinesterase inhibitors (AChEI) can enhance cholinergic transmission and act as anti-inflammatory agents via immunocompetent cells expressing α-7 acetylcholine receptors (AChR). The present study explores the possible role of huperzine A, a reversible and selective AChEI, against D-gal-induced oxidative damage, cell toxicity and inflamm-aging in rat livers. In two-month-old rats with normal liver function, an 8-week administration of D-gal (300 mg/kg subcutaneously (s.c.) injected), significantly increased hepatic impairment, ROS generation and oxidative damage, hepatic senescence, nuclear factor-kappa B (NF-κB) activation and inflammatory responses. An 8-week co-administration of both D-gal (300 mg/kg s.c.) and huperzine A (0.1 mg/kg s.c.) not only significantly decreased hepatic function impairment, ROS generation, oxidative damage, but also suppressed inflamm-aging by inhibiting hepatic replicative senescence, AChE activity, IκBα degradation, NF-κB p65 nuclear translocation and inflammatory responses. The expression levels of pro-inflammatory cytokine mRNA and proteins, such as TNFα, IL-1β and IL-6 decrease significantly, and the protein levels of the anti-inflammatory cytokine IL-10 display an obvious increase. These findings indicated that D-gal-induced hepatic injury and inflamm-aging in the rat liver was associated with the development of a pro-inflammatory phenotype in this organ. D-gal induced damage-associated molecular patterns (DAMPs) because oxidative damages might play an important role in D-gal-induced hepatic sterile inflammation. Huperzine A exhibited protective effects against D-gal-induced hepatotoxicity and inflamm-aging by inhibiting AChE activity and via the activation of the cholinergic anti-inflammatory pathway. The huperzine A mechanism might be involved in the inhibition of DAMPs-mediated NF-κB nuclear localization and activation.

  9. Low doses of ethanol decrease the activity of the angiotensin-converting enzyme in the aorta of aging rats and rats treated with a nitric oxide synthase inhibitor and dexamethasone.

    PubMed

    Emel'yanov, Maksim O; Korystova, Antonina F; Kublik, Ludmila N; Levitman, Maria Kh; Shaposhnikova, Vera V; Korystov, Yuri N

    2012-01-01

    In the present study, the activity of ACE (angiotensin-converting enzyme) in the aorta of senescent rats and rats treated with the NOS (NO synthase) inhibitor L-NAME (NG-nitro-L-arginine methyl ester) or dexamethasone and the effect of low doses of ethanol (0.2-1.2 g/kg of body weight, daily for 8-12 days) on this activity were studied. We found that ACE activity increased with age and in response to L-NAME and dexamethasone treatment. Ethanol at a dose of 0.4 g/kg of body weight per day decreased ACE activity in the aorta of aged rats and of rats treated with L-NAME or dexamethasone to the level of activity in young control rats. The optimal ethanol dose (the dose inducing a maximum decrease in ACE activity) increased with increasing doses of dexamethasone: 0.4 g/kg of body weight per day at 30 μg of dexamethasone/kg of body weight and 0.8 g/kg of body weight per day at 100 μg of dexamethasone/kg of body weight. It was also found that optimal doses of ethanol increased the number of cells in the thymus of rats treated with dexamethasone. The optimal dose of ethanol of 0.4 g/kg of body weight per day, which induced a maximum decrease in ACE activity in rat aorta, corresponded to a dose of 30 g of ethanol/day, which, according to epidemiological data, produces a maximum decrease in the incidence of cardiovascular disease in humans. In conclusion, the decrease in ACE activity in vessels may be one of the main mechanisms of the beneficial effects of low doses of ethanol on human health.

  10. Effects of taxifolin on the activity of angiotensin-converting enzyme and reactive oxygen and nitrogen species in the aorta of aging rats and rats treated with the nitric oxide synthase inhibitor and dexamethasone.

    PubMed

    Arutyunyan, Tamara V; Korystova, Antonina F; Kublik, Ludmila N; Levitman, Maria Kh; Shaposhnikova, Vera V; Korystov, Yuri N

    2013-12-01

    The action of taxifolin on the angiotensin-converting enzyme (ACE) and the formation of reactive oxygen and nitrogen species (ROS/RNS) in the aorta of aging rats and rats treated with nitric oxide synthase inhibitor (N ω-nitro-L-arginine methyl ester (L-NAME)) or dexamethasone have been studied. The ACE activity in aorta sections was determined by measuring the hydrolysis of hippuryl-L-histidyl-L-leucine, and the ROS/RNS production was measured by oxidation of dichlorodihydrofluorescein. It was shown that taxifolin at a dose of 30-100 μg/kg/day decreases the ACE activity in the aorta of aging rats and of rats treated with L-NAME or dexamethasone to the level of the ACE activity in young control rats. Taxifolin (100 μg/kg/day) was found to also reduce the amount of ROS/RNS in the aorta that increased as a result of L-NAME intake. L-NAME treatment increases the contribution of 5-lipoxygenase and NADPH oxidase to ROS/RNS production in the aorta, while taxifolin (100 μg/kg/day) decreases the contribution of these enzymes to the normal level.

  11. The changes in the hypothalamo-pituitary-gonadal axis of streptozotocin-treated male rats depend from age at diabetes onset.

    PubMed

    Pitton, I; Bestetti, G E; Rossi, G L

    1987-01-01

    The influence of age at diabetes onset and of capillary microangiopathy on the severity and evolution of hypothalamo-pituitary-gonadal changes was studied morphologically and morphometrically in male rats 4 and 8 months after streptozotocin injection. At each time period we studied 2 groups of rats, one made diabetic before (age 1 month), the other after puberty (age 3 months), and compared them with corresponding controls. The size of hypothalamic axons, numerical density and size of pituitary gonadotrophs, size of testicular tubules, and basement membrane thickness of retinal capillaries were measured. Major differences were found at 8 months. Changes of pituitary glands (i.e. small and numerous gonadotrophs) and testes (i.e. small tubular size) were more important in pre- than in postpubertal diabetic rats. This was a consequence of the aggravating prepubertal diabetes between 4 and 8 months. On the contrary, these changes partially regressed in postpubertal diabetic animals. Pituitary and testicular changes were correlated. Other lesions, such as swollen axonal processes in the hypothalamus, increased thickness of seminiferous epithelium and of capillary basement membranes, though very evident in diabetics, were independent from age at induction. Neither microangiopathy nor glycemia were correlated with any other change which confirmed their secondary role in diabetic neuroendocrine disorders. Thus, two types of diabetic disorders of the hypothalamo-pituitary-gonadal axis could be distinguished: 1) those with irreversible effects on immature yet partially reversible effects on mature structures; and 2) those independent from age at induction.

  12. Changes in serotonin (5-HT) and brain-derived neurotrophic factor (BDFN) expression in frontal cortex and hippocampus of aged rat treated with high tryptophan diet.

    PubMed

    Musumeci, Giuseppe; Castrogiovanni, Paola; Castorina, Sergio; Imbesi, Rosa; Szychlinska, Marta Anna; Scuderi, Soraya; Loreto, Carla; Giunta, Salvatore

    2015-10-01

    Age-related cognitive decline is accompanied by an alteration in neurotransmitter synthesis and a dysregulation of neuroplasticity-related molecules such as serotonin (5-HT) and brain-derived neurotrophic factor (BDFN). It has been previously demonstrated that hyperserotonemia induced by l-Tryptophan (TrP) enriched diet protect against memory deficits during physiological aging. Since 5-HT is closely associated to BDNF, we aimed to investigate the effect of high TrP diet on 5-HT levels and BDNF expression in Frontal Cortex (FC) and Hippocampus (Hp) of aged rats. We found that the raising of systemic 5-HT levels by chronic diet (1 month) containing high TrP significantly prevents age-related decline of BDNF protein expression in both brain areas as indicated by ELISA and Western Blot analyses. Interestingly, immunohistochemical analyses confirmed that high TrP diet significantly elevates the number of 5-HT immunoreactive fibers in both brain areas tested and this correlated with BDNF increase in the FC and hippocampal regions CA1, CA2, CA3 and a strikingly down-regulation of neurotrophin levels in the dentate gyrus (DG) of aged rats. Altogether, these finding provide evidence that enhanced TrP intake and the consequent increase in 5-HT neurotransmission may act as a modulator of BDNF system suggesting a possible mechanism for the protective role of serotonergic system on memory impairment occurring along normal aging process.

  13. Growth hormone prevents neuronal loss in the aged rat hippocampus.

    PubMed

    Azcoitia, Iñigo; Perez-Martin, Margarita; Salazar, Veronica; Castillo, Carmen; Ariznavarreta, Carmen; Garcia-Segura, Luis M; Tresguerres, Jesus A F

    2005-05-01

    Decline of growth hormone (GH) with aging is associated to memory and cognitive alterations. In this study, the number of neurons in the hilus of the dentate gyrus has been assessed in male and female Wistar rats at 3, 6, 12, 14, 18, 22 and 24 months of age, using the optical fractionator method. Male rats had more neurons than females at all the ages studied. Significant neuronal loss was observed in both sexes between 22 and 24 months of age. In a second experiment, 22 month-old male and female rats were treated for 10 weeks with 2 mg/kg/day of GH or saline. At 24 months of age, animals treated with GH had more neurons in the hilus than animals treated with saline. These findings indicate that GH is neuroprotective in old animals and that its administration may ameliorate neuronal alterations associated to aging.

  14. [Cycloferon in treating duodenal ulcers in rats].

    PubMed

    Bul'on, V V; Khnychenko, L K; Sapronov, N S; Kuznetsova, N N; Anikin, V B; arinenko, R Iu; Kovalenko, A L; Alekseeva, L E

    2001-01-01

    The possibility of using cycloferon (interferon inductor) for a complex treatment (in combination with the main drug solcoseryl possessing pronounced therapeutic properties) of duodenum ulcers was experimentally studied in male rats. The experiments showed a considerable difference in the interferon status of animals with model duodenum ulcers treated with cycloferon, solcoseryl, their combination, and placebo (control). The healing effect of solcoseryl administered in combination with cycloferon exceeded that of each component administered separately.

  15. Tocotrienol rich fraction reverses age-related deficits in spatial learning and memory in aged rats.

    PubMed

    Taridi, Nursiati Mohamad; Abd Rani, Nazirah; Abd Latiff, Azian; Ngah, Wan Zurinah Wan; Mazlan, Musalmah

    2014-09-01

    Little is known about the effect of vitamin E on brain function. Therefore, in this study we evaluated the effect of tocotrienol rich fraction (TRF) on behavioral impairment and oxidative stress in aged rats. Thirty-six male Wistar rats (young: 3-months-old; aged: 21-months-old) were treated with either the control (olive oil) or TRF (200 mg/kg) for 3 months. Behavioral studies were performed using the open field test and Morris water maze (MWM) task. Blood was taken for assessment of DNA damage, plasma malondialdehyde (MDA) and vitamin E, and erythrocyte antioxidant enzyme activity. Brains were also collected to measure vitamin E levels. Results showed that aged rats exhibited reduced exploratory activity, enhanced anxiety and decreased spatial learning and memory compared with young rats. DNA damage and plasma MDA were increased, and vitamin E levels in plasma and brain were reduced in aged rats. Aged rats supplemented with TRF showed a markedly reduced level of anxiety, improved spatial learning and memory, reduced amount and severity of DNA damage, a reduced level of MDA, and increased levels of antioxidant enzyme activity and plasma/brain vitamin E compared with age-matched controls. In conclusion, TRF supplementation reverses spatial learning and memory decline and decreases oxidative stress in aged rats.

  16. Metformin Alleviates Altered Erythrocyte Redox Status During Aging in Rats.

    PubMed

    Garg, Geetika; Singh, Sandeep; Singh, Abhishek Kumar; Rizvi, Syed Ibrahim

    2017-02-01

    Metformin, a biguanide drug commonly used to treat type 2 diabetes, has been noted to function as a caloric restriction mimetic. Its antidiabetic effect notwithstanding, metformin is currently being considered an antiaging drug candidate, although the molecular mechanisms have not yet been unequivocally established. This study aims to examine whether short-term metformin treatment can provide protective effects against oxidative stress in young and old-age rats. Young (age 4 months) and old (age 24 months) male Wistar rats were treated with metformin (300 mg/kg b.w.) for 4 weeks. At the end of the treatment period, an array of biomarkers of oxidative stress were evaluated, including plasma antioxidant capacity measured in terms of ferric reducing ability of plasma (FRAP), reactive oxygen species (ROS), lipid peroxidation (MDA), reduced glutathione (GSH), total plasma thiol (SH), plasma membrane redox system (PMRS), protein carbonyl (PCO), advanced oxidation protein products (AOPPs), and advanced glycation end products (AGEs) in control and experimental groups. Metformin treatment resulted in an increase in FRAP, GSH, SH, and PMRS activities in both age groups compared to respective controls. On the other hand, treated groups exhibited significant reductions in ROS, MDA, PCO, AOPP, and AGE level. Save for FRAP and protein carbonyl, the effect of metformin on all other parameters was more pronounced in old-aged rats. Metformin caused a significant increase in the PMRS activity in young rats, however, the effect was less pronounced in old rats. These findings provide evidence with respect to restoration of antioxidant status in aged rats after short-term metformin treatment. The findings substantiate the putative antiaging role of metformin.

  17. Grape Powder Improves Age-Related Decline in Mitochondrial and Kidney Functions in Fischer 344 Rats

    PubMed Central

    Ali, Quaisar

    2016-01-01

    We examined the effects and mechanism of grape powder- (GP-) mediated improvement, if any, on aging kidney function. Adult (3-month) and aged (21-month) Fischer 344 rats were treated without (controls) and with GP (1.5% in drinking water) and kidney parameters were measured. Control aged rats showed higher levels of proteinuria and urinary kidney injury molecule-1 (KIM-1), which decreased with GP treatment in these rats. Renal protein carbonyls (protein oxidation) and gp91phox-NADPH oxidase levels were high in control aged rats, suggesting oxidative stress burden in these rats. GP treatment in aged rats restored these parameters to the levels of adult rats. Moreover, glomerular filtration rate and sodium excretion were low in control aged rats suggesting compromised kidney function, which improved with GP treatment in aged rats. Interestingly, low renal mitochondrial respiration and ATP levels in control aged rats were associated with reduced levels of mitochondrial biogenesis marker MtTFA. Also, Nrf2 proteins levels were reduced in control aged rats. GP treatment increased levels of MtTFA and Nrf2 in aged rats. These results suggest that GP by potentially regulating Nrf2 improves aging mitochondrial and kidney functions. PMID:27528887

  18. Perirhinal Cortex Hyperexcitability in Pilocarpine-Treated Epileptic Rats

    PubMed Central

    Benini, Ruba; Longo, Daniela; Biagini, Giuseppe; Avoli, Massimo

    2016-01-01

    The perirhinal cortex (PC), which is heavily connected with several epileptogenic regions of the limbic system such as the entorhinal cortex and amygdala, is involved in the generation and spread of seizures. However, the functional alterations occurring within an epileptic PC network are unknown. Here, we analyzed this issue by using in vitro electrophysiology and immunohistochemistry in brain tissue obtained from pilocarpine-treated epileptic rats and age-matched, nonepileptic controls (NECs). Neurons recorded intracellularly from the PC deep layers in the two experimental groups had similar intrinsic and firing properties and generated spontaneous depolarizing and hyperpolarizing postsynaptic potentials with comparable duration and amplitude. However, spontaneous and stimulus-induced epileptiform discharges were seen with field potential recordings in over one-fifth of pilocarpine-treated slices but never in NEC tissue. These network events were reduced in duration by antagonizing NMDA receptors and abolished by NMDA + non-NMDA glutamatergic receptor antagonists. Pharmacologically isolated isolated inhibitory postsynaptic potentials had reversal potentials for the early GABAA receptor-mediated component that were significantly more depolarized in pilocarpine-treated cells. Experiments with a potassium-chloride cotransporter 2 antibody identified, in pilocarpine-treated PC, a significant immunostaining decrease that could not be explained by neuronal loss. However, interneurons expressing parvalbumin and neuropeptide Y were found to be decreased throughout the PC, whereas cholecystokinin-positive cells were diminished in superficial layers. These findings demonstrate synaptic hyper-excitability that is contributed by attenuated inhibition in the PC of pilocarpine-treated epileptic rats and underscore the role of PC networks in temporal lobe epilepsy. PMID:20865722

  19. Fetal growth in rats treated with lapachol.

    PubMed

    Felício, André Carvalho; Chang, Cláudia Veiga; Brandão, Marcos Antônio; Peters, Vera Maria; Guerra, Martha de Oliveira

    2002-10-01

    Lapachol is a naphthoquinone well known for its therapeutic potential. Previous studies have shown that lapachol does not interfere with embryonic development during the pre-implantation period. However, when administered during the organogenic period at the same dose level, it induces a high fetal death incidence. To evaluate the effect of lapachol during fetogenesis, 20 pregnant Wistar rats were randomly divided into two groups: vehicle (10 mL of a 50% aqueous ethanol solution/kg body weight) and treated (100 mg of lapachol/kg body weight). Lapachol was administered from the 17th to 20th day of pregnancy. The following variables were analyzed: maternal body weight from 16th to 21st day of pregnancy, food intake from 17th to 21st day of pregnancy, clinical signs of physical discomfort, ovarian weights, implantations, resorptions and mortality indices, fetal and placenta weights, external malformations, and fetal organ weights. Results indicated that lapachol was not toxic to mothers, although it was fetotoxic leading to fetal growth retardation.

  20. Grape powder treatment prevents anxiety-like behavior in a rat model of aging.

    PubMed

    Patki, Gaurav; Ali, Quaisar; Pokkunuri, Indira; Asghar, Mohammad; Salim, Samina

    2015-06-01

    Earlier, we have reported that grape powder (GP) treatment prevented pharmacologic and psychological stress-induced anxiety-like behavior and memory impairment in rats. Protective effects of GP were attributed to its antioxidant effects. In this study, we tested the hypothesis that age-associated behavioral and cognitive deficits such as anxiety and memory impairment will be ameliorated with GP treatment. Using a National Institute of Aging recommended rodent model of aging, we examined a potentially protective role of antioxidant-rich GP in age-associated anxiety-like behavior and memory impairment. Male Fischer 344 rats were randomly assigned into 4 groups: young rats (3 months old) provided with tap water or with 15 g/L GP dissolved in tap water for 3 weeks, aged rats (21 months old) provided with tap water or with GP-treated tap water for 3 weeks (AG-GP). Anxiety-like behavior was significantly greater in aged rats compared with young rats, GP-treated young rats, or aged control rats (P < .05). Also, GP treatment prevented age-induced anxiety-like behavior in AG-GP rats (P < .05). Neither short-term nor long-term age-associated memory deficits improved with GP treatment in AG-GP rats. Furthermore, aged rats showed increased level of physiological stress (corticosterone) and increased oxidative stress in the plasma (8-isoprostane) as well as in selected brain areas (protein carbonylation). Grape powder treatment prevented age-induced increase in corticosterone levels and plasma 8-isoprostane levels in aged rats (P < .05), whereas protein carbonylation was recovered in the amygdala region only (P < .05). Grape powder by regulating oxidative stress ameliorates age-induced anxiety-like behavior in rats, whereas age-associated memory deficits seem unaffected with GP treatment.

  1. Corrupted colonic crypt fission in carcinogen-treated rats

    PubMed Central

    2017-01-01

    Background The colonic crypts in rats reproduce themselves by symmetric fission at the base of the crypts, and proceeding upwards, generate two separate identical crypts. Recently we reported corrupted colonic crypt fission (CCCF) in rats with colonic carcinoma. Here we investigated whether CCCF also occurred in the colonic mucosa without carcinoma in carcinogen-treated rats. Methods Filed Swiss-roll sections from 35 male rats (25 treated with 1,2-dimethyhydrazine (DMH) suspended in EDTA solution, and 10 EDTA-treated) were reviewed. CCCF were regarded those with either asymmetric basal fission, asymmetric lateral sprouting/lateral fission, basal dilatations, or spatial aberrations of the normal (vertical) axis. Results 202 CCCF (38%) were recorded amongst 533 crypts with fission in DMH-treated rats, and only one CCCF (0.1%) was found amongst 571 crypts with fission in EDTA-treated rats (p<0.05). The basal aspect of four adenomas included in Swiss roll sections exhibited CCCF lined either with indigenous (non-dysplastic) epithelium or with dysplastic epithelium. Conclusion It was demonstrated that CCCF without dysplasia develop in carcinogen-treated SD rats. As judged by the figures presented, the possibility that the epithelium in those corrupted crypts was successively replaced by top-down growing dysplastic cells, could not be totally rejected. This is the first report showing that non-dysplastic CCCF may antedate the very early stages of colonic carcinogenesis in SD rats. PMID:28273142

  2. Enhanced LTP in aged rats: Detrimental or compensatory?

    PubMed

    Pinho, Júlia; Vale, Ruben; Batalha, Vânia L; Costenla, Ana Rita; Dias, Raquel; Rombo, Diogo; Sebastião, Ana M; de Mendonça, Alexandre; Diógenes, Maria José

    2017-03-01

    Age-dependent memory deterioration has been well documented and yet an increase in rat hippocampal LTP upon aging has been reported. This poses the question of whether the enhanced LTP is a cause or an attempt to compensate the memory deficits described in aged rats. Hippocampal slices from young, adult and aged Wistar rats were pre-incubated, with an NMDA receptor (NMDAR) antagonist, memantine (1 μM, 4 h), and hippocampal LTP was evaluated. The results show that memantine significantly decreases the larger LTP magnitude recorded in hippocampal slices from aged rats without compromising LTP recorded in slices from young and adult animals. To unveil the impact of in vivo administration of memantine, different doses (1, 5 and 10 mg/kg/day) or saline vehicle solution were intraperitoneally administered, for 15-20 days, to both young and aged animals. Memantine did not significantly affect neither the place learning of young animals, evaluated by Morris Water Maze, nor LTP recorded from hippocampal slices from the same group of animals. However, memantine (5 and 10 mg/kg/day) significantly decreased the large LTP recorded in hippocampal slices from aged animals. Moreover, aged animals treated with memantine (10 mg/kg/day) showed a significantly compromised place learning when compared to aged control animals. Overall, these results suggest that the larger LTP observed in aged animals is a compensatory phenomenon, rather than pathological. The finding that age-dependent blockade of LTP by a NMDAR antagonist leads to learning deficits, implies that the increased LTP observed upon aging may be playing an important role in the learning process.

  3. Coccomyxa Gloeobotrydiformis Improves Learning and Memory in Intrinsic Aging Rats.

    PubMed

    Sun, Luning; Jin, Ying; Dong, Liming; Sui, Hai-Juan; Sumi, Ryo; Jahan, Rabita; Hu, Dahai; Li, Zhi

    2015-01-01

    Declining in learning and memory is one of the most common and prominent problems during the aging process. Neurotransmitter changes, oxidative stress, mitochondrial dysfunction and abnormal signal transduction were considered to participate in this process. In the present study, we examined the effects of Coccomyxa gloeobotrydiformis (CGD) on learning and memory ability of intrinsic aging rats. As a result, CGD treated (50 mg/kg·d or 100 mg/kg ·d for a duration of 8 weeks) 22-month-old male rats, which have shown significant improvement on learning and spatial memory ability compared with control, which was evidently revealed in both the hidden platform tasks and probe trials. The following immunohistochemistry and Western blot experiments suggested that CGD could increase the content of Ach and thereby improve the function of the cholinergic neurons in the hippocampus, and therefore also improving learning and memory ability of the aged rats by acting as an anti-inflammatory agent. The effects of CGD on learning and memory might also have an association with the ERK/CREB signalling. The results above suggest that the naturally made drug CGD may have several great benefit as a multi-target drug in the process of prevention and/or treatment of age-dependent cognitive decline and aging process.

  4. Incentive relativity in middle aged rats.

    PubMed

    Justel, N; Mustaca, A; Boccia, M; Ruetti, E

    2014-01-24

    Response to a reinforcer is affected by prior experience with different reward values of that reward, a phenomenon known as incentive relativity. Two different procedures to study this phenomenon are the incentive downshift (ID) and the consummatory anticipatory negative contrast (cANC), the former is an emotional-cognitive protocol and the latter cognitive one. Aged rodents, as also well described in aged humans, exhibit alterations in cognitive functions. The main goal of this work was to evaluate the effect of age in the incentive' assessment using these two procedures. The results indicated that aged rats had an adequate assessment of the rewards but their performance is not completely comparable to that of young subjects. They recover faster from the ID and they had a cognitive impairment in the cANC. The results are discussed in relation to age-related changes in memory and emotion.

  5. Behavioral effects of amphetamine in streptozotocin-treated rats

    PubMed Central

    Sevak, Rajkumar J.; Koek, Wouter; Daws, Lynette C.; Owens, William Anthony; Galli, Aurelio; France, Charles P.

    2009-01-01

    Experimentally-induced diabetes can modify the behavioral and neurochemical effects of drugs acting on dopamine systems, possibly through insulin-related regulation of dopamine transporter activity. In this study, several behavioral procedures were used to examine possible changes in sensitivity to amphetamine and other drugs in rats rendered diabetic by a single injection of streptozotocin. Conditioned place preference developed to food (Froot Loops®) in both control and diabetic rats, demonstrating that conditioned place preference with tactile stimuli can occur in streptozotocin-treated rats. Baseline locomotion was lower in streptozotocin-treated as compared to control rats, although amphetamine significantly increased locomotion in all rats. Conditioned place preference developed to amphetamine regardless of whether rats had received streptozotocin or saline. A second study compared the potency of drugs to decrease lever pressing maintained by food, before and after streptozotocin treatment. Gamma-hydroxybutyrate and amphetamine were less potent after streptozotocin while the potency of raclopride, quinpirole, ketamine, haloperidol and cocaine was not significantly changed by streptozotocin. While markedly affecting locomotion, body weight and blood glucose, streptozotocin only modestly affected sensitivity to the behavioral effects of amphetamine and other drugs; these results fail to confirm previous reports of decreased behavioral actions of stimulants in diabetic rats. PMID:18155695

  6. Behavioral effects of amphetamine in streptozotocin-treated rats.

    PubMed

    Sevak, Rajkumar J; Koek, Wouter; Daws, Lynette C; Owens, William Anthony; Galli, Aurelio; France, Charles P

    2008-02-26

    Experimentally-induced diabetes can modify the behavioral and neurochemical effects of drugs acting on dopamine systems, possibly through insulin-related regulation of dopamine transporter activity. In this study, several behavioral procedures were used to examine possible changes in sensitivity to amphetamine and other drugs in rats rendered diabetic by a single injection of streptozotocin. Conditioned place preference developed to food (Froot Loops) in both control and diabetic rats, demonstrating that conditioned place preference with tactile stimuli can occur in streptozotocin-treated rats. Baseline locomotion was lower in streptozotocin-treated as compared to control rats, although amphetamine significantly increased locomotion in all rats. Conditioned place preference developed to amphetamine regardless of whether rats had received streptozotocin or saline. A second study compared the potency of drugs to decrease lever pressing maintained by food, before and after streptozotocin treatment. Gamma-hydroxybutyrate and amphetamine were less potent after streptozotocin while the potency of raclopride, quinpirole, ketamine, haloperidol and cocaine was not significantly changed by streptozotocin. While markedly affecting locomotion, body weight and blood glucose, streptozotocin only modestly affected sensitivity to the behavioral effects of amphetamine and other drugs; these results fail to confirm previous reports of decreased behavioral actions of stimulants in diabetic rats.

  7. The pituitary - Aging and spaceflown rats

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Grindeland, R. E.

    1991-01-01

    Decrements in growth hormone (GH) release we observed in two spaceflight experiments and four tail-suspended rat studies mimic age-associated changes in the mammalian pituitary GH system seen by Meites and others. The spaceflight data suggest that formation of high molecular weight bioactive disulfide-linked aggregates of the 20 and 22K monomeric GH forms may be reduced in microgravity, thereby, reducing target tissue activity. Correlative studies to confirm spaceflight as a model for pituitary GH system aging should include: (1) investigation of mechanisms of intracellular hormone packaging, (2) consequences to biological activity of the hormone molecule, and (3) study of intracellular microtubule dynamics.

  8. The effect of aging on acetaminophen pharmacokinetics, toxicity and Nrf2 in Fischer 344 rats.

    PubMed

    Mach, John; Huizer-Pajkos, Aniko; Cogger, Victoria C; McKenzie, Catriona; Le Couteur, David G; Jones, Brett E; de Cabo, Rafael; Hilmer, Sarah N

    2014-04-01

    We investigated the effect of aging on hepatic pharmacokinetics and the degree of hepatotoxicity following a toxic dose of acetaminophen. Young and old male Fischer 344 rats were treated with 800 mg/kg acetaminophen (young n = 8, old n = 5) or saline (young n = 9, old n = 9). Serum measurements showed old rats treated with acetaminophen had significantly lower serum alanine aminotransferase and higher acetaminophen and acetaminophen glucuronide levels and creatinine, compared with acetaminophen treated young rats (p < .05). Immunoblotting and activity assays showed old saline-treated rats had twofold lower cytochrome P450 2E1 activity and threefold higher NAD(P)H quinone oxireductase 1 protein expression and activity than young saline-treated rats (p < .05), although Nrf2, glutathione cysteine ligase-modulatory subunit, glutathione cysteine ligase-catalytic subunit, and cytochrome P450 2E1 protein expressions were unchanged. Primary hepatocytes isolated from young rats treated with 10 mM acetaminophen had lower survival than those from old rats (52.4% ± 5.8%, young; 83.6% ± 1.7%, old, p < .05). The pharmacokinetic changes described may decrease susceptibility to acetaminophen-induced hepatotoxicity but may increase risk of nephrotoxicity in old age.

  9. Emphysema model in rats treated intratracheally with elastase

    SciTech Connect

    Yokoyama, E.; Nambu, Z.; Uchiyama, I.; Kyono, H.

    1987-04-01

    Pulmonary functions, morphology, and morphometry were examined in rats at 3, 7, and 10 weeks after a single intratracheal administration of 6.5 units of porcine pancreatic elastase in order to obtain a model of pulmonary emphysema which would be suitable for studying the responses of emphysematous lungs to atmospheric pollutants. Functional residual capacity and residual volume of the elastase-treated rats increased at all the times studied, but their total lung capacity increased only at 7 and 10 weeks compared with those of the saline-treated control rats. The increase in static lung compliance and the decrease in peak flow and maximum flow at 50% of total lung capacity during forced expiration were also observed in all except the 3-week elastase animals. The elastase-treated lungs showed morphological changes characteristic of emphysematous lesions. The increase in mean linear intercept length and the decrease in total alveolar surface area were demonstrated by these elastase-treated lungs. Based on these results, they conclude that an adequate and suitable model of pulmonary emphysemia could be obtained in rats 7-10 weeks after treatment with the present dose of elastase.

  10. Microarray analysis of thioacetamide-treated type 1 diabetic rats

    SciTech Connect

    Devi, Sachin S.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-04-01

    It is well known that diabetes imparts high sensitivity to numerous hepatotoxicants. Previously, we have shown that a normally non-lethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats due to inhibited tissue repair allowing progression of liver injury. On the other hand, DB rats exposed to 30 mg TA/kg exhibit delayed tissue repair and delayed recovery from injury. The objective of this study was to investigate the mechanism of impaired tissue repair and progression of liver injury in TA-treated DB rats by using cDNA microarray. Gene expression pattern was examined at 0, 6, and 12 h after TA challenge, and selected mechanistic leads from microarray experiments were confirmed by real-time RT-PCR and further investigated at protein level over the time course of 0 to 36 h after TA treatment. Diabetic condition itself increased gene expression of proteases and decreased gene expression of protease inhibitors. Administration of 300 mg TA/kg to DB rats further elevated gene expression of proteases and suppressed gene expression of protease inhibitors, explaining progression of liver injury in DB rats after TA treatment. Inhibited expression of genes involved in cell division cycle (cyclin D1, IGFBP-1, ras, E2F) was observed after exposure of DB rats to 300 mg TA/kg, explaining inhibited tissue repair in these rats. On the other hand, DB rats receiving 30 mg TA/kg exhibit delayed expression of genes involved in cell division cycle, explaining delayed tissue repair in these rats. In conclusion, impaired cyclin D1 signaling along with increased proteases and decreased protease inhibitors may explain impaired tissue repair that leads to progression of liver injury initiated by TA in DB rats.

  11. Aging effects on oxidative phosphorylation in rat adrenocortical mitochondria.

    PubMed

    Solinas, Paola; Fujioka, Hisashi; Radivoyevitch, Tomas; Tandler, Bernard; Hoppel, Charles L

    2014-06-01

    Does aging in itself lead to alteration in adrenocortical mitochondrial oxidative phosphorylation? Mitochondria from Fischer 344 (F344) rats (6 and 24 months old), Brown Norway rats (6 and 32 months old) and F344-Brown Norway hybrid rats (6 and 30 months old) were compared. Mitochondria were isolated from extirpated adrenal cortex. The yields of mitochondria were quantitatively similar in all rat strains irrespective of age. In order to assess the activity of each mitochondrial complex, several different substrates were tested and the rate of oxidative phosphorylation measured. Aging does not affect mitochondrial activity except in the F344 rat adrenal cortex where the maximal ADP-stimulated oxidative phosphorylation decreased with age. We hypothesize that impaired synthesis of steroid hormones by the adrenal cortex with age in F344 rats might be due to decreased adrenocortical mitochondrial oxidative phosphorylation. We conclude that aging results in adrenocortical mitochondria effects that are non-uniform across different rat strains.

  12. Pineal gland: influence on gonads of male rats treated with androgen 3 days after birth.

    PubMed

    Reiter, R J; Hoffman, J C; Rubin, P H

    1968-04-26

    Either blinding or the injection of 1 milligram of testosterone propionate into male Sprague-Dawley rats, 3 days old, results in testes and accessory organs (seminal vesicles and coagulating glands) that are smaller than normal when the rats are 72 days old. The response to blinding is prevented by removal of the pineal gland, whereas the response to treatment with testosterone is unaffected by pinealectomy. Combination of the two treatments in 3-day- old rats causes testes to be less than one-third their normal size at 72 days of age; pinealectomy in these rats permits the reproductive organs to grow to the same size as those in the androgen-treated animals.

  13. Role of topical peptides in preventing or treating aged skin.

    PubMed

    Gorouhi, F; Maibach, H I

    2009-10-01

    Ageing, a basic biological process seen in all living creatures, is not preventable. Surgical and topical modalities have been invented and substances were applied topically to alter the ageing process. Peptides and proteins, frequently used for this purpose, were categorized into four groups: signal peptides, enzyme-inhibitor peptides, neurotransmitter-inhibitor peptides and carrier peptides. We comprehensively review eligible studies -including controlled ex vivo or in vivo efficacy studies on any topical peptide or protein that has been administered to treat signs and symptoms of ageing.

  14. Cardiac and thermal homeostasis in the aging Brown Norway rat.

    EPA Science Inventory

    The Brown Norway (BN) rat is a popular strain for aging studies. There is little information on effects of age on baseline cardiac and thermoregulatory parameters in undisturbed BN rats even though cardiac and thermal homeostasis is linked to many pathological deficits in the age...

  15. Chronic ethanol consumption depresses hypothalamic-pituitary-adrenal function in aged rats

    SciTech Connect

    Nolan, C.J.; Bestervelt, L.L.; Mousigian, C.A.; Maimansomsuk, P.; Yong Cai; Piper, W.N. )

    1991-01-01

    In separate experiments, nine (n=20) and fifteen (n=12) month old rats were treated with either 6% ethanol or 12% sucrose in the drinking water to examine the effect of chronic ethanol consumption on the hypothalamic-pituitary-adrenal axis of aged rats. Blood was collected and plasma concentrations of adrenocorticotropin (ACTH) and corticosterone were determined by radioimmunoassay. Adrenal glands were cleaned, quartered and used to test in vitro responsiveness to ACTH. Anterior pituitary glands from all 15 month old rats and one half of the nine month old rats were collected, frozen and extracted for measurement of tissue ACTH concentration. The remaining anterior pituitary glands from the nine month old rats were challenged with corticotropin releasing hormone (CRH) to test in vitro responsiveness. In nine month old rats, chronic ethanol consumption decreased plasma ACTH and corticosterone. Pituitary ACTH concentrations were unchanged in treated nine month old rats, but the amount of pituitary ACTH released in response to CRH was decreased in rats consuming ethanol. In vitro responsiveness of the adrenal gland to ACTH in nine month old rats consuming ethanol was unchanged. Plasma ACTH and corticosterone concentrations were also decreased in 15 month old rats chronically consuming ethanol. No differences were noted in responsiveness of the adrenal gland or in the amount of pituitary ACTH due to ethanol consumptions in 15 month old rats.

  16. Norepinephrine-induced diuresis in chronically ethanol-treated rats

    SciTech Connect

    Pohorecky, L.A. )

    1989-01-01

    Previous research from this laboratory indicated that noradrenergic mechanisms might mediate ethanol diuresis. Experiments described here examined changes in sensitivity of noradrenergic mechanisms in animals chronically treated with ethanol. Norepinephrine hydrochloride (0-12 ug intracerebroventricularly) produced dose-dependent diuresis in control and ethanol treated rats on the first day of treatment. Tolerance to ethanol diuresis was present after 10 day of ethanol treatment. Lack of responsiveness to norepinephrine-induced diuresis was evident only on the 20th day of treatment in both the ethanol and dextrin-maltose groups of rats. These results indicate a temporal dissociation between the tolerance to ethanol-induced and norepinephrine-induced diuresis and suggest that norepinephrine may not play a primary role in the development of tolerance to the diuretic action of ethanol.

  17. Memory and hippocampal architecture following short-term midazolam in western diet-treated rats.

    PubMed

    Rosenberger, Dorothea S; Falangola, Maria F; Ledreux, Aurélie; Nie, Xingju; Suhre, Wendy M; Boger, Heather A; Granholm, Ann-Charlotte

    2016-05-16

    The impact of short-term benzodiazepine exposure on cognition in middle-aged or older patients is a highly debated topic among anesthesiologists, critical care physicians and public media. "Western diet" (WD) consumption is linked to impaired cognition as well. The combination of benzodiazepines with substantial exposure to WD might set the stage for increased hippocampal vulnerability for benzodiazepines leading to exaggerated cognitive impairment in the postoperative period. In this study, Fischer 344 rats were fed either WD or standard rodent diet from 5 to 10.5 months of age. Rats were exposed to midazolam or placebo two days prior to an MRI scan using Diffusional Kurtosis Imaging (DKI) to assess brain microstructural integrity, followed by behavioral testing using a water radial arm maze. Hippocampal tissue was collected to assess alterations in protein biochemistry in brain regions associated with learning and memory. Our results showed that rats exposed to the combination of midazolam and WD had significantly delayed time of learning and exhibited spatial memory impairment. Further, we observed an overall increase of kurtosis metrics in the hippocampus and increased expression of the mitochondrial protein VDAC2 in midazolam-treated rats. Our data suggest that both the short-acting benzodiazepine midazolam and WD contribute to negatively affect the brain in middle-aged rats. This study is the first application of DKI on the effects of midazolam and WD exposure, and the findings demonstrate that diffusion metrics are sensitive indicators of changes in the complexity of neurite architecture.

  18. Sustained Fos expression is observed in the developing brainstem auditory circuits of kanamycin-treated rats.

    PubMed

    Lee, Jae Ho; Kim, Hee Jung; Suh, Myung-Whan; Ahn, Seung Cheol

    2011-11-14

    It has been demonstrated that kanamycin treatment during early developmental period induces partial cochlear destruction and enhanced glutamatergic transmission at the medial nucleus of the trapezoid body (MNTB) - the lateral superior olive (LSO) synapses in the superior olivary complex (SOC). As c-fos was expected to be expressed in the SOC by kanamycin-induced cochlear damage, the expression of c-fos protein (Fos) was investigated using immunohistochemistry in kanamycin-treated rat pups. In the control rat pups less than postnatal (P) day 9 in age, Fos-like immunoreactivity (Fos-IR) was transiently observed in the MNTB and LSO on P6, but disappeared on P9, which reflects a physiologic process. In contrast, in kanamycin-treated rats, Fos-IR was consistently observed through P9. Because a significant increase in terminal uridine deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick-end labeling (TUNEL) and glial fibrillary acidic protein (GFAP) IR was not demonstrated in the MNTB and LSO of kanamycin-treated rats, the increased Fos-IR does not appear to indicate an ongoing pathologic process, but may be related to the increased activity caused by the disturbance in excitatory and inhibitory balance between brainstem auditory circuits.

  19. Effect of caffeine on rat offspring from treated dams.

    PubMed

    Aeschbacher, H U; Milon, H; Poot, A; Würzner, H P

    1980-11-01

    Pregnant Sprague-Dawley rats were given caffeine at 1.0, 0.5 and 0.25 g/kg diet during gestation and lactation. At birth, half of the pups from control and treated rats at each dose level were exchanged and cross fostered. Two litters were produced by each animal from each of the experimental groups. Caffeine at dietary concentrations of 0.5 and 0.25 g/kg throughout gestation and lactation had no significant effect on birth weight, litter size or development. There was also no effect at these doses following treatment during either gestation alone, or lactation alone. At 1.0 g/kg there was a slight reduction of birth weight, as well as a trend towards lower weight gain in litters from dams fed the test diet throughout gestation and lactation.

  20. Sympathetic neuroaxonal dystrophy in the aged rat pineal gland.

    PubMed

    Schmidt, Robert E; Dorsey, Denise A; Parvin, Curtis A; Beaudet, Lucie N

    2006-10-01

    Dysfunction of circadian melatonin production by the pineal gland in aged humans and rats is thought to reflect the functional loss of its sympathetic innervation. Our ultrastructural neuropathologic studies of the sympathetic innervation of the pineal gland of aged (24 months old) Fischer-344 and Sprague-Dawley rats showed loss of nerve terminals as well as the development of neuroaxonal dystrophy (NAD), an ultrastructurally distinctive distal axonopathy, far in excess of that in young control rats. Immunolocalization of tyrosine hydroxylase confirmed the age-related loss of normal noradrenergic innervation and development of NAD. NAD was more frequent in aged female rats compared to males and was particularly severe in aged female Sprague-Dawley rats compared to Fischer-344 rats. Pineal NGF content was significantly increased or unchanged in female and male aged Fischer-344 rats, respectively, compared to young controls. The rat pineal is a sensitive experimental model for the quantitative ultrastructural examination of age-related neuropathological changes in nerve terminals of postganglionic noradrenergic sympathetic axons, changes which may reflect similar changes in the diffusely distributed sympathetic innervation of other targeted endorgans.

  1. Synaptic plasticity preserved with arachidonic acid diet in aged rats.

    PubMed

    Kotani, Susumu; Nakazawa, Hiroe; Tokimasa, Takayuki; Akimoto, Kengo; Kawashima, Hiroshi; Toyoda-Ono, Yoshiko; Kiso, Yoshinobu; Okaichi, Hiroshige; Sakakibara, Manabu

    2003-08-01

    We examined whether synaptic plasticity was preserved in aged rats administered an arachidonic acid (AA) containing diet. Young male Fischer-344 rats (2 mo of age), and two groups of aged rats of the same strain (2 y of age) who consumed either a control diet or an AA ethyl ester-containing diet for at least 3 mo were used. In the Morris water maze task, aged rats on the AA diet had tendency to show better performance than aged rats on the control diet. Long-term potentiation induced by tetanic stimulation was recorded from a 300 microm thick hippocampal slice with a 36 multi-electrode-array positioned at the dendrites of CA1 pyramidal neurons. The degree of potentiation after 1 h in aged rats on the AA diet was comparable as that of young controls. Phospholipid analysis revealed that AA and docosahexaenoic acid were the major fatty acids in the hippocampus in aged rats. There was a correlation between the behavioral measure and the changes in excitatory postsynaptic potential slope and between the physiologic measure and the total amount of AA in hippocampus.

  2. Therapeutic Strategies to Treat Dry Eye in an Aging Population

    PubMed Central

    Ezuddin, Nisreen S.; Alawa, Karam A.; Galor, Anat

    2015-01-01

    Dry eye (DE) is a prevalent ocular disease that primarily affects the elderly. Affecting up to 30% of adults aged 50 years and older, dry eye affects both visual function and quality of life. Symptoms of dry eye which include ocular pain (aching, burning), visual disturbances, and tearing can be addressed with therapeutic agents that target dysfunction of the meibomian glands, lacrimal glands, goblet cells, ocular surface and/or neural network. This review provides an overview of the efficacy, use, and limitations of current therapeutic interventions being used to treat DE. PMID:26123947

  3. Reproductive toxicity of a single dose of 1,3-dinitrobenzene in two ages of young adult male rats

    EPA Science Inventory

    These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-dinitrobenzene (m-DNB). Young adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24,...

  4. Evaluation of Chromosomal Instability in Diabetic Rats Treated with Naringin

    PubMed Central

    A. Bakheet, Saleh; M. Attia, Sabry

    2011-01-01

    We used the bone marrow DNA strand breaks, micronucleus formations, spermatocyte chromosomal aberrations, and sperm characteristic assays to investigate the chromosomal instability in somatic and germinal cells of diabetic rats treated with multiple doses of naringin. The obtained results revealed that naringin was neither cytotoxic nor genotoxic for the rats at all tested doses. Moreover, naringin significantly reduced the diabetes-induced chromosomal instability in somatic and germinal cells in a dose-dependent manner. In addition, diabetes induced marked biochemical alterations characteristic of oxidative stress including enhanced lipid peroxidation, accumulation of oxidized glutathione, reduction in reduced glutathione, and accumulation of intracellular reactive oxygen species. Treatment with naringin ameliorated these biochemical markers dose-dependently. In conclusion, naringin confers an appealing protective effect against diabetes-induced chromosomal instability towards rat somatic and germinal cells which might be explained partially via diminishing the de novo free radical generation induced by hyperglycemia. Thus, naringin might be a good candidate to reduce genotoxic risk associated with hyperglycemia and may provide decreases in the development of secondary malignancy and abnormal reproductive outcomes risks, which seems especially important for diabetic patients. PMID:21941606

  5. Neuronal Function in Male Sprague Dawley Rats During Normal Ageing.

    PubMed

    Idowu, A J; Olatunji-Bello, I I; Olagunju, J A

    2017-03-06

    During normal ageing, there are physiological changes especially in high energy demanding tissues including the brain and skeletal muscles. Ageing may disrupt homeostasis and allow tissue vulnerability to disease. To establish an appropriate animal model which is readily available and will be useful to test therapeutic strategies during normal ageing, we applied behavioral approaches to study age-related changes in memory and motor function as a basis for neuronal function in ageing in male Sprague Dawley rats. 3 months, n=5; 6 months, n=5 and 18 months, n=5 male Sprague Dawley Rats were tested using the Novel Object Recognition Task (NORT) and the Elevated plus Maze (EPM) Test. Data was analyzed by ANOVA and the Newman-Keuls post hoc test. The results showed an age-related gradual decline in exploratory behavior and locomotor activity with increasing age in 3 months, 6 months and 18 months old rats, although the values were not statistically significant, but grooming activity significantly increased with increasing age. Importantly, we established a novel finding that the minimum distance from the novel object was statistically significant between 3 months and 18 months old rats and this may be an index for age-related memory impairment in the NORT. Altogether, we conclude that the male Sprague Dawley rat show age-related changes in neuronal function and may be a useful model for carrying out investigations into the mechanisms involved in normal ageing.

  6. Hypertension and impairment of endothelium-dependent relaxation of arteries from spontaneously hypertensive and L-NAME-treated Wistar rats.

    PubMed

    Sekiguchi, F; Miyake, Y; Hirakawa, A; Nakahira, T; Yamaoka, M; Shimamura, K; Yamamoto, K; Sunano, S

    2001-04-01

    Effects of chronic treatment of normotensive Wistar rats with N(omega)-nitro-L-arginine methyl ester (L-NAME) on blood pressure and on endothelium-dependent relaxation of the aorta, carotid and iliac arteries were studied. The endothelium-dependent relaxation was compared in arteries from normotensive Wistar Kyoto rats (WKY) and genetically hypertensive rats (stroke-prone spontaneously hypertensive rats, SHRSP). Chronic treatment of normotensive Wistar rats with L-NAME caused an elevation of blood pressure. The elevated blood pressure at 15 weeks of age was significantly higher in these animals than that of untreated Wistar rats, but lower than that of SHRSP. Endothelium-dependent relaxation of the arteries induced by acetylcholine (ACh) was almost abolished by chronic treatment with L-NAME. The remaining small relaxation in arteries from L-NAME-treated rats was completely inhibited by application of L-NAME (10(-4) M). In such preparations, higher concentrations of ACh induced a contraction, which was abolished by removal of the endothelium or by an application of indomethacin (10(-5) M). Endothelium-independent relaxation induced by sodium nitroprusside was similar between preparations from untreated and L-NAME-treated Wistar rats. Endothelium-dependent relaxation was significantly impaired in preparations from SHRSP, when compared with that in those from WKY. However, the impairment was less prominent in preparations from SHRSP than in those from L-NAME-treated rats. These results suggest that the impairment of endothelium-dependent relaxation in the arteries from L-NAME-treated rats is not due to the elevated blood pressure resulting from the chronic treatment, and that impairment of NO synthesis by the endothelium does not play a major role in the initiation of hypertension in SHRSP.

  7. Effects of melatonin on aluminium-induced neurobehavioral and neurochemical changes in aging rats.

    PubMed

    Allagui, M S; Feriani, A; Saoudi, M; Badraoui, R; Bouoni, Z; Nciri, R; Murat, J C; Elfeki, A

    2014-08-01

    This study aimed to investigate the potential protective effects of melatonin (Mel) against aluminium-induced neurodegenerative changes in aging Wistar rats (24-28months old). Herein, aluminium chloride (AlCl3) (50mg/kg BW/day) was administered by gavage, and melatonin (Mel) was co-administered to a group of Al-treated rats by an intra-peritoneal injection at a daily dose of 10mg/kg BW for four months. The findings revealed that aluminium administration induced a significant decrease in body weight associated with marked mortality for the old group of rats, which was more pronounced in old Al-treated rats. Behavioural alterations were assessed by 'open fields', 'elevated plus maze' and 'Radial 8-arms maze' tests. The results demonstrated that Mel co-administration alleviated neurobehavioral changes in both old and old Al-treated rats. Melatonin was noted to play a good neuroprotective role, reducing lipid peroxidation (TBARs), and enhancing enzymatic (SOD, CAT and GPx) activities in the brain organs of old control and old Al-treated rats. Mel treatment also reversed the decrease of AChE activity in the brain tissues, which was confirmed by histological sections. Overall, the results showed that Mel administration can induce beneficial effects for the treatment of Al-induced neurobehavioral and neurochemical changes in the central nervous system (CNS).

  8. JV Task 119 - Effects of Aging on Treated Activated Carbons

    SciTech Connect

    Edwin Olson; Lucinda Hamre; John Pavlish; Blaise Mibeck

    2009-03-25

    For both the United States and Canada, testing has been under way for electric utilities to find viable and economical mercury control strategies to meet pending future mercury emission limits. The technology that holds the most promise for mercury control in low-chlorine lignite to meet the needs of the Clean Air Act in the United States and the Canada-Wide Standards in Canada is injection of treated activated carbon (AC) into the flue gas stream. Most of the treated carbons are reported to be halogenated, often with bromine. Under a previous multiyear project headed by the Energy & Environmental Research Center (EERC), testing was performed on a slipstream unit using actual lignite-derived flue gas to evaluate various sorbent technologies for their effectiveness, performance, and cost. Testing under this project showed that halogenated ACs performed very well, with mercury capture rates often {ge} 90%. However, differences were noted between treated ACs with respect to reactivity and capacity, possibly as a result of storage conditions. Under certain conditions (primarily storage in ambient air), notable performance degradation had occurred in mercury capture efficiency. Therefore, a small exploratory task within this project evaluated possible differences resulting from storage conditions and subsequent effects of aging that might somehow alter their chemical or physical properties. In order to further investigate this potential degradation of treated (halogenated) ACs, the EERC, together with DOE's National Energy Technology Laboratory, the North Dakota Industrial Commission (NDIC), the Electric Power Research Institute (EPRI), SaskPower, and Otter Tail Power Company, assessed the aging effects of brominated ACs for the effect that different storage durations, temperatures, and humidity conditions have on the mercury sorption capacity of treated ACs. No aging effects on initial capture activity were observed for any carbons or conditions in the investigation

  9. Heterologous mesenchymal stem cells successfully treat femoral pseudarthrosis in rats

    PubMed Central

    2012-01-01

    Background This study evaluated the effectiveness of treating pseudarthrosis in rats by using bone marrow cell suspensions or cultures of bone marrow mesenchymal stromal cells Methods Thirty-eight specific pathogen-free (SPF) animals were randomly assigned to four groups: Group 1, Control, without surgical intervention; Group 2 (Placebo), experimental model of femoral pseudarthrosis treated only with saline solution; Group 3, experimental model of femoral pseudarthrosis treated with heterologous bone marrow cells suspension; Group 4, experimental model of femoral pseudarthrosis treated with cultures of heterologous mesenchymal stromal cells from bone marrow. When pseudarthrosis was confirmed by simple radiological studies, digital radiography and histopathology after a 120-day postoperative period, Groups 2, 3 and 4 were treated as above. At 30, 60 and 90 days after the treatment, all animals were evaluated by simple radiological studies, and at the end of the experiment, the animals were assessed by computed axial tomography and anatomopathological and histomorphometric examinations. Results Injected cells were detected in the areas affected by pseudarthrosis using scintigraphy within the first 24 hours after their administration. After 60 days, the animals of Group 3 showed callus formation while the animals of Group 4 presented periosteal reaction and had some consolidated areas. In contrast, Group 2 showed a predominance of fibro-osteoid tissue. After 90 days, bone consolidation and remodeling was observed in all animals from Group 3 whereas animals from Group 4 exhibited partial consolidation and those ones from Group 2 persisted with pseudarthrosis. Conclusion The treatment with heterologous bone marrow cells suspension proved to be effective in the treatment of pseudarthrosis whereas cultures of heterologous bone marrow mesenchymal stromal cells did not show the same potential to aid bone healing. PMID:22429995

  10. Aging-induced alterations in female rat colon smooth muscle: the protective effects of hormonal therapy.

    PubMed

    Pascua, P; Camello-Almaraz, C; Pozo, M J; Martin-Cano, F E; Vara, E; Fernández-Tresguerres, J A; Camello, P J

    2012-06-01

    Aging is associated to oxidative damage and alterations in inflammatory and apoptotic pathways. Aging impairs secretion of several hormones, including melatonin and estrogens. However, the mechanisms involved in aging of smooth muscle are poorly known. We have studied the changes induced by aging in the colonic smooth muscle layer of female rats and the protective effect of hormonal therapy. We used young, aged, and ovariectomized aged female rats. Two groups of ovariectomized rats (22 months old) were treated either with melatonin or with estrogen for 10 weeks before sacrifice. Aging induced oxidative imbalance, evidenced by H(2)O(2) accumulation, lipid peroxidation, and decreased catalase activity. The oxidative damage was enhanced by ovariectomy. In addition, aged colonic muscle showed enhanced expression of the pro-inflammatory enzyme cyclooxygenase 2. Expression of the activated forms of caspases 3 and 9 was also enhanced in aged colon. Melatonin and estrogen treatment prevented the oxidative damage and the activation of caspases. In conclusion, aging of colonic smooth muscle induces oxidative imbalance and activation of apoptotic and pro-inflammatory pathways. Hormonal therapy has beneficial effects on the oxidative and apoptotic changes associated to aging in this model.

  11. Diet-induced ketosis improves cognitive performance in aged rats.

    PubMed

    Xu, Kui; Sun, Xiaoyan; Eroku, Bernadette O; Tsipis, Constantinos P; Puchowicz, Michelle A; LaManna, Joseph C

    2010-01-01

    Aging is associated with increased susceptibility to hypoxic/ischemic insult and declines in behavioral function which may be due to attenuated adaptive/defense responses. We investigated if diet-induced ketosis would improve behavioral performance in the aged rats. Fischer 344 rats (3- and 22-month-old) were fed standard (STD) or ketogenic (KG) diet for 3 weeks and then exposed to hypobaric hypoxia. Cognitive function was measured using the T-maze and object recognition tests. Motor function was measured using the inclined-screen test. Results showed that KG diet significantly increased blood ketone levels in both young and old rats. In the aged rats, the KG diet improved cognitive performance under normoxic and hypoxic conditions; while motor performance remained unchanged. Capillary density and HIF-1alpha levels were elevated in the aged ketotic group independent of hypoxic challenge. These data suggest that diet-induced ketosis may be beneficial in the treatment of neurodegenerative conditions.

  12. The anti-osteoporotic effect of Eurycoma Longifolia in aged orchidectomised rat model.

    PubMed

    Shuid, Ahmad Nazrun; Abu Bakar, Mohd Firdaus; Abdul Shukor, Tajul Ariff; Muhammad, Norliza; Mohamed, Norazlina; Soelaiman, Ima Nirwana

    2011-09-01

    Osteoporosis in elderly men is becoming an important health issue with the aging society. Elderly men with androgen deficiency are exposed to osteoporosis and can be treated with testosterone replacement. In this study, Eurycoma longifolia (EL), a plant with androgenic effects, was supplemented to an androgen-deficient osteoporotic aged rat as alternative to testosterone. Aged 12 months old Sprague-Dawley rats were divided into groups of normal control (NC), sham-operated (SO), orchidectomised-control (OrxC), orchidectomised and supplemented with EL (Orx + El) and orchidectomised and given testosterone (Orx + T). After 6 weeks of treatment, serum osteocalcin, serum terminal C-telopeptide Type 1 collagen (CTX) and the fourth lumbar bone calcium were measured. There were no significant differences in the osteocalcin levels before and after treatment in all the groups. The CTX levels were also similar for all the groups before treatment. However, after treatment, orchidectomy had caused significant elevation of CTX compared to normal control rats. Testosterone replacements in orchidectomised rats were able to prevent the rise of CTX. Orchidectomy had also reduced the bone calcium level compared to normal control rats. Both testosterone replacement and EL supplementation to orchidectomised rats were able to maintain the bone calcium level, with the former showing better effects. As a conclusion, EL prevented bone calcium loss in orchidectomised rats and therefore has the potential to be used as an alternative treatment for androgen deficient osteoporosis.

  13. An Observational Assessment Method for Aging Laboratory Rats

    PubMed Central

    Phillips, Pamela M; Jarema, Kimberly A; Kurtz, David M; MacPhail, Robert C

    2010-01-01

    The rapid growth of the aging human population highlights the need for laboratory animal models to study the basic biologic processes of aging and susceptibility to disease, drugs, and environmental pollutants. Methods are needed to evaluate the health of aging animals over time, particularly methods for efficiently monitoring large research colonies. Here we describe an observational assessment method that scores appearance, posture, mobility, and muscle tone on a 5-point scale that can be completed in about 1 min. A score of 1 indicates no deterioration, whereas a score of 5 indicates severe deterioration. Tests were applied to male Brown Norway rats between 12 and 36 mo of age (n = 32). The rats were participating concurrently in experiments on the behavioral effects of intermittent exposure (approximately every 4 mo) to short-acting environmental chemicals. Results demonstrated that aging-related signs of deterioration did not appear before 18 mo of age. Assessment scores and variability then increased with age. Body weights increased until approximately 24 mo, then remained stable, but decreased after 31 mo for the few remaining rats. The incidence of death increased slightly from 20 to 28 mo of age and then rose sharply; median survival age was approximately 30 mo, with a maximum of 36 mo. The results indicate that our observational assessment method supports efficient monitoring of the health of aging rats and may be useful in studies on susceptibility to diseases, drugs, and toxicants during old age. PMID:21205442

  14. Hypolipidemic effect of β-caryophyllene to treat hyperlipidemic rats.

    PubMed

    Baldissera, Matheus D; Souza, Carine F; Grando, Thirssa H; Doleski, Pedro H; Boligon, Aline A; Stefani, Lenita M; Monteiro, Silvia G

    2017-02-01

    The aim of this study was to evaluate the effect of β-caryophyllene on hypercholesterolemia using a model of hyperlipidemia induced by Triton WR-1339 in rats, as well as its possible effect on hepatic antioxidant enzymes. Thus, total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured in serum, while reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), hepatic 3-hydroxy-3-methylglutayl coenzyme A (HMG-CoA) reductase, superoxide dismutase (SOD), and catalase (CAT) activities were measured in the hepatic tissue. In addition, seric concentrations of β-caryophyllene were measured to perform correlation studies. Serum samples from hypercholesterolemic rats show higher (p < 0.05) levels of total cholesterol, triglycerides, and LDL cholesterol, and lower (p < 0.05) levels of HDL cholesterol compared to non-hypercholesterolemic rats. β-Caryophyllene treatment reduced (p < 0.05) the levels of total cholesterol, triglycerides and LDL cholesterol, similar to the reference drug simvastatin. However, HDL cholesterol levels did not increase with the treatment. β-Caryophyllene treatment was able to inhibit the HMG-CoA reductase activity, as well as to prevent the increase on ROS and TBARS levels, and ameliorate the antioxidant system. In summary, our findings demonstrated that β-caryophyllene has hypolipidemic effect via inhibition of the hepatic HMG-CoA reductase, like the standard drug simvastatin, and this inhibition suggests a possible mechanism of hypolipidemic action. Thus, our results indicate that β-caryophyllene can be used to treat dyslipidemic diseases because it exerts a similar effect as the reference drug, protecting the liver against lipid damage and improving the hepatic antioxidant defense system.

  15. Copper and zinc in CCl/sub 4/ treated rats

    SciTech Connect

    Loyke, H.F.

    1984-04-01

    The role of two trace metals, copper and zinc, are important in maintaining blood pressure and the effect of carbon tetrachloride (CCl/sub 4/) has been found to be a depressor. Experimental renal hypertension has been reduced to normotension after multiple subcutaneous injections of CCl/sub 4/. By dose adjustment, the degree of liver damage has been reduced to a level of mild to moderate degree of fatty metamorphosis of the liver. It is possible that the depressor effect could be mediated by imbalance of copper and/or zinc. In the present study, copper and zinc levels were determined following CCl/sub 4/ treatment. The present work used normotensive rats treated for periods, which, in hypertensive animals, caused the blood pressure to fall.

  16. NEUROMODULATORY EFFECTS OF THYMOQUINONE IN EXTENUATING OXIDATIVE STRESS IN CHLORPROMAZINE TREATED RATS.

    PubMed

    Safhi, Mohammed Mohsin

    2016-01-01

    The present study was undertaken to evaluate the possible protective effect of thymoquinone on chlorpromazine induced catalepsy, locomotor activity and cerebral oxidative stress in rats. The rats were divided into four groups, each group containing eight animals. The animals were evaluated after repeated administration of chlorpromazine (CPZ) 30 min before the administration of thymoquinone (TQ) for 21 days. Catalepsy was assessed using block method whereas the locomotor activity was assessed using acceleratory rotarod and actophotometer. Markers of oxidative stress parameters (LPO, GSH, GPx, GR, GST and CAT) were evaluated in the brain of rats. The cataleptic scores were significantly increased in CPZ treated rats when compared with normal control rats. Oral administration of TQ (5 and 10 mg/kg) significantly decreased cataleptic scores when compared with chlorpromazine (CPZ) treated rats. The muscle coordination and spontaneous locomotor activity was significantly decreased in CPZ treated rats when compared with normal control rats. Treatment with TQ significantly improved the muscle coordination and spontaneous locomotor activity when compared with CPZ treated rats. TQ treated rats significantly reduced the elevated levels of lipid peroxidation (LPO), increased levels of antioxidant enzymes i.e., reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and catalase (CAT) when compared with CPZ treated rats. The results clearly suggest that supplementation with TQ can be used to preclude CPZ induced extrapyramidal side effects and may find a role in reducing the oxidative stress.

  17. A study of remote spatial memory in aged rats.

    PubMed

    Winocur, Gordon; Moscovitch, Morris; Rosenbaum, R Shayna; Sekeres, Melanie

    2010-01-01

    The effect of aging on remote spatial memory was tested in a group of 2-year-old rats (VR-O) that, as young adults, were reared for 3 months in a complex 'village' environment. The VR-O rats exhibited significant savings in finding the locations of specific reward compartments within the village, relative to a group of old rats (VNR-O) experiencing the village for the first time. The VNR-O rats were also impaired, relative to naive young rats, in learning the reward locations. Probe tests indicated that the VR-O rats retained allocentric spatial memory for the environment and were not using sensory or other non-spatial cues to guide behaviour. Overall, the results indicate that the aged rats experienced a decline in the ability to learn and remember detailed spatial relationships and that the VR-O group's successful performance on the remote spatial memory test was guided by a form of schematic memory that captured the essential features of the village environment. The potential contribution of the hippocampus to the pattern of lost and spared learning and memory observed in the aged rats was discussed.

  18. The Laboratory Rat: Relating Its Age With Human's

    PubMed Central

    Sengupta, Pallav

    2013-01-01

    By late 18th or early 19th century, albino rats became the most commonly used experimental animals in numerous biomedical researches, as they have been recognized as the preeminent model mammalian system. But, the precise correlation between age of laboratory rats and human is still a subject of debate. A number of studies have tried to detect these correlations in various ways, But, have not successfully provided any proper association. Thus, the current review attempts to compare rat and human age at different phases of their life. The overall findings indicate that rats grow rapidly during their childhood and become sexually mature at about the sixth week, but attain social maturity 5-6 months later. In adulthood, every day of the animal is approximately equivalent to 34.8 human days (i.e., one rat month is comparable to three human years). Numerous researchers performed experimental investigations in albino rats and estimated, in general, while considering their entire life span, that a human month resembles every-day life of a laboratory rat. These differences signify the variations in their anatomy, physiology and developmental processes, which must be taken into consideration while analyzing the results or selecting the dose of any research in rats when age is a crucial factor. PMID:23930179

  19. Effects of vasopressin on electrolyte transport across isolated colon from normal and dexamethasone-treated rats.

    PubMed Central

    Bridges, R J; Rummel, W; Wollenberg, P

    1984-01-01

    Vasopressin enhanced the absorption of Na+ and Cl- across the short-circuited colon descendens from normal rats. This effect of vasopressin results from an increase in the mucosal to serosal movement of Na+ and Cl- and a decrease in the serosal to mucosal movement of Cl- and was accompanied with a decrease in the short-circuit current (ISC). Neither the base-line absorption of Na+ and Cl-, the vasopressin-induced increase in Na+ and Cl- absorption nor the decrease in ISC were inhibited by amiloride in the colon from normal rats. Colon descendens from rats treated for 3 days with dexamethasone had remarkably higher transmural potential difference (p.d.), tissue conductance (Gt) and ISC. The absorption of Na+ across the short-circuited colon descendens from dexamethasone-treated rats was increased 3-fold when compared to colon from normal rats. The absorption of Cl- in normal rats was reversed to Cl- secretion in treated rats. Amiloride rapidly and reversibly decreased the p.d., Gt and ISC in colon from dexamethasone-treated rats. The transport of Na+ was nearly completely inhibited by amiloride in treated rats. In contrast to its enhancing effects on Na+ absorption in colon from normal rats vasopressin did not enhance Na+ absorption in colon from dexamethasone-treated rats. This enhancement of Cl- absorption by vasopressin was retained in colon from treated rats. This enhancement of Cl- transport was due solely to a decrease in the serosal to mucosal movement of Cl- and was accompanied with a decrease in ISC and Gt. The results support the hypothesis that vasopressin causes inhibition of the electrogenic secretion of Cl- in colon from dexamethasone-treated rats. Furthermore, the results suggest that the increase in the mucosal to serosal movement of Na+ and Cl- and the decrease in the serosal to mucosal movement of Cl- in colon from normal rats are caused by independent effects of vasopressin. PMID:6491990

  20. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2017-01-12

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  1. Locomotion, physical development, and brain myelination in rats treated with ionizing radiation in utero

    SciTech Connect

    Zaman, M.S.

    1989-01-01

    Effects of ionizing radiation on the emergence of locomotion skill and some physical development parameters were studied in laboratory rats (Fisher F-344 inbred strain). Rats were treated with 3 different doses of radiation (150 R, 15 R, and 6.8 R) delivered on the 20th day of the prenatal life. Results indicated that relatively moderate (15 R) to high (150 R) doses of radiation have effects on certain locomotion and physical development parameters. Exposure to 150 R affected pivoting, cliff-avoidance, upper jaw tooth eruption, body weight, and organs, such as brain, cerebral cortex, ovary, kidney, heart and spleen weights. Other parameters, such as negative geotaxis, eye opening, and lower jaw tooth eruption appeared to be affected in the 150 R treated animals. Exposure to 15 R affected pivoting and cliff-avoidance parameters. The cerebral cortex weight of the 15 R treated animals was found to be reduced at the age of day 30. Exposure to 6.8 R had no adverse effects on these parameters. Prenatal exposure to 150 R of radiation reduced the cerebral cortex weight by 22.07% at 30 days of age, and 20.15% at 52 days of age which caused a reduction in cerebral cortex myelin content by 20.16, and 22.89% at the ages of day 30 and day 52 respectively. Exposure to 150 R did not affect the myelin content of the cerebellum or the brain stem; or the myelin concentration (mg myelin/g brain tissue weight) of the cerebral cortex, cerebellum, and the brain stem. Exposure to 15 R, and 6.8 R did not affect either the myelin content or the myelin concentration of these brain areas.

  2. Strain differences in urinary factors that promote calcium oxalate crystal formation in the kidneys of ethylene glycol-treated rats.

    PubMed

    Li, Yan; McMartin, Kenneth E

    2009-05-01

    Ethylene glycol (EG)-induced hyperoxaluria is the most commonly employed experimental regimen as an animal model of calcium oxalate (CaOx) stone formation. The variant sensitivity to CaOx among different rat strains has not been fully explored, although the Wistar rat is known to accumulate more CaOx in kidney tissue after low-dose EG exposure than in the Fischer 344 (F344) rats. Supersaturation of CaOx in tubular fluid contributes to the amount of CaOx crystal formation in the kidney. We hypothesized that the urinary supersaturation of CaOx in Wistar rats is higher than that of F344 rats, thereby allowing for greater CaOx crystal deposition in the Wistar rat. Age-matched male Wistar and F344 rats were treated with 0.75% EG or drinking water for 8 wk. Twenty-four-hour urine was collected at 0, 2, 4, 6, and 8 wk for analysis of key electrolytes to calculate the CaOx supersaturation. Plasma oxalate level was also measured. Our data confirmed the different sensitivity to renal toxicity from EG between the two rat strains (Wistar > F344). After EG treatment, the plasma oxalate level and urine oxalate excretion were markedly greater in the Wistar rats than in the F344 rats, while urine calcium was slightly decreased in Wistars. Thus, the CaOx supersaturation in urine of Wistar rats was higher, which led to a greater crystal deposition in kidney in Wistar rats. These studies suggest that during EG treatment, changes in urine electrolytes and in CaOx supersaturation occur to a greater extent in the Wistar rat, in agreement with its greater sensitivity to EG toxicity.

  3. Tocotrienol improves learning and memory deficit of aged rats

    PubMed Central

    Kaneai, Nozomi; Sumitani, Kazumi; Fukui, Koji; Koike, Taisuke; Takatsu, Hirokatsu; Urano, Shiro

    2016-01-01

    To define whether tocotrienol (T-3) improves cognitive deficit during aging, effect of T-3 on learning and memory functions of aged rats was assessed. It was found that T-3 markedly counteracts the decline in learning and memory function in aged rats. Quantitative analysis of T-3 content in the rat brain showed that the aged rats fed T-3 mixture-supplemented diet revealed the transport of α- and γ-T-3 to the brain. In contrast, normal young rats fed the same diet did not exhibit brain localization. Furthermore, the T-3 inhibited age-related decreases in the expression of certain blood brain barrier (BBB) proteins, including caludin-5, occludin and junctional adhesion molecule (JAM). It was found that the activation of the cellular proto-oncogene c-Src and extracellular signal-regulated protein kinase (ERK), in the mitogen-activated protein kinase (MAPK) cell signaling pathway for neuronal cell death, was markedly inhibited by T-3. These results may reveal that aging induces partial BBB disruption caused by oxidative stress, thereby enabling the transport of T-3 through the BBB to the central nervous system, whereupon neuronal protection may be mediated by inhibition of c-Src and/or ERK activation, resulting in an improvement in age-related cognitive deficits. PMID:27013777

  4. No effect of testosterone on behavior in aged Wistar rats

    PubMed Central

    Borbélyová, Veronika; Domonkos, Emese; Bábíčková, Janka; Tóthová, Ľubomíra; Bosý, Martin; Hodosy, Július; Celec, Peter

    2016-01-01

    In men, aging is accompanied by a gradual decline in androgen secretion. Studies suggest beneficial effects of endogenous and exogenous testosterone on affective behavior and cognitive functions. The aim of this study was to describe behavioral and cognitive sex differences and to analyze the effects of long-term androgen deficiency in aged male rats. Thirty-months old rats divided into three groups (males, females and males gonadectomized as young adults) underwent a battery of behavioral tests assessing locomotor activity, anxiety, memory, anhedonia, sociability and depression-like behavior. No major effect of gonadectomy was found in any of the analyzed behavioral measures in male rats. The only consistent sex difference was confirmed in depression-like behavior with longer immobility time observed in males. In an interventional experiment, a single dose of testosterone had no effect on gonadectomized male and female rats in the forced swim test. In contrast to previous studies this comprehensive behavioral phenotyping of aged rats revealed no major role of endogenous testosterone. Based on our results long-term hypogonadism does not alter the behavior of aged male rats, neither does acute testosterone treatment. Whether these findings have any consequences on androgen replacement therapy in aged men remains to be elucidated. PMID:27852981

  5. Effects of ageing and pharmacological hypothyroidism on pituitary-thyroid axis of Dutch-Miranda and Wistar rats.

    PubMed

    Moreira, D G; Marassi, M P; Corrêa da Costa, V M; Carvalho, D P; Rosenthal, D

    2005-04-01

    To evaluate the ability of the aged rat pituitary to increase TSH secretion in response to major decreases in serum thyroid hormones, hypothyroidism was induced by methimazole in young and old, male and female, Dutch-Miranda and Wistar rats. Before MMI-treatment there were no differences in serum TSH of young and old rats, but serum T(4) was significantly decreased in aged rats from both genders and strains, while serum T(3) was significantly decreased in aged male rats from both strains, and in old Wistar females. MMI treatment significantly decreased serum T(4) and T(3) in all treated animals, and progressively increased serum TSH in both male and female rats, but the increase was significantly smaller in the elder rats. The pituitary TSH content was higher in Wistar than in Dutch-Miranda rats, of both genders, and was not significantly affected by age. MMI treatment decreased the pituitary TSH in both young and old Dutch-Miranda rats, but in the Wistar strain only the old females had a significant decrease. Our results show that the ability of the pituitary thyrotrophs to increase hormonal secretion in response to decreased levels of thyroid hormones is impaired in the old rat, even when the thyroid hormone levels are dramatically reduced.

  6. Chronic Ampakine Treatments Stimulate Dendritic Growth and Promote Learning in Middle-Aged Rats

    PubMed Central

    Lauterborn, Julie C.; Palmer, Linda C.; Jia, Yousheng; Pham, Danielle T.; Hou, Bowen; Wang, Weisheng; Trieu, Brian H.; Cox, Conor D.; Kantorovich, Svetlana

    2016-01-01

    Positive allosteric modulators of AMPA-type glutamate receptors (ampakines) have been shown to rescue synaptic plasticity and reduce neuropathology in rodent models of cognitive disorders. Here we tested whether chronic ampakine treatment offsets age-related dendritic retraction in middle-aged (MA) rats. Starting at 10 months of age, rats were housed in an enriched environment and given daily treatment with a short half-life ampakine or vehicle for 3 months. Dendritic branching and spine measures were collected from 3D reconstructions of Lucifer yellow-filled CA1 pyramidal cells. There was a substantial loss of secondary branches, relative to enriched 2.5-month-old rats, in apical and basal dendritic fields of vehicle-treated, but not ampakine-treated, 13-month-old rats. Baseline synaptic responses in CA1 were only subtly different between the two MA groups, but long-term potentiation was greater in ampakine-treated rats. Unsupervised learning of a complex environment was used to assess treatment effects on behavior. Vehicle- and drug-treated rats behaved similarly during a first 30 min session in the novel environment but differed markedly on subsequent measures of long-term memory. Markov sequence analysis uncovered a clear increase in the predictability of serial movements between behavioral sessions 2 and 3 in the ampakine, but not vehicle, group. These results show that a surprising degree of dendritic retraction occurs by middle age and that this can be mostly offset by pharmacological treatments without evidence for unwanted side effects. The functional consequences of rescue were prominent with regard to memory but also extended to self-organization of behavior. SIGNIFICANCE STATEMENT Brain aging is characterized by a progressive loss of dendritic arbors and the emergence of impairments to learning-related synaptic plasticity. The present studies show that dendritic losses are evident by middle age despite housing in an enriched environment and can be

  7. Prolactin and aging: X-irradiated and estrogen-induced rat mammary tumorigenesis

    SciTech Connect

    Ito, A.; Naito, M.; Watanabe, H.; Yokoro, K.

    1984-07-01

    Both sexes of inbred WF rats at either 8 or 28-60 weeks of age were exposed to 200 rad whole-body radiation, 2.5 or 5.0 mg 17 beta-estradiol (E2), or both agents The female rats treated with E2 alone or with both X-rays and E2 at 8 weeks of age showed a high incidence of mammary carcinomas (MCA), a large increase in pituitary weight, and a rise in serum prolactin (PRL) levels. However, the same treatments to males did not induce MCA despite a moderate increase in both pituitary weight and serum PRL. Ovariectomy prior to E2 treatment failed to modify the occurrence of MCA or pituitary tumors. When X-rays and E2 were given to female rats at 28-60 weeks of age, pituitary weight, serum PRL levels, and the incidence of MCA were unaffected. When the E2 pellet was kept for the first 24 weeks and withdrawn during the last 12 weeks, the incidence of MCA, pituitary weight, and serum PRL was low. It was concluded that: 1) the pituitary glands of young female rats were susceptible to E2 treatment but were insensitive in older females, and 2) the occurrence of MCA in female rats appeared to be promoted by elevated PRL levels secreted by E2-induced pituitary tumors. Mammary tissue of male rats was less sensitive to PRL levels in the development of MCA.

  8. Tart cherries improve working memory in aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aged rats show impaired performance on cognitive tasks that require the use of spatial learning and memory. In previous studies, we have shown the beneficial effects of various dark-colored berry fruits (blueberries, strawberries, and blackberries) in reversing age-related deficits in behavioral and...

  9. Red raspberries can improve motor function in aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Many foods rich in antioxidant and anti-inflammatory compounds have been shown to increase health and reduce markers of aging. A number of berry fruits high in polyphenols are known to ameliorate age-related declines in cellular, cognitive and behavioral function in rats. OBJECTIVES: Thi...

  10. Acai fruit improves motor and cognitive function in aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aged rats show impaired performance on motor and cognitive tasks that require the use of spatial learning and memory. In previous studies, we have shown the beneficial effects of various berry fruits (blueberries, strawberries, and blackberries) in reversing age-related deficits in behavioral and ne...

  11. Toluene effects on the motor activity of adolescent, young-adult, middle-age and senescent male Brown Norway rats.

    PubMed

    MacPhail, R C; Farmer, J D; Jarema, K A

    2012-01-01

    Life stage is an important risk factor for toxicity. Children and aging adults, for example, are more susceptible to certain chemicals than are young adults. In comparison to children, relatively little is known about susceptibility in older adults. Additionally, few studies have compared toxicant susceptibility across a broad range of life stages. Results are presented for behavioral evaluations of male Brown Norway rats obtained as adolescents (1 month), or young (4 months), middle-age (12 months) and senescent (24 months) adults. Motor activity was evaluated in photocell devices during 30-min sessions. Age-related baseline characteristics and sensitivity to toluene (0, 300, 650, or 1000mg/kg, p.o.) were determined. In Experiment 1, young-adult, middle-age and senescent rats were treated with corn-oil vehicle before five weekly test sessions. Baselines of horizontal and vertical activity decreased with age, but each age-group's averages remained stable across weeks of testing. Baseline activity of older rats was more variable than that of the young adults; older rats were also more variable individually from week to week. Toluene (1000mg/kg) increased horizontal activity proportionately more in senescent rats (ca. 300% of control) than in middle-age or young-adult rats (ca.145-175% of control). Experiment 2 established toluene dose-effect functions in individual adolescent, young-adult, middle-age and senescent rats; each rat received all treatments, counterbalanced across four weekly sessions. Toluene produced dose-related increases in horizontal activity that increased proportionately with age. Experiment 3 replicated the effects of toluene (1000mg/kg) in Experiment 1, showing that toluene-induced increases in horizontal activity were greatest in the oldest rats. Collectively, the results show that aging increased susceptibility to toluene and also increased variability in toluene response. Given the rapid growth of the aged population, further research is

  12. Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

    PubMed

    Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

    2013-06-01

    Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

  13. Protective effect of supercritical fluid rosemary extract, Rosmarinus officinalis, on antioxidants of major organs of aged rats.

    PubMed

    Posadas, S J; Caz, V; Largo, C; De la Gándara, B; Matallanas, B; Reglero, G; De Miguel, E

    2009-01-01

    Rosemary leaves, "Rosmarinus officinalis", possess a variety of antioxidant, anti-tumoral and anti-inflammatory bioactivities. We hypothesized that rosemary extract could enhance antioxidant defenses and improve antioxidant status in aged rats. This work evaluates whether supplementing their diet with supercritical fluid (SFE) rosemary extract containing 20% antioxidant carnosic acid (CA) reduces oxidative stress in aged rats. Aged Wistar rats (20 months old) were included in the study. Rats were fed for 12 weeks with a standard kibble (80%) supplemented with turkey breast (20%) containing none or one of two different SFE rosemary concentrations (0.2% and 0.02%). After sacrifice, tissue samples were collected from heart and brain (cortex and hippocampus). Enzyme activities of catalase (CAT), glutathione peroxidase (GPX), superoxide dismutase (SOD) and nitric oxide synthase (NOS) were quantitatively analyzed. Lipid peroxidation and levels of reactive oxygen species (ROS) were also determined. Rosemary decreased lipid peroxidation in both brain tissues. The levels of catalase activities in heart and cortex were decreased in the rosemary-treated groups. The SFE rosemary-treated rats presented lower NOS levels in heart and lower ROS levels in hippocampus than the control rats. Supplementing the diet of aged rats with SFE rosemary extract produced a decrease in antioxidant enzyme activity, lipid peroxidation and ROS levels that was significant for catalase activity in heart and brain, NOS in heart, and LPO and ROS levels in different brain tissues. These observations suggest that the rosemary supplement improved the oxidative stress status in old rats.

  14. Long-term visual object recognition memory in aged rats.

    PubMed

    Platano, Daniela; Fattoretti, Patrizia; Balietti, Marta; Bertoni-Freddari, Carlo; Aicardi, Giorgio

    2008-04-01

    Aging is associated with memory impairments, but the neural bases of this process need to be clarified. To this end, behavioral protocols for memory testing may be applied to aged animals to compare memory performances with functional and structural characteristics of specific brain regions. Visual object recognition memory can be investigated in the rat using a behavioral task based on its spontaneous preference for exploring novel rather than familiar objects. We found that a behavioral task able to elicit long-term visual object recognition memory in adult Long-Evans rats failed in aged (25-27 months old) Wistar rats. Since no tasks effective in aged rats are reported in the literature, we changed the experimental conditions to improve consolidation processes to assess whether this form of memory can still be maintained for long term at this age: the learning trials were performed in a smaller box, identical to the home cage, and the inter-trial delays were shortened. We observed a reduction in anxiety in this box (as indicated by the lower number of fecal boli produced during habituation), and we developed a learning protocol able to elicit a visual object recognition memory that was maintained after 24 h in these aged rats. When we applied the same protocol to adult rats, we obtained similar results. This experimental approach can be useful to study functional and structural changes associated with age-related memory impairments, and may help to identify new behavioral strategies and molecular targets that can be addressed to ameliorate memory performances during aging.

  15. Age exacerbates chronic catecholamine-induced impairments in contractile reserve in the rat.

    PubMed

    Liles, John T; Ida, Kevin K; Joly, Kristin M; Chapo, Joseph; Plato, Craig F

    2011-08-01

    Contractile reserve decreases with advancing age and chronic isoproterenol (ISO) administration is a well-characterized model of cardiac hypertrophy known to impair cardiovascular function. This study evaluated whether nonsenescent, mature adult rats are more susceptible to detrimental effects of chronic ISO administration than younger adult rats. Rats received daily injections of ISO (0.1 mg/kg sc) or vehicle for 3 wk. ISO induced a greater impairment in contractile reserve [maximum of left ventricular pressure development (Δ+dP/dt(max))] in mature adult ISO-treated (MA-ISO) than in young adult ISO-treated rats (YA-ISO) in response to infusions of mechanistically distinct inotropes (digoxin, milrinone; 20-200 μl·kg(-1)·min(-1)), while basal and agonist-induced changes in heart rate and systolic arterial pressure (SAP) were not different across groups. ISO decreased expression of the calcium handling protein, sarco(endo)plasmic reticulum Ca(2+)-ATPase-2a, in MA-ISO compared with YA, YA-ISO, and MA rats. Chronic ISO also induced greater increases in cardiac hypertrophy [left ventricular (LV) index: 33 ± 3 vs. 22 ± 5%] and caspase-3 activity (34 vs. 5%) in MA-ISO relative to YA-ISO rats. Moreover, β-myosin heavy chain (β-MHC) and atrial natriuretic factor (ANF) mRNA expression was significantly elevated in MA-ISO. These results demonstrate that adult rats develop greater impairments in systolic performance than younger rats when exposed to chronic catecholamine excess. Reduced contractile reserve may result from calcium dysregulation, increased caspase-3 activity, or increased β-MHC and ANF expression. Although several studies report age-related declines in systolic performance in older and senescent animals, the present study demonstrates that catecholamine excess induces reductions in systolic performance significantly earlier in life.

  16. Asporin and the mineralization process in fluoride-treated rats.

    PubMed

    Houari, Sophia; Wurtz, Tilmann; Ferbus, Didier; Chateau, Danielle; Dessombz, Arnaud; Berdal, Ariane; Babajko, Sylvie

    2014-06-01

    Microarray analysis of odontoblastic cells treated with sodium fluoride has identified the asporin gene as a fluoride target. Asporin is a member of the small leucine-rich repeat proteoglycan/protein (SLRP) family that is believed to be important in the mineralization process. In this study, asporin expression and distribution were investigated by systematic analysis of dentin and enamel, with and without fluoride treatment. Specific attention was focused on a major difference between the two mineralized tissues: the presence of a collagenous scaffold in dentin, and its absence in enamel. Normal and fluorotic, continually growing incisors from Wistar rats treated with 2.5 to 7.5 mM sodium fluoride (NaF) were studied by immunochemistry, in situ hybridization, Western blotting, and RT-qPCR. Asporin was continuously expressed in odontoblasts throughout dentin formation as expected. Asporin was also found, for the first time, in dental epithelial cells, particularly in maturation-stage ameloblasts. NaF decreased asporin expression in odontoblasts and enhanced it in ameloblasts, both in vivo and in vitro. The inverse response in the two cell types suggests that the effector, fluoride, is a trigger that elicits a cell-type-specific reaction. Confocal and ultrastructural immunohistochemistry evidenced an association between asporin and type 1 collagen in the pericellular nonmineralized compartments of both bone and dentin. In addition, transmission electron microscopy revealed asporin in the microenvironment of all cells observed. Thus, asporin is produced by collagen-matrix-forming and non-collagen-matrix-forming cells but may have different effects on the mineralization process. A model is proposed that predicts impaired mineral formation associated with the deficiency and excess of asporin.

  17. Effect of Eurycoma longifolia Jack on orientation activities in middle-aged male rats.

    PubMed

    Ang, H H; Lee, K L

    2002-12-01

    The effects of various fractions of Eurycoma longifolia Jack were studied on the orientation activities of the inbred, adult middle-aged Sprague-Dawley rats, 9 months old and retired breeders towards the receptive females (anogenital sniffing, licking, mounting), the environment (climbing, raring, exploration), themselves (nongenital grooming, genital grooming) and mobility (restricted, unrestricted) after treating these subjects twice daily for 10 days. Results showed that subjects treated with 800 mg/kg of E. longifolia Jack increased orientation activities towards the receptive females (anogenital sniffing, licking and mounting), increased genital grooming towards themselves and restricted movements to a particular area of the cage but decreased interest in the external environment (climbing, raring, exploration) as compared with the controls during the investigation period. In conclusion, this study gives further evidences that different fractions of E. longifolia Jack modified the orientation activities of the middle-aged male rats.

  18. Age-related changes in conditioned flavor preference in rats.

    PubMed

    Renteria, Adam F; Silbaugh, Bryant C; Tolentino, Jerlyn C; Gilbert, Paul E

    2008-03-17

    Age-related changes have been documented in regions of the brain shown to process reward information. However, few studies have examined the effects of aging on associative memory for reward. The present study tested 7- and 24-month-old rats on a conditioned flavor preference task. Half of the rats in each age group received an unsweetened grape-flavored solution (CS-) on odd-numbered days and a sweetened cherry-flavored solution (CS+) on even-numbered days. The remaining rats in each age group received a sweetened grape-flavored solution (CS+) on odd-numbered days and an unsweetened cherry-flavored solution (CS-) on even-numbered days. During the acquisition phase of testing, the designated solution (CS+ or CS-) was presented to each rat for 15 min daily across six consecutive days. On the preference phase, each rat received unsweetened cherry and unsweetened grape-flavored solutions simultaneously for 15 min daily across four consecutive days. The 7-month-old rats showed a significant preference for the flavor that was previously sweetened during the acquisition phase (CS+) compared to the previously unsweetened solution (CS-) when the two unsweetened solutions were presented simultaneously during the preference phase of testing. In contrast, the 24-month-old rats did not show a preference and consumed roughly equal amounts of the previously sweetened (CS+) and unsweetened (CS-) solutions. Thus, the data suggest that the ability to form flavor-reward associations declines with increasing age, resulting in impaired conditioned flavor preference.

  19. Functional characterization of cutaneous mechanoreceptor properties in aged rats.

    PubMed

    Reinke, H; Dinse, H R

    1996-10-04

    We investigated the effects of aging on rapidly (RA) and slowly adapting (SA) cutaneous mechanoreceptors by means of single fiber recordings and evoked sensory nerve action potentials (EAPs) of the hindpaw of the N. plantaris in adult and old Wistar rats. EAPs revealed comparable shapes and amplitudes in all animals of all age groups. In old rats, conduction velocities were slightly (15%) lengthened. The mechanoreceptor composition was different from adults, resulting in a lower number of SA units. We were not able to detect significant differences in the sizes of receptive fields and in the thresholds between old and adult animals. The absence of significant age-related changes in the cutaneous periphery of the hindpaw is discussed in respect to the previously reported alterations of cortical receptive field properties in old rats.

  20. GM1 enhances dopaminergic markers in the brain of aged rats.

    PubMed

    Goettl, V M; Zhang, H; Burrows, A C; Wemlinger, T A; Neff, N H; Hadjiconstantinou, M

    2003-10-01

    A number of presynaptic markers are compromised in the dopaminergic neurons of aged Sprague-Dawley rats (22 months old) compared with young rats (3 months old). Indeed, in the striatum of the aged rats there is a diminished capacity to transport dopamine (DA), to bind the dopamine transporter (DAT) marker mazindol, to bind the vesicular monoamine transporter 2 (VMAT2) marker dihydrotetrabenazine, and to release DA under basal conditions or after induction by K(+) or amphetamine. Furthermore, the expression of DAT and VMAT2 mRNA in the midbrain is suppressed. GM1 ganglioside, 30 mg/kg ip daily, administered for 30 days, restores the afore-mentioned markers to values approaching those for young rats. Taken together with our published observations that GM1 partially restores tyrosine hydroxylase activity and DA metabolism in aged nigrostriatal and mesoaccumbal neurons and improves their morphology, our work suggests that GM1 might act as a dopaminergic neurotrophic factor in the aged brain and be a useful adjuvant for treating age-associated dopaminergic deficits.

  1. Cross-activation and Detraining Effects of Tongue Exercise in Aged Rats

    PubMed Central

    Schaser, Allison J.; Ciucci, Michelle R.; Connor, Nadine P.

    2015-01-01

    Voice and swallowing deficits can occur with aging. Tongue exercise paired with a swallow may be used to treat swallowing disorders, but may also benefit vocal function due to cross-system activation effects. It is unknown how exercise-based neuroplasticity contributes to behavior and maintenance following treatment. Eighty rats were used to examine behavioral parameters and changes in neurotrophins after tongue exercise paired with a swallow. Tongue forces and ultrasonic vocalizations were recorded before and after training/detraining in young and old rats. Tissue was analyzed for neurotrophin content. Results showed tongue exercise paired with a swallow was associated with increased tongue forces at all ages. Gains diminished after detraining in old rats. Age-related changes in vocalizations, neurotrophin 4 (NT4), and brain derived neurotrophic factor (BDNF) were found. Minimal cross-system activation effects were observed. Neuroplastic benefits were demonstrated with exercise in old rats through behavioral improvements and up-regulation of BDNF in the hypoglossal nucleus. Tongue exercise paired with a swallow should be developed, studied, and optimized in human clinical research to treat swallowing and voice disorders in elderly people. PMID:26477376

  2. Cross-activation and detraining effects of tongue exercise in aged rats.

    PubMed

    Schaser, Allison J; Ciucci, Michelle R; Connor, Nadine P

    2016-01-15

    Voice and swallowing deficits can occur with aging. Tongue exercise paired with a swallow may be used to treat swallowing disorders, but may also benefit vocal function due to cross-system activation effects. It is unknown how exercise-based neuroplasticity contributes to behavior and maintenance following treatment. Eighty rats were used to examine behavioral parameters and changes in neurotrophins after tongue exercise paired with a swallow. Tongue forces and ultrasonic vocalizations were recorded before and after training/detraining in young and old rats. Tissue was analyzed for neurotrophin content. Results showed tongue exercise paired with a swallow was associated with increased tongue forces at all ages. Gains diminished after detraining in old rats. Age-related changes in vocalizations, neurotrophin 4 (NT4), and brain derived neurotrophic factor (BDNF) were found. Minimal cross-system activation effects were observed. Neuroplastic benefits were demonstrated with exercise in old rats through behavioral improvements and up-regulation of BDNF in the hypoglossal nucleus. Tongue exercise paired with a swallow should be developed, studied, and optimized in human clinical research to treat swallowing and voice disorders in elderly people.

  3. Tongue muscle plasticity following hypoglossal nerve stimulation in aged rats

    PubMed Central

    Connor, Nadine P.; Russell, John A.; Jackson, Michelle A.; Kletzien, Heidi; Wang, Hao; Schaser, Allison J.; Leverson, Glen E.; Zealear, David L.

    2012-01-01

    Introduction Age-related decreases in tongue muscle mass and strength have been reported. It may be possible to prevent age-related tongue muscle changes using neuromuscular electrical stimulation (NMES). Our hypothesis was that alterations in muscle contractile properties and myosin heavy chain composition would be found following NMES. Methods Fifty-four young, middle-aged and old Fischer 344/Brown Norway rats were included. Twenty-four rats underwent bilateral electrical stimulation of the hypoglossal nerves for 8 weeks and were compared with control or sham rats. Muscle contractile properties and myosin heavy chain (MHC) in the genioglossus (GG), styloglossus (SG) and hyoglossus (HG) muscles were examined. Results In comparison with unstimulated control rats, we found reduced muscle fatigue, increased contraction and half decay times and increased twitch and tetanic tension. Increased Type I MHC was found, except for GG in old and middle-aged rats. Discussion Transitions in tongue muscle contractile properties and phenotype were found following NMES. PMID:23169566

  4. Reduced ability of calcitriol to promote augmented dopamine release in the lesioned striatum of aged rats.

    PubMed

    Cass, Wayne A; Peters, Laura E

    2017-04-05

    Parkinson's disease (PD) is a progressive and debilitating neurodegenerative disorder that affects over one million people in the United States. Previous studies, carried out in young adult rats, have shown that calcitriol, the active metabolite of vitamin D, can be neuroprotective in 6-hydroxydopamine (6-OHDA) models of PD. However, as PD usually affects older individuals, the ability of calcitriol to promote dopaminergic recovery was examined in lesioned young adult (4 month old), middle-aged (14 month old) and aged (22 month old) rats. Animals were given a single injection of 12 μg 6-OHDA into the right striatum. Four weeks later they were administered vehicle or calcitriol (1.0 μg/kg, s.c.) once a day for eight consecutive days. In vivo microdialysis experiments were carried out three weeks after the calcitriol or vehicle treatments to measure potassium and amphetamine evoked overflow of DA from both the left and right striata. In control animals treated with 6-OHDA and vehicle there were significant reductions in evoked overflow of DA on the lesioned side of the brain compared to the contralateral side. The calcitriol treatments significantly increased evoked overflow of DA from the lesioned striatum in both the young adult and middle-aged rats. However, the calcitriol treatments did not significantly augment DA overflow in the aged rats. Postmortem tissue levels of striatal DA were also increased in the young and middle-aged animals, but not in the aged animals. In the substantia nigra, the calcitriol treatments led to increased levels of DA in all three age groups. Thus, the effects of calcitriol were similar in the young adult and middle-aged animals, but in the aged animals the effects of calcitriol were diminished. These results suggest that calcitriol may help promote recovery of dopaminergic functioning in injured nigrostriatal neurons; however, the effectiveness of calcitriol may be reduced in aging.

  5. The metabolic response to postnatal leptin in rats varies with age and may be litter dependent.

    PubMed

    Granado, M; Diaz, F; Fuente-Martín, E; García-Cáceres, C; Argente, J; Chowen, J A

    2014-06-01

    Hyperleptinemia during postnatal life induces long-term effects on metabolism. However, these effects are controversial as both increased and decreased propensity towards obesity has been reported. To further analyze the effects of chronic neonatal hyperleptinemia on the subsequent metabolic profile, male Wistar rats proceeding from 18 different litters (8 pups/litter) received a daily subcutaneous injection of either saline (10 ml/kg, n=36) or leptin (3 μg/g, n=36) from postnatal day (PND) 2 to PND9. Rats were sacrificed at 10, 40, or 150 days of age. At 10 days of age, leptin treated rats had decreased body weight (p<0.001) and body fat (p<0.05). Leptin levels and glycemia were increased (p<0.01), whereas insulin, total lipids, triglycerides and glycerol levels were decreased (p<0.05). At PND40 rats receiving leptin had increased glycemia (p<0.01) and plasma HDL and LDL levels, but decreased total lipids (p<0.05). At PND150 neonatal leptin treatment induced different effects in rats raised in different litters. Rats from litter 1 had increased body weight (p<0.05), body fat (p<0.01), and plasma leptin (p<0.001), cholesterol (p<0.001), triglyceride (p<0.001), total lipid (p<0.001), LDL (p<0.05), and glycerol (p<0.001) levels. In rats from litter 2 these parameters did not differ from controls. Rats from litter 3 had decreased body weight (p<0.05), visceral fat (p<0.01) and plasma leptin (p<0.001), cholesterol (p<0.001), triglyceride (p<0.001), glycerol (p<0.001), and HDL (p<0.001) levels. In conclusion, the metabolic response to postnatal leptin varies with age, with the response in adulthood being variable and most likely influenced by other factors, including the genetic make-up.

  6. Chronic Oral Administration of the Arginase Inhibitor 2(S)-amino-6-boronohexanoic Acid (ABH) Improves Erectile Function in Aged Rats

    PubMed Central

    Segal, Robert; Hannan, Johanna L.; Liu, Xiaopu; Kutlu, Omer; Burnett, Arthur L.; Champion, Hunter C.; Kim, Jae Hyung; Steppan, Jochen; Berkowitz, Dan E.; Bivalacqua, Trinity J.

    2014-01-01

    Arginase expression and activity have been noted to be heightened in conditions associated with erectile dysfunction, including aging. Previously, arginase inhibition by chronic administration of the arginase inhibitor 2-(S)-amino-6-boronohexanoic acid (ABH) has been shown to improve endothelial dysfunction in aged rats. The objective of this study was to assess whether chronic oral ABH administration affects cavernosal erectile function. Rats were divided into 4 groups: young control, young treated with arginase inhibitor, aged control, and aged treated with arginase inhibitor. Arginase activity was measured and presented as a proportion of young untreated rats. In vivo erectile responses to cavernous nerve stimulation were measured in all cohorts. The cavernous nerve was stimulated with a graded electrical stimulus, and the intracavernosal/ mean arterial pressure ratios and total intracavernosal pressure were recorded. Arginase activity was elevated in the aged rats compared with young controls; however, arginase activity was significantly decreased in aged rats treated with ABH. With the addition of ABH, erectile responses improved in the aged rats (P < .05). Oral inhibition of arginase with ABH results in improved erectile function in aged rats, resulting in erectile hemodynamics similar to young rats. This represents the first documentation of systemic arginase inhibition positively affecting corporal cavernosal function. PMID:22492840

  7. Chronic oral administration of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) improves erectile function in aged rats.

    PubMed

    Segal, Robert; Hannan, Johanna L; Liu, Xiaopu; Kutlu, Omer; Burnett, Arthur L; Champion, Hunter C; Kim, Jae Hyung; Steppan, Jochen; Berkowitz, Dan E; Bivalacqua, Trinity J

    2012-01-01

    Arginase expression and activity have been noted to be heightened in conditions associated with erectile dysfunction, including aging. Previously, arginase inhibition by chronic administration of the arginase inhibitor 2-(S)-amino-6-boronohexanoic acid (ABH) has been shown to improve endothelial dysfunction in aged rats. The objective of this study was to assess whether chronic oral ABH administration affects cavernosal erectile function. Rats were divided into 4 groups: young control, young treated with arginase inhibitor, aged control, and aged treated with arginase inhibitor. Arginase activity was measured and presented as a proportion of young untreated rats. In vivo erectile responses to cavernous nerve stimulation were measured in all cohorts. The cavernous nerve was stimulated with a graded electrical stimulus, and the intracavernosal/mean arterial pressure ratios and total intracavernosal pressure were recorded. Arginase activity was elevated in the aged rats compared with young controls; however, arginase activity was significantly decreased in aged rats treated with ABH. With the addition of ABH, erectile responses improved in the aged rats (P < .05). Oral inhibition of arginase with ABH results in improved erectile function in aged rats, resulting in erectile hemodynamics similar to young rats. This represents the first documentation of systemic arginase inhibition positively affecting corporal cavernosal function.

  8. Oxidative stress induces the decline of brain EPO expression in aging rats.

    PubMed

    Li, Xu; Chen, Yubao; Shao, Siying; Tang, Qing; Chen, Weihai; Chen, Yi; Xu, Xiaoyu

    2016-10-01

    Brain Erythropoietin (EPO), an important neurotrophic factor and neuroprotective factor, was found to be associated with aging. Studies found EPO expression was significantly decreased in the hippocampus of aging rat compared with that of the youth. But mechanisms of the decline of the brain EPO during aging remain unclear. The present study utilized a d-galactose (d-gal)-induced aging model in which the inducement of aging was mainly oxidative injury, to explore underlying mechanisms for the decline of brain EPO in aging rats. d-gal-induced aging rats (2months) were simulated by subcutaneously injecting with d-gal at doses of 50mg·kg(-1), 150mg·kg(-1) and 250mg·kg(-1) daily for 8weeks while the control group received vehicle only. These groups were all compared with the aging rats (24months) which had received no other treatment. The cognitive impairment was assessed using Morris water maze (MWM) in the prepared models, and the amount of β-galactosidase, the lipid peroxidation product malondialdehyde (MDA) level and the superoxide dismutase (SOD) activity in the hippocampus was examined by assay kits. The levels of EPO, EPOR, p-JAK2 and hypoxia-inducible factor-2α (HIF-2α) in the hippocampus were detected by western blot. Additionally, the correlation coefficient between EPO/EPOR expression and MDA level was analyzed. The MWM test showed that compared to control group, the escape latency was significantly extended and the times of crossing the platform was decreased at the doses of 150mg·kg(-1) and 250mg·kg(-1) (p<0.05). Also, the amount of β-galactosidase and the MDA level in the hippocampus were significantly increased but the SOD activity was significantly decreased (p<0.05, 0.01 and 0.01, respectively). Similar to aging rats, the expressions of EPO, EPOR, p-JAK2, and HIF-2αin the brain of d-gal-treated rats were significantly decreased (p<0.05) at 150mg·kg(-1) and 250mg·kg(-1). Interestingly, negative correlations were found between EPOR (r=-0

  9. 77 FR 27815 - Aging Management of Stainless Steel Structures and Components in Treated Borated Water

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-11

    ... COMMISSION Aging Management of Stainless Steel Structures and Components in Treated Borated Water AGENCY..., ``Aging Management of Stainless Steel Structures and Components in Treated Borated Water.'' This LR-ISG... stainless steel structures and components exposed to treated borated water. The NRC published Revision 2...

  10. Antihyperglycemic Effect of Quercetin in Ovariectomized Rats Treated with Tamoxifen.

    PubMed

    Silva, Fernanda Coleraus; Bramatti, Isabella Calvo; Toledo, Adrieli Gorlin; Salles, Fernando Marques; Itinose, Ana Maria; Marek, Carla Brugin

    2017-03-01

    Tamoxifen is effective in breast cancer therapy in postmenopausal women; however, it causes adverse effects that alter the glycolytic pathway and induce hyperglycemia. Quercetin, a flavonoid with antioxidant potential, inhibits butyrylcholinesterase (BuChE), which is positively associated with hyperglycemia. Therefore, this study investigated the effect of quercetin on tamoxifen-induced hyperglycemia, using BuChE activity as a bioindicator in adult ovariectomized Wistar rats. The ovariectomized rats were treated orally for 14 days with different concentrations of quercetin (2.5, 7.5, 22.5, and 67.5 mg.kg(-1) b.w.) and tamoxifen (5 mg.kg(-1) b.w.). Subsequently, they were euthanized; blood and tissue samples were collected. The following biochemical parameters were analyzed: plasma glucose levels and BuChE activity in the plasma, liver, intestine, and adipose tissue. The most effective dose of quercetin in reducing hyperglycemia was 22.5 mg.kg(-1) b.w. (Que/TAM 4.5/1, P < .00000), although the doses of 2.5 (Que/TAM 0.5/1, P < .05) and 7.5 mg.kg(-1) b.w. (Que/TAM 1.5/1, P < .05) were also effective. The BuChE activity decreased in the intestine at all tested doses of quercetin coadministered with tamoxifen (P < .01); however, in adipose tissue, there was a biphasic activity with a decrease (P < .05) and increase (P < .05) in activity at doses of 7.5 and 22.5 mg.kg(-1) b.w. of quercetin, respectively. However, the correlation between BuChE and glucose levels was not significant (P > .05). In summary, the findings of the present study suggest that quercetin when associated with tamoxifen decreases in plasma glucose levels. Furthermore, in these cases, BuChE should not be used as an indicator of hyperglycemia.

  11. Increased brain-predicted aging in treated HIV disease

    PubMed Central

    Underwood, Jonathan; Caan, Matthan W.A.; De Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W.N.M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B.L.M.; Winston, Alan; Reiss, Peter; Sharp, David J.

    2017-01-01

    Objective: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. Methods: A large sample of virologically suppressed HIV-positive adults (n = 162, age 45–82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18–90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age − chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. Results: HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (−0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Conclusion: Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. PMID:28258081

  12. Effects of monascin on anti-inflammation mediated by Nrf2 activation in advanced glycation end product-treated THP-1 monocytes and methylglyoxal-treated wistar rats.

    PubMed

    Lee, Bao-Hong; Hsu, Wei-Hsuan; Huang, Tao; Chang, Yu-Ying; Hsu, Ya-Wen; Pan, Tzu-Ming

    2013-02-13

    Hyperglycemia is associated with advanced glycation end products (AGEs). This study was designed to evaluate the inhibitory effects of monascin on receptor for advanced glycation end product (RAGE) signal and THP-1 monocyte inflammation after treatment with S100b, a specific ligand of RAGE. Monascin inhibited cytokine production by S100b-treated THP-1 monocytes via up-regulation of nuclear factor-erythroid 2-related factor-2 (Nrf2) and alleviated p47phox translocation to the membrane. Methylglyoxal (MG, 600 mg/kg bw) was used to induce diabetes in Wistar rats. Inhibitions of RAGE and p47phox by monascin were confirmed by peripheral blood mononuclear cells (PBMCs) of MG-induced rats. Silymarin (SM) was used as a positive control group. It was found that monascin promoted heme oxygenase-1 (HO-1) expression mediated by Nrf2. Suppressions of AGEs, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-β) in serum of MG-induced rats were attenuated in the monascin administration group treated with retinoic acid (RA). RA treatment resulted in Nrf2 inactivation by increasing RA receptor-α (RARα) activity, suggesting that RA acts as an inhibitor of Nrf2. The results showed that monascin exerted anti-inflammatory and antioxidative effects mediated by Nrf2 to prevent the development of diseases such as type 2 diabetes caused by inflammation.

  13. Atorvastatin reverses age-related reduction in rat hepatic PPARalpha and HNF-4.

    PubMed

    Sanguino, Elena; Roglans, Nuria; Alegret, Marta; Sánchez, Rosa M; Vázquez-Carrera, Manuel; Laguna, Juan C

    2005-08-01

    Old rats are resistant to fibrate-induced hypolipidemia owing to a reduction in hepatic peroxisome proliferator-activated receptor alpha (PPARalpha). We tested whether the age-related decrease in PPARalpha is prevented by atorvastatin (ATV), a hypolipidemic statin. We determined the activity and expression of Liver X receptor alpha (LXRalpha) and PPARalpha in the liver of 18-month-old rats treated with 10 mg kg(-1) of ATV for 21 days. We measured fatty acid oxidation (FAO), the expression of PPARalpha-target genes, liver triglyceride (TG) and cholesteryl ester (CE) contents and plasma concentrations of TG, cholesterol, glucose, nonesterified fatty acids (NEFA), insulin and leptin. While old female rats were practically unresponsive, ATV-treated old males showed lower liver TG (-41%) and CE (-48%), and plasma TG (-35%), glucose (-18%) and NEFA (-39%). Age-related alterations in LXRalpha expression and binding activity were reverted in ATV-treated old males. These changes were related to an increase in hepatic FAO (1.2-fold), and PPARalpha mRNA (2.2-fold), PPARalpha protein (1.6-fold), and PPARalpha-binding activity. Hepatic nuclear factor-4 (HNF-4) and chicken ovalbumin upstream-transcription factor-II participate in the transcriptional regulation of the PPARalpha gene, while peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) behaves as a PPAR coactivator. Ageing reduced the hepatic content of HNF-4 (74%) and PGC-1 (77%) exclusively in male rats. ATV administration to old males enhanced the hepatic expression and binding activity (two-fold) of HNF-4. ATV-induced changes in hepatic HNF-4 and PPARalpha may be responsible for the improvement of the lipid metabolic phenotype produced by ATV administration to senescent male rats.

  14. Atorvastatin reverses age-related reduction in rat hepatic PPARα and HNF-4

    PubMed Central

    Sanguino, Elena; Roglans, Nuria; Alegret, Marta; Sánchez, Rosa M; Vázquez-Carrera, Manuel; Laguna, Juan C

    2005-01-01

    Old rats are resistant to fibrate-induced hypolipidemia owing to a reduction in hepatic peroxisome proliferator-activated receptor α (PPARα). We tested whether the age-related decrease in PPARα is prevented by atorvastatin (ATV), a hypolipidemic statin. We determined the activity and expression of Liver X receptor α (LXRα) and PPARα in the liver of 18-month-old rats treated with 10 mg kg−1 of ATV for 21 days. We measured fatty acid oxidation (FAO), the expression of PPARα-target genes, liver triglyceride (TG) and cholesteryl ester (CE) contents and plasma concentrations of TG, cholesterol, glucose, nonesterified fatty acids (NEFA), insulin and leptin. While old female rats were practically unresponsive, ATV-treated old males showed lower liver TG (−41%) and CE (−48%), and plasma TG (−35%), glucose (−18%) and NEFA (−39%). Age-related alterations in LXRα expression and binding activity were reverted in ATV-treated old males. These changes were related to an increase in hepatic FAO (1.2-fold), and PPARα mRNA (2.2-fold), PPARα protein (1.6-fold), and PPARα-binding activity. Hepatic nuclear factor-4 (HNF-4) and chicken ovalbumin upstream-transcription factor-II participate in the transcriptional regulation of the PPARα gene, while peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) behaves as a PPAR coactivator. Ageing reduced the hepatic content of HNF-4 (74%) and PGC-1 (77%) exclusively in male rats. ATV administration to old males enhanced the hepatic expression and binding activity (two-fold) of HNF-4. ATV-induced changes in hepatic HNF-4 and PPARα may be responsible for the improvement of the lipid metabolic phenotype produced by ATV administration to senescent male rats. PMID:15912134

  15. Age-related changes of serum lipoprotein oxidation in rats.

    PubMed

    Nakamura, Yukiko Kawashima; Omaye, Stanley Teruo

    2004-01-23

    Oxidation of low-density lipoprotein (LDL) may be a prelude to atherogenesis and directly age related. To assess whether there may be relationship between age and plasma lipoprotein (LP) oxidation, we studied copper-mediated LP oxidation isolated from the blood of 2 months, 7 months, and 15 months old rats. We determined whether the susceptibility of LP to oxidation might be related to vitamin C levels in serum, vitamin E levels in LP, or the total antioxidant capacity (TAC) of serum or LP. Serum vitamin C content was inversely related to age, malondialdehyde (MDA) propagation rate, and maximum change of MDA concentrations. However, there were no significant relationships between age and serum TAC, LP TAC, serum vitamin E, or the ratio of LP vitamin E to serum vitamin C content. The lag phase of MDA formation was significantly decreased with age and the ratio of LP vitamin E content to serum vitamin C content, increased with age. Maximum change of MDA concentration was positively correlated with the ratio of LP vitamin E contents to serum vitamin C concentration. Thus, as the rat ages, vitamin C status decreases with an increased LP susceptibility to oxidation. It is tempting to speculate that enhanced LP oxidation in older rats may reflect a reduced amount of recycling of LDL vitamin E by serum vitamin C.

  16. Ozone ameliorates age-related oxidative stress changes in rat liver and kidney: effects of pre- and post-ageing administration.

    PubMed

    Safwat, M H; El-Sawalhi, M M; Mausouf, M N; Shaheen, A A

    2014-05-01

    The ageing process is known to be accompanied by increased oxidative stress and compromised antioxidant defenses. Controlled ozone administration has been shown to be effective in various pathophysiological conditions with an underlying oxidative burden. However, its effect on the biochemical alterations associated with the ageing process has been rarely studied. Therefore, the present work was carried out to study the role of ozone in counteracting the state of oxidative stress associated with ageing in rat liver and kidneys using two experimental models. In the pre-ageing model, ozone was administered prior to the onset of ageing at adulthood and continued after the start of the ageing process (3-month-old rats until the age of 15 months). While in the post-ageing model, ozone was administered after ageing has begun and lasted for one month (14-month-old rats until the age of 15 months). The pre-ageing ozone administration effectively reduced lipid and protein oxidation markers, namely, malondialdehyde and protein carbonyl levels and decreased lipofuscin pigment deposition in rat liver and kidneys. Moreover, it significantly restored hepatic and renal reduced glutathione (GSH) contents and normalized cytosolic hepatic glutathione peroxidase activity. Similar but less pronounced effects were observed in the post-ageing ozone-treated group. Nevertheless, in the latter model ozone administration failed to significantly affect liver and kidney lipofuscin levels, as well as kidney GSH contents. These data provide evidences for potentially positive effects of pre-ageing ozone therapy in neutralizing chronic oxidative stress associated with ageing in rat liver and kidneys.

  17. Obestatin and insulin in pancreas of newborn diabetic rats treated with exogenous ghrelin.

    PubMed

    Turk, Neslihan; Dağistanli, Fatma Kaya; Sacan, Ozlem; Yanardag, Refiye; Bolkent, Sema

    2012-07-01

    The aim of the study was to evaluate the effect of ghrelin treatment on obestatin, insulin gene expression and biochemical parameters in the pancreas of newborn-streptozocin (STZ) diabetic rats. Rats were divided into 4 groups. Group I: control rats treated with physiological saline; group II: control rats treated with 100 μg/kg/day ghrelin; group III: two days after birth rats that received 100mg/kg STZ injected as a single dose to induce neonatal diabetes; group IV: neonatal-STZ-diabetic rats treated with ghrelin for four weeks. Sections of the pancreas were examined with immunohistochemistry for the expression of obestatin and insulin and in situ hybridization for the expression of insulin mRNA. The blood glucose levels were measured. Tissue homogenates were used for protein, glutathione, lipid peroxidation and non-enzymatic glycosylation levels and antioxidant enzyme analysis. There was a significant difference in blood glucose levels in newborn-STZ-diabetic rats compared to ghrelin treated diabetic rats at weeks 1, 2 and 4. In group IV, pancreatic non-enzymatic glycosylation and lipid peroxidation levels were decreased, however, glutathione levels and enzymatic activities were increased. Insulin peptide and mRNA (+) signals in islets of Langerhans and obestatin immunopositive cell numbers showed an increase in group IV compared to group III. These results suggest that administration of ghrelin to newborn rats may prevent effects of diabetes.

  18. Alfacalcidol increases cancellous bone in low turnover, fatty marrow sites in aged, orchidectomized rats.

    PubMed

    Tian, X Y; Chen, H Y; Setterberg, R B; Li, M; Jee, W S S

    2009-01-01

    The objectives of this study were to determine the responses of cancellous bone in the distal tibial metaphysis (DTM), a low turnover, fatty (yellow) marrow site, to sham-aged, orchidectomy (ORX) and alfacalcidol treatment in sham-aged and ORX rats. Eighteen-month-old male sham and ORX rats were treated with 0.1 and 0.2 microg/kg alfacalcidol 5 days/wk p.o. for 12 weeks, double fluorescent labeled, and the DTM were processed for bone histomorphometry analyses. The current study found the DTM in sham-aged male rats were resistant to age-related and ORX-induced cancellous bone loss and alfacalcidol-induced bone gain, findings that differ from that in the proximal tibial metaphysis (PTM) and lumbar vertebral body (LVB), two high turnover, red marrow bone sites. However, alfacalcidol treatment increased DTM bone mass in ORX rats where bone turnover was elevated by androgen deficiency. These results in concert with the previously positive findings in red marrow bone sites following alfacalcidol treatment suggest that alfacalcidol is more effective in increasing cancellous bone mass in the skeletal sites with higher bone turnover.

  19. Age-related bone loss in the LOU/c rat model of healthy ageing.

    PubMed

    Duque, Gustavo; Rivas, Daniel; Li, Wei; Li, Ailian; Henderson, Janet E; Ferland, Guylaine; Gaudreau, Pierrette

    2009-03-01

    Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time. Histochemical staining of undecalcified bone showed a significant reduction in cortical and trabecular bone by 20 months of age. The reduction in mineralized tissue was accompanied by reduced numbers of osteoblasts and osteoclasts and a significant increase in marrow adiposity. Biochemical markers of bone turnover, C-telopeptide and osteocalcin, correlated with the age-related bone loss whereas the calciotropic hormones PTH and vitamin D remained unchanged over time. In summary, aged LOU rats exhibit low-turnover bone loss and marrow fat infiltration, which are the hallmarks of senile osteoporosis, and thus represent a novel model in which to study the molecular mechanisms leading to this disorder.

  20. Tetrahydroxystilbene glucoside improves learning and (or) memory ability of aged rats and may be connected to the APP pathway.

    PubMed

    Hou, Ying; Yang, Qidong; Zhou, Lin; Du, Xiaoping; Li, Min; Yuan, Mei; Zhou, Zhiwen; Li, Zhenguo

    2011-11-01

    The aim of this study is to evaluate the protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) on learning and (or) memory deficit in aged rats, as well as to explore the possible connection between TSG and the β-amyloid precursor protein (APP) pathway. Sprague-Dawley rats were randomly divided into a young control group (age, 4 months), an aged control group (age, 22 months), and a TSG-treated group (age, 22 months). TSG at doses of 50 mg·kg(-1)·day(-1) was intragastrically administered to 22-month-old rats for 4 weeks. The learning and (or) memory ability was measured using the Morris water maze (MWM) test, and the mRNA and protein expression of APP pathway proteins was measured by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively. The aged rats exhibited obvious learning and (or) memory deficit when compared with the young rats, but TSG treatment significantly improved the learning and (or) memory ability in the aged rats, as noted from the MWM test. RT-PCR and Western blot analysis showed an increase in the expression of beta-site APP cleaving enzyme 1 (BACE1) and A Disintegrin And Metalloproteinase 17 (ADAM17) in aged rats, and a decrease in ADAM10; however, TSG treatment significantly increased the mRNA and protein expression of ADAM10 (p < 0.01, compared with aged control rats). These results provide solid evidence for the therapeutic effect of TSG on age-related cognitive impairment, especially spatial learning and memory deficit. TSG might exert this effect through the APP pathway, although further studies on the topic are required.

  1. Spontaneous running activity in male rats - Effect of age

    NASA Technical Reports Server (NTRS)

    Mondon, C. E.; Dolkas, C. B.; Sims, C.; Reaven, G. M.

    1985-01-01

    Variations in the intensity and the patterns of spontaneous running activity in wheel cages were studied in male rats aged 7 weeks to one year. Daily running records were obtained for periods of 12 mo, and 24-hour recordings were made for selected runners in order to study variations in running activity during the day. The data indicate that for rats running over two miles/day, the maximum running intensity can be divided into two groups: a group of high achievers running 8 miles/day; and a group of moderate achievers running 4.8 miles/day. For both groups spontaneous activity reached a maximum after 4-5 weeks. An hourly pattern of running activity during the day was identified in rats of increasing age who averaged 9.0, 4.5, 2.6, and 1.2 miles/day, respectively. Progressive losses were observed in both the speed and the duration of spontaneous running as the rats increased in age, with the intensity of exercise falling below 2 miles/day after 7-8 months of age.

  2. Spontaneous Object Recognition Memory in Aged Rats: Complexity versus Similarity

    ERIC Educational Resources Information Center

    Gamiz, Fernando; Gallo, Milagros

    2012-01-01

    Previous work on the effect of aging on spontaneous object recognition (SOR) memory tasks in rats has yielded controversial results. Although the results at long-retention intervals are consistent, conflicting results have been reported at shorter delays. We have assessed the potential relevance of the type of object used in the performance of…

  3. Structural alterations in the seminiferous tubules of rats treated with immunosuppressor tacrolimus

    PubMed Central

    Caneguim, Breno H; Cerri, Paulo S; Spolidório, Luís C; Miraglia, Sandra M; Sasso-Cerri, Estela

    2009-01-01

    Background Tacrolimus (FK-506) is an immunosuppressant that binds to a specific immunophilin, resulting in the suppression of the cellular immune response during transplant rejection. Except for some alterations in the spermatozoa, testicular morphological alterations have not been described in rats treated with tacrolimus. In the present study, we purpose to evaluate if the treatment with tacrolimus at long term of follow-up interferes in the integrity of the seminiferous tubules. Methods Rats aging 42-day-old received daily subcutaneous injections of 1 mg/kg/day of tacrolimus during 30 (T-30) and 60 (T-60) days; the rats from control groups (C-30 and C-60) received saline solution. The left testes were fixed in 4% formaldehyde and embedded in glycol methacrylate for morphological and morphometric analyses while right testes were fixed in Bouin's liquid and embedded in paraffin for detection of cell death by the TUNEL method. The epithelial and total tubular areas as well as the stages of the seminiferous epithelium and the number of spermatocytes, spermatids and Sertoli cells (SC) per tubule were obtained. Results In the treated groups, seminiferous tubules irregularly outlined showed disarranged cellular layers and loss of germ cells probably due to cell death, which was revealed by TUNEL method. In addition to germ cells, structural alterations in the SC and folding of the peritubular tissue were usually observed. The morphometric results revealed significant decrease in the number of SC, spermatocytes, spermatids and significant reduction in the epithelial and total tubular areas. Conclusion Tacrolimus induces significant histopathological disorders in the seminiferous tubules, resulting in spermatogenic damage and reduction in the number of Sertoli cells. A careful evaluation of the peritubular components will be necessary to clarify if these alterations are related to the effect of FK-506 on the peritubular tissue. PMID:19243597

  4. Alterations in mystacial pad innervation in the aged rat.

    PubMed

    Fundin, B T; Bergman, E; Ulfhake, B

    1997-11-01

    It is well established that sensory perception becomes impaired with advancing age and that, in parallel, dystrophy and degeneration of axons occur in sensory pathways. In this study, the impact of aging was examined in the mystacial pad, which receives a large variety of sensory nerve endings organized in a highly predictable pattern. Mystacial pad specimens from aged (30 months old) and young adult (2-3 months old) female Sprague-Dawley rats were processed, in parallel, for immunohistochemical analyses with antibodies against human neuronal cytoplasmic protein (protein gene product 9.5), transmitter enzymes, and several neuropeptides. Several changes in cutaneous innervation including both degenerative and regenerative processes were evident in the aged rat: (1) the Merkel endings and lanceolate endings that emanate from large-caliber afferents in the whisker follicles were reduced and showed signs of degeneration. Furthermore, a reduction of piloneural complexes at the intervibrissal hairs were evident, but only in aged rats that showed more severe behavioral sensorimotor disturbances. In contrast, Ruffini endings as well as mechanoreceptors emanating from medium-caliber axons, i.e., transverse lanceolate and reticular endings, appeared normal. (2) A reduction was evident among two sets of unmyelinated epidermal endings; however, the epidermal innervation affiliated with the intervibrissal hairs appeared normal in the aged rat. (3) A loss of sympathetic neuropeptide tyrosine (NPY) or tyrosine hydroxylase-immunoreactive (IR) and somatosensory Calcitonin gene-related peptide (CGRP)-IR perivascular axons was paralleled by an increase in presumed parasympathetic NPY/CGRP-IR axons. (4) Two "novel" networks of fine-caliber axons were observed in the outer and inner root sheaths of the whisker follicles in the aged rat. (5) NPY was present in a population of small-caliber, somatosensory CGRP-IR axons in the aged rat. This may represent a de novo synthesis, since

  5. Mitochondria-targeted antioxidant preserves contractile properties and mitochondrial function of skeletal muscle in aged rats

    PubMed Central

    Javadov, Sabzali; Jang, Sehwan; Rodriguez-Reyes, Natividad; Rodriguez-Zayas, Ana E.; Hernandez, Jessica Soto; Krainz, Tanja; Wipf, Peter; Frontera, Walter

    2015-01-01

    Mitochondrial dysfunction plays a central role in the pathogenesis of sarcopenia associated with a loss of mass and activity of skeletal muscle. In addition to energy deprivation, increased mitochondrial ROS damage proteins and lipids in aged skeletal muscle. Therefore, prevention of mitochondrial ROS is important for potential therapeutic strategies to delay sarcopenia. This study elucidates the pharmacological efficiency of the new developed mitochondria-targeted ROS and electron scavenger, XJB-5-131 (XJB) to restore muscle contractility and mitochondrial function in aged skeletal muscle. Male adult (5-month old) and aged (29-month old) Fischer Brown Norway (F344/BN) rats were treated with XJB for four weeks and contractile properties of single skeletal muscle fibres and activity of mitochondrial ETC complexes were determined at the end of the treatment period. XJB-treated old rats showed higher muscle contractility associated with prevention of protein oxidation in both muscle homogenate and mitochondria compared with untreated counterparts. XJB-treated animals demonstrated a high activity of the respiratory complexes I, III, and IV with no changes in citrate synthase activity. These data demonstrate that mitochondrial ROS play a causal role in muscle weakness, and that a ROS scavenger specifically targeted to mitochondria can reverse age-related alterations of mitochondrial function and improve contractile properties in skeletal muscle. PMID:26415224

  6. Mitochondria-targeted antioxidant preserves contractile properties and mitochondrial function of skeletal muscle in aged rats.

    PubMed

    Javadov, Sabzali; Jang, Sehwan; Rodriguez-Reyes, Natividad; Rodriguez-Zayas, Ana E; Soto Hernandez, Jessica; Krainz, Tanja; Wipf, Peter; Frontera, Walter

    2015-11-24

    Mitochondrial dysfunction plays a central role in the pathogenesis of sarcopenia associated with a loss of mass and activity of skeletal muscle. In addition to energy deprivation, increased mitochondrial ROS damage proteins and lipids in aged skeletal muscle. Therefore, prevention of mitochondrial ROS is important for potential therapeutic strategies to delay sarcopenia. This study elucidates the pharmacological efficiency of the new developed mitochondria-targeted ROS and electron scavenger, XJB-5-131 (XJB) to restore muscle contractility and mitochondrial function in aged skeletal muscle. Male adult (5-month old) and aged (29-month old) Fischer Brown Norway (F344/BN) rats were treated with XJB for four weeks and contractile properties of single skeletal muscle fibres and activity of mitochondrial ETC complexes were determined at the end of the treatment period. XJB-treated old rats showed higher muscle contractility associated with prevention of protein oxidation in both muscle homogenate and mitochondria compared with untreated counterparts. XJB-treated animals demonstrated a high activity of the respiratory complexes I, III, and IV with no changes in citrate synthase activity. These data demonstrate that mitochondrial ROS play a causal role in muscle weakness, and that a ROS scavenger specifically targeted to mitochondria can reverse age-related alterations of mitochondrial function and improve contractile properties in skeletal muscle.

  7. Calorie restriction: A new therapeutic intervention for age-related dry eye disease in rats

    SciTech Connect

    Kawashima, Motoko; Kawakita, Tetsuya; Okada, Naoko; Ogawa, Yoko; Murat, Dogru; Nakamura, Shigeru; Nakashima, Hideo; Shimmura, Shigeto; Shinmura, Ken; Tsubota, Kazuo

    2010-07-09

    A decrease in lacrimal gland secretory function is closely related to aging and leads to an increased prevalence of dry eye syndrome. Since calorie restriction (CR) is considered to prevent functional decline of various organs due to aging, we hypothesized that CR could prevent age-related lacrimal dysfunction. Six-month-old male Fischer 344 rats were randomly divided into ad libitum (AL) and CR (-35%) groups. After 6 months of CR, tear function was examined under conscious state. After euthanasia, lacrimal glands were subjected to histological examination, tear protein secretion stimulation test with Carbachol, and assessment of oxidative stress with 8-hydroxy-2 deoxyguanosine (8-OHdG) and 4-hydroxynonenal (HNE) antibodies. CR significantly improved tear volume and tended to increase tear protein secretion volume after stimulation with Carbachol compared to AL. The acinar unit density was significantly higher in the CR rats compared to AL rats. Lacrimal glands in the CR rats showed a lesser degree of interstitial fibrosis. CR reduced the concentration of 8-OHdG and the extent of staining with HNE in the lacrimal gland, compared to AL. Furthermore, our electron microscopic observations showed that mitochondrial structure of the lacrimal gland obtained from the middle-aged CR rats was preserved in comparison to the AL rats. Collectively, these results demonstrate for the first time that CR may attenuate oxidative stress related damage in the lacrimal gland with preservation of lacrimal gland functions. Although molecular mechanism(s) by which CR maintains lacrimal gland function remains to be resolved, CR might provide a novel therapeutic strategy for treating dry eye syndrome.

  8. Treating medullary thyroid cancer in the age of targeted therapy

    PubMed Central

    Cabanillas, Maria E; Hu, Mimi I; Jimenez, Camilo; Grubbs, Elizabeth G; Cote, Gilbert J

    2015-01-01

    Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor deriving from the thyroid parafollicular cell. Thyroidectomy continues to serve as the primary initial treatment for this cancer. Because standard cytotoxic chemotherapy has proven ineffective, reoperation and external beam radiation therapy had been the only tools to treat recurrences or distant disease. The discovery that aberrant activation of RET, a receptor tyrosine kinase, is a primary driver of MTC tumorigenesis led to clinical trials using RET-targeting tyrosine kinase inhibitors. The successes of those trials led to the approval of vandetanib and cabozantinib for treating patients with progressive or symptomatic MTC. The availability of these drugs, along with additional targeted therapies in development, requires a thoughtful reconsideration of the approach to treating patients with unresectable locally advanced and/or metastatic progressive MTC. PMID:25908961

  9. Ameliorative effect of traditional Japanese medicine yokukansan on age-related impairments of working memory and reversal learning in rats.

    PubMed

    Mizoguchi, K; Shoji, H; Tanaka, Y; Tabira, T

    2011-03-17

    Aging is thought to impair prefrontal cortical (PFC) structure-sensitive cognitive functions and flexibility, such as working memory and reversal learning. A traditional Japanese medicine, yokukansan (YKS), is frequently used to treat age-related neurodegenerative disorders such as Alzheimer's disease in Japan, but its pharmacological properties have not been elucidated. The present study was designed to examine whether YKS improves age-related cognitive deficits using aged rats. YKS was administered to 21-month-old rats for 3 months. The ability to learn initially a reward rule for a T-maze discrimination task (initial learning) was examined in young control (4-month-old), aged control (24-month-old) and YKS-treated aged (24-month-old) rats. Subsequently, working memory and reversal learning were examined in delayed alternation and reversal discrimination T-maze tasks, respectively. Locomotor activity was also measured in new environments. Although performance accuracy in the initial learning procedure did not differ among any experimental groups, accuracy in the delayed alternation task was significantly decreased in aged rats compared to young rats. Aged rats also showed significant decreases in accuracy in the reversal discrimination task. YKS treatment significantly ameliorated the age-related decreases in accuracy in the delayed alternation and reversal discrimination tasks. The ameliorative effects of YKS on impaired delayed alternation performance were reduced by intracranial infusions of a dopamine D1 receptor antagonist, SCH 23390, into the prelimbic cortical region of the PFC, and the YKS effects on impaired reversal learning were done by the infusions into the orbitofrontal cortex (OFC). Locomotor activity did not change in any experimental group. Thus, YKS ameliorated age-related impairments of working memory and reversal learning, which might be mediated by a dopaminergic mechanism in the PFC structure. These investigations provide information

  10. Eleutheroside B or E enhances learning and memory in experimentally aged rats.

    PubMed

    Huang, Debin; Hu, Zehua; Yu, Zhaofen

    2013-04-25

    Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer's disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or E (50, 100, 200 mg/kg), and rats injected with Huperzine A or PBS were used as controls. At 4 weeks after administration, behavioral tests showed that the escape latencies and errors in searching for the platform in a Morris water maze were dose-dependently reduced in rats treated with medium and high-dose eleutheroside B or E. Hematoxylin-eosin staining showed that the number of surviving hippocampal neurons was greater and pathological injury was milder in three eleutheroside B or E groups compared with model group. Hippocampal homogenates showed enhanced cholinesterase activity, and dose-dependent increases in acetylcholine content and decreases in choline content following eleutheroside B or E treatment, similar to those seen in the Huperzine A group. These findings indicate that eleutheroside B or E improves learning and memory in aged rats. These effects of eleutheroside B or E may be mediated by activation of cholinesterase or enhanced reuse of choline to accelerate the synthesis of acetylcholine in hippocampal neurons.

  11. The effect of L-carnitine on T-maze learning ability in aged rats.

    PubMed

    Lohninger, S; Strasser, A; Bubna-Littitz, H

    2001-06-01

    L-carnitine is of considerable interest because of its capacity to counteract several physiological and pathological phenomena typical of brain aging processes. We examined the effects of L-carnitine on the learning ability of old rats. 100 mg/kg per body weight per day L-carnitine was administered orally to old (21 months) male Sprague-Dawley rats (OLD-CAR) for a period of 2 months. Old (21 months, OLD-CO) and young (7 months, YG-CO) control animals received tap water exclusively. Performance of the OLD-CAR and OLD-CO was compared with that of YG-CO in a multiple T-maze. The mean run time values showed a significant (P=0.01) difference of the OLD-CAR rats to the OLD-CO but no significant differences between OLD-CAR and YG-CO. For the T-maze parameter mean correct responses we were able to demonstrate that L-carnitine treated old rats made significantly (P=0.03) less errors and significantly (P=0.01) more animals reached the T-maze goal compared with OLD-CO but no significant differences were observed between OLD-CAR and YG-CO. The results of the present study clearly demonstrate that carnitine treatment improves the learning ability of old rats and seems to be able to reduce the loss of cognitive functions that occur with aging.

  12. Fluoxetine Enhances Neurogenesis in Aged Rats with Cortical Infarcts, but This is not Reflected in a Behavioral Recovery.

    PubMed

    Sun, Xiaoyu; Zhou, Zhike; Liu, Tingting; Zhao, Mei; Zhao, Shanshan; Xiao, Ting; Jolkkonen, Jukka; Zhao, Chuansheng

    2016-02-01

    Age is associated with poor outcome and impaired functional recovery after stroke. Fluoxetine, which is widely used in clinical practice, can regulate hippocampal neurogenesis in young rodents. As the rate of neurogenesis is dramatically reduced during aging, we studied the effect of post-stroke fluoxetine treatment on neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of dentate gyrus (DG) and whether this would be associated with any behavioral recovery after the cortical infarct in aged rats. Aged rats were randomly assigned to four groups: sham-operated rats, sham-operated rats treated with fluoxetine, rats subjected to cerebral ischemia, and rats with ischemia treated with fluoxetine. Focal cortical ischemia was induced by intracranial injection of vasoconstrictive peptide, endothelin-1 (ET-1). Fluoxetine was administered in the drinking water for 3 weeks starting 1 week after ischemia at a dose of 18 mg/kg/day. Behavioral recovery was evaluated on post-stroke days 29 to 31 after which the survival rate and fate of proliferating cells in the SVZ and DG were assessed by immunohistochemistry. Apoptosis was measured with the TUNEL assay. The results indicated that chronic fluoxetine treatment after stroke enhanced the proliferation of newborn neurons in the SVZ, but not in SGZ, and it suppressed perilesional apoptosis. Fluoxetine treatment did not affect the survival or differentiation of newly generated cells in the SVZ i.e., the enhanced neurogenesis was not translated into a behavioral outcome.

  13. Resetting of central and peripheral circadian oscillators in aged rats.

    PubMed

    Davidson, Alec J; Yamazaki, Shin; Arble, Deanna M; Menaker, Michael; Block, Gene D

    2008-03-01

    The mammalian circadian timing system is affected by aging. Analysis of the suprachiasmatic nucleus (SCN) and of other circadian oscillators reveals age-related changes which are most profound in extra-SCN tissues. Some extra-SCN oscillators appear to stop oscillating in vivo or display altered phase relationships. To determine whether the dynamic behavior of circadian oscillators is also affected by aging we studied the resetting behavior of the Period1 transcriptional rhythm of peripheral and central oscillators in response to a 6h advance or delay in the light schedule. We employed a transgenic rat with a luciferase reporter to allow for real-time measurements of transcriptional rhythmicity. While phase resetting in the SCN following an advance or a delay of the light cycle appears nearly normal in 2-year-old rats, resynchronization of the liver was seriously disrupted. In addition, the arcuate nucleus and pineal gland exhibited faster resetting in aged rats relative to 4-8-month-old controls. The consequences of these deficits are unknown, but may contribute to organ and brain diseases in the aged as well as the health problems that are common in older shift-workers.

  14. RESETTING OF CENTRAL AND PERIPHERAL CIRCADIAN OSCILLATORS IN AGED RATS

    PubMed Central

    Davidson, Alec J.; Yamazaki, Shin; Arble, Deanna M.; Menaker, Michael; Block, Gene D.

    2006-01-01

    The mammalian circadian timing system is affected by aging. Analysis of the suprachiasmatic nucleus (SCN) and of other circadian oscillators reveals age-related changes which are most profound in extra-SCN tissues. Some extra-SCN oscillators appear to stop oscillating in vivo or display altered phase relationships. To determine whether the dynamic behavior of circadian oscillators is also affected by aging we studied the resetting behavior of the Period1 transcriptional rhythm of peripheral and central oscillators in response to a 6 hr advance or delay in the light schedule. We employed a transgenic rat with a luciferase reporter to allow for real-time measurements of transcriptional rhythmicity. While phase-resetting in the SCN following an advance or a delay of the light cycle appears nearly normal in 2-year old rats, resynchronization of the liver was seriously disrupted. In addition, the arcuate nucleus and pineal gland exhibited faster resetting in aged rats relative to 4-8 month-old controls. The consequences of these deficits are unknown, but may contribute to organ and brain diseases in the aged as well as the health problems that are common in older shift-workers. PMID:17129640

  15. Immuno-neutralization of circulating relaxin does not alter the breast cancer-protective action of parity in MNU-treated rats.

    PubMed

    Steinetz, Bernard G; Sherwood, O David; Lasano, Sally; Horton, Lori; Bosland, Maarten C

    2004-04-01

    Early pregnancy and childbirth protects women against future development of breast cancer by an unknown mechanism. Parity likewise reduces mammary cancer incidence in rats exposed to the carcinogen, N-methyl-N-nitrosourea (MNU), providing a model for the human phenomenon. We hypothesized that relaxin, a 6KD luteal mammotropic hormone of pregnancy, might be the anti-cancer pregnancy factor, and that induced relaxin deficiency during rat gestation would restore carcinogen sensitivity. Forty-one pregnant (age 50 days) and 25 age-matched virgin Sprague-Dawley rats were used. Relaxin deficiency was induced by injecting mouse monoclonal anti-rat relaxin antibody (MCA1) days 12-18 of gestation. Pregnant controls were injected with vehicle or mouse IgG on the same schedule. Because MCA1 disrupts parturition, all rats underwent cesarean section on day 22. At age 100 days, all rats were injected i.v. with MNU (50mg/Kg) and examined daily for tumors until euthanized at age 240 days. Mammary tumor incidence and frequency were significantly (p<0.01) reduced and tumor latency was increased (p<0.001) in primiparous as compared with virgin rats. However, tumor incidence, type, size and latency were similar in MCA1-treated and control primiparous rats. Thus, luteal relaxin does not appear to be the factor responsible for resistance to breast cancer.

  16. Aged rats are hypo-responsive to acute restraint: implications for psychosocial stress in aging

    PubMed Central

    Buechel, Heather M.; Popovic, Jelena; Staggs, Kendra; Anderson, Katie L.; Thibault, Olivier; Blalock, Eric M.

    2013-01-01

    Cognitive processes associated with prefrontal cortex and hippocampus decline with age and are vulnerable to disruption by stress. The stress/stress hormone/allostatic load hypotheses of brain aging posit that brain aging, at least in part, is the manifestation of life-long stress exposure. In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation), and aged humans are well-understood to be more vulnerable to the negative consequences of such new-onset chronic psychosocial stress events. However, the mechanistic underpinnings of this age-related shift in chronic psychosocial stress response, or the initial acute phase of that chronic response, have been less well-studied. Here, we separated young (3 month) and aged (21 month) male F344 rats into control and acute restraint (an animal model of psychosocial stress) groups (n = 9–12/group). We then assessed hippocampus-associated behavioral, electrophysiological, and transcriptional outcomes, as well as blood glucocorticoid and sleep architecture changes. Aged rats showed characteristic water maze, deep sleep, transcriptome, and synaptic sensitivity changes compared to young. Young and aged rats showed similar levels of distress during the 3 h restraint, as well as highly significant increases in blood glucocorticoid levels 21 h after restraint. However, young, but not aged, animals responded to stress exposure with water maze deficits, loss of deep sleep and hyperthermia. These results demonstrate that aged subjects are hypo-responsive to new-onset acute psychosocial stress, which may have negative consequences for long-term stress adaptation and suggest that age itself may act as a stressor occluding the influence of new onset stressors. PMID:24575039

  17. Systemic elevation of interleukin-15 in vivo promotes apoptosis in skeletal muscles of young adult and aged rats.

    PubMed

    Pistilli, Emidio E; Alway, Stephen E

    2008-08-15

    In this study, we tested the hypothesis that systemic elevation of IL-15 would attenuate apoptosis in skeletal muscles of aged rats. IL-15 was administered to young adult (n=6) and aged (n=6) rats for 14 days. Apoptosis was quantified using an ELISA assay and verified through TUNEL staining of muscle sections. As expected, apoptosis was greater in muscles from aged control rats, compared to age-matched control. Apoptosis was also greater in the muscles from young adult and aged rats treated with IL-15. These increases in apoptosis were associated with decreases in muscle mass of IL-15 treated rats. These data do not support our initial hypothesis and suggest that systemic elevation of IL-15 promotes apoptosis in skeletal muscle. The proposed anti-apoptotic property of IL-15 may be specific to cell-type and/or the degree of muscle pathology present; however, additional research is required to more clearly decipher its role in skeletal muscle.

  18. Effects of Aged Garlic Extract on Left Ventricular Diastolic Function and Fibrosis in a Rat Hypertension Model

    PubMed Central

    Hara, Yuki; Noda, Akiko; Miyata, Seiko; Minoshima, Makoto; Sugiura, Mari; Kojima, Jun; Otake, Masafumi; Furukawa, Mayuko; Cheng, Xian Wu; Nagata, Kohzo; Murohara, Toyoaki

    2013-01-01

    Daily consumption of garlic is known to lower the risk of hypertension and ischemic heart disease. In this study, we examined whether aged garlic extract (AGE) prevents hypertension and the progression of compensated left ventricular (LV) hypertrophy in Dahl salt-sensitive (DS) rats. DS rats were randomly divided into three groups: those fed an 8% NaCl diet until 18 weeks of age (8% NaCl group), those additionally treated with AGE (8% NaCl + AGE group), and control rats maintained on a diet containing 0.3% NaCl until 18 weeks of age (0.3% NaCl group). AGE was administered orally by gastric gavage once a day until 18 weeks of age. LV mass was significantly higher in the 8% NaCl + AGE group than in the 0.3% NaCl group at 18 weeks of age, but significantly lower in the 8% NaCl + AGE group than in the 8% NaCl group. No significant differences were observed in systolic blood pressure (SBP) between the 8% NaCl and 8% NaCl + AGE groups at 12 and 18 weeks of age. LV end-diastolic pressure and pressure half-time at 12 and 18 weeks of age were significantly lower in the 8% NaCl + AGE group compared with the 8% NaCl group. AGE significantly reduced LV interstitial fibrosis at 12 and 18 weeks of age. Chronic AGE intake attenuated LV diastolic dysfunction and fibrosis without significantly decreasing SBP in hypertensive DS rats. PMID:24172194

  19. Aging-dependent changes in the effect of daily melatonin supplementation on rat metabolic and behavioral responses.

    PubMed

    Rasmussen, D D; Mitton, D R; Larsen, S A; Yellon, S M

    2001-08-01

    Pineal melatonin secretion has been reported to commonly decrease with aging, whereas intra-abdominal adiposity, plasma insulin and plasma leptin levels tend to increase. We recently demonstrated that daily melatonin administration starting at middle age suppressed male rat intra-abdominal fat, plasma leptin and plasma insulin to youthful levels, suggesting that aging-related changes in pineal melatonin secretion and in energy regulation may be functionally related. Accordingly, we have now investigated the effects of daily melatonin treatment on energy regulation in young versus middle-aged male Sprague Dawley rats. Addition of melatonin to the drinking water (0.2 microg/mL) produced nocturnal and diurnal plasma melatonin concentrations in middle-aged rats (12 months) equivalent to those of young adult (5 months) rats. Administration of this melatonin dosage every day for 10 wk starting at 10 months of age suppressed (P < 0.01) relative intra-abdominal fat, non-fasted plasma insulin and plasma leptin by 27, 39, and 51%, respectively (vs. vehicle-treated controls). In contrast, administration of melatonin for 10 wk starting at 3 months of age did not significantly alter (P> 0.10) any of these parameters. The melatonin administration stimulated (102%, P < 0.001) behavioral responsiveness of the middle-aged rats in a test of response to novelty, restoring youthful levels, but did not significantly alter behavioral responsiveness of the young rats. These results suggest that suppression of intra-abdominal adiposity and plasma leptin and insulin levels and stimulation of behavioral responsiveness in response to daily exogenous melatonin begins at middle age, coincident with and likely dependent upon the aging-associated decline in endogenous pineal melatonin secretion. These results further suggest that appropriate melatonin supplementation may potentially provide therapy or prophylaxis not only for the insulin resistance, increased intra-abdominal fat and resulting

  20. Low intensity laser therapy accelerates muscle regeneration in aged rats

    PubMed Central

    Vatansever, Fatma; Rodrigues, Natalia C.; Assis, Livia L.; Peviani, Sabrina S.; Durigan, Joao L.; Moreira, Fernando M.A.; Hamblin, Michael R.; Parizotto, Nivaldo A.

    2013-01-01

    Background Elderly people suffer from skeletal muscle disorders that undermine their daily activity and quality of life; some of these problems can be listed as but not limited to: sarcopenia, changes in central and peripheral nervous system, blood hypoperfusion, regenerative changes contributing to atrophy, and muscle weakness. Determination, proliferation and differentiation of satellite cells in the regenerative process are regulated by specific transcription factors, known as myogenic regulatory factors (MRFs). In the elderly, the activation of MRFs is inefficient which hampers the regenerative process. Recent studies found that low intensity laser therapy (LILT) has a stimulatory effect in the muscle regeneration process. However, the effects of this therapy when associated with aging are still unknown. Objective This study aimed to evaluate the effects of LILT (λ=830 nm) on the tibialis anterior (TA) muscle of aged rats. Subjects and methods The total of 56 male Wistar rats formed two population sets: old and young, with 28 animals in each set. Each of these sets were randomly divided into four groups of young rats (3 months of age) with n=7 per group and four groups of aged rats (10 months of age) with n=7 per group. These groups were submitted to cryoinjury + laser irradiation, cryoinjury only, laser irradiation only and the control group (no cryoinjury/no laser irradiation). The laser treatment was performed for 5 consecutive days. The first laser application was done 24 h after the injury (on day 2) and on the seventh day, the TA muscle was dissected and removed under anesthesia. After this the animals were euthanized. Histological analyses with toluidine blue as well as hematoxylin-eosin staining (for counting the blood capillaries) were performed for the lesion areas. In addition, MyoD and VEGF mRNA was assessed by quantitative polymerase chain reaction. Results The results showed significant elevation (p<0.05) in MyoD and VEGF genes expression levels

  1. Radioiodine sensitivity of parafollicular C cells in aged Long-Evans rats

    SciTech Connect

    Ott, R.A.; Hofmann, C.; Oslapas, R.; Nayyar, R.; Paloyan, E.

    1987-12-01

    An earlier study from our laboratory demonstrated that the incidence of thyroid C cell neoplasia in aging Long-Evans rats was high. When radioactive iodine was administered to 8-week-old Long-Evans rats, this incidence was reduced, although thyroid follicular cell neoplasia was increased. The aim of this study was to determine whether iodine-131 administered to an aged population of Long-Evans rats with established C cell hyperplasia would have a C cell ablative effect as pronounced as that observed in studies of young rats. For this study, 180 18-month-old Long-Evans rats (90 male and 90 female) were used. Baseline serum calcitonin levels were determined, and control and experimental groups containing equal numbers of animals were designated. /sup 131/I was administered by intraperitoneal injection to the experimental group, while equal volumes of saline solution were given to the control group. Blood samples for determination of serum calcitonin levels were obtained at 6-week intervals until the rats were 24 months old. Thyroid glands were then removed, and tissues were fixed, sectioned, and stained with hematoxylin and eosin and with peroxidase-antiperoxidase (PAP) using an anticalcitonin antibody. Examination of thyroid tissues showed that the incidence of C cell neoplasia was significantly reduced in irradiated animals as compared with nonirradiated controls (chi 2 analysis, p less than 0.05). PAP staining demonstrated diminished intracytoplasmic calcitonin in the radiation-treated group. Analysis of serum calcitonin levels over time showed significantly lower levels in the irradiated rat group than in the nonirradiated group (p less than 0.006).

  2. Endotoxemia in newborn rats attenuates acute pancreatitis at adult age.

    PubMed

    Jaworek, J; Konturek, S J; Macko, M; Kot, M; Szklarczyk, J; Leja-Szpak, A; Nawrot-Porabka, K; Stachura, J; Tomaszewska, R; Siwicki, A; Pawlik, W W

    2007-03-01

    Bacterial endotoxin (lipopolysaccharide, LPS), at high concentration is responsible for sepsis, and neonatal mortality, however low concentration of LPS protected the pancreas against acute damage. The aim of this study was to investigate the effect of exposition of suckling rats to LPS on the course of acute pancreatitis at adult age. Suckling rat (30-40g) received intraperitoneal (i.p.) injection of saline (control) or LPS from Escherichia coli or Salmonella typhi (5, 10 or 15 mg/kg-day) during 5 consecutive days. Two months later these rats have been subjected to i.p. cearulein infusion (25 microg/kg) to produce caerulein-induced pancreatitis (CIP). The following parameters were tested: pancreatic weight and morphology, plasma amylase and lipase activities, interleukin 1beta (IL-1 beta), interleukin 6 (IL-6), and interleukin 10 (IL-10) plasma concentrations. Pancreatic concentration of superoxide dismutase (SOD) and lipid peroxidation products; malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) have been also measured. Caerulein infusion produced CIP in all animals tested, that was confirmed by histological examination. In the rats, which have been subjected in the neonatal period of life to LPS at doses 10 or 15 mg/kg-day x 5 days, all manifestations of CIP have been reduced. In these animals acute inflammatory infiltration of pancreatic tissue and pancreatic cell vacuolization have been significantly diminished. Also pancreatic weight, plasma lipase and alpha-amylase activities, as well as plasma concentrations of IL-1beta and IL-6 have been markedly decreased, whereas plasma anti-inflammatory IL-10 concentration was significantly increased in these animals as compared to the control rats, subjected in the infancy to saline injection instead of LPS. Caerulein-induced fall in pancreatic SOD concentration was reversed and accompanied by significant reduction of MDA + 4 HNE in the pancreatic tissue. The effects of LPS derived from E. coli or S. typhi were similar

  3. Chinese medicinal herbs in treating model rats with hepatic fibrosis.

    PubMed

    Zhou, Yun-Xiao; Chen, Jiu; Li, Jian-Ping; Wang, Yan-Li; Jin, Xiao-Dong

    2009-12-30

    The objective of this study was to examine the effects of Chinese medicine formula-Yu Zhang Dan (YZD, composed of Herba Lysimachiae, Rhizoma Polygoni Cuspidati, Radix Curcumae) on the model rats with hepatic fibrosis. Forty male Sprague-Dawley (SD) rats were used in the present study, and they were separated randomly into 4 groups: a normal control group (Group A, n=5), a model control (Group B, n=15), a high dose of YZD (Group C, n=10), and a low dose of YZD (Group D, n=10). Hepatic fibrosis in rats was induced by carbon tetrachloride (CCl(4)). The variation of the serum alanine transaminase (ALT), aspartate aminotransferase (AST), hyaluronate acid (HA), laminin (LN), type • • procollagen peptide (P• •NP), L-Glutathione (GSH) was respectively measured with radioimmunoassay (RIA) and detection of transforming growth factor-beta 1 (TGF-β1) and smooth muscle alpha actin (α-SMA) was conducted with immunohistochemistry. The ALT, AST HA, LN and PIII NP levels in the serum of the model control group were significantly higher than those of the normal control group (P<0.05), and both of the high dose of YZD and low dose of YZD significantly decreased the ALT, AST HA, LN and PIII NP levels of the model rats (P<0.05). The TGF-β1 and α-SMA levels of the model control group were significantly higher than those of the normal control group (P<0.05), and both of the high dose of YZD and low dose of YZD significantly decreased the TGF-β1 levels of the model rats (P<0.05) , and only the high dose of YZD significantly decreased the α-SMA levels of the model rats (P<0.05). The expression of TGF-β1 and α-SMA in the liver tissues of the rats were in the cytoplasm of the cells. It may be through decreasing the ALT, AST, HA, LN and PIII NP levels in the serum of the model rats and decreasing the expression of TGF-β1 and α-SMA in the liver tissues of the model rats that YZD significantly relieved the hepatic fibrosis.

  4. Protection against hyperoxia by serum from endotoxin treated rats: absence of superoxide dismutase induction

    SciTech Connect

    Berg, J.T.; Smith, R.M.

    1988-01-01

    Endotoxin greatly reduces lung injury and pleural effusions in adult rats exposed to normobaric hyperoxia (> 98% oxygen for 60 hours). This study reports that serum from endotoxin treated donor rats protects serum recipients against hyperoxic lung injury without altering lung superoxide dismutase (SOD) activity. Rats pretreated with endotoxin alone were protected and exhibited an increase in lung SOD activity as previously reported by others. Protection by serum was not due to the transfer of residual endotoxin or SOD. These results show, that protection from oxygen toxicity can occur in rats without an increase in lung SOD and suggest that a serum factor may be involved.

  5. Effect of prostaglandin E/sub 2/ on the small intestine of indomethacin-treated rats

    SciTech Connect

    Romain, N.; Dandrifosse, G.; Forget, P.; Lepoint, A.

    1987-09-07

    In the present study, the protective effect of PGE/sub 2/ on intestinal damage in indomethacin-treated adult rats was investigated. Ileal integrity was evaluated making use of different biochemical and histological parameters : activities of sucrase, maltase and diamine oxidase; concentrations of DNA, putrescine, spermidine and spermine; incorporation of /sup 3/H-thymidine into DNA; mitotic index and mucosal thickness. Results expressed per g of mucosal weight, showed that : - maltase and diamine oxidase activities as well as DNA, spermidine and spermine concentrations decreased markedly in indomethacin-treated rats when compared to control rats; - the decrease of maltase activity as well as DNA, spermidine and spermine concentration was less pronounced in PGE/sub 2/-treated rats when compared to indomethacin-treated rats; - /sup 3/H-thymidine incorporation into DNA and mitotic index values showed no significant variation in the course of different treatments; - mucosal thickness increased strongly, the PGE/sub 2/-protected rats. The authors suggest that PGE/sub 2/ could protect the rat's intestinal mucosa against the effects of indomethacin through a trophic action on intestinal villi. 15 references, 3 tables.

  6. Antiaging Effect of Metformin on Brain in Naturally Aged and Accelerated Senescence Model of Rat.

    PubMed

    Garg, Geetika; Singh, Sandeep; Singh, Abhishek Kumar; Rizvi, Syed Ibrahim

    2017-01-09

    Metformin, a biguanide, is a widely used antidiabetic drug, which inhibits gluconeogenesis and is used to treat hyperglycemia in type 2 diabetes. Through activation of AMPK (AMP-activated protein kinase) pathway, metformin also mimics caloric restriction health benefits. Aging causes substantial molecular to morphological changes in brain, the brain cells being more susceptible toward oxidative stress mediated damages due to the presence of high lipid content and higher oxygen consumption. Wistar rats (naturally aged and d-galactose induced rat model) were supplemented with metformin (300 mg/kg b.w. orally) for 6 weeks. The biomarkers of oxidative stress such as antioxidant capacity (ferric reducing antioxidant potential [FRAP]), malondialdehyde (MDA), reduced glutathione (GSH), protein carbonyl (PCO), reactive oxygen species (ROS), acetylcholinesterase (AChE) activity, and nitric oxide (NO) were measured in brain tissues of control and experimental groups. The results indicate that metformin treatment augmented the levels of FRAP and GSH in naturally aged, and d-gal induced aging model groups compared to the respective controls. In contrast, metformin treated groups exhibited significant reduction in MDA, PCO, ROS, and NO levels and a significant increase in AChE activity in induced aging rats. The administration of d-galactose upregulated the expression of sirtuin-2, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) and downregulated the expression of Beclin-1. Metformin supplementation downregulated the d-galactose induced expressions of sirtuin-2, IL-6, and TNF-α expression, whereas upregulated the Beclin-1 expression. Our data confirm that metformin restores the antioxidant status and improves healthy brain aging through the activation of autophagy and reduction in inflammation.

  7. Effect of Aging on Adipose Tissue Inflammation in the Knee Joints of F344BN Rats.

    PubMed

    Fu, Yao; Huebner, Janet L; Kraus, Virginia B; Griffin, Timothy M

    2016-09-01

    The infrapatellar fat pad (IFP) secretes inflammatory mediators in osteoarthritic knees, but the effect of aging on IFP inflammation is unknown. We tested the hypothesis that aging increases basal and interleukin-1β (IL-1β)-stimulated IFP inflammation in 10-, 20-, and 30-month-old male F344BN F1-hybrid rats. IFPs were cultured ex vivo for 24 hours and treated ±1ng/mL IL-1β to simulate injury-induced inflammation. IFP inflammation was evaluated by measuring secreted cytokine concentrations and by quantitative expression of immunoregulatory and pro- and anti-adipogenic genes. With age, osteoarthritis pathology increased and IFP mass decreased. Although adipocyte size did not change with age, variation in adipocyte size was positively associated with synovial thickness independent of age whereas associations with cartilage damage were age dependent. In the absence of IL-1β, aging was associated with a significant increase in IFP secretion of tumor necrosis factor α by 67% and IL-13 by 35% and a reduction in the expression of immunoregulatory M2 macrophage genes. However, following an IL-1β challenge, adipogenesis markers decreased and pro- and anti-inflammatory cytokines increased independent of age. The lone exception was leptin, which decreased >70% with age. Thus, although aging promotes osteoarthritis risk by increasing basal inflammation, our findings also revealed a potentially protective effect of aging by decreasing IL-1β-stimulated leptin production.

  8. Mitochondrial and Metabolic Gene Expression in the Aged Rat Heart

    PubMed Central

    Barton, Gregory P.; Sepe, Joseph J.; McKiernan, Susan H.; Aiken, Judd M.; Diffee, Gary M.

    2016-01-01

    Aging is associated with a decline in cardiac function. Exercise intervention has been suggested as a way to improve this decrement. Age-related decline in cardiac function is associated with decreases in fatty acid oxidation, mitochondrial function, and AMP-activated protein kinase (AMPK) activity. The molecular mechanisms involved with age-related changes in mitochondrial function and substrate metabolism are poorly understood. We determined gene expression differences in hearts of Young (6 mo), Old (33 mo), and old exercise trained (Old + EXE) (34 mo) FBN rats, using Qiagen PCR arrays for Glucose, Fatty acid, and Mitochondrial metabolism. Old rats demonstrated decreased (p < 0.05) expression for key genes in fatty acid oxidation, mitochondrial function, and AMPK signaling. There were no differences in the expression of genes involved in glucose metabolism with age. These gene expression changes occurred prior to altered protein translation as we found no differences in the protein content of peroxisome proliferator activated receptor gamma, coactivators 1 alpha (PGC-1α), peroxisome proliferator activated receptor alpha (PPARα), and AMPKα2 between young and old hearts. Four months of exercise training did not attenuate the decline in the gene expression in aged hearts. Despite this lack of change in gene expression, exercise-trained rats demonstrated increased exercise capacity compared to their sedentary counterparts. Taken together, our results show that differential expression of genes associated with fatty acid metabolism, AMPK signaling and mitochondrial function decrease in the aging heart which may play a role in age-related declines in fatty acid oxidation, AMPK activity, and mitochondrial function in the heart. PMID:27601998

  9. Middle-aged rats orally supplemented with gel-encapsulated catechin favorably increases blood cytosolic NADPH levels.

    PubMed

    Cueno, Marni E; Tamura, Muneaki; Ochiai, Kuniyasu

    2015-04-15

    Green tea catechins are primarily known to function as free radical scavengers and have several beneficial uses. Orally supplemented catechin (OSC) was previously shown to increase mitochondrial heme and catalase levels in rat heart blood, however, its effect in the cytosol has not been elucidated. Here, we determined the effects of OSC in the rat heart blood cytosol. We used middle-aged (40 week-old) and young (4 week-old) rats throughout the study. We isolated blood cytosol, verified its purity, and determined heme, hydrogen peroxide (H2O2) levels, catalase (CAT) activities, gp91(phox) amounts, NADP and NAD pools, sirtuin 1 (SIRT1) and glutathione reductase (GR) activities, and free fatty acids (FFA). We established that OSC is associated with decreased heme-dependent H2O2 amounts while increasing heme-independent CAT activity. Moreover, we found that OSC-related decrease in NAD(+) amounts among middle-aged rats is associated to increased NADPH levels and SIRT1 activity. In contrast, we associated OSC-related decrease in NAD(+) amounts among young rats to decreased NADPH levels and increased SIRT1 activity. This highlights a major difference between catechin-treated middle-aged and young rats. Furthermore, we observed that cytosolic FFA and GR levels were significantly increased only among OSC-treated middle-aged rats which we hypothesize are related to increased NADPH levels. This insinuates that OSC treatment allows higher catechin amounts to enter the bloodstream of middle-aged rats. We propose that this would favorably increase NADPH amounts and lead to the simultaneous decrease in NADPH-related pro-oxidant activity and increase in NADPH-related biomolecules and anti-oxidant activities.

  10. Alveolar bone dynamics in osteoporotic rats treated with raloxifene or alendronate: confocal microscopy analysis

    NASA Astrophysics Data System (ADS)

    Ramalho-Ferreira, Gabriel; Faverani, Leonardo Perez; Grossi-Oliveira, Gustavo Augusto; Okamoto, Tetuo; Okamoto, Roberta

    2015-03-01

    In this study, the characteristics of the alveolar bone of rats with induced osteoporosis were examined. Thirty-two rats were divided into four groups according to the induction of osteoporosis and drugs administered: OG, osteoporotic rats without treatment (negative control); SG, rats which underwent sham surgery ovariectomy (SHAM); alendronate (AG), osteoporotic rats treated with alendronate; and RG, osteoporotic rats treated with raloxifene (RG). On the 8th day after ovariectomy and SHAM surgeries, drug therapy was started with AG or RG. On the 52nd day, 20 mg/kg calcein was administered to all of the rats, and on the 80th day, 20 mg/kg alizarin red was administered. Euthanasia was performed on the 98th day. The bone area marked by fluorochromes was calculated and data were subjected to two-way ANOVA test and Tukey's post-hoc test (p<0.05). The comparison of the induced osteoporosis groups showed no statistically significant differences in bone turnover only between RG and SG (p=0.074) and AG and OG (p=0.138). All other comparisons showed significant differences (p<0.001). The largest bone turnover was observed in RG and SG groups. RG was the medication that improved the dynamics of the alveolar bone of rats with induced osteoporosis, resembling that of healthy rats.

  11. Zinc content of maturing spermatozoa in oestrogen treated rats.

    PubMed

    Srivastava, A; Chowdhury, A R; Setty, B S

    1983-02-01

    Zinc content of spermatozoa collected from the caput and cauda portions of the rat epididymis was determined by atomic absorption spectroscopy. The results showed about 60% reduction in the spermatozoal zinc content by the time they reach the cauda epididymis. This reduction was inhibited in rats receiving micro dose oestrogen which induced 'functional' sterility. It appears that the fall in zinc content of spermatozoa during their transport in the epididymis is related to sperm maturation and that oestrogen treatment interferes with this reduction in sperm zinc content.

  12. Zinc content in epididymal spermatozoa of metoclopramide-treated rats.

    PubMed

    Kaminska, B; Rozewicka, L; Dominiak, B; Mielnicka, M; Mikulska, D

    1987-01-01

    Zinc content was determined separately in spermatozoa taken from epididymal caput and cauda in rats. It was revealed that spermatozoa transported from the epididymal caput to the cauda reduce about 54% of zinc. This reduction is significantly inhibited in spermatozoa of rats receiving metoclopramide. That is also accompanied by a fall of testosterone level in blood serum and of delta 5, 3 beta-HSD activity in Leydig cells. It was found out that the reduction of zinc in spermatozoa at the time of their passage through the epididymis is the process that depends on androgens.

  13. The Effect of Eurycoma Longifolia Jack on Spermatogenesis in Estrogen-Treated Rats

    PubMed Central

    Wahab, Norhazlina Abdul; Mokhtar, Norfilza M.; Halim, Wan Nurul Heriza A; Das, Srijit

    2010-01-01

    INTRODUCTION: There is little data concerning the ability of Eurycoma longifolia Jack (EL) to reverse the inhibitory effects of estrogen on testosterone production and spermatogenesis. The aim of the present study was to determine the effect of EL on testicular histology and sperm count in estrogen-treated male rats. METHODS: Adult male Sprague-Dawley rats weighing 200–250 g were divided into four groups of six rats each. Group A (control) was given solvent in the same manner as the treated groups were given EL. Group B was treated with EL (8 mg/kg body weight) orally. Group C was treated with estradiol (E2) (intramuscular dose of 500 μg/kg body weight), and group D received a combined treatment of oral EL and intramuscular E2. After fourteen consecutive days of treatment, rats from all groups were sacrificed and subjected to spermatogenic and epididymal sperm cell counts. RESULTS: The spermatogenic cell count in the E2-treated group was significantly decreased as compared to the control (p < 0.05) and EL+E2-treated groups (p < 0.05). A similar finding was found for the epididymal sperm count; the E2-treated group had a significant decrease in the count compared to the control (p < 0.05) and EL+E2-treated groups (p < 0.05). Rats that were treated with EL alone exhibited significantly higher sperm counts and sperm motility when compared to the control group (p < 0.05). CONCLUSIONS: EL extract acts as a potential agent for reversing the effects of estrogen by increasing spermatogenesis and sperm counts in rats after fourteen consecutive days of treatment. PMID:20126351

  14. Cytidine diphosphate choline administration activates brain cytidine triphosphate: phosphocholine cytidylytransferase in aged rats.

    PubMed

    Giménez, R; Soler, S; Aguilar, J

    1999-10-08

    Beneficial effects of cytidine (5') diphosphocholine (CDP-choline) administration on several diseases including brain aging, ischemia and stroke are based on an increase in membrane phospholipid turnover. We have studied the possible involvement of CTP:phosphocholine cytidylyltransferase (CT) in this mechanism by measuring its gene expression and enzyme activity in the brains of young and aged rats treated with 500 mg/kg per day of CDP-choline. Older animals showed higher (57%) of total CT activity in particulate (active) fraction than younger animals (46%). Treatment of aged animals for 8, 16, or 60 days had no effect on the CT gene expression but increased activation of the CT by translocation to membranes. The particulate fraction rose from 57% of total activity to more than 65% after 2 months of treatment. This may explain the long-term repairing effects of CDP-choline on damaged membranes of aged animals.

  15. Effect of long-term administration of cordycepin from Cordyceps militaris on testicular function in middle-aged rats.

    PubMed

    Sohn, Sang-Hyun; Lee, Su-Chan; Hwang, Seock-Yeon; Kim, Sung-Won; Kim, Il-Woung; Ye, Michael B; Kim, Si-Kwan

    2012-10-01

    This study was carried out to examine the potential beneficial effect of cordycepin on the decline of testicular function induced with age. A total of 30 male Sprague-Dawley rats (twenty-four 12-month-olds and six 2-month-olds) were divided into five groups. The young control (YC) and middle-aged control (MC) groups received vehicle only. Cordycepin-treated groups were administered daily doses of oral cordycepin at 5, 10, and 20 mg/kg body weight for 4 months. As a result, the MC group exhibited epididymal weight loss, decreased sperm motility, and reduced spermatogenesis compared to the young control group. Interestingly, the epididymal weights of middle-aged rats were dose-dependently increased by treatment with cordycepin. Cordycepin also improved calcium levels and decreased urea and nitrogen, uric acid, and creatinine in the blood of middle-aged rats. In addition, cordycepin significantly increased sperm motility and the progressiveness of sperm movement. All cordycepin-treated groups showed well-arranged spermatogonia, densely packed cellular material, and increased numbers of mature spermatozoa in the seminiferous lumen compared to the middle-aged control group. These results indicate that long-term administration of cordycepin can counteract the decline of testicular function in middle-aged rats.

  16. Lycium barbarum polysaccharides prevent memory and neurogenesis impairments in scopolamine-treated rats.

    PubMed

    Chen, Weiwei; Cheng, Xiang; Chen, Jinzhong; Yi, Xin; Nie, Dekang; Sun, Xiaohui; Qin, Jianbing; Tian, Meiling; Jin, Guohua; Zhang, Xinhua

    2014-01-01

    Lycium barbarum is used both as a food additive and as a medicinal herb in many countries, and L. barbarum polysaccharides (LBPs), a major cell component, are reported to have a wide range of beneficial effects including neuroprotection, anti-aging and anticancer properties, and immune modulation. The effects of LBPs on neuronal function, neurogenesis, and drug-induced learning and memory deficits have not been assessed. We report the therapeutic effects of LBPs on learning and memory and neurogenesis in scopolamine (SCO)-treated rats. LBPs were administered via gastric perfusion for 2 weeks before the onset of subcutaneous SCO treatment for a further 4 weeks. As expected, SCO impaired performance in novel object and object location recognition tasks, and Morris water maze. However, dual SCO- and LBP-treated rats spent significantly more time exploring the novel object or location in the recognition tasks and had significant shorter escape latency in the water maze. SCO administration led to a decrease in Ki67- or DCX-immunoreactive cells in the dentate gyrus and damage of dendritic development of the new neurons; LBP prevented these SCO-induced reductions in cell proliferation and neuroblast differentiation. LBP also protected SCO-induced loss of neuronal processes in DCX-immunoreactive neurons. Biochemical investigation indicated that LBP decreased the SCO-induced oxidative stress in hippocampus and reversed the ratio Bax/Bcl-2 that exhibited increase after SCO treatment. However, decrease of BDNF and increase of AChE induced by SCO showed no response to LBP administration. These results suggest that LBPs can prevent SCO-induced cognitive and memory deficits and reductions in cell proliferation and neuroblast differentiation. Suppression of oxidative stress and apoptosis may be involved in the above effects of LBPs that may be a promising candidate to restore memory functions and neurogenesis.

  17. Lycium barbarum Polysaccharides Prevent Memory and Neurogenesis Impairments in Scopolamine-Treated Rats

    PubMed Central

    Chen, Jinzhong; Yi, Xin; Nie, Dekang; Sun, Xiaohui; Qin, Jianbing; Tian, Meiling; Jin, Guohua; Zhang, Xinhua

    2014-01-01

    Lycium barbarum is used both as a food additive and as a medicinal herb in many countries, and L. barbarum polysaccharides (LBPs), a major cell component, are reported to have a wide range of beneficial effects including neuroprotection, anti-aging and anticancer properties, and immune modulation. The effects of LBPs on neuronal function, neurogenesis, and drug-induced learning and memory deficits have not been assessed. We report the therapeutic effects of LBPs on learning and memory and neurogenesis in scopolamine (SCO)-treated rats. LBPs were administered via gastric perfusion for 2 weeks before the onset of subcutaneous SCO treatment for a further 4 weeks. As expected, SCO impaired performance in novel object and object location recognition tasks, and Morris water maze. However, dual SCO- and LBP-treated rats spent significantly more time exploring the novel object or location in the recognition tasks and had significant shorter escape latency in the water maze. SCO administration led to a decrease in Ki67- or DCX-immunoreactive cells in the dentate gyrus and damage of dendritic development of the new neurons; LBP prevented these SCO-induced reductions in cell proliferation and neuroblast differentiation. LBP also protected SCO-induced loss of neuronal processes in DCX-immunoreactive neurons. Biochemical investigation indicated that LBP decreased the SCO-induced oxidative stress in hippocampus and reversed the ratio Bax/Bcl-2 that exhibited increase after SCO treatment. However, decrease of BDNF and increase of AChE induced by SCO showed no response to LBP administration. These results suggest that LBPs can prevent SCO-induced cognitive and memory deficits and reductions in cell proliferation and neuroblast differentiation. Suppression of oxidative stress and apoptosis may be involved in the above effects of LBPs that may be a promising candidate to restore memory functions and neurogenesis. PMID:24505383

  18. Growth is compromised in rats fed ozone-treated casein

    SciTech Connect

    Kasai, T.; Iwashita, A.; Kiriyama, S. )

    1993-05-01

    Modified casein containing few phenylalanine residues and no other aromatic amino acid residues was obtained by ozonolysis of casein. Although 68% of phenylalanine was decomposed by ozonolysis of casein, ozonolysis caused alterations beyond the destruction of aromatic amino acid residues. Nearly the same degree of decomposition of amino acid residues was observed in casein ozonated after predigestion by pepsin. Rats were fed diets containing 8% casein supplemented with methionine and aspartic acid (8C-AA), 8% ozonated casein supplemented with methionine and free amino acids lost by ozonolysis (8OC-AA), 8% casein ozonated after predigestion by pepsin supplemented with methionine and free amino acids lost during preparation (8POC-AA) or 7.6% amino acid mixture. The growth of rats fed the 8OC-AA diet was significantly lower than that of those fed 8C-AA or 7.6AA diets. The growth of rats fed the 8POC-AA diet was comparable to growth of those fed 8OC-AA. The biological values of the 8OC-AA and 8POC-AA were comparable to that of 8C-AA, but true digestibility of 8OC-AA was significantly lower than that of 8C-AA. True digestibility 8POC-AA was significantly improved relative to 8OC-AA, but the growth of rats fed 8POC-AA was not improved relative to that of those fed 8OC-AA. Kidney and cecum weights of rats fed 8OC-AA and 8POC-AA were significantly heavier than those of the 8C-AA-fed group, although histopathological examination of kidneys showed no deterioration compared to that of the 8C-AA-fed group.

  19. Differential expression of sirtuins in the aging rat brain

    PubMed Central

    Braidy, Nady; Poljak, Anne; Grant, Ross; Jayasena, Tharusha; Mansour, Hussein; Chan-Ling, Tailoi; Smythe, George; Sachdev, Perminder; Guillemin, Gilles J.

    2015-01-01

    Although there are seven mammalian sirtuins (SIRT1-7), little is known about their expression in the aging brain. To characterize the change(s) in mRNA and protein expression of SIRT1-7 and their associated proteins in the brain of “physiologically” aged Wistar rats. We tested mRNA and protein expression levels of rat SIRT1-7, and the levels of associated proteins in the brain using RT-PCR and western blotting. Our data shows that SIRT1 expression increases with age, concurrently with increased acetylated p53 levels in all brain regions investigated. SIRT2 and FOXO3a protein levels increased only in the occipital lobe. SIRT3-5 expression declined significantly in the hippocampus and frontal lobe, associated with increases in superoxide and fatty acid oxidation levels, and acetylated CPS-1 protein expression, and a reduction in MnSOD level. While SIRT6 expression declines significantly with age acetylated H3K9 protein expression is increased throughout the brain. SIRT7 and Pol I protein expression increased in the frontal lobe. This study identifies previously unknown roles for sirtuins in regulating cellular homeostasis and healthy aging. PMID:26005404

  20. Cerebrovascular hemodynamic correlates of aging in the Lou/c rat: a model of healthy aging.

    PubMed

    Dubeau, S; Ferland, G; Gaudreau, P; Beaumont, E; Lesage, F

    2011-06-15

    The LOU/c rat is an inbred strain considered a model of healthy aging. It exhibits a longer free disease lifespan and a low adiposity throughout life. While this animal model has been shown to maintain eating behavior and neuroendocrine, metabolic and cognitive functions with age, no study has yet investigated vascular correlates in this model of healthy aging. In the present work, multispectral optical imaging was used to investigate the hemodynamic response in the somatosensory cortex of LOU/c rats following forepaw stimulation in three age groups, 4, 24 and 40months. Results indicate reduced hemodynamic responses in the contralateral somatosensory cortex between young (4months) and older groups following stimulation. This decrease was associated with an increase in the spatial extent of activation. The ipsilateral response did not change with aging leading to decreased laterality. Estimations of the relative change in the local cerebral metabolic rate of oxygen during stimulation based on multimodal data showed no significant change with age. The exponent describing the relation between blood volume and blood flow changes, Grubb's parameter, did display a significant change with age which may suggest vessel compliance modifications. This work finds its relevance in recent findings underlying the importance of vascular changes with aging and its impact on neurodegenerative disease.

  1. Rat Plasma Oxidation Status After Nigella Sativa L. Botanical Treatment in CCL(4)-Treated Rats.

    PubMed

    Soleimani, Hengameh; Ranjbar, Akram; Baeeri, Maryam; Mohammadirad, Azadeh; Khorasani, Reza; Yasa, Narguess; Abdollahi, Mohammad

    2008-01-01

    ABSTRACT Nigella sativa Linn. (family Ranunculaceae), commonly known as black cumin, is native to the Mediterranean area and has been used for thousands of years as a health and beauty aid. The present study investigated the protective effects of Nigella sativa (NS) extract (NSE) and oil (NSO) on CCl(4)-induced nitrosative stress and protein oxidation in rat. CCl(4) (0.8 mg/kg) was used as an aid for induction of nitrosative stress. In vitro antioxidant potential was tested in the presence of 2,4-dinitrophenylhyrdazine (DPPH) as an organic nitrogen radical. Doses of 0.2, 0.3, and 1 mg/kg of the NS extract and oil were administered to CCL(4)-treated rats for 10 days. At the end of treatment, blood was taken from rats under anesthesia and plasma was separated. The concentration of nitric oxide (NO), total antioxidant power (TAP), carbonyl molecules (CM) as measure of protein oxidation (PO), tumor necrosis factor-alpha (TNF-alpha), and total thiol molecules (TTM) were measured in plasma. In vitro evaluation of antioxidant effects of NSE and NSO showed that the highest antioxidant activity (80%) was observed with the concentration of 10 and 20 mg/ml, respectively, that were equal to vitamin E (200 mg/ml). Administration of CCL(4) increased plasma PO, NO, TNF-alpha and decreased TAP and TTM. Both NSE and NSO showed significant protection against CCl(4)-induced changes in biochemical parameters, but not dose-dependently. Doses of 0.3 and 1 mg/kg were more effective than doses of 0.2 mg/kg for both NSE and NSO, but dose of 1 mg/kg was the most effective one. The results indicate the potential of NS in preventing CCL(4)-induced toxic nitrosative stress. It is concluded that NS has marked antioxidant potentials that may be beneficial in alleviating complications of many illnesses related to oxidative/nitrosative stress in humans, but preclinical safety measures should be completed before clinical trials.

  2. 76 FR 69292 - Aging Management of Stainless Steel Structures and Components in Treated Borated Water

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-08

    ... COMMISSION Aging Management of Stainless Steel Structures and Components in Treated Borated Water AGENCY... Staff Guidance (LR-ISG), LR- ISG-2011-01, ``Aging Management of Stainless Steel Structures and... Learned (GALL) Report for the aging management of stainless steel structures and components exposed...

  3. Inflammation and hyperalgesia in rats neonatally treated with capsaicin: effects on two classes of nociceptive neurons in the superficial dorsal horn.

    PubMed

    Ren, K; Williams, G M; Ruda, M A; Dubner, R

    1994-11-01

    To address the mechanisms of hyperalgesia and dorsal horn plasticity following peripheral tissue inflammation, the effects of adjuvant-induced inflammation of the rat hindpaw on behavioral nociception and nociceptive neuronal activity in the superficial dorsal horn were examined in neonatally capsaicin-treated rats 6-8 weeks of age. Capsaicin treatment resulted in an 82% loss of unmyelinated fibers in L5 dorsal roots, a dramatic reduction of substance P-like immunoreactivity in the spinal cord, and a significant decrease in the percentage of dorsal horn nociceptive neurons that responded to C-fiber stimulation and noxious heating of the skin. The thermal nociceptive threshold was significantly increased in capsaicin-treated rats, but behavioral hyperalgesia to thermal stimuli still developed in response to inflammation. Following inflammation, there was a significant decrease in mechanical threshold and an increase in response duration to mechanical stimuli in both vehicle- and capsaicin-treated rats, suggesting that a state of mechanical hyperalgesia was also induced. The capsaicin treatment appears to have differential effects on nociceptive specific (NS) and wide-dynamic-range (WDR) neurons in inflamed rats. Expansion of the receptive fields of nociceptive neurons, a measure of the effect of inflammation-induced CNS plasticity, was less extensive for NS than for WDR neurons in capsaicin-treated rats. Compared to vehicle-treated rats, a smaller population of NS neurons, but a similar percentage of WDR neurons, had background activity in inflamed capsaicin-treated rats. C-fiber strength electrical stimulation of the sciatic nerve produced expansion of the receptive fields in a greater portion of NS neurons (53%, P < 0.05) in capsaicin- than in vehicle-treated rats (32%). There was no difference in stimulation-induced expansion of the receptive fields for WDR neurons between vehicle- or capsaicin-treated rats. An N-methyl-D-aspartate receptor antagonist, MK-801

  4. Delay in growth and the development of nephritis in rats treated with interferon preparations in the neonatal period.

    PubMed Central

    Gresser, I.; Morel-Maroger, L.; Châtelet, F.; Maury, C.; Tovey, M.; Bandu, M. T.; Buywid, J.; Delauche, M.

    1979-01-01

    Suckling rats were injected for 14 to 17 days with potent rat-cell-culture interferon preparations or various heterologous interferon or control preparations. Only treatment with rat interferon resulted in a delay in growth and maturation of different organs and the subsequent development of an "immune complex" type nephritis. Thus, 38 of 43 rats treated with rat interferon developed a severe glomerulonephritis. Thus, 38 of 43 rats treated with rat interferon developed a severe glomerulonephritis, whereas only 3 of 99 rats in the various control groups had minimal renal lesions. Deposits of IgG and C3 along the glomerular basement membrane were only seen in interferon-treated rats. Images Figure 6 Figure 3 Figure 2 Figure 5 Figure 4 Figure 1 PMID:156503

  5. Carbohydrate digestibility predicts colon carcinogenesis in azoxymethane-treated rats.

    PubMed

    Jacobsen, Helene; Poulsen, Morten; Dragsted, Lars Ove; Ravn-Haren, Gitte; Meyer, Otto; Lindecrona, Rikke Hvid

    2006-01-01

    The purpose of this study was to compare the effect of carbohydrate structure and digestibility on azoxymethane (AOM)-induced colon carcinogenesis. Five groups of male Fischer 344 rats each comprising 30 animals were injected with AOM and fed a high-fat diet with 15% of various carbohydrates. The carbohydrate sources used were sucrose, cornstarch (a linear starch, reference group), potato starch (a branched starch), a short-chained oligofructose (Raftilose), and a long-chained inulin-type fructan (Raftiline). An interim sacrifice was performed after 9 wk to investigate markers of carbohydrate digestibility, including caecal fermentation (caecum weight and pH) and glucose and lipid metabolism [glucose, fructoseamine, HbA1c, triglycerides, and insulin-like growth factor (IGF) 1]. In addition potential early predictors of carcinogenicity [cell proliferation and aberrant crypt foci (ACF)] at 9 wk and their correlation to colon cancer risk after 32 wk were investigated. Tumor incidence was significantly reduced in animals fed oligofructose, and the number of tumors per animal was significantly reduced in animals fed inulin and oligofructose at 32 wk after AOM induction compared to the reference group fed sucrose. Increased caecum weight and decreased caecal pH were seen in groups fed oligofructose, inulin, and potato starch. Plasma triglyceride was decreased in rats fed oligofructose and inulin. Cell proliferation was increased in the proximal colon of rats fed sucrose, oligofructose, and inulin, and the number of cells per crypt decreased in rats fed oligofructose and inulin. The total number of ACF's was unaffected by treatment, and the size and multiplicity of ACF was unrelated to tumor development. It was concluded that less digestible carbohydrates with an early effect on caecum fermentation and plasma triglyceride decreased subsequent tumor incidence and multiplicity. This was unrelated to ACF, cell proliferation, and other markers of glucose and lipid metabolism.

  6. Antiamnesic effect of stevioside in scopolamine-treated rats

    PubMed Central

    Sharma, Deepika; Puri, Munish; Tiwary, Ashok K.; Singh, Nirmal; Jaggi, Amteshwar Singh

    2010-01-01

    The present study was undertaken to explore the potential of stevioside in memory dysfunction of rats. Memory impairment was produced by scopolamine (0.5 mg/kg, i.p.) in animals. Morris water maze (MWM) test was employed to assess learning and memory. Brain acetylcholinestrase enzyme (AChE) activity was measured to assess the central cholinergic activity. The levels of brain thiobarbituric acid-reactive species (TBARS) and reduced glutathione (GSH) were estimated to assess the degree of oxidative stress. Scopolamine administration induced significant impairment of learning and memory in rats, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and brain oxidative stress (increase in TBARS and decrease in GSH) levels. Pretreatment of stevioside (250 mg/kg dose orally) significantly reversed scopolamine-induced learning and memory deficits along with attenuation of scopolamine-induced rise in brain AChE activity and brain oxidative stress levels. It may be concluded that stevioside exerts a memory-preservative effect in cognitive deficits of rats possibly through its multiple actions. PMID:20871768

  7. Validation of anti-aging drugs by treating age-related diseases.

    PubMed

    Blagosklonny, Mikhail V

    2009-03-28

    Humans die from age-related diseases, which are deadly manifestations of the aging process. In order to extend life span, an anti-aging drug must delay age-related diseases. All together age-related diseases are the best biomarker of aging. Once a drug is used for treatment of any one chronic disease, its effect against other diseases (atherosclerosis, cancer, prostate enlargement, osteoporosis, insulin resistance, Alzheimer's and Parkinson's diseases, age-related macular degeneration) may be evaluated in the same group of patients. If the group is large, then the anti-aging effect could be validated in a couple of years. Startlingly, retrospective analysis of clinical and preclinical data reveals four potential anti-aging modalities.

  8. [Age-related characteristics of experimental hypothyroidism in rats].

    PubMed

    Hromakova, I A; Zil'berman, S Ts; Konovalenko, O O

    2002-01-01

    The rate of both the synthesis of liver and plasma proteins and RNA-1 and RNA-2 polymerase activities in liver were studied in rats of various ages at experimental hypothyroidism. There has been marked more significant decrease in plasma protein synthesis with age. Both the rate of liver and plasma protein synthesis have been shown to be reduced at experimental hypothyroidism but synthesis of plasma proteins was inhibited to a greater extent. Considerable changes were observed neither in liver and plasma protein synthesis nor in the balance between these two groups of the protein synthesis in old rats. RNA-1 and RNA-2 polymerase activities decreased at hypothyroidism. At all ages the activity of bound enzymes decreased to a larger extent as compared to free forms. The activity of RNA-polymerase 2 was more inhibited than that of RNA-polymerase 1. Reducing protein- and RNA-synthetic processes in the liver with age correlated with the peculiarities of the carbohydrate metabolism: in those young animals with an impaired glucose tolerance the inhibitory effect of hypothyroidism on the intensity of protein and RNA synthesis was more potent as compared to old animals.

  9. Oxidative Damage in the Aging Heart: an Experimental Rat Model

    PubMed Central

    Marques, Gustavo Lenci; Neto, Francisco Filipak; Ribeiro, Ciro Alberto de Oliveira; Liebel, Samuel; de Fraga, Rogério; Bueno, Ronaldo da Rocha Loures

    2015-01-01

    Introduction: Several theories have been proposed to explain the cause of ‘aging’; however, the factors that affect this complex process are still poorly understood. Of these theories, the accumulation of oxidative damage over time is among the most accepted. Particularly, the heart is one of the most affected organs by oxidative stress. The current study, therefore, aimed to investigate oxidative stress markers in myocardial tissue of rats at different ages. Methods: Seventy-two rats were distributed into 6 groups of 12 animals each and maintained for 3, 6, 9, 12, 18 and 24 months. After euthanasia, the heart was removed and the levels of non-protein thiols, lipid peroxidation, and protein carbonylation, as well as superoxide dismutase and catalase activities were determined. Results: Superoxide dismutase, catalase activity and lipid peroxidation were reduced in the older groups of animals, when compared with the younger group. However, protein carbonylation showed an increase in the 12-month group followed by a decrease in the older groups. In addition, the levels of non-protein thiols were increased in the 12-month group and not detected in the older groups. Conclusion: Our data showed that oxidative stress is not associated with aging in the heart. However, an increase in non-protein thiols may be an important factor that compensates for the decrease of superoxide dismutase and catalase activity in the oldest rats, to maintain appropriate antioxidant defenses against oxidative insults. PMID:27006709

  10. Immunohistochemical distribution of leptin in kidney tissues of melatonin treated diabetic rats.

    PubMed

    Elis Yildiz, S; Deprem, T; Karadag Sari, E; Bingol, S A; Koral Tasci, S; Aslan, S; Nur, G; Sozmen, M

    2015-05-01

    We examined using immunohistochemistry the distribution of leptin in kidney tissues of melatonin treated, streptozotocin (STZ) diabetic rats. The animals were divided into five groups: control, sham, melatonin-treated, diabetic and melatonin-treated diabetic. Kidney sections were prepared and stained with hematoxylin and eosin, and Crossman's triple staining for histological examination. The immunohistochemical localization of leptin in the kidney tissue was determined using the streptavidin-biotin-peroxidase method. We determined that on days 7 and 14, the leptin immunoreactivity of the diabetic and melatonin-treated diabetic groups was weaker than for the other groups. Weak immunoreactivity was found in the proximal and distal tubules of the kidney in the diabetic and melatonin-treated diabetic groups on days 7 and 14, and strong immunoreactivity was found in the control, sham and melatonin groups. Melatonin application had no significant effect on leptin production in the kidney tissues of diabetic rats.

  11. Nampt Expression Decreases Age-Related Senescence in Rat Bone Marrow Mesenchymal Stem Cells by Targeting Sirt1

    PubMed Central

    Ma, Cao; Pi, Chenchen; Yang, Yue; Lin, Lin; Shi, Yingai; Li, Yan; Li, Yulin; He, Xu

    2017-01-01

    Senescence restricts the development of applications involving mesenchymal stem cells (MSCs) in research fields, such as tissue engineering, and stem cell therapeutic strategies. Understanding the mechanisms underlying natural aging processes may contribute to the development of novel approaches to preventing age-related diseases or slowing individual aging processes. Nampt is a rate-limiting NAD biosynthetic enzyme that plays critical roles in energy metabolism, cell senescence and maintaining life spans. However, it remains unknown whether Nampt influences stem cell senescence. In this study, the function of Nampt was investigated using a rat model of natural aging. Our data show that Nampt expression was significantly lower in MSCs obtained from aged rats than in those obtained from young rats during physiological aging. Reducing the level of Nampt in aged MSCs resulted in lower intracellular concentrations of NAD+ and downregulated Sirt1 expression and activity. After the Nampt inhibitor FK866 was added, young MSCs were induced to become aged cells. The enhanced senescence was correlated with NAD+ depletion and Sirt1 activity attenuation. In addition, Nampt overexpression attenuated cell senescence in aged MSCs. Our findings provide a new explanation for the mechanisms underlying stem cell senescence and a novel target for delaying stem cell senescence and preventing and treating age-related diseases. PMID:28125705

  12. Depressive-like behavior in adrenocorticotropic hormone-treated rats blocked by memantine.

    PubMed

    Tokita, Kenichi; Fujita, Yuko; Yamaji, Takayuki; Hashimoto, Kenji

    2012-08-01

    Hyperactivity of the hypothalamic pituitary-adrenal (HPA) axis plays a role in the pathophysiology of major depressive disorder (MDD). Recent studies suggest the role of the glutamatergic system in the pathophysiology of MDD, and N-methyl-D-aspartate (NMDA) receptor antagonists have shown antidepressant effects in both preclinical and clinical studies. However, little is known about the role of adrenocorticotropic hormone (ACTH) specifically in the glutamatergic response to HPA axis activation. Glutamate is an NMDA receptor agonist, and glycine and D-serine act as co-agonists. Here, we measured brain concentrations of these amino acids in rats given repeated administration of ACTH (100 μg/rat/day, sc, for 14 days). Further, we also evaluated behavioral effects of memantine, a non-competitive NMDA antagonist, on immobility time in the forced swimming test and on locomotor activity in ACTH-treated rats. Compared with control rats, glutamine, glycine, L-serine, and D-serine levels were increased in the hippocampus of ACTH-treated rats; glutamate, glutamine, glycine, L-serine, and D-serine were increased in the cerebellum; and glutamine and glycine were increased in the frontal cortex and striatum, all with statistical significance. Remarkably, these increases in agonists and co-agonists might have led to the augmentation of NMDA receptor activity. ACTH treatment increased immobility time in the forced swimming test and decreased locomotor activity in rats. On the contrary, memantine (10 mg/kg, ip) significantly decreased immobility time in the forced swimming test and increased locomotor activity in ACTH-treated rats. Furthermore, imipramine (15 mg/kg, ip) did not alter immobility time in the forced swimming test whereas this drug significantly decreased locomotor activity in ACTH-treated rats. These results suggest that depressive-like behaviors by chronic ACTH treatment could be blocked by memantine.

  13. Factors affecting mammary tumor incidence in chlorotriazine-treated female rats: hormonal properties, dosage, and animal strain.

    PubMed Central

    Eldridge, J C; Tennant, M K; Wetzel, L T; Breckenridge, C B; Stevens, J T

    1994-01-01

    Chlorotriazines are widely used in agriculture as broadleaf herbicides. The compounds specifically inhibit photosynthesis, and, as such, display little interaction with animal systems. However, a 24-month feeding study with atrazine (ATR) revealed a significant dose-related increase of mammary tumors in female Sprague-Dawley (SD) rats. Because numerous studies indicated that ATR had a low mutagenic and oncogenic potential, it was decided to test a hypothesis that the herbicide possessed endocrine activity. Among tests for estrogenic action, oral dosing of ATR up to 300 mg/kg did not stimulate uterine weight of ovariectomized rats. However, ATR administration did reduce estrogen-stimulated uterine weight gain. Further evidence of inhibition came from measures of [3H]-thymidine incorporation into uterine DNA of ATR-treated immature rats. Again, no intrinsic estrogenic activity was observed up to a 300-mg/kg dose. In vitro, ATR competed poorly against estradiol binding to cytosolic receptors, with an approximate IC50 of 10(-5) M. Atrazine administration to SD and Fischer-344 (F-344) rats for 12 months, up to 400 ppm in food, was correlated with significant alterations of estrous cycling activity; but there was a divergent strain response. SD rats showed an increased number of days in vaginal estrus, increased plasma estradiol, and decreased plasma progesterone by 9 to 12 months of treatment. F-344 rats did not demonstrate treatment-related affects. A study of ultrastructure in the hypothalamic arcuate nucleus of female SD rats that were fed diaminochlorotriazine (DACT), an ATR metabolite, suggested that age-associated glial pathology was enhanced by treatment.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 8. PMID:7737039

  14. Atorvastatin improves Y-maze learning behaviour in nicotine treated male albino rats.

    PubMed

    Das S, Syam; Nair, Saritha S; Kavitha, S; Febi, John; Indira, M

    2015-11-01

    Nicotine is a parasympathomimetic alkaloid present in tobacco which can induce hyperlipidemia and has a direct effect on neural functions. Statins, competitive inhibitors of 3-hydroxymethyl-3-glutaryl-coenzyme-A reductase, are cholesterol lowering drugs. It has some neuroprotective effects. Hence we analysed the combined effect of nicotine and statin on the learning behaviour of male albino rats. We employed Y-Maze conditional discrimination task. Rats were divided into 4 groups with six rats in each group. (1) Control, (2) Atorvastatin (10mg/kgb.wt), (3) Nicotine (0.6mg/kgb.wt) and (4) Atorvastatin (10mg/kgb.wt)+Nicotine (0.6mg/kgb.wt). After 30days of treatment rats from each group were selected for behavioural study and they were observed for 30days. At the end of the experimental period rats were sacrificed, and brain and liver were dissected out for further biochemical analysis. Nicotine treated group showed least performance in learning in comparison with control, atorvastatin and atorvastatin+nicotine treated groups. Co-administration of atorvastatin and nicotine improved learning behaviour compared to nicotine treated group. Reactive oxygen species level was significantly increased in nicotine group compared to control. The level of neurotransmitter serotonin which has a significant role in learning was found to be decreased in nicotine treated group compared to the control group. Activity of Na(+) K(+) ATPase, Ca(2+) ATPase and glutathione content was significantly reduced in nicotine treated group compared to control. The activity of acetylcholine esterase was significantly increased in the nicotine treated group. Expression studies showed significant decrease in N-methyl D-aspartate receptors and increase in mono amine oxidase-A and mono amine oxidase-B in nicotine treated group and was reversed in atorvastatin + nicotine treated group. It can be concluded that co-administration of nicotine with statin ameliorates the neural functional alterations caused

  15. Dietary chloride does not correlate with urinary thromboxane in deoxycorticosterone acetate-treated rats.

    PubMed

    Theriot, J A; Passmore, J C; Jimenez, A E; Fleming, J T

    2000-06-01

    Renal vascular resistance in deoxycorticosterone acetate (DOCA) salt-treated uninephrectomized rats is increased by high dietary chloride. Because DOCA salt-hypertensive rats exhibit an increased urinary excretion of thromboxane B2 (TXB2), a metabolite of thromboxane A2 (TXA2), the increased TXB2 excretion by DOCA salt-treated rats could relate to elevated dietary chloride, increased blood pressure, and/or the presence of intact renal tubules. We hypothesized that high NaCl intake, resulting in an elevated tubular chloride excretion, stimulates TXA2 production. A result of that production could be renal vasoconstriction. Baseline blood pressures were measured for 10 days, and then the rats were treated with DOCA (30 mg/kg) and fed (1) normal NaCl, (2) normal sodium with high chloride, or (3) high sodium chloride (NaCl) for 4.5 weeks. Next, the rats were uninephrectomized (1K) or unihydronephrectomized (1KHK) to yield one kidney without an intact tubular system and therefore no macula densa. Two and a half weeks later, urinary excretion of TXB2 was determined. DOCA-high NaCl-fed 1KHK or 1K rats had significant increases in systemic blood pressure to 172 +/- 12 and 190 +/- 5 mm Hg, respectively, compared with no significant increase in blood pressure among the other groups. Urinary TXB2 excretion was increased to 29 +/- 4 pg per 24 hours per gram of body weight in all DOCA-treated 1KHK and 1K animals regardless of diet compared with DOCA-treated animals with two intact kidneys (13 +/- 2 pg per 24 hours per gram of body weight). DOCA treatment in rats with one functional kidney results in the excretion of high levels of urinary TXB2 unrelated to dietary chloride load, blood pressure, or intact renal tubules.

  16. Vascular endothelial function is improved by oral glycine treatment in aged rats.

    PubMed

    Gómez-Zamudio, Jaime H; García-Macedo, Rebeca; Lázaro-Suárez, Martha; Ibarra-Barajas, Maximiliano; Kumate, Jesús; Cruz, Miguel

    2015-06-01

    Glycine has been used to reduce oxidative stress and proinflammatory mediators in some metabolic disorders; however, its effect on the vasculature has been poorly studied. The aim of this work was to explore the effect of glycine on endothelial dysfunction in aged rats. Aortic rings with intact or denuded endothelium were obtained from untreated or glycine-treated male Sprague-Dawley rats at 5 and 15 months of age. Concentration-response curves to phenylephrine (PHE) were obtained from aortic rings incubated with N(G)-nitro-l-arginine methyl ester (l-NAME), superoxide dismutase (SOD), indomethacin, SC-560, and NS-398. Aortic mRNA expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase 4 (NOX-4), cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2), tumour necrosis factor (TNF)-α, and interleukin-1 β was measured by real time RT-PCR. The endothelial modulation of the contraction by PHE was decreased in aortic rings from aged rats. Glycine treatment improved this modulator effect and increased relaxation to acetylcholine. Glycine augmented the sensitivity for PHE in the presence of l-NAME and SOD. It also reduced the contraction by incubation with indomethacin, SC-560, and NS-398. Glycine increased the mRNA expression of eNOS and decreased the expression of COX-2 and TNF-α. Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability.

  17. GABAB receptor GTP-binding is decreased in the prefrontal cortex but not the hippocampus of aged rats

    PubMed Central

    McQuail, Joseph A.; Bañuelos, Cristina; LaSarge, Candi L.; Nicolle, Michelle M.; Bizon, Jennifer L.

    2011-01-01

    GABAB receptors (GABABRs) have been linked to a wide range of physiological and cognitive processes and are of interest for treating a number of neurodegenerative and psychiatric disorders. As many of these diseases are associated with advanced age, it is important to understand how the normal aging process impacts GABABR expression and signaling. Thus, we investigated GABABR expression and function in the prefrontal cortex (PFC) and hippocampus of young and aged rats characterized in a spatial learning task. Baclofen-stimulated GTP-binding and GABABR1 and GABABR2 proteins were reduced in the PFC of aged rats but these reductions were not associated with spatial learning abilities. In contrast, hippocampal GTP-binding was comparable between young and aged rats but reduced hippocampal GABABR1 expression was observed in aged rats with spatial learning impairment. These data demonstrate marked regional differences in GABABR complexes in the adult and aged brain and could have implications for both understanding the role of GABAergic processes in normal brain function and the development of putative interventions that target this system. PMID:22169202

  18. Vasodilator responses to dopamine in rat perfused mesentery are age-dependent.

    PubMed Central

    Wanstall, J. C.; O'Donnell, S. R.

    1989-01-01

    1. Dose-dependent vasodilator responses to dopamine, isoprenaline, noradrenaline, 3-isobutyl-1-methylxanthine (IBMX) and sodium nitroprusside were obtained in isolated perfused mesentery preparations, taken from reserpine-treated rats of different ages. The preparations were pretreated with phenoxybenzamine (1 microM) and perfused with physiological salt solution containing cocaine (10 microM), additional KCl (20 mM) and vasopressin (0.1 microM). 2. Vasodilator responses to dopamine were abolished by the dopamine1 (DA1)-selective antagonist SCH 23390 (10 nM) and those to isoprenaline by propranolol (1 microM), but the vasodilator responses to noradrenaline were abolished only when SCH 23390 and propranolol were used together. This indicated that dopamine was acting via DA1-receptors, isoprenaline via beta-adrenoceptors and that noradrenaline could act via DA1-receptors and beta-adrenoceptors in this preparation. 3. Responses to all the vasodilator drugs decreased in magnitude between the ages of 1 and 2 months. Responses to dopamine declined further in 4 month-old rats and were negligible at 6 or 22-24 months of age. Responses to isoprenaline were well maintained up to 6 months of age, but were negligible at 22-24 months. 4. It is concluded that, in the rat mesenteric vasculature, there is a non-specific decline in responses to vasodilator drugs during development (1 to 2 months). Subsequently there is a specific decline in DA1-receptor-mediated and beta-adrenoceptor-mediated responses; the former are lost at an earlier age than the latter. This different time course suggests that age influences receptor numbers, or their coupling to adenylate cyclase, rather than a post-receptor event in the adenylate cyclase/cyclic AMP pathway. PMID:2804550

  19. Somatostatin, insulin and glucagon secretion by the perfused pancreas from the cysteamine-treated rat

    SciTech Connect

    Silvestre, R.A.; Miralles, P.; Moreno, P.; Villanueva, M.L.; Marco, J.

    1986-02-13

    In rats, administration of a single dose of cysteamine (300 mg/kg, intragastrically) induces a depletion of pancreatic somatostatin content (approximately 60%) without modifying pancreatic insulin or glucagon content. In perfused pancreases from cysteamine-treated rats, there was a lack of somatostatin response to glucose, arginine or tolbutamide. In the absence of stimulated somatostatin release, the secretory responses of insulin and glucagon to glucose, to arginine, and to tolbutamide were not significantly different from those observed in pancreases from control rats. Our data do not support the concept that pancreatic somatostatin plays a major role in the control of insulin and glucagon release.

  20. Stimulation of adrenal DNA synthesis in cadmium-treated male rats

    SciTech Connect

    Nishiyama, S.; Nakamura, K.

    1984-07-01

    Cadmium chloride (CdCl2) at a dose of 1 mg/kg body wt was injected into male rats of the Wistar strain, weighing 250 g on the average, twice a day (12-hr intervals) for 7 consecutive days. DNA and RNA contents and (/sup 3/H)-thymidine and (/sup 3/H)-uridine incorporation into the acid-insoluble fraction significantly increased in the adrenals of rats treated with Cd for 2 and 7 consecutive days. Adrenal protein content and weight also significantly increased. These results indicate that continued treatment with Cd stimulates DNA and RNA synthesis in the adrenal cortex, which in turn results in the increase of the total protein contents of the adrenal gland and subsequently in the enlargement of the gland. Serum adrenocorticotrophin (ACTH) and insulin levels in Cd-treated rats were not higher than control levels, suggesting that the stimulation of DNA synthesis in the adrenals of Cd-treated rats is due to factor(s) other than serum ACTH and insulin. Treatment with Cd inhibited DNA synthesis in cultured adrenocortical cells at concentrations of 10(-4) to 10(-8) M, suggesting that Cd does not directly stimulate DNA synthesis in the adrenal gland in vivo. Although the adrenal gland became enlarged, the total adrenal corticosterone content decreased significantly. The decrease of total adrenal corticosterone content may be due to the fall in serum ACTH level of Cd-treated rats.

  1. Natural killer (NK) activity of pit cells perfused from livers of rats treated with ethanol

    SciTech Connect

    Albornoz, L.; Jones, J.M.; Crutchfield, C.; Veech, R.L. Univ. of Arkansas Medical Sciences, Little Rock )

    1991-03-11

    The liver is the major site of ethanol (ETOH) metabolism. Liver sinusoids contain lymphocytes with NK activity. The authors treated LEW rats for 2 weeks with i.p. injection of 1.25 ml 25% ETOH/kg 3 times/week and 5% ETOH in drinking water. Livers were perfused at 5-fold physiological pressure and cells obtained were banded on 1.077 density Ficoll. Their cytotoxicity was tested against {sup 51}Cr-labeled YAC-1 or U937 and compared to spleen and blood lymphocytes. In untreated rats, pit cell NK activity was 2-fold that of splenic lymphocytes and 4-fold that of blood lymphocytes. Compared to controls, ETOH-treated rats exhibited a 30 to 90% rise in pit cell NK activity detected with YAC-1 or U937 targets. The pit cell enhanced NK activity in ETOH-treated rats was further increased if polyinosinicpolycytidilic acid was injection i.p. 18 hours before the assay. Blood and spleen lymphocyte NK activity of ETOH-treated rats was also greater than in controls. There was no evidence that ETOH merely redistributed lymphocytes among the tissues. Although ETOH acutely inhibits NK activity in vitro, chronic ETOH increases in vivo.

  2. Electrophysiological observations in hippocampal slices from rats treated with the ketogenic diet.

    PubMed

    Stafstrom, C E; Wang, C; Jensen, F E

    1999-11-01

    The electrophysiological effects of the high-fat, low-carbohydrate ketogenic diet (KD) were assessed in normal and epileptic [kainic-acid(KA)-treated] adult rats using hippocampal slices. In the first set of experiments, normal rats were fed the KD or a standard control diet for 6-8 weeks (beginning on postnatal day 56, P56), after which they were sacrificed for hippocampal slices. All rats on the KD became ketotic. The baseline effects of the KD were determined by comparing extracellular measures of synaptic transmission and responses to evoked stimulation, and hippocampal excitability was tested in Mg(2+)-free medium. There were no differences in EPSP slope, input/output relationship, responses to evoked stimulation or Mg(2+)-free burst frequency between slices from control and KD-fed rats. In another set of experiments, rats were made epileptic by intraperitoneal injection of kainic acid (KA) on P54, which caused status epilepticus followed by the development of spontaneous recurrent seizures (SRS) over the next few weeks. Two days after KA-induced status, rats were divided into a control-fed group and a KD-fed group. Animals on the KD had significantly fewer SRS over the ensuing 8 weeks. In hippocampal slices from KA-treated, KD-fed rats, there were fewer evoked CA1 population spikes than from slices of control-fed rats. These results suggest that the KD does not alter baseline electrophysiological parameters in normal rats. In rats made chronically epileptic by administration of KA, KD treatment was associated with fewer spontaneous seizures and reduced CA1 excitability in vitro. Therefore, at least part of the KD mechanism of action may involve long-term changes in network excitability.

  3. Deficits in coordinated motor behavior and in nigrostriatal dopaminergic system ameliorated and VMAT2 expression up-regulated in aged male rats by administration of testosterone propionate.

    PubMed

    Wang, Li; Kang, Yunxiao; Zhang, Guoliang; Zhang, Yingbo; Cui, Rui; Yan, Wensheng; Tan, Huibing; Li, Shuangcheng; Wu, Baiyila; Cui, Huixian; Shi, Geming

    2016-06-01

    The effects of testosterone propionate (TP) supplements on the coordinated motor behavior and nigrostriatal dopaminergic (NSDA) system were analyzed in aged male rats. The present study showed the coordinated motor behavioral deficits, the reduced activity of NSDA system and the decreased expression of vesicular monoamine transporter 2 (VMAT2) in 24 month-old male rats. Long term TP treatment improved the motor coordination dysfunction with aging. Increased tyrosine hydroxylase and dopamine transporter, as well as dopamine and its metabolites were found in the NSDA system of TP-treated 24 month-old male rats, indicative of the amelioratory effects of TP supplements on NSDA system of aged male rats. The enhancement of dopaminergic (DAergic) activity of NSDA system by TP supplements might underlie the amelioration of the coordinated motor dysfunction in aged male rats. TP supplements up-regulated VMAT2 expression in NSDA system of aged male rats. Up-regulation of VMAT2 expression in aged male rats following chronic TP treatment might be involved in the maintenance of DAergic function of NSDA system in aged male rats.

  4. Binding and action of glucagon in isolated adipocytes from cortisol-treated rats.

    PubMed

    Calle, C; Sanchez-Casas, P; Simón, M A; Mayor, P

    1987-05-29

    Evidence for pre-receptor, receptor and post-receptor glucagon defects was investigated in adipocytes from cortisol-treated rats. A decrease in glucagon binding due to a decreased number of receptors was observed. No changes in receptor affinity were detected. Both, the lipolytic response of glucagon and the ability of glucagon to increase basal and theophylline-stimulated cAMP accumulation remained unaltered. Moreover, a hyperglucagonemia accompanied by an increase in glucagon degradation in the serum of cortisol-treated rats was observed. Such alterations could represent a new mechanism by which glucocorticoids exert their biological actions.

  5. The effects and mechanism of estrogen on rats with Parkinson’s disease in different age groups

    PubMed Central

    Li, Xue-Zhong; Sui, Chen-Yan; Chen, Qiang; Zhuang, Yuan-Su; Zhang, Hong; Zhou, Xiao-Ping

    2016-01-01

    Objective: In order to investigate the effect and mechanism of estrogen in rotenone-induced Parkinson’s disease (PD) rats in different age groups. Methods: we established rat models of PD by rotenone at different interventions. Then, behavioral tests, immunohistochemistry, western blot, high-performance liquid chromatography-electrochemical detector (HPLC-ECD) and electron microscopy were performed. Results: Results revealed the following: (1) Rotenone significantly reduced rotarod latencies in senile rats, prolonged their climbing pole time, and decreased TH positive cells, DA and its metabolite, DOPAC. Estrogen ameliorated this effect, in which weaker effects were observed in younger rats compared with older rats. (2) Rotenone increased the expression of LC3-II in older rats, but estrogen and tamoxifen did not show the same effect. (3) Rotenone increased the number of autophagosomes, but estrogen increased the proportion of autolysosomes/autophagosomes in the rotenone-treated group. (4) U0126 could reduce the number of autophagosomes in the rotenone-treated group, but this did not change the proportion of autolysosome/autophagosome in combining rotenone with the estrogen group. Rapamycin did not increase the number of autophagosomes in the rotenone-treated group, but combining rapamycin with estrogen and rotenone was able to further increase the proportion of autolysome/autophagosomes. Therefore, we speculate that the senile rat model of PD was more reliable than that in young rats. Conclusions: In addition, estrogen could promote autophagy maturation through the ERK pathway, and had an obvious therapeutic effect on the rat model of PD. PMID:27829998

  6. [Study on effect of astragali radix polysaccharides in improving learning and memory functions in aged rats and its mechanism].

    PubMed

    Yao, Hui; Gu, Li-Jia; Guo, Jian-You

    2014-06-01

    To observe the effect of Astragali Radix polysaccharides (APS) on the learning and memory functions of aged rats, in order to explore its mechanism for improving the learning and memory functions. Natural aging female SD rats were selected in the animal model and randomly divided into the control group, the APS low-dose group (50 mg x kg(-1)), the APS high-dose group (150 mg x kg(-1)) and the piracetam-treated group (560 mg x kg(-1)). They were orally administered with the corresponding drugs for consecutively 60 days. Besides, a young control group was set. The learning and memory functions of the rats were tested by the open-field test and the Morris water maze task. The Western-blot method was used to observe the levels of relevant neural plasticity protein N-methyl-D-aspartate receptor (NMDA receptor) in hippocampus, calcium/calmodulin dependent protein kinase II (CaMK II), protein kinase (PKA), the phosphorylation level of CAMP response element binding protein (CREB) and the protein expression of brain derived neurotrophic factor(BDNF). In this study, the authors found that the learning and memory functions and the hippocampus neural plasticity protein expression of the aged rat group were much lower than that of the young control group (P < 0.01). Compared with the aged rat group, the APS group showed the significant improvement in the impaired learning and memory functions of aged rats and the up-regulation in the hippocampus neural plasticity protein expression. The results showed that APS may improve the learning and memory functions of aged rats by increasing the expressions of relevant neural plasticity proteins.

  7. Identification of a conserved gene signature associated with an exacerbated inflammatory environment in the hippocampus of aging rats.

    PubMed

    Pardo, Joaquín; Abba, Martin C; Lacunza, Ezequiel; Francelle, Laetitia; Morel, Gustavo R; Outeiro, Tiago F; Goya, Rodolfo G

    2017-04-01

    There have been a few descriptive studies in aged rodents about transcriptome changes in the hippocampus, most of them in males. Here, we assessed the age changes in spatial memory performance and hippocampal morphology in female rats and compared those changes with changes in the hippocampal transcriptome. Old rats displayed significant deficits in spatial memory. In both age groups, hole exploration frequency showed a clear peak at hole 0 (escape hole), but the amplitude of the peak was significantly higher in the young than in the old animals. In the hippocampus, there was a dramatic reduction in neurogenesis, whereas reactive microglial infiltrates revealed an inflammatory hippocampal state in the senile rats. Hippocampal RNA-sequencing showed that 210 genes are differentially expressed in the senile rats, most of them being downregulated. Our RNA-Seq data showed that various genes involved in the immune response, including TYROBP, CD11b, C3, CD18, CD4, and CD74, are overexpressed in the hippocampus of aged female rats. Enrichment analysis showed that the pathways overrepresented in the senile rats matched those of an exacerbated inflammatory environment, reinforcing our morphologic findings. After correlating our results with public data of human and mouse hippocampal gene expression, we found an 11-gene signature of overexpressed genes related to inflammatory processes that was conserved across species. We conclude that age-related hippocampal deficits in female rats share commonalities between human and rodents. Interestingly, the 11-gene signature that we identified may represent a cluster of immune and regulatory genes that are deregulated in the hippocampus and possibly other brain regions during aging as well as in some neurodegenerative diseases and low-grade brain tumors. Our study further supports neuroinflammation as a promising target to treat cognitive dysfunction in old individuals and some brain tumors. © 2017 Wiley Periodicals, Inc.

  8. Metabolic Profile of Offspring from Diabetic Wistar Rats Treated with Mentha piperita (Peppermint).

    PubMed

    Barbalho, Sandra M; Damasceno, Débora C; Spada, Ana Paula Machado; da Silva, Vanessa Sellis; Martuchi, Karla Aparecida; Oshiiwa, Marie; Machado, Flávia M V Farinazzi; Mendes, Claudemir Gregório

    2011-01-01

    This study aimed at evaluating glycemia and lipid profile of offspring from diabetic Wistar rats treated with Mentha piperita (peppermint) juice. Male offspring from nondiabetic dams (control group: 10 animals treated with water and 10 treated with peppermint juice) and from dams with streptozotocin-induced severe diabetes (diabetic group: 10 animals treated with water and 10 treated with peppermint juice) were used. They were treated during 30 days, and, after the treatment period, levels of glycemia, triglycerides, total cholesterol, and fractions were analyzed in the adult phase. The offspring from diabetic dams treated with peppermint showed significantly reduced levels of glucose, cholesterol, LDL-c, and triglycerides and significant increase in HDL-c levels. The use of the M. piperita juice has potential as culturally appropriate strategy to aid in the prevention of DM, dyslipidemia, and its complications.

  9. Metabolic Profile of Offspring from Diabetic Wistar Rats Treated with Mentha piperita (Peppermint)

    PubMed Central

    Barbalho, Sandra M.; Damasceno, Débora C.; Spada, Ana Paula Machado; da Silva, Vanessa Sellis; Martuchi, Karla Aparecida; Oshiiwa, Marie; Machado, Flávia M. V. Farinazzi; Mendes, Claudemir Gregório

    2011-01-01

    This study aimed at evaluating glycemia and lipid profile of offspring from diabetic Wistar rats treated with Mentha piperita (peppermint) juice. Male offspring from nondiabetic dams (control group: 10 animals treated with water and 10 treated with peppermint juice) and from dams with streptozotocin-induced severe diabetes (diabetic group: 10 animals treated with water and 10 treated with peppermint juice) were used. They were treated during 30 days, and, after the treatment period, levels of glycemia, triglycerides, total cholesterol, and fractions were analyzed in the adult phase. The offspring from diabetic dams treated with peppermint showed significantly reduced levels of glucose, cholesterol, LDL-c, and triglycerides and significant increase in HDL-c levels. The use of the M. piperita juice has potential as culturally appropriate strategy to aid in the prevention of DM, dyslipidemia, and its complications. PMID:21647314

  10. Fixed-ratio discrimination training as replacement therapy in Parkinson's disease: studies in a 6-hydroxydopamine-treated rat model.

    PubMed

    Van Keuren, K R; Stodgell, C J; Schroeder, S R; Tessel, R E

    1998-01-05

    Severe 6-hydroxydopamine (6-OHDA)-induced neostriatal dopamine (DA) depletion is generally held to be irreversible. Adult rats administered 6-OHDA soon after weaning, or neonatally, respectively model Parkinson's disease (PD) and Lesch-Nyhan syndrome (LNS). Prior studies in our laboratory indicate that prolonged training on incrementally more difficult fixed-ratio (FR) discriminations can reverse 'irreversible' 6-OHDA-induced neostriatal DA depletion in adult LNS rats. The present study evaluated the effects of such training on neostriatal DA depletion and its functional consequences in adult PD and control (vehicle-injected) rats. After recovery from 6-OHDA-induced hypophagia, rats were sacrificed to assess neostriatal DA depletion magnitude, or were food-deprived and either subjected to food-maintained operant FR discrimination training or allowed to remain in their home cages. 6-OHDA treatment antagonized amphetamine (AMP)-induced increases in brief rearing behavior and locomotor activity in 3-month-old PD rats prior to training, and reduced operant response rates throughout training without affecting learning rates. One week after training, AMP-increased locomotor and brief-rearing frequencies were augmented in all groups except trained controls, and the prior inhibitory effect of 6-OHDA treatment on AMP-increased behavioral frequencies was essentially eliminated. Cumulative apomorphine (APO) dose-effect curve (0.1-3.2 mg/kg) construction 3 weeks post-training revealed that 6-OHDA treatment abolished APO-induced intense licking behavior. However, training eliminated the hyperresponsiveness of 6-OHDA-treated rats to the locomotor- and brief-rearing stimulant effects of APO but did not affect the depletion of neostriatal DA. Nevertheless, 6-OHDA-induced increases in neostriatal DOPAC/DA and HVA/DA ratios were normalized by age/food-deprivation while that of 3MT/DA was not. These findings suggest that training reduces the functional responsiveness of at least some

  11. [GLIATILIN CORRECTION OF WORKING AND REFERENCE SPATIAL MEMORY IMPAIRMENT IN AGED RATS].

    PubMed

    Tyurenkov, I N; Volotova, E V; Kurkin, D V

    2015-01-01

    This work was aimed at evaluating the influence of gliatilin administration on the spatial memory in aged rats. Cognitive function and spatial memory in animals was evaluated using radial (8-beam) maze test. Errors of working spatial memory and reference memory were used as indicators of impaired cognitive function. It was found that aged (24-month) rats compared with younger (6-months) age group exhibited cognitive impairment, as manifested by deterioration of short- and long-term memory processes. Course administration of gliatilin in rats of the older age group at a dose of 100 mg/kg resulted in significant improvement of the working and reference spatial memory in aged rats.

  12. Epigallocatechin-3-gallate improves plantaris muscle recovery after disuse in aged rats.

    PubMed

    Alway, Stephen E; Bennett, Brian T; Wilson, Joseph C; Edens, Neile K; Pereira, Suzette L

    2014-02-01

    Aging exacerbates muscle loss and slows the recovery of muscle mass and function after disuse. In this study we investigated the potential that epigallocatechin-3-gallate (EGCg), an abundant catechin in green tea, would reduce signaling for apoptosis and promote skeletal muscle recovery in the fast plantaris muscle and the slow soleus muscle after hindlimb suspension (HLS) in senescent animals. Fischer 344 × Brown Norway inbred rats (age 34 months) received either EGCg (50 mg/kg body weight), or water daily by gavage. One group of animals received HLS for 14 days and a second group of rats received 14 days of HLS, then the HLS was removed and they recovered from this forced disuse for 2 weeks. Animals that received EGCg over the HLS followed by 14 days of recovery, had a 14% greater plantaris muscle weight (p<0.05) as compared to the animals treated with the vehicle over this same period. Plantaris fiber area was greater after recovery in EGCg (2715.2±113.8 μm(2)) vs. vehicle treated animals (1953.0±41.9 μm(2)). In addition, activation of myogenic progenitor cells was improved with EGCg over vehicle treatment (7.5% vs. 6.2%) in the recovery animals. Compared to vehicle treatment, the apoptotic index was lower (0.24% vs. 0.52%), and the abundance of pro-apoptotic proteins Bax (-22%), and FADD (-77%) was lower in EGCg treated plantaris muscles after recovery. While EGCg did not prevent unloading-induced atrophy, it improved muscle recovery after the atrophic stimulus in fast plantaris muscles. However, this effect was muscle specific because EGCg had no major impact in reversing HLS-induced atrophy in the slow soleus muscle of old rats.

  13. Recovery of presynaptic dopaminergic functioning in rats treated with neurotoxic doses of methamphetamine.

    PubMed

    Cass, W A; Manning, M W

    1999-09-01

    Repeated administration of methamphetamine (METH) to animals can result in long-lasting decreases in striatal dopamine (DA) content. In addition, the evoked overflow of striatal DA is reduced in rats 1 week after neurotoxic doses of METH. However, whether these functional changes in DA release are permanent or tend to recover over time has not been established. In the present study we used in vivo electrochemistry and microdialysis to examine evoked overflow of DA in the striatum of METH-treated rats at several time points after treatment to determine if DA overflow would spontaneously recover. Male Fischer-344 rats were administered METH (5 mg/kg, s.c. ) or saline four times in one day at 2 hr intervals. In vivo electrochemistry experiments in anesthetized rats, and in vivo microdialysis studies in awake rats, were carried out 1 week, 1 month, 6 months, and 12 months after treatment. At 1 week after treatment there were significant decreases in potassium- and amphetamine-evoked overflow of DA, and in clearance of DA, in the striatum of the METH-treated animals. Basal extracellular levels of DA and its metabolites were also decreased. Evoked overflow had partially recovered by 1 month. By 6 months evoked overflow of DA appeared to be normal in the METH-treated rats. However, whole tissue levels of striatal DA were still significantly decreased. All parameters were back to control values by 12 months. These results suggest that presynaptic dopaminergic functioning can recover to normal levels in the striatum of METH-treated rats by 12 months after treatment.

  14. Effect of Boswellia serrata gum resin on the morphology of hippocampal CA1 pyramidal cells in aged rat.

    PubMed

    Hosseini-sharifabad, Mohammad; Esfandiari, Ebrahim

    2015-01-01

    Experimental evidence indicates that administration of Boswellia resin, known as olibanum or Frankincense, increases memory power. It is reported that beta boswellic acid, the major component of Boswellia serrata gum resin, could enhance neurite outgrowth and branching in hippocampal neurons. We therefore studied whether Boswellia treatment produces morphological changes in the superior region of cornu ammonis (CA1) in aged rats. Sixteen male Wistar rats, 24 months of age, were randomly divided in experimental and control groups. The experimental group was orally administered Boswellia serrata gum resin (100 mg/kg per day for 8 weeks) and the control group received a similar volume of water. The Cavalieri principle was employed to estimate the volumes of CA1 hippocampal field, and a quantitative Golgi study was used to analysis of dendritic arborizations of CA1 pyramidal cells. Comparisons revealed that Boswellia-treated aged rats had greater volumes than control animals in stratum pyramidale and stratum radiatum lacunosum-moleculare. The neurons of CA1 in experimental rats had more dendritic segments (40.25 ± 4.20) than controls (30.9 ± 4.55), P = 0.001. The total dendritic length of CA1 neurons was approximately 20 % larger in the experimental group compared to control. Results also indicated that the aged rats treated with Boswellia resin had more numerical branching density in the apical dendrites of CA1 pyramidal neurons. The results of the present study show that long-term administration of Boswellia resin can attenuate age-related dendritic regression in CA1 pyramidal cells in rat hippocampus.

  15. Mitochondria-targeted ROS scavenger improves post-ischemic recovery of cardiac function and attenuates mitochondrial abnormalities in aged rats.

    PubMed

    Escobales, Nelson; Nuñez, Rebeca E; Jang, Sehwan; Parodi-Rullan, Rebecca; Ayala-Peña, Sylvette; Sacher, Joshua R; Skoda, Erin M; Wipf, Peter; Frontera, Walter; Javadov, Sabzali

    2014-12-01

    Mitochondria-generated reactive oxygen species (ROS) play a crucial role in the pathogenesis of aging and age-associated diseases. In this study, we evaluated the effects of XJB-5-131 (XJB), a mitochondria-targeted ROS and electron scavenger, on cardiac resistance to ischemia-reperfusion (IR)-induced oxidative stress in aged rats. Male adult (5-month old, n=17) and aged (29-month old, n=19) Fischer Brown Norway (F344/BN) rats were randomly assigned to the following groups: adult (A), adult+XJB (AX), aged (O), and aged+XJB (OX). XJB was administered 3 times per week (3mg/kg body weight, IP) for four weeks. At the end of the treatment period, cardiac function was continuously monitored in excised hearts using the Langendorff technique for 30 min, followed by 20 min of global ischemia, and 60-min reperfusion. XJB improved post-ischemic recovery of aged hearts, as evidenced by greater left ventricular developed-pressures and rate-pressure products than the untreated, aged-matched group. The state 3 respiration rates at complexes I, II and IV of mitochondria isolated from XJB-treated aged hearts were 57% (P<0.05), 25% (P<0.05) and 28% (P<0.05), respectively, higher than controls. Ca(2+)-induced swelling, an indicator of permeability transition pore opening, was reduced in the mitochondria of XJB-treated aged rats. In addition, XJB significantly attenuated the H2O2-induced depolarization of the mitochondrial inner membrane as well as the total and mitochondrial ROS levels in cultured cardiomyocytes. This study underlines the importance of mitochondrial ROS in aging-induced cardiac dysfunction and suggests that targeting mitochondrial ROS may be an effective therapeutic approach to protect the aged heart against IR injury.

  16. Deferoxamine reduces intracerebral hemorrhage-induced white matter damage in aged rats.

    PubMed

    Ni, Wei; Okauchi, Masanobu; Hatakeyama, Tetsuhiro; Gu, Yuxiang; Keep, Richard F; Xi, Guohua; Hua, Ya

    2015-10-01

    Iron contributes to c-Jun N-terminal kinases (JNK) activation in young rats and white matter injury in piglets after intracerebral hemorrhage (ICH). In the present study, we examined the effect of deferoxamine on ICH-induced white matter injury and JNK activation and in aged rats. Male Fischer 344 rats (18months old) had either an intracaudate injection of 100μl of autologous blood or a needle insertion (sham). The rats were treated with deferoxamine or vehicle with different regimen (dosage, duration and time window). White matter injury and activation of JNK were examined. We found that a dose of DFX should be at more than 10mg/kg for a therapeutic duration more than 2days with a therapeutic time window of 12h to reduce ICH-induced white matter loss at 2months. ICH-induced white matter injury was associated with JNK activation. The protein levels of phosphorylated-JNK (P-JNK) were upregulated at day-1 after ICH and then gradually decreased. P-JNK immunoreactivity was mostly located in white matter bundles. ICH-induced JNK activation was reduced by DFX treatment. This study demonstrated that DFX can reduce ICH-induced JNK activation and white matter damage.

  17. Beta-hydroxy-beta-methylbutyrate (HMB) ameliorates age-related deficits in water maze performance, especially in male rats.

    PubMed

    Kougias, Daniel G; Hankosky, Emily R; Gulley, Joshua M; Juraska, Janice M

    2017-03-01

    Beta-hydroxy-beta-methylbutyrate (HMB) is commonly supplemented to maintain muscle in elderly and clinical populations and has potential as a nootropic. Previously, we have shown that in both male and female rats, long-term HMB supplementation prevents age-related dendritic shrinkage within the medial prefrontal cortex (mPFC) and improves cognitive flexibility and working memory performance that are both age- and sex-specific. In this study, we further explore the cognitive effects by assessing visuospatial learning and memory with the Morris water maze. Female rats were ovariectomized at 11months of age to model human menopause. At 12months of age, male and female rats received relatively short- or long-term (1- or 7-month) dietary HMB (450mg/kg/dose) supplementation twice a day prior to testing. Spatial reference learning and memory was assessed across four days in the water maze with four trials daily and a probe trial on the last day. Consistent with previous work, there were age-related deficits in water maze performance in both sexes. However, these deficits were ameliorated in HMB-treated males during training and in both sexes during probe trial performance. Thus, HMB supplementation prevented the age-related decrement in water maze performance, especially in male rats.

  18. Oxygen nano-bubble water reduces calcium oxalate deposits and tubular cell injury in ethylene glycol-treated rat kidney.

    PubMed

    Hirose, Yasuhiko; Yasui, Takahiro; Taguchi, Kazumi; Fujii, Yasuhiro; Niimi, Kazuhiro; Hamamoto, Shuzo; Okada, Atsushi; Kubota, Yasue; Kawai, Noriyasu; Itoh, Yasunori; Tozawa, Keiichi; Sasaki, Shoichi; Kohri, Kenjiro

    2013-08-01

    Renal tubular cell injury induced by oxalate plays an important role in kidney stone formation. Water containing oxygen nano-bubbles (nanometer-sized bubbles generated from oxygen micro-bubbles; ONB) has anti-inflammatory effects. Therefore, we investigated the inhibitory effects of ONB water on kidney stone formation in ethylene glycol (EG)-treated rats. We divided 60 rats, aged 4 weeks, into 5 groups: control, the water-fed group; 100 % ONB, the 100 % ONB water-fed group; EG, the EG treated water-fed group; EG + 50 % ONB and EG + 100 % ONB, water containing EG and 50 % or 100 % ONB, respectively. Renal calcium oxalate (CaOx) deposition, urinary excretion of N-acetyl-β-D-glucosaminidase (NAG), and renal expression of inflammation-related proteins, oxidative stress biomarkers, and the crystal-binding molecule hyaluronic acid were compared among the 5 groups. In the control and 100 % ONB groups, no renal CaOx deposits were detected. In the EG + 50 % ONB and EG + 100 % ONB groups, ONB water significantly decreased renal CaOx deposits, urinary NAG excretion, and renal monocyte chemoattractant protein-1, osteopontin, and hyaluronic acid expression and increased renal superoxide dismutase-1 expression compared with the EG group. ONB water substantially affected kidney stone formation in the rat kidney by reducing renal tubular cell injury. ONB water is a potential prophylactic agent for kidney stones.

  19. Effects of Age on Thermal Sensitivity in the Rat

    PubMed Central

    King, C. D.; Morgan, D.; Carter, C. S.; Vierck, C. J.

    2010-01-01

    Age-dependent changes in thermal sensitivity were evaluated with reflex- and operant-based assessment strategies in animals ranging in age from 8 to 32 months. The impact of inflammatory injury on thermal sensitivity was also determined in animals of different ages. The results showed that operant measures of escape behavior are needed to demonstrate significant changes in thermal sensitivity across the life span of female Long-Evans rats. Increased escape from both heat (44.5°C) and cold (1.5°C–15°C) was observed for older animals, with a greater relative increase in sensitivity to cold. Physical performance deficits were demonstrated with aging but were not associated with changes in escape responding. Reflex responding to cold stimulation was impaired in older animals but was also influenced by physical disabilities. Reflex responding to heat was not affected by increasing age. Inflammation induced by formalin injections in the dorsal hindpaw increased thermal sensitivity significantly more in older animals than in their younger counterparts. PMID:20185437

  20. Effects of age on thermal sensitivity in the rat.

    PubMed

    Yezierski, R P; King, C D; Morgan, D; Carter, C S; Vierck, C J

    2010-04-01

    Age-dependent changes in thermal sensitivity were evaluated with reflex- and operant-based assessment strategies in animals ranging in age from 8 to 32 months. The impact of inflammatory injury on thermal sensitivity was also determined in animals of different ages. The results showed that operant measures of escape behavior are needed to demonstrate significant changes in thermal sensitivity across the life span of female Long-Evans rats. Increased escape from both heat (44.5 degrees C) and cold (1.5 degrees C-15 degrees C) was observed for older animals, with a greater relative increase in sensitivity to cold. Physical performance deficits were demonstrated with aging but were not associated with changes in escape responding. Reflex responding to cold stimulation was impaired in older animals but was also influenced by physical disabilities. Reflex responding to heat was not affected by increasing age. Inflammation induced by formalin injections in the dorsal hindpaw increased thermal sensitivity significantly more in older animals than in their younger counterparts.

  1. Chronic administration of resveratrol prevents morphological changes in prefrontal cortex and hippocampus of aged rats.

    PubMed

    Monserrat Hernández-Hernández, Elizabeth; Serrano-García, Carolina; Antonio Vázquez-Roque, Rubén; Díaz, Alfonso; Monroy, Elibeth; Rodríguez-Moreno, Antonio; Florán, Benjamin; Flores, Gonzalo

    2016-05-01

    Resveratrol may induce its neuroprotective effects by reducing oxidative damage and chronic inflammation apart from improving vascular function and activating longevity genes, it also has the ability to promote the activity of neurotrophic factors. Morphological changes in dendrites of the pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been reported in the brain of aging humans, or in humans with neurodegenerative diseases such as Alzheimer's disease. These changes are reflected particularly in the decrement of both the dendritic tree and spine density. Here we evaluated the effect of resveratrol on the dendrites of pyramidal neurons of the PFC (Layers 3 and 5), CA1- and CA3-dorsal hippocampus (DH) as well as CA1-ventral hippocampus, dentate gyrus (DG), and medium spiny neurons of the nucleus accumbens of aged rats. 18-month-old rats were administered resveratrol (20 mg/kg, orally) daily for 60 days. Dendritic morphology was studied by the Golgi-Cox stain procedure, followed by Sholl analysis on 20-month-old rats. In all resveratrol-treated rats, a significant increase in dendritic length and spine density in pyramidal neurons of the PFC, CA1, and CA3 of DH was observed. Interestingly, the enhancement in dendritic length was close to the soma in pyramidal neurons of the PFC, whereas in neurons of the DH and DG, the increase in dendritic length was further from the soma. Our results suggest that resveratrol induces modifications of dendritic morphology in the PFC, DH, and DG. These changes may explain the therapeutic effect of resveratrol in aging and in Alzheimer's disease.

  2. CREB overexpression in dorsal CA1 ameliorates long-term memory deficits in aged rats

    PubMed Central

    Yu, Xiao-Wen; Curlik, Daniel M; Oh, M Matthew; Yin, Jerry CP; Disterhoft, John F

    2017-01-01

    The molecular mechanisms underlying age-related cognitive deficits are not yet fully elucidated. In aged animals, a decrease in the intrinsic excitability of CA1 pyramidal neurons is believed to contribute to age-related cognitive impairments. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents facilitates cognition, and increases intrinsic excitability. However, it has yet to be tested if increasing CREB expression also ameliorates age-related behavioral and biophysical deficits. To test this hypothesis, we virally overexpressed CREB in CA1 of dorsal hippocampus. Rats received CREB or control virus, before undergoing water maze training. CREB overexpression in aged animals ameliorated the long-term memory deficits observed in control animals. Concurrently, cells overexpressing CREB in aged animals had reduced post-burst afterhyperpolarizations, indicative of increased intrinsic excitability. These results identify CREB modulation as a potential therapy to treat age-related cognitive decline. DOI: http://dx.doi.org/10.7554/eLife.19358.001 PMID:28051768

  3. Nicotine ameliorates impairment of working memory in methamphetamine-treated rats.

    PubMed

    Mizoguchi, Hiroyuki; Ibi, Daisuke; Takase, Fumiaki; Nagai, Taku; Kamei, Hiroyuki; Toth, Erika; Sato, Jun; Takuma, Kazuhiro; Yamada, Kiyofumi

    2011-06-20

    Nicotine is hypothesized to have therapeutic effects on attentional and cognitive abnormalities in psychosis. In this study, we investigated the effect of nicotine on impaired spatial working memory in repeated methamphetamine (METH)-treated rats. Rats were administered METH (4 mg/kg, s.c.) once a day for 7 days, and their working memory was assessed with a delayed spatial win-shift task in a radial arm maze. The task consisted of two phases, a training phase and a test phase, separated by a delay. Control animals showed impaired performance in the test phase when the delay time was increased to 120 min or longer, while METH-treated rats showed impaired performance with a shorter delay time of 90 min. Memory impairment in METH-treated rats persisted for at least 14 days after drug withdrawal. METH-induced impairment of working memory was reversed by nicotine (0.3mg/kg, p.o., for 7 days), but the effect was diminished 7 days after the withdrawal. In control rats, nicotine decreased the number of working memory errors in the test with delay time of 120 min when administered before the training phase. Neither post-training nor pre-test administration of nicotine had any effect on working memory. These findings suggest that nicotine may have some protective effect against the impairment of working memory.

  4. Antioxidant effect of Cytisus scoparius against carbon tetrachloride treated liver injury in rats.

    PubMed

    Raja, S; Ahamed, K F H Nazeer; Kumar, V; Mukherjee, Kakali; Bandyopadhyay, A; Mukherjee, Pulok K

    2007-01-03

    The study was aimed to investigate the antioxidant activity of Cytisus scoparius L. (Family: Leguminosae) on CCl(4) (carbon tetrachloride) treated oxidative stress in Wistar albino rats. CCl(4) injection induced oxidative stress by a significant rise in serum glutamate oxaloacetate transaminases (SGOT), serum glutamate pyruvate transaminases (SGPT), lactate dehydrogenase (LDH) and thiobarbituric acid reactive substances (TBARS) along with reduction of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-s-transferase (GST) and glutathione reductase (GRD). Pretreatment of rats with different doses of plant extract (250 and 500mg/kg) significantly lowered SGOT, SGPT, LDH and TBARS levels against CCl(4) treated rats. GSH and hepatic enzymes like SOD, CAT, GPx, GRD, and GST were significantly increased by treatment with the plant extract, against CCl(4) treated rats. The activity of extract at the dose of 500mg/kg was comparable to the standard drug, silymarin (25mg/kg). Based on these results, it was observed that Cytisus scoparius extract protects liver from oxidative stress induced by CCl(4) in rats and thus helps in evaluation of the traditional claim on this plant.

  5. METABOLIC RATE AS A FUNCTION OF AGE IN BROWN NORWAY AND LONG-EVANS RATS.

    EPA Science Inventory

    Brown Norway (BN) rats are commonly used in aging studies but relatively little is known on their metabolism as it varies with age. In fact, there is considerable disagreement on the wholebody metabolism of aging rats with some studies indicating a decrease and others showing an...

  6. Biochemical and immunohistochemical changes in delta-9-tetrahydrocannabinol-treated type 2 diabetic rats.

    PubMed

    Coskun, Zeynep Mine; Bolkent, Sema

    2014-01-01

    The regulation of glucose, lipid metabolism and immunoreactivities of insulin and glucagon peptides by delta-9-tetrahydrocannabinol (Δ(9)-THC) in diabetes were examined in an experimental rat model. Male Sprague-Dawley rats were divided into four groups: (1) control, (2) Δ(9)-THC treated, (3) diabetic, and (4) diabetic+Δ(9)-THC. The type 2 diabetic rat model was established by intraperitoneal (i.p.) injection of nicotinamide (85 mg/kg body weight) followed after 15 min by i.p. injection of streptozotocin (STZ) at 65 mg/kg of body weight. Δ(9)-THC and Δ(9)-THC treated diabetic groups received 3mg/kg/day of Δ(9)-THC for 7 days. The immunolocalization of insulin and glucagon peptides was investigated in the pancreas using a streptavidin-biotin-peroxidase technique. High density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), very low density lipoprotein cholesterol (VLDL), triglycerides (TG), total cholesterol (TC) and total protein (TP) levels were measured in serum. Total islet area percent of insulin immunoreactive cells slightly changed in diabetic+Δ(9)-THC rats compared to diabetic animals. However, the area percent of glucagon immunoreactive cells showed a decrease in diabetic+Δ(9)-THC rats compared to that of diabetic animals alone. Serum TC, HDL and LDL levels of diabetes+Δ(9)-THC group showed a decrease compared to the diabetic group. These results indicate that Δ(9)-THC may serve a protective role against hyperlipidemia and hyperglycemia in diabetic rats.

  7. Tissue distribution and urinary excretion of dimethylated arsenic and its metabolites in dimethylarsinic acid- or arsenate-treated rats

    SciTech Connect

    Adair, Blakely M.; Moore, Tanya; Conklin, Sean D.; Creed, John T.; Wolf, Douglas C.; Thomas, David J. . E-mail: thomas.david@epa.gov

    2007-07-15

    Adult female Fisher 344 rats received drinking water containing 0, 4, 40, 100, or 200 parts per million of dimethylarsinic acid or 100 parts per million of arsenate for 14 days. Urine was collected during the last 24 h of exposure. Tissues were then taken for analysis of dimethylated and trimethylated arsenicals; urines were analyzed for these arsenicals and their thiolated derivatives. In dimethylarsinic acid-treated rats, highest concentrations of dimethylated arsenic were found in blood. In lung, liver, and kidney, concentrations of dimethylated arsenic exceeded those of trimethylated species; in urinary bladder and urine, trimethylated arsenic predominated. Dimethylthioarsinic acid and trimethylarsine sulfide were present in urine of dimethylarsinic acid-treated rats. Concentrations of dimethylated arsenicals were similar in most tissues of dimethylarsinic acid- and arsenate-treated rats, including urinary bladder which is the target for dimethylarsinic acid-induced carcinogenesis in the rat. Mean concentration of dimethylated arsenic was significantly higher (P < 0.05) in urine of dimethylarsinic acid-treated rats than in arsenate-treated rats, suggesting a difference between treatment groups in the flux of dimethylated arsenic through urinary bladder. Concentrations of trimethylated arsenic concentrations were consistently higher in dimethylarsinic acid-treated rats than in arsenate-treated rats; these differences were significant (P < 0.05) in liver, urinary bladder, and urine. Concentrations of dimethylthioarsinic acid and trimethylarsine sulfide were higher in urine from dimethylarsinic acid-treated rats than from arsenate-treated rats. Dimethylarsinic acid is extensively metabolized in the rat, yielding significant concentrations of trimethylated species and of thiolated derivatives. One or more of these metabolites could be the species causing alterations of cellular function that lead to tumors in the urinary bladder.

  8. Betanin attenuates oxidative stress and inflammatory reaction in kidney of paraquat-treated rat.

    PubMed

    Tan, Dehong; Wang, Yiheng; Bai, Bing; Yang, Xuelian; Han, Junyan

    2015-04-01

    The effects of natural pigment betanin on oxidative stress and inflammation in kidney of paraquat-treated rat were investigated. Paraquat was injected intraperitoneally into rats to induce renal damage. The rats were randomly divided into four groups: a control group, a paraquat group, and two paraquat groups that were treated with betanin at 25 and 100 mg/kg/d three days before and two days after paraquat administration. Treatment with betanin alleviated the paraquat-incurred acute kidney injury, evidenced by histological improvement, reduced serum and urine markers for kidney injury. Betanin antagonized the paraquat-induced inflammation, indicated by reduced expression of inducible nitric oxide synthase and cyclooxygenase, blunted activation of nuclear factor kappa B, and diminished lysosomal protease activities. Betanin also decreased oxidative stress elicited by paraquat. In conclusion, betanin may have a protective effect against paraquat-induced acute kidney damage. The mechanisms of the protection appear to be the inhibition of oxidative stress and inflammation.

  9. Anthriscus nemorosa essential oil inhalation prevents memory impairment, anxiety and depression in scopolamine-treated rats.

    PubMed

    Bagci, Eyup; Aydin, Emel; Ungureanu, Eugen; Hritcu, Lucian

    2016-12-01

    Anthriscus nemorosa (Bieb.) Sprengel is used for medicinal purposes in traditional medicine around the world, including Turkey. Ethnobotanical studies suggest that Anthriscus essential oil could improve memory in Alzheimer's disease. The current study was hypothesized to investigate the beneficial effects of inhaled Anthriscus nemorosa essential oil on memory, anxiety and depression in scopolamine-treated rats. Anthriscus nemorosa essential oil was administered by inhalation in the doses of 1% and 3% for 21 continuous days and scopolamine (0.7mg/kg) was injected intraperitoneally 30min before the behavioral testing. Y-maze and radial arm-maze tests were used for assessing memory processes. Also, the anxiety and depressive responses were studied by elevated plus-maze and forced swimming tests. As expected, the scopolamine alone-treated rats exhibited the following: decrease the percentage of the spontaneous alternation in Y-maze test, increase the number of working and reference memory errors in radial arm-maze test, decrease of the exploratory activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming time and increase of immobility time within forced swimming test. However, dual scopolamine and Anthriscus nemorosa essential oil-treated rats showed significant improvement of memory formation and exhibited anxiolytic- and antidepressant-like effects in scopolamine-treated rats. These results suggest that Anthriscus nemorosa essential oil inhalation can prevent scopolamine-induced memory impairment, anxiety and depression.

  10. Effect of O-ethylrutoside on serum and hepatic lipids in acute ethanal-treated rats.

    PubMed

    Wójcicki, J

    1977-01-01

    The serum total lipids, triglycerides, total cholesterol and free fatty acid concentrations, as well as hepatic triglyceride and cholesterol levels, were increased in acutely ethanol-treated rats. Treatment of ethanol-given animals with o-ethylrutoside resulted in a significant reduction in all examined fractions of serum lipids and in the hepatic total cholesterol level.

  11. Pixe analysis of trace elements in tissues of rats treated with anticonvulsants

    NASA Astrophysics Data System (ADS)

    Hurd, R. W.; Van Rinsvelt, H. A.; Kinyua, A. M.; O'Neill, M. P.; Wilder, B. J.; Houdayer, A.; Hinrichsen, P. F.

    1987-04-01

    Several lines of evidence implicate metals in epilepsy. Anticonvulsant drugs are noted to alter levels of metals in humans and animals. PIXE analysis was used to investigate effects of three anticonvulsant drugs on tissue and brain cortex trace elements. The content of zinc and copper was increased in liver and spleen of rats treated with anticonvulsants while selenium was decreased in cortex.

  12. Molecular mechanisms involved in the hormonal prevention of aging in the rat.

    PubMed

    Tresguerres, Jesús A F; Kireev, Roman; Tresguerres, Ana F; Borras, Consuelo; Vara, Elena; Ariznavarreta, Carmen

    2008-02-01

    Previous data from our group have provided support for the role of GH, melatonin and estrogens in the prevention of aging of several physiological parameters from bone, liver metabolism, vascular activity, the central nervous system (CNS), the immune system and the skin. In the present work data on the molecular mechanisms involved are presented. A total of 140 male and female rats have been submitted to different treatments over 10 weeks, between 22 and 24 months of age. Males have been treated with GH and melatonin. Females were divided in two groups: intact and castrated at 12 months of age. The first group was treated with GH and melatonin and the second with the two latter compounds and additionally with estradiol and Phytosoya. Aging was associated with a reduction in the number of neurons of the hylus of the dentate gyrus of the hippocampus and with a reduction of neurogenesis. GH treatment increased the number of neurons but did not increase neurogenesis thus suggesting a reduction of apoptosis. This was supported by the reduction in nucleosomes and the increase in Bcl2 observed in cerebral homogenates together with an increase in sirtuin2 and a reduction of caspases 9 and 3. Melatonin, estrogen and Phytosoya treatments increased neurogenesis but did not enhance the total number of neurons. Aging induced a significant increase in mitochondrial nitric oxide in the hepatocytes, together with a reduction in the mitochondrial fraction content in cytochrome C and an increase of this compound in the cytosolic fraction. Reductions of glutathione peroxidase and glutathione S-transferase were also detected, thus indicating oxidative stress and possibly apoptosis. Treatment for 2.5 months of old rats with GH and melatonin were able to significantly and favourably affect age-induced deteriorations, thus reducing oxidative damage. Keratinocytes obtained from old rats in primary culture showed an increase in lipoperoxides, caspases 8 and 3 as well as a reduction in Bcl2

  13. Further evidence of benzene carcinogenicity. Results on Wistar rats and Swiss mice treated by ingestion.

    PubMed

    Maltoni, C; Conti, B; Perino, G; Di Maio, V

    1988-01-01

    Wistar rats and Swiss mice were treated by ingestion (stomach tube) with benzene in olive oil at a dose of 500 and 0 mg/kg b.w. once daily, 4-5 days weekly, for 104 weeks (rats) or for 78 weeks (mice). In Wistar rats, benzene caused Zymbal gland carcinomas, carcinomas of the oral cavity, and carcinomas of the nasal cavities, and an increase in the incidence of total malignant tumors. In Swiss mice, benzene produced Zymbal gland carcinomas and dysplasias and an increase in the incidence of mammary carcinomas (in females), lung tumors, and total malignant tumors. These experiments further confirm that benzene is a multipotential carcinogen as was shown before by long-term bioassays performed on Sprague-Dawley rats in the same Experimental Unit.

  14. Carvacrol and Pomegranate Extract in Treating Methotrexate-Induced Lung Oxidative Injury in Rats

    PubMed Central

    Şen, Hadice Selimoğlu; Şen, Velat; Bozkurt, Mehtap; Türkçü, Gül; Güzel, Abdulmenap; Sezgi, Cengizhan; Abakay, Özlem; Kaplan, Ibrahim

    2014-01-01

    Background This study was designed to evaluate the effects of carvacrol (CRV) and pomegranate extract (PE) on methotrexate (MTX)-induced lung injury in rats. Material/Methods A total of 32 male rats were subdivided into 4 groups: control (group I), MTX treated (group II), MTX+CRV treated (group III), and MTX+PE treated (group IV). A single dose of 73 mg/kg CRV was administered intraperitoneally to rats in group III on Day 1 of the investigation. To group IV, a dose of 225 mg/kg of PE was administered via orogastric gavage once daily over 7 days. A single dose of 20 mg/kg of MTX was given intraperitoneally to groups II, III, and IV on Day 2. The total duration of experiment was 8 days. Malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) were measured from rat lung tissues and cardiac blood samples. Results Serum and lung specimen analyses demonstrated that MDA, TOS, and OSI levels were significantly greater in group II relative to controls. Conversely, the TAC level was significantly reduced in group II when compared to the control group. Pre-administering either CRV or PE was associated with decreased MDA, TOS, and OSI levels and increased TAC levels compared to rats treated with MTX alone. Histopathological examination revealed that lung injury was less severe in group III and IV relative to group II. Conclusions MTX treatment results in rat lung oxidative damage that is partially counteracted by pretreatment with either CRV or PE. PMID:25326861

  15. Enhancement of Skeletal Muscle in Aged Rats Following High-Intensity Stretch-Shortening Contraction Training.

    PubMed

    Rader, Erik P; Naimo, Marshall A; Layner, Kayla N; Triscuit, Alyssa M; Chetlin, Robert D; Ensey, James; Baker, Brent A

    2016-08-03

    Exercise is the most accessible, efficacious, and multifactorial intervention to improve health and treat chronic disease. High-intensity resistance exercise, in particular, also maximizes skeletal muscle size and strength-outcomes crucial at advanced age. However, such training is capable of inducing muscle maladaptation when misapplied at old age. Therefore, characterization of parameters (e.g., mode and frequency) that foster adaptation is an active research area. To address this issue, we utilized a rodent model that allowed training at maximal intensity in terms of muscle activation and tested the hypothesis that muscles of old rats adapt to stretch-shortening contraction (SSC) training, provided the training frequency is sufficiently low. At termination of training, normalized muscle mass (i.e., muscle mass divided by tibia length) and muscle quality (isometric force divided by normalized muscle mass) were determined. For young rats, normalized muscle mass increased by ∼20% regardless of training frequency. No difference was observed for muscle quality values after 2 days versus 3 days per week training (0.65 ± 0.09 N/mg/mm vs. 0.59 ± 0.05 N/mg/mm, respectively). For old rats following 3 days per week training, normalized muscle mass was unaltered and muscle quality was 30% lower than young levels. Following 2 days per week training at old age, normalized muscle mass increased by 17% and muscle quality was restored to young levels. To investigate this enhanced response, oxidative stress was assessed by lipid peroxidation quantification. For young rats, lipid peroxidation levels were unaltered by training. With aging, baseline levels of lipid peroxidation increased by 1.5-fold. For old rats, only 2 days per week training decreased lipid peroxidation to levels indistinguishable from young values. These results imply that, appropriately scheduled high-intensity SSC training at old age is capable of restoring muscle to a younger phenotype in terms

  16. Effect of age and methacholine on the rate and coronary flow of isolated hearts of diabetic rats.

    PubMed

    Li, X S; Tanz, R D; Chang, K S

    1989-08-01

    1. Isolated hearts perfused by the method of Langendorff from 6, 12 and 24 week streptozotocin (STZ) diabetic rats displayed a significant bradycardia following 60 min equilibration. The rate of hearts from 12-week diabetic rats (164 +/- 17) displayed the greatest bradycardia compared to age-matched controls (268 +/- 15; P less than 0.001), and diabetics treated with insulin (232 +/- 17; P less than 0.01), but by 52 weeks the heart rate of the 3 groups was similar. With advancing age the effect of STZ diabetes on the rate of rat isolated perfused hearts remained unchanged but the rate of the control and diabetic + insulin groups declined. 2. Hearts from 6-52 week STZ-treated rats were found to be more sensitive to the negative chronotropic effect of methacholine, the greatest difference occurring in hearts from the 12 week animals. Atropine (10(-7) M) did not affect the resting heart rate of age-matched controls or diabetics but blocked methacholine (2.6 x 10(-6) M)-induced bradycardia in both, suggesting that the site of action of diabetic bradycardia is not the muscarinic receptors. 3. At the end of equilibration there was a significant decrease in coronary flow in hearts from 12 week diabetic animals. In spontaneously beating diabetic rat hearts administration of methacholine (2.6 x 10(-6) M) produced a significantly greater decrease in coronary flow in the 12, 24 and 52 week diabetic hearts. When electrically paced (5 Hz) however, there was no difference in response to methacholine between the three groups except at 52 weeks between the age-matched control and diabetic groups. This suggests that the more pronounced reduction induced by methacholine on the coronary flow of diabetic hearts is secondary to its negative chronotropic effect. 4. In general, hearts from diabetic animals treated with insulin respond similarly to their agematched controls in the presence and absence of methacholine.

  17. Polyphenols decreased liver NADPH oxidase activity, increased muscle mitochondrial biogenesis and decreased gastrocnemius age-dependent autophagy in aged rats.

    PubMed

    Laurent, Caroline; Chabi, Beatrice; Fouret, Gilles; Py, Guillaume; Sairafi, Badie; Elong, Cecile; Gaillet, Sylvie; Cristol, Jean Paul; Coudray, Charles; Feillet-Coudray, Christine

    2012-09-01

    This study explored major systems of reactive oxygen species (ROS) production and their consequences on oxidative stress, mitochondriogenesis and muscle metabolism in aged rats, and evaluated the efficiency of 30-day oral supplementation with a moderate dose of a red grape polyphenol extract (RGPE) on these parameters. In the liver of aged rats, NADPH oxidase activity was increased and mitochondrial respiratory chain complex activities were altered, while xanthine oxidase activity remained unchanged. In muscles, only mitochondrial activity was modified with aging. The oral intake of RGPE decreased liver NADPH oxidase activity in the aged rats without affecting global oxidative stress, suggesting that NADPH oxidase was probably not the dominant detrimental source of production of O(2)·(-) in the liver. Interestingly, RGPE supplementation increased mitochondrial biogenesis and improved antioxidant status in the gastrocnemius of aged rats, while it had no significant effect in soleus. RGPE supplementation also decreased age-dependent autophagy in gastrocnemius of aged rats. These results extended existing findings on the beneficial effects of RGPE on mitochondriogenesis and muscle metabolism in aged rats.

  18. Reductions in water and sodium intake by aged male and female rats.

    PubMed

    Begg, Denovan P; Sinclair, Andrew J; Weisinger, Richard S

    2012-11-01

    Aging results in reduced water and sodium intake responses in male rats. Because sex differences exist for water and sodium ingestion of young adult animals, we hypothesized that these sex differences would protect against the diminished water and sodium ingestion of aged female rats. Water and sodium intakes were examined in male and female young adult and aged Brown Norway rats in response to dipsogenic stimuli. Aged rats of both sexes consumed less water than young adult rats in response to 24-h water deprivation, thermal dehydration and hypertonic NaCl injection, but not to peripheral angiotensin II. Aged females consumed more water than males in response to hypertonic NaCl injection. Following sodium depletion, intake of 0.5 M NaCl solution over 2 h was higher in young adult rats than in aged rats. Aged animals had reduced angiotensin receptor 1A (AT(1A)) and atrial natriuretic peptide (ANP) mRNA expression in hypothalamic tissue with no sex differences. These data indicate that female rats are not protected from water and sodium intake deficits that occur in aging and that sex differences in sodium intake in young adult rats are eliminated with aging.

  19. Rat hippocampal GABAergic molecular markers are differentially affected by ageing.

    PubMed

    Vela, José; Gutierrez, Antonia; Vitorica, Javier; Ruano, Diego

    2003-04-01

    We previously reported that the pharmacological properties of the hippocampal GABAA receptor and the expression of several subunits are modified during normal ageing. However, correlation between these post-synaptic modifications and pre-synaptic deficits were not determined. To address this issue, we have analysed the mRNA levels of several GABAergic molecular markers in young and old rat hippocampus, including glutamic acid decarboxylase enzymes, parvalbumin, calretinin, somatostatin, neuropeptide Y and vasoactive intestinal peptide (VIP). There was a differential age-related decrease in these interneuronal mRNAs that was inversely correlated with up-regulation of the alpha1 GABA receptor subunit. Somatostatin and neuropeptide Y mRNAs were most frequently affected (75% of the animals), then calretinin and VIP mRNAs (50% of the animals), and parvalbumin mRNA (25% of the animals) in the aged hippocampus. This selective vulnerability was well correlated at the protein/cellular level as analysed by immunocytochemistry. Somatostatin interneurones, which mostly innervate principal cell distal dendrites, were more vulnerable than calretinin interneurones, which target other interneurones. Parvalbumin interneurones, which mostly innervate perisomatic domains of principal cells, were preserved. This age-dependent differential reduction of specific hippocampal inteneuronal subpopulations might produce functional alterations in the GABAergic tone which might be compensated, at the post-synaptic level, by up-regulation of the expression of the alpha1 GABAA receptor subunit.

  20. Dopamine receptor dysregulation in hippocampus of aged rats underlies chronic pulsatile L-Dopa treatment induced cognitive and emotional alterations.

    PubMed

    Hernández, Vito S; Luquín, Sonia; Jáuregui-Huerta, Fernando; Corona-Morales, Aleph A; Medina, Mauricio P; Ruíz-Velasco, Silvia; Zhang, Limei

    2014-07-01

    L-Dopa is the major symptomatic therapy for Parkinson's disease, which commonly occurs in elderly patients. However, the effects of chronic use on mood and cognition in old subjects remain elusive. In order to compare the effects of a chronic pulsatile L-Dopa treatment on emotional and cognitive functions in young (3 months) and old (18 months) intact rats, an L-Dopa/carbidopa treatment was administered every 12 h over 4 weeks. Rats were assessed for behavioural despair (repeated forced swimming test, RFST), anhedonia (sucrose preference test, SPT) and spatial learning (Morris water maze, MWM) in the late phase of treatment (T). Neuronal expression of Fos in the hippocampus at the early and late phases of T, as well as after MWM was studied. The density and ratio of dopamine D5r, D3r and D2r receptors were also evaluated in the hippocampus using immunohistochemistry and confocal microscopy. Young rats showed similar patterns during behavioural tests, whereas aged treated rats showed increased immobility counts in RFST, diminished sucrose liquid intake in SPT, and spatial learning impairment during MWM. Fos expression was significantly blunted in the aged treated group after MWM. The density of D5r, D3r and D2r was increased in both aged groups. The treatment reduced the ratio of D5r/D3r and D5r/D2r in both groups. Moreover, aged treated subjects had significant lower values of D5r/D3r and higher values of D5r/D2r when compared with young treated subjects. These results indicate that chronic L-Dopa treatment in itself could trigger emotional and cognitive dysfunctions in elderly subjects through dopamine receptor dysregulation.

  1. Toxicity profiles in rats treated with tumorigenic and nontumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and myclobutanil.

    PubMed

    Wolf, Douglas C; Allen, James W; George, Michael H; Hester, Susan D; Sun, Guobin; Moore, Tanya; Thai, Sheau-Fung; Delker, Don; Winkfield, Ernest; Leavitt, Sharon; Nelson, Gail; Roop, Barbara C; Jones, Carlton; Thibodeaux, Julie; Nesnow, Stephen

    2006-01-01

    Conazoles are a class of azole based fungicides used in agriculture and as pharmaceutical products. They have a common mode of antifungal action through inhibition of ergosterol biosynthesis. Some members of this class have been shown to be hepatotoxic and will induce mouse hepatocellular tumors and/or rat thyroid follicular cell tumors. The particular mode of toxic and tumorigenic action for these compounds is not known, however it has been proposed that triadimefon-induced rat thyroid tumors arise through the specific mechanism of increased TSH. The present study was designed to identify commonalities of effects across the different conazoles and to determine unique features of the tissue responses that suggest a toxicity pathway and a mode of action for the observed thyroid response for triadimefon. Male Wistar/Han rats were treated with triadimefon (100, 500, 1800 ppm), propiconazole (100, 500, 2500 ppm), or myclobutanil (100, 500, 2000 ppm) in feed for 4, 30, or 90 days. The rats were evaluated for clinical signs, body and liver weight, histopathology of thyroid and liver, hepatic metabolizing enzyme activity, and serum T3, T4, TSH, and cholesterol levels. There was a dose-dependent increase in liver weight but not body weight for all treatments. The indication of cytochrome induction, pentoxyresorufin O-dealkylation (PROD) activity, had a dose-related increase at all time points for all conazoles. Uridine diphopho-glucuronosyl transferase (UDPGT), the T4 metabolizing enzyme measured as glucuronidation of 1-naphthol, was induced to the same extent after 30 and 90 days for all three conazoles. Livers from all high dose treated rats had centrilobular hepatocyte hypertrophy after 4 days, while only triadimefon and propiconazole treated rats had hepatocyte hypertrophy after 30 days, and only triadimefon treated rats had hepatocyte hypertrophy after 90 days. Thyroid follicular cell hypertrophy, increased follicular cell proliferation, and colloid depletion were

  2. Treatment with dexamethasone and vitamin D3 attenuates neuroinflammatory age-related changes in rat hippocampus.

    PubMed

    Moore, Michelle; Piazza, Alessia; Nolan, Yvonne; Lynch, Marina A

    2007-10-01

    Among the changes which occur in the brain with age is an increase in hippocampal concentration of proinflammatory cytokines like interleukin-1beta (IL-1beta) and an increase in IL-1beta-induced signaling. Here we demonstrate that the increase in IL-1beta concentration is accompanied by an increase in expression of IL-1 type I receptor (IL-1RI) and an age-related increase in microglial activation, as shown by increased expression of the cell surface marker, major histocompatibility complex II (MHCII) and increased MHCII staining. The evidence indicates that these age-related changes were abrogated in hippocampus of aged rats treated with dexamethasone and vitamin D3. Similarly, the age-related increases in activation of the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), as well as caspase-3 and PARP were all attenuated in hippocampal tissue prepared from rats that received dexamethasone and vitamin D3. The data indicate that dexamethasone and vitamin D3 ameliorated the age-related increase in IFNgamma and suggest that IFNgamma may be the trigger leading to microglial activation, since it increases MHCII mRNA and IL-1beta release from cultured glia. In parallel with its ability to decrease microglial activation in vivo, we report that treatment of cultured glia with dexamethasone and vitamin D3 blocked the lipopolysaccharide increased MHCII mRNA and IL-1beta concentration, while the IL-1beta-induced increases in activation of JNK and caspase 3 in cultured neurons were also reversed by treatment with dexamethasone and vitamin D3. The data suggest that the antiinflammatory effect of dexamethasone and vitamin D3 derives from their ability to downreguate microglial activation.

  3. No correlation is found for vegetables between antioxidant capacity and potential benefits in improving antioxidant function in aged rats

    PubMed Central

    Ji, Linlin; Gao, Weina; Wei, Jingyu; Wu, Jianquan; Yang, Jijun; Meng, Bin; Guo, Changjiang

    2014-01-01

    Vegetables vary greatly in antioxidant capacity in vitro. This study was to investigate the actions of three vegetables different remarkably in antioxidant capacity in vitro on antioxidant function in aged rats. Sixty female aged Wistar rats were randomly assigned to the control, lotus root, rape and cucumber (high, moderate and low in antioxidant capacity, respectively) treated groups. After 6 weeks of feeding, there were no significant differences in plasma FRAP value and contents of vitamin C, vitamin E, uric acid and total phenolics among different groups, whereas the content of reduced glutathione was significantly higher in the rape and cucumber groups. Plasma superoxide dismutase activity also was significantly increased in the rape and cucumber groups. Plasma contents of malondialdehyde, carbonyls and hemolysis were decreased significantly in 3 vegetable-treated groups. Meanwhile, urinary 8-hydroxy-2'-deoxyguanosine excretion was lower significantly in the rape group and the ratio of comet tail length to total length of blood mononuclear cells was decreased significantly in 3 vegetables treated groups. These results suggest that 3 vegetables tested are effective in improving antioxidant function to some extent in aged rats and no correlation is found between antioxidant capacity in vitro and improvements of antioxidant function. The benefits observed in this study may come from additive or synergistic combinations of antioxidants contained in vegetables. PMID:24895483

  4. Green tea polyphenols supplementation improves bone microstructure in orchidectomized middle-Aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our recent study shows that green tea polyphenols (GTP) attenuate trabecular bone loss in ovariectomized middle-aged female rats. To investigate whether GTP prevents bone loss in male rats, 40 rats with and without oriectomy (ORX) were assigned to 4 groups in a 2 (sham vs. ORX)× 2 (no GTP and 0.5% G...

  5. The Effects and Possible Mechanisms of Puerarin to Treat Endometriosis Model Rats

    PubMed Central

    Zhao, Li; Zhang, Danying; Zhai, Dongxia; Shen, Wei; Bai, Lingling; Liu, Yiqun; Cai, Zailong; Li, Ji; Yu, Chaoqin

    2015-01-01

    Objective. To explore the effects of puerarin to treat endometriosis (EMT) model rats and the possible regulatory mechanisms. Methods. EMT model rats were surgically induced by autotransplantion of endometrial tissues. The appropriate dosage of puerarin to treat EMT model rats was determined by observing the pathologic morphology of ectopic endometrial tissues and by detecting the levels of estradiol (E2) and prostaglandin E2 (PGE2) of both serum and ectopic endometrial tissues. The related genes and proteins of ectopic endometrial tissues were analyzed by Real-time PCR and immunohistochemistry (IHC) to explore the possible mechanisms. Results. Puerarin could reduce the levels of E2 and PGE2 and prevent the growth of ectopic endometrium tissues by inhibiting the expression of aromatase cytochrome P450 (p450arom) and cyclooxygenase-2 (cox-2); puerarin could adjust the anabolism of E2 by upregulating the expression of 17β-hydroxysteroid-2 (17β-hsd-2) and downregulating the expression of 17β-hydroxysteroid-1 (17β-hsd-1) of the ectopic endometrium tissues; puerarin could increase the expression of ERβ and improve the inflammatory microenvironment of EMT model rats. Conclusions. Our data suggest that puerarin has a therapeutic effect on EMT model rats and could be a potential therapeutic agent for the treatment of EMT in clinic. PMID:25815028

  6. Protective effects of a catechin-rich extract on the hippocampal formation and spatial memory in aging rats.

    PubMed

    Rodrigues, Jorge; Assunção, Marco; Lukoyanov, Nikolay; Cardoso, Armando; Carvalho, Félix; Andrade, José Paulo

    2013-06-01

    Green tea (GT) displays strong anti-oxidant and anti-inflammatory properties mostly attributed to (-)-epigallocatechin-3-gallate (EGCG), while experiments focusing on other catechins are scarce. With the present work we intended to analyze the neuroprotective effects of prolonged consumption of a GT extract (GTE) rich in catechins but poor in EGCG and other GT bioactive components that could also afford benefit. The endpoints evaluated were aging-induced biochemical and morphological changes in the rat hippocampal formation (HF) and behavioral alterations. Male Wistar rats aged 12 months were treated with GTE until 19 months of age. This group of animals was compared with control groups aged 19 (C-19M) or 12 months (C-12M). We found that aging increased oxidative markers but GTE consumption protected proteins and lipids against oxidation. The age-associated increase in lipofuscin content and lysosomal volume was also prevented by treatment with GTE. The dendritic arborizations of dentate granule cells of GTE-treated animals presented plastic changes accompanied by an improved spatial learning evaluated with the Morris water maze. Altogether our results demonstrate that the consumption of an extract rich in catechins other than EGCG protected the HF from aging-related declines contributing to improve the redox status and preventing the structural damage observed in old animals, with repercussions on behavioral performance.

  7. Spontaneous appearance of uterine tumors in vehicle and 3-methylcholanthrene-treated Wistar rats.

    PubMed

    Anger, Dana L; Crankshaw, Denis J; Foster, Warren G

    2006-11-01

    During the conduct of a study designed to determine the effect of 3-methylcholanthrene (3-MC), a synthetic polycyclic aromatic hydrocarbon (PAH) that acts through the aryl hydrocarbon receptor (AhR), on uterine contractility in Wistar rats, uterine tumors were identified in both vehicle and 3-MC-treated animals. The objective of the current study was to describe the histological characteristics of these tumors. Sexually mature female rats (110 days old) were treated with 70 micro mol/kg 3-MC or vehicle (olive oil) for 4 days and euthanized by exsanguination. At necropsy uterine tumors were unexpected findings in two vehicle and four 3-MC-treated rats. The tumors appeared as multiple unilateral or bilateral subserosal nodes. No tumors were found in other tissues on gross inspection. Prior to necropsy, tumor-presenting animals were acyclic and arrested in a state of persistent proestrus. Haematoxylin and eosin staining of tumor sections revealed nests of acidophilic granule-containing cells within a highly vascular stroma of the uterine wall below the muscularis. Positive periodic acid Schiff (PAS) staining suggested the presence of glycogen or glycophospholipids within these granules, however, negative PAS diastase staining indicated that the acidophilic bodies were not composed of glycogen. The tumors are histologically similar to human dysgerminomas. We conclude that these tumors are unrelated to treatment and are of a granular type not previously documented in Wistar rats.

  8. Studies on organ weights in naproxen treated rats after intermittent exposure to simulated high altitude

    NASA Astrophysics Data System (ADS)

    Saha, R. C.; Biswas, H. M.

    1990-06-01

    Rats were exposed intermittently for 8h per day over 6 days at simulated high altitude of 20 000 feet. One group of altitude-exposed animals was treated with naproxen, a prostaglandin inhibiting drug. Significant reduction in body weight gain was observed in both altitude-exposed and drug-treated altitude-exposed animals compared to the control group. Right and left ventricular weights and weights of the adrenal glands were increased significantly in altitude-exposed and altitude-exposed drug-treated animals. The weight of the spleen was increased significantly in altitude-exposed animals whereas no such increase of splenic weight was observed in drug-treated altitude-exposed group of animals. On the other hand, the weight of the liver was decreased significantly in both cases. In drug-treated altitude-exposed animals, the unaltered splenic weight was thought to be due to inhibition of the erythropoietic activity.

  9. Zinc improves the immune function and the proliferation of lymphocytes in Cadmium-treated rats

    PubMed Central

    Hassan, Iftekhar; Bashandy, Samir; Taha, Nael Abu; Mahmood, Amer; Alomar, Suliman; Alhazza, Iibrahim; Mashaly, Ashraf; Rady, Ahmed

    2014-01-01

    The effects of Cadmium (Cd) exposure and the treatment with Zinc (Zn) on immune functions of splenocytes and cultured lymphocytes of rats were studied. The exposure of rats to Cd was at a dose of 2.2 mg/kg CdCl2, injected subcutaneously four times weekly for 2 months. Rats were supplemented with Zn (2.2 mg/kg ZnCl2, injected subcutaneously four times weekly for 2 months) one hour prior to Cd exposure. Spleens were removed and splenocytes were isolated and cultured. The proliferation capacity of lymphocytes and their homing to the spleen were studied. Ribonucleic acid (RNA) was extracted from stimulated lymphocytes in order to analyse gene expressions using RT-PCR. Accordingly, proliferation of lymphocytes was found to be suppressed in Cd-treated rats, both in vivo and in vitro. Zinc served to activate the proliferation of B and T lymphocytes in Cd-treated rats both in vivo and in vitro. Antigen-activated lymphocytes showed that Cd impaired the mRNA expression of CD68, Ccl22 and CXCL10. Zinc was not found to restore mRNA expression of these genes to the normal levels. Zinc was found to decrease the MDA level with replenishment of activity of key antioxidant enzymes and proteins in Cd-pre-treated animals significantly. Moreover, the histopathological examination of spleen samples also agreed with the molecular, immunological and redox findings. Hence, Zn is able to restore the normal structure, redox status and immunity in Cd-induced damage in the rat model system. PMID:26155160

  10. Insufficient renal 1-alpha hydroxylase and bone homeostasis in aged rats with insulin resistance or type 2 diabetes mellitus.

    PubMed

    Chang-Quan, Huang; Bi-Rong, Dong; Ping, He; Zhen-Chan, Lu

    2008-01-01

    This study aimed to explore the relationship between insufficient renal 1-alpha hydroxylase (IRH) and bone homeostasis in type 2 diabetes mellitus (T2DM) or insulin resistance (IR) and to investigate whether IR plays a major role in the pathogenesis of both IRH and bone loss in T2DM. The experimental animal models of T2DM, IR, IR treated with vitamin D (VD), IR treated with 1-alpha hydroxyvitamin D (1alpha(OH) D, the product of renal 1-alpha hydroxylase), T2DM treated with VD, and T2DM treated with 1alpha(OH) D were established on 18-month-old male Wistar rats. For rats in each animal model and normal control rats, IR was detected by euglycemic insulin clamp technique (EICT) and glucose infusion rate (GIR, an index of IR) was calculated. Levels of serum 25-hydroxyvitamin D (25(OH)D) and serum active vitamin D (1,25(OH)(2)D) were determined by radioimmunoassay (RIA), and 1,25(OH)(2)D/25(OH)D ratio (1,25-25-R, an index of renal 1-alpha hydroxylase activity in vivo) was calculated; and bone mineral density (BMD) in femoral bone and lumbar vertebrae was measured by dual-energy X-ray absorption (DEXA). No significant difference was observed among the levels of 25(OH)D in all the rats. In IR rats, 1,25(OH)(2)D level, 1,25-25-R, and BMD level were significantly higher than those in T2DM rats and were lower than those in normal control rats. In the aged rats with T2DM or IR, administration of VD had no effect on 25(OH)D level, 1,25(OH)(2)D level, 1,25-25-R, and BMD level. Administration of 1alpha(OH) D had also no effect on 25(OH)D level but increased 1,25(OH)(2)D level, 1,25-25-R, and BMD level. For the aged rats with T2DM or IR, GIR positively correlated with both levels of 1,25(OH)(2)D and BMD, and 1,25-25-R positively and significantly correlated with levels of BMD. In T2DM or IR, IRH is a precipitating factor for bone loss. IR seems to play a major role in the pathogenesis of both IRH and bone loss in T2DM.

  11. Neuroprotective Effects of Aged Garlic Extract on Cognitive Dysfunction and Neuroinflammation Induced by β-Amyloid in Rats

    PubMed Central

    Nillert, Nutchareeporn; Pannangrong, Wanassanun; Welbat, Jariya Umka; Chaijaroonkhanarak, Wunnee; Sripanidkulchai, Kittisak; Sripanidkulchai, Bungorn

    2017-01-01

    Neuroinflammation is pathological evidence of Alzheimer’s disease (AD) that likely starts as a host defense response to the damaging effects of the β-amyloid (Aβ) deposits in the brain. The activation of microglia may promote the neurodegenerative process through the release of proinflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), which may lead to neuronal damage and eventual death. Aged garlic extract (AGE) has been reported to have multiple biological activities, including anti-inflammatory effects. Therefore, the objective of this study was to investigate the effect of AGE on Aβ (1-42)-induced cognitive dysfunction and neuroinflammation. Adult male Wistar rats were given AGE (125, 250, and 500 mg/kg BW, body weight), orally administered, daily for 56 days. They were then injected with 1 μL of aggregated Aβ (1-42) into the lateral ventricles; bilaterally. Seven days later, their recognition memory was evaluated using a novel object recognition (NOR) test. Then the rats were sacrificed to investigate the alteration of microglia cells, IL-1β and TNFα in the cerebral cortex and hippocampus. The results indicated that AGE at doses of 250 and 500 mg/kg BW significantly improved short-term recognition memory in cognitively impaired rats. In addition, AGE significantly minimized the inflammatory response by reducing the activation of microglia and IL-1β to the levels found in the control, which is similar to the results found in Celebrex-treated rats. In conclusion, AGE may be useful for improving the short-term recognition memory and relieve the neuroinflammation in Aβ-induced rats. PMID:28054940

  12. Uric acid plasma level and urine pH in rats treated with ambroxol.

    PubMed

    Drewa, Tomasz; Wolski, Zbigniew; Gruszka, Marzena; Misterek, Bartosz; Lysik, Joanna

    2007-01-01

    It was a chance discovery that ambroxol parenteral administration led to urinary bladder stone formation in rats. This study was undertaken to examine the serum uric acid levels and urine pH in rats after ambroxol parenteral treatment. Ambroxol influence on the uric acid level was measured in 5 rats (Rattus sp.) treated with 60 mg/kg (dissolved in injection water, sc, daily) during 2 weeks. Ambroxol influence on urine pH was examined on 45 rats divided into 3 groups. Rats from the 1st and 2nd group received 30 and 60 mg/kg/24h ambroxol, respectively. Urine was collected once daily and measured with strip kit. All values were presented as the means with standard deviations. The Student t test was used to compare the means, p < 0.05 was considered as significant. Dynamics of pH changes was measured in 4 rats treated with 60 mg/kg/24h of ambroxol. Controls received 1 mL of injection water sc. Serum uric acid level increased up to 8.7 +/- 1.0 mg/dL vs. 5.7 +/- 1.0 mg/dL in control (p < 0.002). In the 1st and 2nd group urine pH increased up to 7.5 +/- 0.5 and 7.6 +/- 0.5 vs. 6.7 +/- 0.4 (p < 0.05). Ambroxol withdrawal resulted in sequential urine pH decrease. 11 days after interruption of ambroxol therapy pH reached the starting value. Urine pH changes and possible disturbances in uric acid metabolic pathway may influence on the stone formation in rats after ambroxol parenteral treatment. The influence of ambroxol on urinary tract GAG layer and the balance between xanthine and CaOx in the urine should be checked.

  13. Sipa1l1 is an early biomarker of liver fibrosis in CCl4-treated rats

    PubMed Central

    Marfà, Santiago; Morales-Ruiz, Manuel; Oró, Denise; Ribera, Jordi; Fernández-Varo, Guillermo; Jiménez, Wladimiro

    2016-01-01

    ABSTRACT At present, several procedures are used for staging liver fibrosis. However, these methods may involve clinical complications and/or present diagnostic uncertainty mainly in the early stages of the disease. Thus, this study was designed to unveil new non-invasive biomarkers of liver fibrosis in an in vivo model of fibrosis/cirrhosis induction by CCl4 inhalation by using a label-free quantitative LC-MS/MS approach. We analyzed 94 serum samples from adult Wistar rats with different degrees of liver fibrosis and 36 control rats. Firstly, serum samples from 18 CCl4-treated rats were clustered into three different groups according to the severity of hepatic and the serum proteome was characterized by label-free LC-MS/MS. Furthermore, three different pooled serum samples obtained from 16 control Wistar rats were also analyzed. Based on the proteomic data obtained, we performed a multivariate analysis which displayed three main cell signaling pathways altered in fibrosis. In cirrhosis, more biological imbalances were detected as well as multi-organ alterations. In addition, hemopexin and signal-induced proliferation-associated 1 like 1 (SIPA1L1) were selected as potential serum markers of liver fibrogenesis among all the analyzed proteins. The results were validated by ELISA in an independent group of 76 fibrotic/cirrhotic rats and 20 controls which confirmed SIPA1L1 as a potential non-invasive biomarker of liver fibrosis. In particular, SIPA1L1 showed a clear diminution in serum samples from fibrotic/cirrhotic rats and a great accuracy at identifying early fibrotic stages. In conclusion, the proteomic analysis of serum samples from CCl4-treated rats has enabled the identification of SIPA1L1 as a non-invasive marker of early liver fibrosis. PMID:27230648

  14. Loss of perforated synapses in the dentate gyrus: morphological substrate of memory deficit in aged rats.

    PubMed Central

    Geinisman, Y; de Toledo-Morrell, L; Morrell, F

    1986-01-01

    Most, but not all, aged rats exhibit a profound deficit in spatial memory when tested in a radial maze--a task known to depend on the integrity of the hippocampal formation. In this study, animals were divided into three groups based on their spatial memory capacity: young adult rats with good memory, aged rats with impaired memory, and aged rats with good memory. Memory-impaired aged animals showed a loss of perforated axospinous synapses in the dentate gyrus of the hippocampal formation in comparison with either young adults or aged rats with good memory. This finding suggests that the loss of perforated axospinous synapses in the hippocampal formation underlies the age-related deficit in spatial memory. Images PMID:3458260

  15. An evaluation of aversive memory and hippocampal oxidative status in streptozotocin-induced diabetic rats treated with resveratrol.

    PubMed

    Bagatini, Pamela Brambilla; Xavier, Léder Leal; Bertoldi, Karine; Moysés, Felipe; Lovatel, Gisele; Neves, Laura Tartari; Barbosa, Sílvia; Saur, Lisiani; de Senna, Priscylla Nunes; Souto, André Arigony; Siqueira, Ionara Rodrigues; Achaval, Matilde

    2017-01-01

    The present study evaluated the effects of streptozotocin (STZ)-induced diabetes on aversive memory, free radical content and enzymatic antioxidant activity in the hippocampus of adult Wistar rats submitted to oral treatment with resveratrol. Animals were divided into eight groups: non-diabetic rats treated with saline (ND SAL), non-diabetic rats treated with resveratrol at a dose 5mg/kg (ND RSV 5), non-diabetic rats treated with resveratrol at a dose 10mg/kg (ND RSV 10), non-diabetic rats treated with resveratrol at a dose 20mg/kg (ND RSV 20), diabetic rats treated with saline (D SAL), diabetic rats treated with resveratrol at a dose 5mg/kg (D RSV 5), diabetic rats treated with resveratrol at a dose 10mg/kg (D RSV 10) and diabetic rats treated with resveratrol at a dose 20mg/kg (D RSV 20). The animals received oral gavage for 35days. The contextual fear conditioning task was performed to evaluate aversive-based learning and memory. The oxidative status was evaluated in the hippocampus, by measuring the free radical content - using a 2',7'-dichlorofluorescein diacetate probe - and enzymatic antioxidant activities, such as superoxide dismutase and glutathione peroxidase. Our main behavioral results demonstrated that rats from the D RSV 10 and D RSV 20 groups showed an increase in freezing behavior when compared, respectively, to the ND RSV 10 (p<0.01) and ND RSV 20 (p<0.05). Oxidative stress parameters remained unchanged in the hippocampus of all the experimental groups. In contrast to previous experimental findings, our study was unable to detect either cognitive impairments or oxidative stress in the hippocampus of the diabetic rats. We suggest additional long-term investigations be conducted into the temporal pattern of STZ-induced diabetic disruption in memory and hippocampal oxidative status, as well as the effects of resveratrol on these parameters, in a time and dose-dependent manner.

  16. Brain Insulin Administration Triggers Distinct Cognitive and Neurotrophic Responses in Young and Aged Rats.

    PubMed

    Haas, Clarissa B; Kalinine, Eduardo; Zimmer, Eduardo R; Hansel, Gisele; Brochier, Andressa W; Oses, Jean P; Portela, Luis V; Muller, Alexandre P

    2016-11-01

    Aging is a major risk factor for cognitive deficits and neurodegenerative disorders, and impaired brain insulin receptor (IR) signaling is mechanistically linked to these abnormalities. The main goal of this study was to investigate whether brain insulin infusions improve spatial memory in aged and young rats. Aged (24 months) and young (4 months) male Wistar rats were intracerebroventricularly injected with insulin (20 mU) or vehicle for five consecutive days. The animals were then assessed for spatial memory using a Morris water maze. Insulin increased memory performance in young rats, but not in aged rats. Thus, we searched for cellular and molecular mechanisms that might account for this distinct memory response. In contrast with our expectation, insulin treatment increased the proliferative activity in aged rats, but not in young rats, implying that neurogenesis-related effects do not explain the lack of insulin effects on memory in aged rats. Furthermore, the expression levels of the IR and downstream signaling proteins such as GSK3-β, mTOR, and presynaptic protein synaptophysin were increased in aged rats in response to insulin. Interestingly, insulin treatment increased the expression of the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) receptors in the hippocampus of young rats, but not of aged rats. Our data therefore indicate that aged rats can have normal IR downstream protein expression but failed to mount a BDNF response after challenge in a spatial memory test. In contrast, young rats showed insulin-mediated TrkB/BDNF response, which paralleled with improved memory performance.

  17. Prostanoid production in the presence of platelet activation in hypoxic cocaine-treated rats.

    PubMed

    Togna, G; Graziani, M; Sorrentino, C; Caprino, L

    1996-01-01

    To extend our previous in vitro data, we investigated the effects of cocaine on thromboxane A2 (TXA2) and prostacyclin (PGI2) production in vivo in the rat. To obtain the slight platelet activation that our in vitro experiments showed useful to highlight the effect of cocaine, we infused cocaine in rats in the presence of platelet-activating factors (circulation of blood through a perspex vascular device or by infusion of sodium arachidonate) and in various respiratory conditions. Experiments were conducted in rats breathing atmospheric air (normoxic conditions) and in rats breathing an oxygen-poor mixture (hypoxic conditions). In rats under hypoxic conditions cocaine invariably increased TXA2 plasma levels, whereas in normoxic conditions it increased TXA2 only in the presence of platelet-activating factors. Cocaine significantly increased PGI2 plasma levels in arachidonate-treated rats in hypoxic respiratory conditions; in normoxic conditions cocaine left PGI2 levels unchanged. These results support the hypothesis that in cocaine users who have concomitant pathological conditions able to activate platelets, such as atherosclerosis, coronary vasospasm or ischaemia, or both, cocaine may contribute to the onset of thrombotic phenomena by interfering with the prostaglandin system.

  18. Different effect of handle region peptide on β-cell function in different sexes of rats neonatally treated with sodium L-glutamate.

    PubMed

    Wu, Yi-xi; Sun, Ru-qiong; Yin, Guo-shu; Xu, Dong-chuan; Wang, Ping; Lin, Kun; Lin, Chu-jia; Lin, Shao-da

    2015-03-17

    BACKGROUND The (pro)renin receptor ((P)RR) was reported to be expressed in various tissues including the pancreas, and handle region peptide (HRP) is believed to block the function of (P)RR. This study aimed to investigate the effect of HRP on the glucose tolerance status and β-cell function of female rats, neonatally treated with sodium L-glutamate (MSG) and to compare with the previously reported HRP effect on male rats. MATERIAL AND METHODS Female MSG rats aged 8 weeks were divided into MSG control group and HRP treated group and the normal SD rats served as control. The MSG rats were treated with HRP by osmotic minipumps with dose of 1 mg/kg per day for total 28 days. Glucose tolerance status was evaluated at the end of the study. Islets α-cell and β-cell were marked with insulin antibody and glucagon antibody respectively. The proliferation of islet cells and expression of subunit of NADPH oxidase P22phox were marked by PCNA and P22phox antibody. Picrosirius red staining was performed for evaluating fibrosis of islets. RESULTS HRP improved the glucose status tolerance with decreasing α-cell mass, islets PCNA-positive cells, expression of P22phox and picrosirius red stained areas, and increasing β-cell mass in female MSG rats. The indexes with obviously interacted effect of sexes and HRP for the MSG rats were the AUC of blood glucose concentration (P<0.01), α-cell mass (P<0.05), proliferation of islet cells (P<0.01) and area of picrosirius red staining (P<0.01). CONCLUSIONS HRP improved the glucose tolerance status in the females although it was previously reported to worsen the glucose tolerance in male MSG rats. Different levels of sex hormones may partly account for the disparate effects observed for HRP in different sexes.

  19. Effect of aging on ultrasonic vocalizations and laryngeal sensorimotor neurons in rats.

    PubMed

    Basken, Jaime N; Connor, Nadine P; Ciucci, Michelle R

    2012-06-01

    While decline in vocal quality is prevalent in an aging population, the underlying neurobiological mechanisms contributing to age-related dysphonia are unknown and difficult to study in humans. Development of an animal model appears critical for investigating this issue. Using an established aging rat model, we evaluated if 50-kHz ultrasonic vocalizations in 10, 32-month-old (old) Fischer 344/Brown Norway rats differed from those in 10, 9-month-old (young adult) rats. The retrograde tracer, Cholera Toxin β, was injected to the thyroarytenoid muscle to determine if motoneuron loss in the nucleus ambiguus was associated with age. Results indicated that older rats had vocalizations with diminished acoustic complexity as demonstrated by reduced bandwidth, intensity, and peak frequency, and these changes were dependent on the type of 50-kHz vocalization. Simple calls of old rats had reduced bandwidth, peak frequency, and intensity while frequency-modulated calls of old rats had reduced bandwidth and intensity. Surprisingly, one call type, step calls, had increased duration in the aged rats. These findings reflect phonatory changes observed in older humans. We also found significant motoneuron loss in the nucleus ambiguus of aged rats, which suggests that motoneuron loss may be a contributing factor to decreased complexity and quality of ultrasonic vocalizations. These findings suggest that a rat ultrasonic phonation model may be useful for studying age-related changes in vocalization observed in humans.

  20. Vascular wall dysfunction in JCR:LA-cp rats: effects of age and insulin resistance.

    PubMed

    O'brien, S F; Russell, J C; Davidge, S T

    1999-11-01

    We tested the hypothesis that aging and insulin resistance interact to increase vascular dysfunction by comparing the function of isolated mesenteric resistance arteries in obese, insulin-resistant JCR:LA-cp rats and lean, insulin-sensitive rats of the same strain at 3, 6, 9, and 12 mo of age. The peak constrictor responses to norepinephrine, phenylephrine, and high potassium were elevated in arteries from obese rats. Responses to these agents increased with age in both obese and lean rats. An eicosanoid constrictor contributed substantially to vasoconstriction in the arteries from both lean and obese animals. Inhibition of nitric oxide synthase increased the vasoconstrictor response to norepinephrine in both obese and lean rats. This effect increased with age in lean rats only. Vascular relaxation in response to acetylcholine and sodium nitroprusside was impaired in the obese rats and did not alter with age. The results suggest that obese JCR:LA-cp rats have enhanced maximal constriction, which originates in the arterial smooth muscle and increases with age. There is evidence that the ability of the arteries to compensate for the enhanced contractility is impaired in obese rats, particularly with advanced age.

  1. Impaired alpha1-adrenergic responses in aged rat hearts.

    PubMed

    Montagne, Olivier; Le Corvoisier, Philippe; Guenoun, Thierry; Laplace, Monique; Crozatier, Bertrand

    2005-06-01

    To determine age-related changes in the cardiac effect of alpha1-adrenergic stimulation, both cardiomyocyte Ca2+-transient and cardiac protein kinase C (PKC) activity were measured in 3-month- (3MO) and 24-month- (24MO) old Wistar rats. Ca2+ transients obtained under 1 Hz pacing by microfluorimetry of cardiomyocyte loaded with indo-1 (405/480 nm fluorescence ratio) were compared in control conditions (Kreb's solution alone) and after alpha1-adrenergic stimulation (phenylephrine or cirazoline, an alpha1-specific agonist). PKC activity and PKC translocation index (particulate/total activity) were also assayed before and after alpha1-adrenergic stimulation. In 3MO, cirazoline induced a significant increase in Ca2+ transient for a 10(-9) M concentration which returned to control values for larger concentrations. In contrast, in 24MO, we observed a constant negative effect of cirazoline on the Ca2+ transient with a significant decrease at 10(-6) M compared with both baseline and Kreb's solution. Preliminary experiments showed that, in a dose-response curve to phenylephrine, the response of Ca2+ transient was maximal at 10(-7) M. This concentration induced a significant increase in Ca2+ transient in 3MO and a significant decrease in 24MO. The same concentration was chosen to perform PKC activity measurements under alpha1-adrenergic stimulation. In the basal state, PKC particulate activity was higher in 24MO than that in 3MO but was not different in cytosolic fractions; so that the translocation index was higher in 24MO (P < 0.01). After phenylephrine, a translocation of PKC toward the particulate fraction was observed in 3MO but not in 24MO. In conclusion, cardiac alpha1-adrenoceptor response was found to be impaired in aged hearts. The negative effect of alpha1-adrenergic stimulation on Ca2+ transient in cardiomyocytes obtained from old rats can be related to an absence of alpha1-adrenergic-induced PKC translocation.

  2. Protective potential of Bacopa monniera (Brahmi) extract on aluminum induced cerebellar toxicity and associated neuromuscular status in aged rats.

    PubMed

    Tripathi, S; Mahdi, A A; Hasan, M; Mitra, K; Mahdi, F

    2011-02-12

    The present study attempts to assess the comparative effects of Bacopa monniera, (40 mg/kg body weight) and donepezil (2.5 mg/kg b. wt) on aluminum (100 mg / kg b. wt. of AlCl3) mediated oxidative damage in the cerebellum of aged rats (24 months) along with the associated dysfunctioning of neuromuscular coordination and motor activity. A significant decrease in the activities of antioxidant enzymes and increased total reacting oxygen species, lipid and protein peroxidation products observed in aluminum exposed rats. We observed that treatment with B. monniera extract restored the altered antioxidant enzyme activities more, when compared with donepezil. However, acetylcholinesterase showed similar effect both in donepezil and B. monniera treated groups. The content of aluminum was increased in all experimental groups, however, iron content was found increased in all groups except the B. monniera treated groups. Moreover, aluminum treated groups of rats exhibited significant changes in behavioral profiles but these changes were in both B. monniera and donepezil treated groups. The light microscopic and ultrastructural studies revealed damaged Purkinje's neurons and altered granular cell layer along with the increased accumulation of lipofuscin granules in aluminum treated animals. These changes were quite less pronounced in B. monniera group than that of donepezil and this may be due to the reduction of excess iron content by B. monniera. On the basis of our results it may be concluded that Al may be linked with cerebellar degeneration and neuromuscular disorders while Bacopa monniera extract helps in reversing these changes.

  3. Liver necrosis induced by acute intraperitoneal ethanol administration in aged rats.

    PubMed

    Giavarotti, Leandro; D'Almeida, Vania; Giavarotti, Karin A S; Azzalis, Ligia A; Rodrigues, Luciano; Cravero, Amerys A M; Videla, Luis A; Koch, Osvaldo R; Junqueira, Virginia B C

    2002-03-01

    It is generally agreed that the deleterious pathophysiological effects of ethanol are caused, at least partially by an increase in free radical production. However, little attention has been directed to the effects of ethanol upon elderly organisms. Male Wistar rats at ages 3, 6, 12, 18 and 24 months were treated either with a single i.p. dose of 35% ethanol (v/v) at 3 g ethanol/kg body weight or an isovolumetric amount of 0.9% saline solution. We then assessed the plasma levels of transaminases and hepatic levels of oxidative stress-related parameters, followed by liver histological evaluation. The younger rats (3 months old) were not affected by the treatment with ethanol with respect to any of the studied parameters except for a lowering of total hepatic GSH and an increase in hepatic thiobarbituric acid reactants (TBARS) formation, while animals older than 3 months were increasingly more affected by the treatment. Acute ethanol treatment elicited the similar responses to those in the 3 months-old group, plus a decrease in the hepatic and plasma levels of beta-carotene and the plasma level of alpha-tocopherol, as well as an increase in the activity of plasma transaminases. In the 12,18 and 24 months old groups, there was increasing liver necrosis. These findings suggest that liver damage induced by acute ethanol administration in elderly rats may involve a lack of antioxidants.

  4. Changes in antioxidant defense status in hypercholesterolemic rats treated with Ajuga iva.

    PubMed

    Bouderbala, S; Lamri-Senhadji, M; Prost, J; Lacaille-Dubois, M A; Bouchenak, M

    2008-06-01

    The aim of the study was to investigate the effect of aqueous extract of Ajuga iva (Ai) on serum and tissues lipid peroxidation as well as antioxidant enzymes activities in red blood cells (RBC) and tissues, in high hypercholesterolemic rats (HC). Male Wistar rats (n=12) were fed on 1% cholesterol-enriched diet for 15d. After this adaptation phase, hypercholesterolemic rats (total cholesterol=6.5+/-0.6mol/l) were divided into two groups fed the same diet and treated or not with Ai for 15d. Thiobarbituric acid reactive substances (TBARS) concentrations in serum, LDL-HDL(1), HDL(2) and HDL(3) were respectively, 5-, 7.8-, 2.3- and 5-fold lower in Ai treated than untreated hypercholesterolemic groups. TBARS concentrations were 1.4-fold lower in heart and 2.8-fold higher in kidney in Ai-HC treated than untreated HC group. Superoxide dismutase activity was respectively, 1.2- and 1.4-fold higher in RBC and muscle in Ai treated than untreated group. In RBC, Ajuga iva treatment enhanced glutathione peroxidase (GSH-Px) (+9%) and glutathione reductase (GSSH-Red) (+12%) in Ai-HC treated than untreated HC group. GSSH-Red activity was 1.4- and 1.5-fold higher in adipose tissue and heart, respectively and 3.7-fold lower in kidney in Ai treated than untreated group. Liver catalase activity was 1.6-fold higher in Ai treated than untreated group. Adipose tissue and muscle total glutathione content represented in Ai treated group 35% and 36% of the value noted in untreated group. Nitric oxide values of liver, adipose tissue and heart were 3.3-, 2.5- and 3.4-fold higher in Ai-HC than HC group. Ajuga iva treatment enhanced alpha-tocopherol contents (+25%) in Ai treated than untreated group. In conclusion, Ajuga iva treatment is more effective to improve the antioxidant capacity of RBC than that of tissues. Indeed, Ai is able to reduce the oxidative stress in hypercholesterolemic rats by increasing the antioxidant enzymes activity.

  5. Supplementation with green tea polyphenols improves bone microstructure and quality in aged, orchidectomized rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent studies show that green tea polyphenols (GTP) attenuate bone loss and microstructure deterioration in ovariectomized aged female rats, a model of postmenopausal osteoporosis. However, it is not known if such an osteo-protective role of GTP is demonstrable in androgen-deficient aged rats, a mo...

  6. Age-dependent seizures of absence epilepsy and sleep spindles dynamics in WAG/Rij rats

    NASA Astrophysics Data System (ADS)

    Grubov, Vadim V.; Sitnikova, Evgenia Y.; Pavlov, Alexey N.; Khramova, Marina V.; Koronovskii, Alexey A.; Hramov, Alexander E.

    2015-03-01

    In the given paper, a relation between time-frequency characteristics of sleep spindles and the age-dependent epileptic activity in WAG/Rij rats is discussed. Analysis of sleep spindles based on the continuous wavelet transform is performed for rats of different ages. It is shown that the epileptic activity affects the time-frequency intrinsic dynamics of sleep spindles.

  7. Bone morphometry and differences in bone fluorine containing compounds in rats treated with NaF and MFP.

    PubMed

    Brun, L R; Pera, L I; Rigalli, A

    2010-01-01

    Sodium fluoride (NaF) and sodium monofluorophosphate (MFP) are drugs used to increase bone mass. They have been considered equivalent but the results of the treatments were not always coincident. Most studies have been carried out in osteoporotic women or ovariectomized rats pointing to the result in bone mass rather than at the mechanism of action. Convincing evidence indicates that pharmacokinetic of NaF is different from MFP. While only fluoride is found in bones and plasma of rats treated with NaF, in MFP-treated rats, there are also fluorine (F) bound to plasma alpha-macroglobulin and bone covalently bound F. A significant increase in bone mass of rats was observed after 30 days of treatment with NaF and MFP in young rats. This increase in bone mass correlates with the increase in number and thickness of trabeculas in cancellous bone. In the femur of MFP-treated rats, there was an increase in the inertia momentum of the diaphysis without changes in bone width. In addition, bone F content of MFP-treated animals is twice of the content of NaF-treated rats. This difference is the consequence of bone covalently bound F, which is absent in NaF-treated rats. In addition, alpha-macroglobulin was detected in noncollagenous bone matrix of MFP-treated rats. Although F in feces and plasma did not differ among treatments, the urinary excretion of F was lower in MFP than in NaF-treated rats, which is consistent with the higher bone F content.

  8. Ginsenoside Rg1 prevents cognitive impairment and hippocampus senescence in a rat model of D-galactose-induced aging.

    PubMed

    Zhu, Jiahong; Mu, Xinyi; Zeng, Jin; Xu, Chunyan; Liu, Jun; Zhang, Mengsi; Li, Chengpeng; Chen, Jie; Li, Tinyu; Wang, Yaping

    2014-01-01

    Neurogenesis continues throughout the lifetime in the hippocampus, while the rate declines with brain aging. It has been hypothesized that reduced neurogenesis may contribute to age-related cognitive impairment. Ginsenoside Rg1 is an active ingredient of Panax ginseng in traditional Chinese medicine, which exerts anti-oxidative and anti-aging effects. This study explores the neuroprotective effect of ginsenoside Rg1 on the hippocampus of the D-gal (D-galactose) induced aging rat model. Sub-acute aging was induced in male SD rats by subcutaneous injection of D-gal (120 mg/kg·d) for 42 days, and the rats were treated with ginsenoside Rg1 (20 mg/kg·d, intraperitoneally) or normal saline for 28 days after 14 days of D-gal injection. In another group, normal male SD rats were treated with ginsenoside Rg1 alone (20 mg/kg·d, intraperitoneally) for 28 days. It showed that administration of ginsenoside Rg1 significantly attenuated all the D-gal-induced changes in the hippocampus, including cognitive capacity, senescence-related markers and hippocampal neurogenesis, compared with the D-gal-treated rats. Further investigation showed that ginsenoside Rg1 protected NSCs/NPCs (neural stem cells/progenitor cells) shown by increased level of SOX-2 expression; reduced astrocytes activation shown by decrease level of Aeg-1 expression; increased the hippocampal cell proliferation; enhanced the activity of the antioxidant enzymes GSH-Px (glutathione peroxidase) and SOD (Superoxide Dismutase); decreased the levels of IL-1β, IL-6 and TNF-α, which are the proinflammatory cytokines; increased the telomere lengths and telomerase activity; and down-regulated the mRNA expression of cellular senescence associated genes p53, p21Cip1/Waf1 and p19Arf in the hippocampus of aged rats. Our data provides evidence that ginsenoside Rg1 can improve cognitive ability, protect NSCs/NPCs and promote neurogenesis by enhancing the antioxidant and anti-inflammatory capacity in the hippocampus.

  9. Ginsenoside Rg1 Prevents Cognitive Impairment and Hippocampus Senescence in a Rat Model of D-Galactose-Induced Aging

    PubMed Central

    Zeng, Jin; Xu, Chunyan; Liu, Jun; Zhang, Mengsi; Li, Chengpeng; Chen, Jie; Li, Tinyu; Wang, Yaping

    2014-01-01

    Neurogenesis continues throughout the lifetime in the hippocampus, while the rate declines with brain aging. It has been hypothesized that reduced neurogenesis may contribute to age-related cognitive impairment. Ginsenoside Rg1 is an active ingredient of Panax ginseng in traditional Chinese medicine, which exerts anti-oxidative and anti-aging effects. This study explores the neuroprotective effect of ginsenoside Rg1 on the hippocampus of the D-gal (D-galactose) induced aging rat model. Sub-acute aging was induced in male SD rats by subcutaneous injection of D-gal (120 mg/kg·d) for 42 days, and the rats were treated with ginsenoside Rg1 (20 mg/kg·d, intraperitoneally) or normal saline for 28 days after 14 days of D-gal injection. In another group, normal male SD rats were treated with ginsenoside Rg1 alone (20 mg/kg·d, intraperitoneally) for 28 days. It showed that administration of ginsenoside Rg1 significantly attenuated all the D-gal-induced changes in the hippocampus, including cognitive capacity, senescence-related markers and hippocampal neurogenesis, compared with the D-gal-treated rats. Further investigation showed that ginsenoside Rg1 protected NSCs/NPCs (neural stem cells/progenitor cells) shown by increased level of SOX-2 expression; reduced astrocytes activation shown by decrease level of Aeg-1 expression; increased the hippocampal cell proliferation; enhanced the activity of the antioxidant enzymes GSH-Px (glutathione peroxidase) and SOD (Superoxide Dismutase); decreased the levels of IL-1β, IL-6 and TNF-α, which are the proinflammatory cytokines; increased the telomere lengths and telomerase activity; and down-regulated the mRNA expression of cellular senescence associated genes p53, p21Cip1/Waf1 and p19Arf in the hippocampus of aged rats. Our data provides evidence that ginsenoside Rg1 can improve cognitive ability, protect NSCs/NPCs and promote neurogenesis by enhancing the antioxidant and anti-inflammatory capacity in the hippocampus. PMID

  10. [Studies on transdermal delivery of ferulic acid through rat skin treated by microneedle arrays].

    PubMed

    Yang, Bing; Du, Shou-ying; Bai, Jie; Shang, Ke-xin; Lu, Yang; Li, Peng-yue

    2014-12-01

    In order to investigate the characteristics of transdermal delivery of ferulic acid under the treated of microneedle arrays and the influence on permeability of rat skin capillaries, improved Franz-cells were used in the transdermal delivery experiment with the rat skin of abdominal wall and the length of microneedle arrays, different insertion forces, retention time were studied in the influence of characteristics of transdermal delivery of FA. The amount of FA was determined by HPLC system. Intravenous injection Evans blue and FA was added after microneedle arrays treated. Established inflammation model was built by daubing dimethylbenzene. The amount of Evans blue in the rat skin was read at 590 nm wavelength with a Multiskan Go microplate reader. Compared with passive diffusion group the skin pretreated with microneedle arrays had a remarkable enhancement of FA transport (P <0.01). The accumulation of FA increased with the enhancement of insertion force as to as the increase of retention time. Microneedle arrays with different length had a remarkable enhancement of FA transport, but was not related to the increase of the length. The research of FA on the reduce of permeability of rat skin capillaries indicated that the skin pretreated with microneedle arrays could reduce the content of Evans blue in the skins of rat significantly compared with the untreated group. The permeation rate of ferulic acid transdermal delivery had remarkable increase under the treated of microneedle arrays and the length of microneedle arrays ,the retention time so as to the insertion force were important to the transdermal delivery of ferulic acid.

  11. Estrogen therapy increases BDNF expression and improves post-stroke depression in ovariectomy-treated rats

    PubMed Central

    Su, Qiaoer; Cheng, Yifan; Jin, Kunlin; Cheng, Jianhua; Lin, Yuanshao; Lin, Zhenzhen; Wang, Liuqing; Shao, Bei

    2016-01-01

    The present study investigated the effect of exogenous estrogen on post-stroke depression. Rats were exposed to chronic mild stress following middle cerebral artery occlusion. The occurrence of post-stroke depression was evaluated according to the changes in preference for sucrose and performance in a forced swimming test. Estrogen therapy significantly improved these neurological symptoms, indicating that estrogen is effective in treating post-stroke depression. Increased brain-derived neurotrophic factor (BDNF) expression was reported in the hippocampus of rats that had been treated with estrogen for two weeks, suggesting that BDNF expression may be an important contributor to the improvement of post-stroke depression that is observed following estrogen therapy. PMID:27602095

  12. Locomotion and physical development in rats treated with ionizing radiation in utero

    SciTech Connect

    Zaman, M.S.; Hupp, E.W. Texas Woman's Univ., Houston, TX ); Lancaster, F.E. )

    1993-01-01

    Effects of ionizing radiation on the emergence of locomotor skill, and physical development were studied in laboratory rats (Fisher F-344 inbred strain). Rats were treated with 3 different doses of radiation (150 rad, 15 rad, and 6.8 rad) delivered on the 20th day of prenatal life. Results indicated that relatively moderate (15 rad) to high (150 rad) doses of radiation had effects on certain locomotion and physical development parameters. Exposure to 150 rad delayed pivoting, cliff-avoidance, upper jaw tooth eruption, and decreased body weights. Other parameters, such as negative geotaxis, eye opening, and lower jaw tooth eruption were marginally delayed in the 150 rad treated animals. Exposure to 15 rad delayed pivoting and cliff-avoidance.

  13. Effects of maternal age on teratogenicity of di-n-butyltin diacetate in rats.

    PubMed

    Noda, T; Yamano, T; Shimizu, M

    2001-10-30

    The present study was designed to assess changes in the teratogenic potency of di-n-butyltin diacetate (DBTA) with increasing maternal age in rats. Pregnant Wistar rats of 3, 7.5 or 12 months were treated orally with DBTA at 0, 7.5, 10, 15 or 22 mg/kg on day 8 of gestation. Cesarean sections were performed on day 20 of gestation. Maternal age had greater impact on litter size in the 7.5- and 12-month dams than the 3-month dams. The death of most of the fetuses of the 12-month dams made it difficult to evaluate the teratogenic potency of DBTA. In 3-month groups, fetuses with external malformation, such as cleft mandible, cleft lower lip, ankyloglossia and/or schistoglossia, which are malformations typical of DBTA, were observed at 15 and 22 mg/kg, while similar malformations were observed in 7.5-month groups at doses of 10 mg/kg and above. At 15 and 22 mg/kg, the incidences of these malformations in 7.5-month groups were similar to these from 3-month groups. In our previous studies, however, single DBTA-treatment at 10 mg/kg on day 8 of gestation has not produced such malformations from 3-month dams. The results suggest that the teratogenic potency of DBTA in 7.5-month dams may be greater than in 3-month dams.

  14. Chronic administration of taurine to aged rats improves the electrical and contractile properties of skeletal muscle fibers.

    PubMed

    Pierno, S; De Luca, A; Camerino, C; Huxtable, R J; Camerino, D C

    1998-09-01

    A reduction of resting chloride conductance (GCl) and a decrease of the voltage threshold for contraction are observed during aging in rat skeletal muscle. The above alterations are also observed in muscle of adult rat after taurine depletion. As lower levels of taurine were found by others in aged rats compared to young rats, we tested the hypothesis that a depletion of taurine may contribute to the alteration of the electrical and contractile properties we found in skeletal muscle during aging. This was accomplished by evaluating the potential benefit of a pharmacological treatment with the amino acid. To this aim 25-mo-old Wistar rats were chronically treated (2-3 mo) with taurine (1 g/kg p.o. daily) and the effects of such a treatment were evaluated in vitro on the passive and active membrane electrical properties of extensor digitorum longus muscle fibers by means of current-clamp intracellular microelectrode technique. Excitation-contraction coupling was also evaluated by measuring the voltage threshold for contraction with the intracellular microelectrode "point" voltage clamp method. In parallel muscle and blood taurine contents were determined by high-performance liquid chromatography. Taurine supplementation significantly raised taurine content in muscle toward that found in adult rats. Supplementation also significantly increased GCl vs. the adult value, in parallel the excitability characteristics (threshold current and latency) related to this parameter were ameliorated. The increase of GCl induced by taurine was accompanied by a restoration of the pharmacological sensitivity to the R(+) enantiomer of 2-(p-chlorophenoxy) propionic acid, a specific chloride channel ligand. In parallel also the protein kinase C-mediated modulation of the channel was restored; in fact the potency of 4-beta-phorbol 12, 13-dibutyrate in reducing GCl was lower in taurine-treated muscles vs. untreated aged, being rather similar to that observed in adult. The treatment also

  15. Mitochondrial DNA common deletion increases susceptibility to noise-induced hearing loss in a mimetic aging rat model.

    PubMed

    Yu, Jintao; Wang, Yanjun; Liu, Peng; Li, Qingyu; Sun, Yu; Kong, Weijia

    2014-10-24

    Noise-induced hearing loss (NIHL) is an important occupational health hazard. However, susceptibility to NIHL remains poorly understood. The present study was designed to investigate whether mitochondrial DNA common deletion (CD) increases the susceptibility of individuals to NIHL. A mimetic aging rat model harboring increased CD in the inner ear was established by chronic d-galactose administration, and the synergic effect of CD and noise on hearing sensitivity was assessed. We determined that although developed the same magnitude of temporary threshold shifts and hair cell loss, the d-galactose treated rats with increased CD in the inner ear exhibited a longer hearing recovery process and experienced higher permanent hearing threshold shifts at high frequencies than the saline-treated control rats. Greater supporting cell damage and stria vascularis ultrastructural changes were observed in d-galactose treated rats three weeks after recovery. The results suggested that the elevated CD in the inner ear could increase an individual's susceptibility to NIHL, which likely through a reduction in the self-repairing capability within the cochlea after acoustic injury.

  16. Accuracy of auditory steady state and auditory brainstem responses to detect the preventive effect of polyphenols on age-related hearing loss in Sprague-Dawley rats.

    PubMed

    Sanz-Fernández, Ricardo; Sánchez-Rodriguez, Carolina; Granizo, José Juan; Durio-Calero, Enrique; Martín-Sanz, Eduardo

    2016-02-01

    Aging causes histological, electrophysiological and molecular changes in the cochlea. The free radical theory of aging, has obtained consensus, and the mitochondrion is reported to play a key role in aging as a major source of reactive oxygen species. In the last years, there has been a significant increase in the interest in polyphenols because of the antioxidant properties and their role in the prevention of various diseases associated with oxidative stress, including aging. The aim of this study was to evaluate the preventive effect of different polyphenols on ARHL with auditory-evoked potentials. 100 Healthy female Sprague-Dawley (SD) rats were used for this study. Five groups were created based on the age of the rats, in months: 3, 6, 12, 18 and 24 months old. Two additional groups were created based on the treatment received. In the control group, 50 animals were assigned to no treatment. In the treated group, 50 animals were given a vehicle mixture of polyphenols for the half of the life before euthanization. Nine frequencies were tested (0.5-16 kHz) with ASSR and tone-burst ABR, performed on all of the rats prior to sacrifice. 100-μs auditory clicks ABRs were also recorded. A significant decrease in the audition was detected with ABR and ASSR in both treated and non-treated groups, as the different groups became older. This deterioration was more accurately measured at acute frequencies. Significantly lower thresholds were observed in the treated rats in the 6, 12 and 18-month-old group in the treated rats compared with the control group. All of the thresholds elicited using the ASSR technique were lower than the thresholds obtained using the ABR, regardless of the stimulus type. The present study demonstrated the benefits of the polyphenols, which generated a significant protection against ARHL, with significantly improved ASSR and tone-burst ABR auditory thresholds in rats receiving treatment with polyphenols.

  17. A Rat Model of Sytemic Chemotherapy for Breast Cancer to Evaluate and Treat Chemobrain

    DTIC Science & Technology

    2007-09-01

    and under approval from the USAMRMC Animal Care and Use Review Office (ACURO). Female Sprague-Dawley rats (11-21 weeks old, 200 - 300 g) were...combination CMF or CAF at 65/6.5/65 mg/kg i.p. to Sprague- Dawley females aged 80-150 days and weighing 170-300 grams. These doses were scaled to human...monitor the wellbeing of the animals, weight gain and loss were by far the most informative indicators of overall animal health . As depicted, rats

  18. Increase in lactate dehydrogenase isoenzyme-4 and splenocyte toxicity in methomyl-treated rats.

    PubMed

    Lohitnavy, O; Sinhaseni, P

    1998-09-01

    The toxic effect of methomyl was studied in rats after a single or repeated oral administration. Rats treated with a single dose of methomyl (3, 5, or 7 mg/kg) showed significant increase (P < 0.05) in total lactate dehydrogenase (LDH) activity on day 1. The highest level of LDH activity was observed on day 3 in rats receiving 7 mg/kg of methomyl. The total LDH activity returned to normal on day 7 after dosing. Specific increases in LDH-3 and LDH-4 isoenzyme activities were observed. In rats treated with a single dose of 6 and 8 mg/kg of methomyl, spleen weight and splenocyte viability significantly dropped (P < 0.05) on days 1 and 3, respectively. Splenotoxicity was prevented by pretreatment with 60 mg/kg of N-acetylcysteine. The results suggest that the splenotoxic effect of methomyl is more likely directly related to oxidative cell injury than to cholinesterase inhibition. The significance of cytotoxic effects and the nature of cytotoxicity in relation to reactive oxidative damage deserve further investigation.

  19. Histological changes in testes of rats treated with testosterone, nandrolone, and stanozolol

    PubMed Central

    Mohd Mutalip, Siti Syairah; Surindar Singh, Gurmeet Kaur; Mohd Shah, Aishah; Mohamad, Mashani; Mani, Vasudevan; Hussin, Siti Nooraishah

    2013-01-01

    Background: Anabolic androgenic steroids (AAS) is being used in medical treatments, but AAS also was identified to have the risks of adverse effects towards patients and consumers health. Objective: Present study was conducted to observe the effects of testosterone, nandrolone, and stanozolol (forms of AAS) intake during onset of puberty on the rat testicular histology. Materials and Methods: Juvenile male Sprague-Dawley (SD) rats (n=42) were divided into seven groups and were injected subcutaneously with medium dose of polyethylene glycol-200 (PEG-200) (control), testosterone, nandrolone, and stanozolol for six weeks (PND 41-87). The animals were weighed daily and sacrificed on PND 88. Testes were removed, weighed, and prepared for histological assessment and finally specimens were observed under microscope. Results: The results showed an insignificant increase in mean daily body weight with highest and lowest body weight gained was of 177.6±1.69 gr and 140.0±12.26 gr respectively. There was significant decrease in the testes absolute weight (p≤0.01) in all experimental groups except in the nandrolone 2.5 mg/kg/week treated group. Testicular histology of rats treated with AAS also showed slight changes in the uniformity of arrangements of seminiferous tubules. Conclusion: Data from present study suggests that AAS have been initiating the adverse effects on testicular normal functions in rats during onset of puberty. PMID:24639803

  20. Cholinergic and glutamergic receptor functional regulation in long-term, low dose somatotropin and insulin treatment to ageing rats: rejuvenation of brain function.

    PubMed

    Balakrishnan, Savitha; Mathew, Jobin; Paulose, C S

    2010-01-15

    The role of somatotropin and insulin treatment in the regulation of neurotransmitter levels in the ageing brain is not fully established. We evaluated the long-term, low dose effects of somatotropin and insulin on acetylcholine and glutamate receptor subtypes functional regulation in the cerebral cortex of young (4-16 weeks) and old rats (60-90 weeks). Somatotropin and insulin treated young rats showed significant upregulation in muscarinic M1 and M3 expression whereas in old rats, somatotropin and insulin treatment downregulated M1 and M3 expression. N-methyl-D-aspartate and metabotropic glutamate receptor gene expression were significantly downregulated with somatotropin treatment while insulin treatment showed upregulation in both young and old rats. Acetylcholine esterase activity showed a decrease with age and after somatotropin and insulin treatment, the activity increased in both young and old rats. Electroencephalogram studies confirmed the brain wave activity in both young and old somatotropin and insulin treated rats. The results highlight long-term low dose somatotropin and insulin treatment in regulating cholinergic and glutamergic receptors subtypes in ageing rats and rejuvenation of brain function.

  1. The antioxidant and antigenotoxic effects of pycnogenol(®) on rats treated with cisplatin.

    PubMed

    Aydin, Birsen; Unsal, Meftun; Sekeroglu, Zulal A; Gülbahar, Yavuz

    2011-09-01

    Oxidative stress and inflammation are implicated in the pathogenesis of cisplatin-induced toxicity. Pycnogenol® is known for its strong antioxidant and anti-inflammatory effects. In this study, the possible protective effects of pycnogenol on kidney, bone marrow, and red blood cells in rats treated with cisplatin were investigated. The rats were divided into four groups. Group 1 was the control and groups 2, 3, and 4 were orally treated with pycnogenol (200 mg/kg bw, o.p) for 5 days, treated with cisplatin (7 mg/kg bw, i.p.) on the fifth day and treated with cisplatin plus pycnogenol, respectively. Antioxidative parameters in kidney and red blood cells were measured. Chromosome anomalies in bone marrow and renal histopathology were also investigated. Activities of pro-oxidant enzymes (myeloperoxidase and xanthine oxidase), malondialdehyde, and nitric oxide levels significantly increased but antioxidant enzymes activities decreased in the kidneys and red blood cells after cisplatin treatment. Pycnogenol treatment prior to the administration of cisplatin significantly decreased cisplatin-induced injury, as evidenced by its normalizing these parameters. Chromosomal aberrations decreased and mitotic index frequencies increased in bone marrow treated with cisplatin plus pycnogenol. These findings suggest that pycnogenol may be a useful protective agent against the toxicity associated with cisplatin therapy.

  2. Modulation of oxidative stress by enalapril and valsartan in adrenaline treated rats: a comparative study.

    PubMed

    Huda, S; Akhter, N

    2014-04-01

    Angiotensin (Ang II) II is known to promote oxidative stress in acute myocardial infarction (AMI). Inhibition of renin angiotensin system (RAS) or blockade of Ang II receptors may therefore be effective in reducing oxidative stress during AMI. The study evaluates and compares the protective effect of Angiotensin Converting Enzyme (ACE) inhibitor and AT1 receptor blocker in adrenaline induced oxidative stress in rats. Rats were treated with two successive injections of adrenaline subcutaneously at a dose of 2 mg/kg administered 24 hours apart. In other two groups of rats enalapril (30 mg/kg) or valsartan (30 mg/kg) were given orally once daily through intragastric tube for 2 weeks and then two injections of adrenaline were administered 24 hours apart. Serum Aspertate Transaminase (AST), plasma Malonde Aldehyde (MDA), erythrocyte GSH and serum vitamin E levels were measured 24 hours after the 2nd injection of adrenaline in all the groups. Administration of adrenaline caused significant increase (p < 0.001) in serum AST and plasma MDA levels and decrease (p < 0.001) in erythrocyte GSH and serum vitamin E levels. Pre-treatment of enalapril or valsartan for 14 days reduced (p < 0.001) serum AST and plasma MDA levels and increased the concentration of erythrocyte GSH in enalapril pre-treated group (p < 0.01) and in valsartan pre-treated group (p < 0.05). Pre-treatment of enalapril or valsartan also increased (p < 0.01) serum vitamin E levels in adrenaline treated rats. However, no significant difference was noted between the effect of enalapril and valsartan on serum AST, plasma MDA, erythrocyte GSH and serum vitamin E levels. It may be concluded that both enalapril and valsartan offered cardioprotection in adrenaline induced oxidative stress, but the protection afforded by valsartan was not superior to enalapril.

  3. Blood-brain barrier disruption in the striatum of rats treated with 3-nitropropionic acid.

    PubMed

    Duran-Vilaregut, Joaquim; del Valle, Jaume; Camins, Antoni; Pallàs, Mercè; Pelegrí, Carme; Vilaplana, Jordi

    2009-01-01

    3-nitropropionic acid (3-NPA) is a natural toxin that is used to induce models of Huntington's disease (HD) in experimental animals. Here we injected 3-NPA into Sprague-Dawley rats in order to evaluate its effects on the blood-brain barrier (BBB). Evans blue (EB) extravasation was used to identify injured areas in the brains of the treated animals and immunostainings of endothelial brain barrier antigen (EBA), zona occludens-1 (ZO-1) and laminin were used as markers to characterize the effects of the neurotoxin on the BBB. Treated rats had a significant loss of body weight compared to controls, and a correlation between motor affectation and body weight loss was observed in the former. The lateral part of the striatum was specifically injured in treated animals and the BBB almost disappeared in the core of the injured areas, as evidenced by a high EB extravasation and severe alterations of the immunostainings of the three BBB integrity markers compared to those of control animals. We conclude that the BBB is severely affected in the 3-NPA rat model of HD and that disruption of this barrier is a crucial event during the development of this disease.

  4. Urinary concentrating mechanism and Aquaporin-2 abundance in rats chronically treated with aluminum lactate.

    PubMed

    Mahieu, Stella; Millen, Néstor; Contini, María del Carmen; Gonzalez, Marcela; Molinas, Sara M; Elías, María Mónica

    2006-06-15

    The aim of this work was to study the effects of chronic administration of aluminum (Al) on the urinary concentrating and diluting mechanisms in the distal tubules and collecting ducts. Male Wistar rats were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100g of body weight, i.p., three times per week). After 12 weeks, renal function of control and Al-treated rats was evaluated by clearance techniques. To study urinary concentrating mechanisms, renal function was also measured in control and Al-treated rats deprived of water, after the administration of desmopressin (vasopressin agonist) and after the infusion of hypertonic saline at increasing infusion rates. Sodium and water balance were impaired. We found decreased urinary concentrating ability in situations in which endogenous (thirst or infusion of hypertonic saline) or exogenous plasma antidiuretic hormone was increased. Solute-free water formation, measured during the infusion of hypotonic saline showed normal transport in the thick ascending limb. Aquaporin-2 (AQP2) expression was measured by Western blot to evaluate water permeability in collecting ducts. We found that Al produced downregulation of AQP2 in plasma membranes and intracellular vesicles, that could account for the impaired water handling. Administration of desmopressin increased AQP2 in plasma membranes, suggesting that Al did not impair trafficking of this protein, but could interfere with AQP2 synthesis.

  5. Insulin-exacerbated hypertension in captopril-treated spontaneously hypertensive rats: role of sympathoexcitation.

    PubMed

    Roysommuti, Sanya; Mozaffari, Mahmood S; Wyss, J Michael

    2003-11-01

    Insulin excess exacerbates hypertension in spontaneously hypertensive rats (SHR). This study examined the relative contribution of the renin-angiotensin system and the sympathetic nervous system in this phenomenon. In SHR, daily subcutaneous injections of insulin were initiated either before short-term angiotensin-converting enzyme inhibition with captopril or after lifetime captopril treatment. Insulin treatment resulted in significant increases in mean arterial pressure and heart rate and captopril treatment lowered arterial pressure, but captopril did not lower arterial pressure more in the insulin-treated compared with control rats. To test the contribution of the sympathetic nervous system to this form of hypertension, each rat was intravenously infused with either a ganglionic blocker (i.e., hexamethonium) or a centrally acting alpha2-adrenergic receptor agonist (i.e., clonidine). Administration of either agent largely eliminated the differences in mean arterial pressure and heart rate between the insulin-treated and saline-treated SHR, irrespective of captopril treatment. These data indicate that in SHR, the ability of insulin to increase blood pressure is closely related to sympathoexcitation, which is unresponsive to blockade of angiotensin-converting enzyme.

  6. Effect of age increase on metabolism and toxicity of ethanol in female rats.

    PubMed

    Kim, Young C; Kim, Sung Y; Sohn, Young R

    2003-12-12

    Age-dependent change in the effects of acute ethanol administration on female rat liver was investigated. Female Sprague-Dawley rats, each aged 4, 12, or 50 weeks, received ethanol (2 g/kg) via a catheter inserted into a jugular vein. Ethanol elimination rate (EER), most rapid in the 4 weeks old rats, was decreased as the age advanced. Hepatic alcohol dehydrogenase activity was not altered by age, but microsomal p-nitrophenol hydroxylase activity was significantly greater in the 4 weeks old rats. Relative liver weight decreased with age increase in proportion to reduction of EER. Hepatic triglyceride and malondialdehyde concentrations increased spontaneously in the 50 weeks old nai;ve rats. Ethanol administration (3 g/kg, ip) elevated malondialdehyde and triglyceride contents only in the 4 and the 12 weeks old rats. Hepatic glutathione concentration was increasingly reduced by ethanol with age increase. Ethanol decreased cysteine concentration in the 4 weeks old rats, but elevated it significantly in the older rats. Inhibition of gamma-glutamylcysteine synthetase activity by ethanol was greater with age increase, which appeared to be responsible for the increase in hepatic cysteine. The results indicate that age does not affect the ethanol metabolizing capacity of female rat liver, but the overall ethanol metabolism is decreased in accordance with the reduction of relative liver size. Accordingly induction of acute alcoholic fatty liver is less significant in the old rats. However, progressively greater depletion of glutathione by ethanol in older rats suggests that susceptibility of liver to oxidative damage would be increased as animals grow old.

  7. Biochemical effects in normal and stone forming rats treated with the ripe kernel juice of plantain (musa paradisiaca).

    PubMed

    Devi, V K; Baskar, R; Varalakshmi, P

    1993-01-01

    The effect of Musa paradisiaca stem kernel juice was investigated in experimental urolithiatic rats. Stone forming rats exhibited a significant elevation in the activities of two oxalate synthesizing enzymes - Glycollic acid oxidase and Lactate dehydrogenase. Deposition and excretion of stone forming constituents in kidney and urine were also increased in these rats. The enzyme activities and the level of crystalline components were lowered with the extract treatment. The extract also reduced the activities of urinary alkaline phosphatase, lactate dehydrogenase, r-glutamyl transferase, inorganic pyrophosphatase and β-glucuronidase in calculogenic rats. No appreciable changes were noticed with leucine amino peptidase activity in treated rats.

  8. Accumbal FosB/DeltaFosB immunoreactivity and conditioned place preference in alcohol-preferring AA rats and alcohol-avoiding ANA rats treated repeatedly with cocaine.

    PubMed

    Marttila, Kristiina; Petteri Piepponen, T; Kiianmaa, Kalervo; Ahtee, Liisa

    2007-07-30

    Transcription factor DeltaFosB has been implicated in the psychomotor responses and rewarding effects of drugs of abuse. In the present study, we compared the effects of cocaine on the expression of DeltaFosB-like proteins by immunohistochemistry in striatal brain areas of alcohol-preferring (AA) and alcohol-avoiding (ANA) rats. Cocaine was administered using a previously verified treatment paradigm that sensitized the locomotor response to cocaine in AA but not in ANA rats. We also studied the rewarding effects of cocaine with a conditioned place preference (CPP) paradigm in both lines of rats. Cocaine treatment increased the FosB/DeltaFosB immunoreactivity (IR) in the nucleus accumbens of AA rats but not in ANA rats. In addition, after repeated saline injections the accumbal FosB/DeltaFosB IR was significantly greater in saline-injected AA rats than in ANA rats. In the caudate-putamen cocaine significantly increased FosB/DeltaFosB IR, but no differences were found between the rats of two lines. In the CPP experiment, AA rats treated with cocaine 2.5 mg/kg preferred the cocaine-associated compartment, in contrast to ANA rats, which did not show such a preference. In conclusion, our findings show that AA rats are more sensitive to cocaine than ANA rats, and suggest that one possible mediator for this increased sensitivity could be the increased expression of fosB-derived proteins in the nucleus accumbens of AA rats.

  9. Differential expression of parvalbumin in neonatal phencyclidine-treated rats and socially isolated rats.

    PubMed

    Kaalund, Sanne S; Riise, Jesper; Broberg, Brian V; Fabricius, Katrine; Karlsen, Anna S; Secher, Thomas; Plath, Niels; Pakkenberg, Bente

    2013-02-01

    Decreased parvalbumin expression is a hallmark of the pathophysiology of schizophrenia and has been associated with abnormal cognitive processing and decreased network specificity. It is not known whether this decrease is due to reduced expression of the parvalbumin protein or degeneration of parvalbumin-positive interneurons (PV(+) interneurons). In this study, we examined PV(+) expression in two rat models of cognitive dysfunction in schizophrenia: the environmental social isolation (SI) and pharmacological neonatal phencyclidine (neoPCP) models. Using a stereological method, the optical fractionator, we counted neurons, PV(+) interneurons, and glial cells in the medial prefrontal cortex (mPFC) and hippocampus (HPC). In addition, we quantified the mRNA level of parvalbumin in the mPFC. There was a statistically significant reduction in the number of PV(+) interneurons (p = 0.021) and glial cells (p = 0.024) in the mPFC of neonatal phencyclidine rats, but not in SI rats. We observed no alterations in the total number of neurons, hippocampal PV(+) interneurons, parvalbumin mRNA expression or volume of the mPFC or HPC in the two models. Thus, as the total number of neurons remains unchanged following phencyclidine (PCP) treatment, we suggest that the decreased number of counted PV(+) interneurons represents a reduced parvalbumin protein expression below immunohistochemical detection limit rather than a true cell loss. Furthermore, these results indicate that the effect of neonatal PCP treatment is not limited to neuronal populations.

  10. Nigrostriatal rAAV-mediated GDNF Overexpression Induces Robust Weight Loss in a Rat Model of Age-related Obesity

    PubMed Central

    Manfredsson, Fredric P; Tumer, Nihal; Erdos, Benedek; Landa, Tessa; Broxson, Christopher S; Sullivan, Layla F; Rising, Aaron C; Foust, Kevin D; Zhang, Yi; Muzyczka, Nicholas; Gorbatyuk, Oleg S; Scarpace, Philip J; Mandel, Ronald J

    2009-01-01

    Intraventricular administration of glial cell line–derived neurotrophic factor (GDNF) in primate and humans to study Parkinson's disease (PD) has revealed the potential for GDNF to induce weight loss. Our previous data indicate that bilateral continuous hypothalamic GDNF overexpression via recombinant adeno-associated virus (rAAV) results in significant failure to gain weight in young rats and weight loss in aged rats. Based on these previous results, we hypothesized that because the nigrostriatal tract passes through the lateral hypothalamus, motor hyperactivity mediated by nigrostriatal dopamine (DA) may have been responsible for the previously observed effect on body weight. In this study, we compared bilateral injections of rAAV2/5-GDNF in hypothalamus versus substantia nigra (SN) in aged Brown-Norway X Fisher 344 rats. Nigrostriatal GDNF overexpression resulted in significantly greater weight loss than rats treated in hypothalamus. The nigral or hypothalamic GDNF-induced weight loss was unrelated to motor activity levels of the rats, though some of the weight loss could be attributed to a transient reduction in food intake. Forebrain DA levels did not account for the observed effects on body weight, although GDNF-induced increases in nucleus accumbens DA may have partially contributed to this effect in the hypothalamic GDNF-treated group. However, only nigrostriatal GDNF overexpression induced activation of phosphorylated extracellular signal-regulated kinase (p-ERK) in a small population of corticotrophin-releasing factor [corticotrophin-releasing hormone (CRH)] neurons located specifically in the medial parvocellullar division (MPD) of the paraventricular nucleus of the hypothalamus. Activation of these hypothalamic CRH neurons likely accounted for the observed metabolic effects leading to weight loss in obese rats. PMID:19277011

  11. The effects of strength training and raloxifene on bone health in aging ovariectomized rats.

    PubMed

    Stringhetta-Garcia, Camila Tami; Singulani, Monique Patrício; Santos, Leandro Figueiredo; Louzada, Mário Jefferson Quirino; Nakamune, Ana Cláudia Stevanato; Chaves-Neto, Antonio Hernandes; Rossi, Ana Cláudia; Ervolino, Edilson; Dornelles, Rita Cássia Menegati

    2016-04-01

    The aim of this study was to investigate the effects of strength training (ST) and raloxifene (Ral), alone or in combination, on the prevention of bone loss in an aging estrogen-deficient rat model. Aging Wistar female rats were ovariectomized at 14months and allocated to four groups: (1) non-trained and treated with vehicle, NT-Veh; (2) strength training and treated with vehicle, ST-Veh; (3) non-trained and treated with raloxifene, NT-Ral; and (4) strength training and treated with raloxifene, ST-Ral. ST was performed on a ladder three times per week and Ral was administered daily by gavage (1mg/kg/day), both for 120days. Areal bone mineral density (aBMD), strength, microarchitecture, and biomarkers (osteocalcin, OCN; osteoprotegerin, OPG; and tartrate-resistant acid phosphatase, TRAP) were assessed. Immunohistochemistry was performed for runt-related transcription factor 2 (RUNX2), osterix (OSX), OCN, OPG, TRAP, and receptor activator of nuclear factor kappa-B ligand (RANKL). The rats that performed ST (ST-Veh) or were treated with Ral (NT-Ral) showed significant improvements in aBMD (p=0.001 and 0.004), bone strength (p=0.001), and bone microarchitecture, such as BV/TV (%) (p=0.001), BS/TV (mm(2)/mm(3)) (p=0.023 and 0.002), Conn.Dn (1/mm(3)) (p=0.001), Tb.N (1/mm) (p=0.012 and 0.011), Tb.Th (1/mm) (p=0.001), SMI (p=0.001 and 0.002), Tb.Sp (p=0.001), and DA (p=0.002 and 0.007); there was also a significant decrease in plasma levels of OCN (p=0.001 and 0.002) and OPG (p=0.003 and 0.014), compared with animals in the NT-Veh group. Ral, with or without ST, promoted an increased immunolabeling pattern for RUNX2 (p=0.0105 and p=0.0006) and OSX (p=0.0105), but a reduced immunolabeling pattern for TRAP (p=0.0056) and RANKL (p=0.033 and 0.004). ST increased the immunolabeling pattern for RUNX2 (p=0.0105), and association with Ral resulted in an increased immunolabeling pattern for OPG (p=0.0034) and OCN (p=0.0024). In summary, ST and Ral administration in aged, estrogen

  12. Restorative effects of GDNF on striatal dopamine release in rats treated with neurotoxic doses of methamphetamine.

    PubMed

    Cass, W A; Manning, M W; Bailey, S L

    2000-09-01

    Repeated methamphetamine (METH) administration to animals can result in long-lasting decreases in striatal dopamine (DA) release and content. Glial cell line-derived neurotrophic factor (GDNF) has pronounced effects on dopaminergic systems in vivo, including neuroprotective effects against METH. The present experiments were designed to examine the ability of GDNF to reverse, or accelerate recovery from, METH-induced alterations in striatal DA release. Male Fischer-344 rats were administered METH (5 mg/kg, s.c.) or saline 4 times in one day at 2-hour intervals. Seven days later the animals were anesthetized and given a single injection of 10 microg GDNF, or vehicle, into the right striatum. Three weeks later microdialysis experiments were carried out in both the right and left striata to examine basal and evoked levels of DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). In animals treated with METH followed by vehicle 7 days later, there were significant reductions in potassium- and amphetamine-evoked overflow of DA, and in basal levels of DOPAC and HVA, compared to control animals. In rats treated with METH followed 7 days later with GDNF, there were significant increases in potassium- and amphetamine-evoked overflow of DA on the right, GDNF-treated, side of the brain compared to the left side. Basal levels of DOPAC and HVA were also elevated on the GDNF-treated side of the brain. These results suggest that GDNF can accelerate recovery of dopaminergic release processes in the striatum of rats treated with neurotoxic doses of METH.

  13. Effects of nonsaponin fraction of red ginseng on learning deficits in aged rats.

    PubMed

    Kurimoto, Hiroaki; Nishijo, Hisao; Uwano, Teruko; Yamaguchi, Hidetoshi; Zhong, Yong-Mei; Kawanishi, Kazuko; Ono, Taketoshi

    2004-09-15

    Previously we reported that oral application of red ginseng significantly ameliorated learning deficits in aged rats and young rats with hippocampal lesions. In the present study, we investigated the effects of the nonsaponin fraction of red ginseng on learning deficits in aged rats in behavioral studies and those on long-term potentiation (LTP) in the hippocampal CA3 subfield in young rats in electrophysiological studies. In the behavioral studies, three groups of rats [aged rats with and without oral administration of the nonsaponin fraction of red ginseng and young rats] were tested with the three types of spatial-learning task [distance movement task (DMT), random-reward place search task (RRPST), and place-learning task (PLT)] in a circular open field. The results in the DMT and RRPST indicated that motivational and motor activity was not significantly different among the three groups of rats. However, performance of the aged rats without nonsaponin was significantly impaired in the PLT when compared with the young rats. Treatment with nonsaponin significantly ameliorated deficits in place-navigation learning in the aged rats in the PLT. In the electrophysiological studies, effects of nonsaponin on the LTP in the CA3 subfield of the hippocampal slices were investigated in vitro. Pretreatment with nonsaponin significantly augmented the increase in population spike amplitudes in the CA3 subfield after LTP induction. These results suggest that the nonsaponin fraction of red ginseng contains important substances to improve learning and memory in aged rats and that this amelioration by nonsaponin might be attributed partly to augmentation of LTP in the CA3 subfield.

  14. Combination of Spirulina with glycyrrhizin prevents cognitive dysfunction in aged obese rats

    PubMed Central

    Madhavadas, Sowmya; Subramanian, Sarada

    2015-01-01

    Objectives: To evaluate the cognition enhancing effect of the combination of Spirulina and glycyrrhizin in monosodium glutamate (MSG)-induced obese aged rats. Materials and Methods: Obesity was induced in rats by administration of MSG (intraperitoneally, 4 mg/g body weight) for 14 consecutive days from day 1 after birth. Subsequently, the animals were allowed to grow for 18 months with food and water ad libitum. Hypercholesterolemia, hyperglycemia, leptin resistance, were monitored in these animals. Cognitive status was assessed by Barne's maze task and hippocampal acetylcholinesterase (AChE) levels. Further, the animals were treated with Spirulina (Sp) (oral route, 1 g/Kg body weight, for 30 days) alone or glycyrrhizin (Gly) alone (intraperitoneal route, 0.1 mg/Kg, on day 15 and day 21), or their combination (SpGly). Counting of the treatment days was done by considering first day of Sp administration as day 1. After the completion of 30 days of Spirulina treatment or 2 doses of Gly administration or the combination (SpGly) treatment, the animals were left for 3 weeks. They were then were assessed for their biochemical and cognitive changes. Results: The combination of Sp with Gly showed a significant reduction (P < 0.0001) in glucose, cholesterol, leptin levels in the serum with improvement in cognitive functions with concomitant reduction in AChE activity in the hippocampal tissue homogenates (P < 0.0001) of the obese rats. Conclusion: SpGly combination has a potential role in reversing cognitive dysfunctions associated with aging and obesity. PMID:25821309

  15. Exercise training enhances insulin-stimulated nerve arterial vasodilation in rats with insulin-treated experimental diabetes.

    PubMed

    Olver, T Dylan; McDonald, Matthew W; Grisé, Kenneth N; Dey, Adwitia; Allen, Matti D; Medeiros, Philip J; Lacefield, James C; Jackson, Dwayne N; Rice, Charles L; Melling, C W James; Noble, Earl G; Shoemaker, J Kevin

    2014-06-15

    Insulin stimulates nerve arterial vasodilation through a nitric oxide (NO) synthase (NOS) mechanism. Experimental diabetes reduces vasa nervorum NO reactivity. Studies investigating hyperglycemia and nerve arterial vasodilation typically omit insulin treatment and use sedentary rats resulting in severe hyperglycemia. We tested the hypotheses that 1) insulin-treated experimental diabetes and inactivity (DS rats) will attenuate insulin-mediated nerve arterial vasodilation, and 2) deficits in vasodilation in DS rats will be overcome by concurrent exercise training (DX rats; 75-85% VO2 max, 1 h/day, 5 days/wk, for 10 wk). The baseline index of vascular conductance values (VCi = nerve blood flow velocity/mean arterial blood pressure) were similar (P ≥ 0.68), but peak VCi and the area under the curve (AUCi) for the VCi during a euglycemic hyperinsulinemic clamp (EHC; 10 mU·kg(-1)·min(-1)) were lower in DS rats versus control sedentary (CS) rats and DX rats (P ≤ 0.01). Motor nerve conduction velocity (MNCV) was lower in DS rats versus CS rats and DX rats (P ≤ 0.01). When compared with DS rats, DX rats expressed greater nerve endothelial NOS (eNOS) protein content (P = 0.04). In a separate analysis, we examined the impact of diabetes in exercise-trained rats alone. When compared with exercise-trained control rats (CX), DX rats had a lower AUCi during the EHC, lower MNCV values, and lower sciatic nerve eNOS protein content (P ≤ 0.03). Therefore, vasa nervorum and motor nerve function are impaired in DS rats. Such deficits in rats with diabetes can be overcome by concurrent exercise training. However, in exercise-trained rats (CX and DX groups), moderate hyperglycemia lowers vasa nervorum and nerve function.

  16. Antidiabetic-drug combination treatment for glucose intolerance in adult female rats treated acutely with olanzapine.

    PubMed

    Boyda, Heidi N; Procyshyn, Ric M; Asiri, Yahya; Wu, Claire; Wang, Cathy K; Lo, Ryan; Pang, Catherine C Y; Honer, William G; Barr, Alasdair M

    2014-01-03

    Second generation antipsychotic drugs are routinely used as treatment for psychotic disorders. Many of these compounds, including olanzapine, cause metabolic side-effects such as impaired glucose tolerance and insulin resistance. Individual antidiabetic drugs can help control elevated glucose levels in patients treated with antipsychotics, but the effects of combining antidiabetics, which routinely occurs with Type 2 diabetes mellitus patients, have never been studied. Presently, we compared the effects of the three different antidiabetics metformin (500mg/kg, p.o.), rosiglitazone (30mg/kg, p.o.) and glyburide (10mg/kg, p.o.) on metabolic dysregulation in adult female rats treated acutely with olanzapine. In addition, dual combinations of each of these antidiabetics were compared head-to-head against each other and the individual drugs. The animals received two daily treatments with antidiabetics and were then treated acutely with olanzapine (10mg/kg, i.p.). Fasting glucose and insulin levels were measured, followed by a 2h glucose tolerance test. Olanzapine caused a large and highly significant glucose intolerance compared to vehicle treated rats. Rosiglitazone decreased glucose levels non-significantly, while both metformin and glyburide significantly decreased glucose levels compared to olanzapine-only treated animals. For antidiabetic dual-drug combinations, the rosiglitazone-metformin group showed an unexpected increase in glucose levels compared to all of the single antidiabetic drugs. However, both the metformin-glyburide and rosiglitazone-glyburide groups showed significantly greater reductions in glucose levels following olanzapine than with single drug treatment alone for metformin or rosiglitazone, bringing glucose levels down to values equivalent to vehicle-only treated animals. These findings indicate that further study of antidiabetic dual-drug combinations in patients treated with antipsychotic drugs is warranted.

  17. Myocardial antioxidant status and oxidative stress after combined action of exercise training and ethanol in two different age groups of male albino rats.

    PubMed

    Pushpalatha, K; Nishanth, K; Sathyavelu Reddy, K

    2007-06-01

    The interaction of exercise training and ethanol on the myocardial antioxidant enzymes and the oxidative stress markers was investigated in the Wistar strain male albino rats. We also tested the interactive effects of exercise training and ethanol on the age-associated free radical production and antioxidant defense system. We found a significant decrease (p<0.05) in the activity levels of superoxide dismutase (SOD) and catalase (CAT) in the myocardium of old rats when compared to young rats by 26% and 58%, respectively, suggesting the onset of age-dependent decrease in the myocardial antioxidant enzyme system. In contrast to the decreased antioxidant enzyme activity, xanthine oxidase (XOD) and lipid peroxidation (LPO) levels were elevated, suggesting the age-induced oxidative stress. Exercise training significantly (p < 0.05) elevated the activities of SOD, CAT, XOD and LPO levels in both the age groups of animals. Ethanol consumption significantly lowered the SOD and CAT activities in both the age groups, whereas a significant increase was observed in the XOD and LPO levels. In contrast, the combination of exercise training plus ethanol lowered XOD and LPO levels in both the age groups of rats compared to ethanol treated rats. A significant (p < 0.05) increase in the activities of SOD and CAT was reported in the rats treated with the combination of exercise training plus ethanol. This increase was more pronounced in the younger rats than the older rats. The findings of the present investigation on the potential role of antioxidant enzymes to counter the ethanol-induced pro-oxidants showed an increase with the interaction of exercise training. With age, a decrease in the antioxidant enzyme capacity was observed. This reveals that the old age rats were more affected to the pro-oxidants when compared to the young age rats. In conclusion it is demonstrated that two months treadmill endurance exercise training is beneficial to both young and old rats in improving

  18. Growth inhibition, tumor maturation, and extended survival in experimental brain tumors in rats treated with phenylacetate.

    PubMed

    Ram, Z; Samid, D; Walbridge, S; Oshiro, E M; Viola, J J; Tao-Cheng, J H; Shack, S; Thibault, A; Myers, C E; Oldfield, E H

    1994-06-01

    Phenylacetate is a naturally occurring plasma component that suppresses the growth of tumor cells and induces differentiation in vitro. To evaluate the in vivo potential and preventive and therapeutic antitumor efficacy of sodium phenylacetate against malignant brain tumors, Fischer 344 rats (n = 50) bearing cerebral 9L gliosarcomas received phenylacetate by continuous s.c. release starting on the day of tumor inoculation (n = 10) using s.c. osmotic minipumps (550 mg/kg/day for 28 days). Rats with established brain tumors (n = 12) received continuous s.c. phenylacetate supplemented with additional daily i.p. dose (300 mg/kg). Control rats (n = 25) were treated in a similar way with saline. Rats were sacrificed during treatment for electron microscopic studies of their tumors, in vivo proliferation assays, and measurement of phenylacetate levels in the serum and cerebrospinal fluid. Treatment with phenylacetate extended survival when started on the day of tumor inoculation (P < 0.01) or 7 days after inoculation (P < 0.03) without any associated adverse effects. In the latter group, phenylacetate levels in pooled serum and cerebrospinal fluid samples after 7 days of treatment were in the therapeutic range as determined in vitro (2.45 mM in serum and 3.1 mM in cerebrospinal fluid). Electron microscopy of treated tumors demonstrated marked hypertrophy and organization of the rough endoplasmic reticulum, indicating cell differentiation, in contrast to the scant and randomly distributed endoplasmic reticulum in tumors from untreated animals. In addition, in vitro studies demonstrated dose-dependent inhibition of the rate of tumor proliferation and restoration of anchorage dependency, a marker of phenotypic reversion. Phenylacetate, used at clinically achievable concentrations, prolongs survival of rats with malignant brain tumors through induction of tumor differentiation. Its role in the treatment of brain tumors and other cancers should be explored further.

  19. Determination of DNA damage and telomerase activity in stanozolol-treated rats

    PubMed Central

    Kara, Mehtap; Ozcagli, Eren; Fragkiadaki, Persefoni; Kotil, Tugba; Stivaktakis, Polychronis D.; Spandidos, Demetrios A.; Tsatsakis, Aristides M.; Alpertunga, Buket

    2017-01-01

    Anabolic androgenic steroids (AAS) are performance-enhancing drugs commonly abused by atheletes. Stanozolol is a synthetic testosterone-derived anabolic steroid. Although it is well known that AAS have several side-effects, there are only few toxicological studies available on the toxic effects and mechanisms of action of stanozolol. The aim of this study was to investigate the genotoxic effects of stanozolol and to determine its effects on telomerase activity in Sprague-Dawley male rats. For this purpose, 34 male rats were divided into 5 groups as follows: i) the control group (n=5); ii) the propylene glycol (PG)-treated group (n=5); iii) the stanozolol-treated group (n=8); iv) the PG-treated group subjected to exercise (n=8); and v) the stanozolol-treated group subjected to exercise (n=8). PG is used as a solvent control in our study. Stanozolol (5 mg/kg) and PG (1 ml/kg) were injected subcutaneously 5 days/week for 28 days. After 28 days, the animals were sacrificed, and DNA damage evaluation (comet assay) and telomerase activity assays were then performed using peripheral blood mononuclear cells (PBMCs). Telomerase activity was measured by using the TeloTAGGG Telomerase PCR ELISA PLUS kit. The results of this study revealed that stanozolol treatment induced DNA damage, while exercise exerted a protective effect. Stanozolol treatment without exercise stimulation was associated with a significant increase in telomerase activity in the PBMCs. PMID:28352339

  20. Ultra structural study of the rat cheek epithelium treated with Neem extract.

    PubMed

    Azmi, Muhammad Arshad; Khatoon, Nasira; Ghaffar, Rizwana Abdul

    2015-11-01

    The purpose of this study was to investigate the effects of neem extract (Azadirachta indica A. Juss) on the ultrastructure of the rat oral epithelium, because neem extract has been added in the tooth paste as an anti-plaque-forming substance in Asian countries. The non-toxic dose of 2000 mg/kg body weight of Neem extract (NBE) was applied daily to the surface of buccal epithelium for four weeks and controls did not receive Neem extract. After four weeks cheek epithelial tissues were excised and processed for light microscopy, scanning and transmission electron microscopy. Light microscopy did not show significant differences between NBE-treated and control epithelium. Difference between control and treated rats weight was non-significant. Moreover, time period was also non-significant. Irregular cell surfaces were noticed when compared to control specimens when examined by scanning electron microscopy. Under transmission electron microscopy, wider intercellular spaces were observed in the treated epithelial spinous cellular layers when compared to control. Further, more keratohyalin granules were present in experimental granular cells. It was concluded that present study showed differences between Neem-treated and control in epithelial tissues but these structural differences may not be related to adverse side effects of the Neem extract.

  1. Drinking Water with Red Beetroot Food Color Antagonizes Esophageal Carcinogenesis in N-Nitrosomethylbenzylamine-Treated Rats

    PubMed Central

    Lechner, John F.; Wang, Li-Shu; Rocha, Claudio M.; Larue, Bethany; Henry, Cassandra; McIntyre, Colleen M.; Riedl, Kenneth M.; Schwartz, Steven J.

    2010-01-01

    Abstract This study was undertaken to determine if the oral consumption of red beetroot food color would result in an inhibition of N-nitrosomethylbenzylamine (NMBA)-induced tumors in the rat esophagus. Rats were treated with NMBA and given either regular water ad libitum or water containing 78 μg/mL commercial red beetroot dye, E162. The number of NMBA-induced esophageal papillomas was reduced by 45% (P < .001) in animals that received the food color compared to controls. The treatment also resulted in reduced rates of cell proliferation in both precancerous esophageal lesions and in papillomas of NMBA-treated rats, as measured by immunohistochemical staining of Ki-67 in esophageal tissue specimens. The effects of beetroot food color on angiogenesis (microvessel density by CD34 immunostaining), inflammation (by CD45 immunostaining), and apoptosis (by terminal deoxynucleotidyl transferase dUTP nick end-labeling staining) in esophageal tissue specimens were also determined. Compared to rats treated with NMBA only, the levels of angiogenesis and inflammation in the beetroot color-consuming animals were reduced, and the apoptotic rate was increased. Thus, the mechanism(s) of chemoprevention by the active constituents of red beetroot color include reducing cell proliferation, angiogenesis, and inflammation and stimulating apoptosis. Importantly, consumption of the dye in the drinking water for a period of 35 weeks did not appear to induce any overt toxicity. Based on the fact that red beetroot color contains betanins, which have strong antioxidant activity, it is postulated that these effects are mediated through inhibition of oxygen radical-induced signal transduction. However, the sum of constituents of E162 has not been determined, and other components with other mechanisms may also be involved in antagonizing cancer development. PMID:20438319

  2. Withdrawal and bidirectional cross-withdrawal responses in rats treated with adenosine agonists and morphine.

    PubMed

    Coupar, I M; Tran, B L

    2001-07-06

    The aim of this study was to investigate whether the A1/A2 receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA), and the selective A1 agonist, N6-cyclopentyladenosine (CPA), induced physical dependence by quantifying specific antagonist-precipitated withdrawal syndromes in conscious rats. In addition, the presence of bidirectional cross-withdrawal was also investigated. The agonists were administered s.c. to groups of rats at 12 h intervals. Antagonists were administered s.c., 12 hours after the last dose, followed by observation and measurement of faecal output for 20 min. NECA (4 x 0.03 mg kg(-1), s.c) and CPA (4 x 0.03, 0.1 and 0.3 mg kg(-1), s.c.) induced physical dependence, as shown by the expression of a significant withdrawal syndrome when challenged with the adenosine A1/A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX, 0.1 mg kg(-1), s.c.) and the A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (CPDPX, 0.1 mg kg(-1), s.c.) respectively. The syndromes consisted of teeth chattering and shaking behaviours shown to occur in morphine-dependent animals withdrawn with naloxone viz, paw, body and 'wet-dog' shakes, but with the additional behaviours of head shaking and yawning. In further contrast to the opiate withdrawal syndrome, no diarrhoea occurred in the groups of animals treated with adenosine agonists and withdrawn with their respective antagonists. Bidirectional cross-withdrawal syndromes were also revealed when naloxone (3 mg kg(-1), s.c.) was administered to adenosine agonist pre-treated rats and adenosine antagonists were given to morphine pre-treated rats. This study provides further information illustrating that close links exist between the adenosine and opiate systems.

  3. Drinking water with red beetroot food color antagonizes esophageal carcinogenesis in N-nitrosomethylbenzylamine-treated rats.

    PubMed

    Lechner, John F; Wang, Li-Shu; Rocha, Claudio M; Larue, Bethany; Henry, Cassandra; McIntyre, Colleen M; Riedl, Kenneth M; Schwartz, Steven J; Stoner, Gary D

    2010-06-01

    This study was undertaken to determine if the oral consumption of red beetroot food color would result in an inhibition of N-nitrosomethylbenzylamine (NMBA)-induced tumors in the rat esophagus. Rats were treated with NMBA and given either regular water ad libitum or water containing 78 microg/mL commercial red beetroot dye, E162. The number of NMBA-induced esophageal papillomas was reduced by 45% (P < .001) in animals that received the food color compared to controls. The treatment also resulted in reduced rates of cell proliferation in both precancerous esophageal lesions and in papillomas of NMBA-treated rats, as measured by immunohistochemical staining of Ki-67 in esophageal tissue specimens. The effects of beetroot food color on angiogenesis (microvessel density by CD34 immunostaining), inflammation (by CD45 immunostaining), and apoptosis (by terminal deoxynucleotidyl transferase dUTP nick end-labeling staining) in esophageal tissue specimens were also determined. Compared to rats treated with NMBA only, the levels of angiogenesis and inflammation in the beetroot color-consuming animals were reduced, and the apoptotic rate was increased. Thus, the mechanism(s) of chemoprevention by the active constituents of red beetroot color include reducing cell proliferation, angiogenesis, and inflammation and stimulating apoptosis. Importantly, consumption of the dye in the drinking water for a period of 35 weeks did not appear to induce any overt toxicity. Based on the fact that red beetroot color contains betanins, which have strong antioxidant activity, it is postulated that these effects are mediated through inhibition of oxygen radical-induced signal transduction. However, the sum of constituents of E162 has not been determined, and other components with other mechanisms may also be involved in antagonizing cancer development.

  4. Pulmonary oxygen toxicity in rats treated with cytochrome P-450 inducers

    SciTech Connect

    Ebel, R.E.; Barlow, R.L.; Gregory, E.M.

    1987-05-01

    Pulmonary oxygen toxicity is assumed to result from damage caused by superoxide (O/sub 2//sup -/) hydrogen peroxide (H/sub 2/O/sub 2/) and/or hydroxyl radical (OH) produced by the partial reduction of molecular oxygen (O/sub 2/). The microsomal cytochrome P-450 (P-450) monooxygenase system is known to produce O/sub 2//sup -/ and H/sub 2/O/sub 2/. They have studied the influence of monooxygenase induction using phenobarbital (PB) and ..beta..-naphthoflavone (..beta..-NF) on O/sub 2/ toxicity in the rat. PB- or ..beta..-NF induce hepatic P-450 but only ..beta..-NF induces pulmonary P-450. Pulmonary microsomes produced O/sub 2//sup -/ and H/sub 2/O/sub 2/ at rates (expressed per mg microsomal protein) which did not vary as a function of pretreatment. Rats were exposed to 100% O/sub 2/ for up to 3 days. After 3 days of O/sub 2/, lung weights were about 50% above controls regardless of pretreatment. The microsomal monooxygenase enzymes (P-450, b/sub 5/ and NADPH P-450 reductase) were quantified in liver and lung. Lung microsomal P-450 was reduced after 3 days of O/sub 2/ exposure regardless of pretreatment. The protective enzymes (catalase, superoxide dismutase (SOD) and glutathione (GSH) peroxidase) and non-protein sulfhydryl groups (NPSH) were also quantified in lung and liver samples. Lung NPSH and GSH peroxidase were increased after 3 days of O/sub 2/ exposure regardless of pretreatment while SOD was increased in controls and PB- but not ..beta..-NF-treated rats. Three of 14 ..beta..-NF-treated rats died during O/sub 2/ exposure while no animals in the control or PB-treated groups died.

  5. The genomic response of the ipsilateral and contralateral cortex to stroke in aged rats

    PubMed Central

    Buga, A-M; Sascau, M; Pisoschi, C; Herndon, J G; Kessler, C; Popa-Wagner, A

    2008-01-01

    Aged rats recover poorly after unilateral stroke, whereas young rats recover readily possibly with the help from the contralateral, healthy hemisphere. In this study we asked whether anomalous, age-related changes in the transcriptional activity in the brains of aged rats could be one underlying factor contributing to reduced functional recovery. We analysed gene expression in the periinfarct and contralateral areas of 3-month- and 18-month-old Sprague Dawley rats. Our experimental end-points were cDNA arrays containing genes related to hypoxia signalling, DNA damage and apoptosis, cellular response to injury, axonal damage and re-growth, cell lineage differentiation, dendritogenesis and neurogenesis. The major transcriptional events observed were: (i) Early up-regulation of DNA damage and down-regulation of anti-apoptosis-related genes in the periinfarct region of aged rats after stroke; (ii) Impaired neurogenesis in the periinfarct area, especially in aged rats; (iii) Impaired neurogenesis in the contralateral (unlesioned) hemisphere of both young and aged rats at all times after stroke and (iv) Marked up-regulation, in aged rats, of genes associated with inflammation and scar formation. These results were confirmed with quantitative real-time PCR. We conclude that reduced transcriptional activity in the healthy, contralateral hemisphere of aged rats in conjunction with an early up-regulation of DNA damage-related genes and pro-apoptotic genes and down-regulation of axono- and neurogenesis in the periinfarct area are likely to account for poor neurorehabilitation after stroke in old rats. PMID:18266980

  6. Effect of recombinant human growth hormone on age-related hepatocyte changes in old male and female Wistar rats.

    PubMed

    Castillo, Carmen; Salazar, Veronica; Ariznavarreta, Carmen; Vara, Elena; Tresguerres, Jesus A F

    2004-10-01

    Aging induces changes in several organs, such as the liver, and this process might be due to damage caused by free radicals and inflammatory mediators. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis shows a reduction with age, and this fact could be associated with some age-related changes. The aim of this study was to investigate the effect of GH administration on age-induced alterations in hepatocytes. Two and twenty two month-old male and female Wistar rats were used. Old rats were treated with human recombinant GH for 10 wk. At the end of the treatment, hepatocytes were isolated from the liver and cultured, and different parameters were measured in cells and medium. Plasma IGF-1 was also measured. Aging significantly decreased plasma IGF-1 in males. In females, plasma IGF-1 was also reduced, but not significantly. GH treatment restored plasma IGF-1 levels to values similar to young males. Aging was associated with a significant increase in lipid peroxidation (LPO), nitric oxide (NO), carbon monoxide (CO) and cyclic guanosyl-monophosphate (cGMP), as well as a reduction in adenosyl triphosphate (ATP) and phosphatidylcholine (PC) synthesis. GH administration partially prevented all these changes in males. In females, some of the parameters were significantly improved by GH (ATP, CO, cGMP), while others showed a tendency to improvement, although differences did not reach significance. In conclusion, GH administration could exert beneficial effects against age-related changes in hepatocytes, mainly in males.

  7. Interactions between Kisspeptin Neurons and Hypothalamic Tuberoinfundibular Dopaminergic Neurons in Aged Female Rats

    PubMed Central

    Iwata, Kinuyo; Ikehara, Masaaki; Kunimura, Yuyu; Ozawa, Hitoshi

    2016-01-01

    Kisspeptin neurons in the arcuate nucleus (ARC) regulate prolactin secretion, and are in physical contact with tuberoinfundibular dopaminergic (TIDA) neurons, which inhibit prolactin secretion. Prolactin levels in the blood are increased with advancing age in rats; therefore, we investigated the interactions with TIDA neurons and kisspeptin neurons in aged female rats (24 months of age), relative to those of young adult female rats (9–10 weeks of age). Plasma prolactin levels in the aged rats were significantly higher than those of young adult rats. Tyrosine hydroxylase (TH)-immunoreactive (ir) cell bodies and kisspeptin-ir nerve fibers were found in the dorsomedial ARC of both groups. The number of TH-ir cell bodies in the dorsomedial ARC did not differ significantly between groups. Additionally, no significant differences in the number of TH-ir cells in contact with kisspeptin-ir fibers was observed between groups. However, the number of kisspeptin-ir or Kiss1 mRNA-expressing cells in the ARC was significantly reduced in the aged rats compared with that of the young rats. These results suggest that the contacts between TIDA neurons and kisspeptin neurons are maintained after reproductive senescence, while production of kisspeptin in the ARC decreases significantly during aging. PMID:28127107

  8. Curcuma treatment prevents cognitive deficit and alteration of neuronal morphology in the limbic system of aging rats.

    PubMed

    Vidal, Blanca; Vázquez-Roque, Rubén A; Gnecco, Dino; Enríquez, Raúl G; Floran, Benjamin; Díaz, Alfonso; Flores, Gonzalo

    2017-03-01

    Curcuma is a natural compound that has shown neuroprotective properties, and has been reported to prevent aging and improve memory. While the mechanism(s) underlying these effects are unclear, they may be related to increases in neural plasticity. Morphological changes have been reported in neuronal dendrites in the limbic system in animals and elderly humans with cognitive impairment. In this regard, there is a need to use alternative therapies that delay the onset of morphologies and behavioral characteristics of aging. Therefore, the objective of this study was to evaluate the effect of curcuma on cognitive processes and dendritic morphology of neurons in the prefrontal cortex (PFC), the CA1 and CA3 regions of the dorsal hippocampus, the dentate gyrus, and the basolateral amygdala (BLA) of aged rats. 18-month-old rats were administered curcuma (100 mg/kg) daily for 60 days. After treatment, recognition memory was assessed using the novel object recognition test. Curcuma-treated rats showed a significant increase in the exploration quotient. Dendritic morphology was assessed by Golgi-Cox staining and followed by Sholl analysis. Curcuma-treated rats showed a significant increase in dendritic spine density and dendritic length in pyramidal neurons of the PFC, the CA1 and CA3, and the BLA. The preservation of dendritic morphology was positively correlated with cognitive improvements. Our results suggest that curcuma induces modification of dendritic morphology in the aforementioned regions. These changes may explain how curcuma slows the aging process that has already begun in these animals, preventing deterioration in neuronal morphology of the limbic system and recognition memory.

  9. Caloric restriction increases internal iliac artery and penil nitric oxide synthase expression in rat: comparison of aged and adult rats.

    PubMed

    Ozbek, Emin; Simsek, Abdulmuttalip; Ozbek, Mustafa; Somay, Adnan

    2013-09-26

    Because of the positive corelation between healthy cardiovascular system and sexual life we aimed to evaluate the effect of caloric restriction (CR) on endothelial and neuronal nitric oxide synthase (eNOS, nNOS) expression in cavernousal tissues and eNOS expression in the internal iliac artery in young and aged rats. Young (3 mo, n = 7) and aged (24 mo, n = 7) male Sprague-Dawley rats were subjected to 40% CR and were allowed free access to water for 3 months. Control rats (n = 14) fed ad libitum had free access to food and water at all times. On day 90, rats were sacrificed and internal iliac arteries and penis were removed and parafinized, eNOS and nNOS expression evaluated with immunohistochemistry. Results were evaluated semiquantitatively. eNOS and nNOS expression in cavernousal tis- sue in CR rats were more strong than in control group in both young and old rats. eNOS expression was also higher in the internal iliac arteries of CR rats than in control in young and old rats. As a result of our study we can say that there is a positive link between CR and neurotransmitter of erection in cavernousal tissues and internal iliac arteries. CR has beneficial effect to prevent sexual dysfunction in young and old animals and possible humans.

  10. The influence of zinc on the blood serum of cadmium-treated rats through the rheological properties.

    PubMed

    Moussa, Sherif Aa; Alaamer, Abdulaziz; Abdelhalim, Mohamed A K

    2016-01-01

    The blood rheological properties serve as an important indicator for the early detection of many diseases. This study aimed to investigate the influence of zinc (Zn) on blood serum of cadmium (Cd) intoxication-treated male rats through the rheological properties. The rheological parameters were measured in serum of control, Cd, and Cd+Zn groups at wide range of shear rates (225-1875 s(-1)). The rat blood serum showed a non-significant change in cadmium-treated rats' %torque and shear stress at the lower shear rates (200-600 s(-1)) while a significant increase was observed at the higher shear rates (650-1875 s(-1)) compared with the control. The rat blood serum viscosity increased significantly in the Cd-treated group at each shear rate compared with the control. The viscosity and shear rate exhibited a non-Newtonian behavior for all groups. The increase in blood serum viscosity in Cd-treated male rats might be attributed to destruction or changes in the non-clotting proteins, and other blood serum components. In Cd+Zn-treated rats, the rat blood serum viscosity values returned nearer to the control values at each shear rate. Our results confirmed that Zn displaced Cd or compete with the binding sites for Cd uptake.

  11. The use of insecticide treated nets by age: implications for universal coverage in Africa

    PubMed Central

    Noor, Abdisalan M; Kirui, Viola C; Brooker, Simon J; Snow, Robert W

    2009-01-01

    Background The scaling of malaria control to achieve universal coverage requires a better understanding of the population sub-groups that are least protected and provide barriers to interrupted transmission. Here we examine the age pattern of use of insecticide treated nets (ITNs) in Africa in relation to biological vulnerabilities and the implications for future prospects for universal coverage. Methods Recent national household survey data for 18 malaria endemic countries in Africa were assembled to indentify information on use of ITNs by age and sex. Age-structured medium variant projected population estimates for the mid-point year of the earliest and most recent national surveys were derived to compute the population by age protected by ITNs. Results All surveys were undertaken between 2005 and 2009, either as demographic health surveys (n = 12) or malaria indicator surveys (n = 6). Countries were categorized into three ITN use groups: <10%; 10 to <20%; and ≥20% and projected population estimates for the mid-point year of 2007 were computed. In general, the pattern of overall ITNs use with age was similar by country and across the three country groups with ITNs use initially high among children <5 years of age, sharply declining among the population aged 5-19 years, before rising again across the ages 20-44 years and finally decreasing gradually in older ages. For all groups of countries, the highest proportion of the population not protected by ITNs (38% - 42%) was among those aged 5-19 years. Conclusion In malaria-endemic Africa, school-aged children are the least protected with ITNs but represent the greatest reservoir of infections. With increasing school enrollment rates, school-delivery of ITNs should be considered as an approach to reach universal ITNs coverage and improve the likelihood of impacting upon parasite transmission. PMID:19796380

  12. Urinary Aminopeptidase Activities as Early and Predictive Biomarkers of Renal Dysfunction in Cisplatin-Treated Rats

    PubMed Central

    Quesada, Andrés; Vargas, Félix; Montoro-Molina, Sebastián; O'Valle, Francisco; Rodríguez-Martínez, María Dolores; Osuna, Antonio; Prieto, Isabel; Ramírez, Manuel; Wangensteen, Rosemary

    2012-01-01

    This study analyzes the fluorimetric determination of alanyl- (Ala), glutamyl- (Glu), leucyl-cystinyl- (Cys) and aspartyl-aminopeptidase (AspAp) urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group) received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG), albumin, and neutrophil gelatinase-associated lipocalin (NGAL). Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p<0.011; r2>0.259) with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice. PMID:22792302

  13. Immunohistochemical expression of ghrelin in capsaicin-treated rat ovaries during the different developmental periods

    PubMed Central

    Tütüncü, Ş.; İlhan, T.; Özfiliz, N.

    2016-01-01

    Red hot pepper is a plant that belongs to the Solanaceae family and is known as Capsicum annuum. Capsaicin is the active ingredient of cayenne pepper. Ghrelin is a hormone, which consists of polypeptide structure. Ghrelin also contributes to growth hormone secretion, energy balance, food intake and body weight regulator. The aim of this study was the localization and expression of ghrelin in the ovaries of rats treated with capsaicin during the postnatal development. Ninety female Sprague-Dawley rats (21 d) were used. The rats were randomly divided into 3 groups (n=30 each) as pubertal, post pubertal and adult. Each group was subdivided into three groups. The first subgroup (control) was given no injections. The second subgroup (vehicle) received only 0.3 cc solvent and the third subgroup (experiment) received subcutaneous injection of equal volume of capsaicin (1 mg/kg/d) for 42, 56, and 70 days. Ghrelin immunoreactivity was determined in ovarian follicular granulosa cells, interstitial cells and corpus luteal cells. A ghrelin immunopositive reaction located in the cytoplasm of cells in all groups. These results indicate that prolonged administration of low dose capsaicin does not affect ghrelin expression. However, follicular atresia was seen in lower rate in capsaicin treated group in comparison to other groups. PMID:27656230

  14. Mediation of oxidative stress in hypothalamic ghrelin-associated appetite control in rats treated with phenylpropanolamine.

    PubMed

    Yu, C-H; Chu, S-C; Chen, P-N; Hsieh, Y-S; Kuo, D-Y

    2017-04-01

    Phenylpropanolamine (PPA)-induced appetite control is associated with oxidative stress in the hypothalamus. This study explored whether hypothalamic antioxidants participated in hypothalamic ghrelin system-associated appetite control in PPA-treated rats. Rats were given PPA daily for 4 days, and changes in food intake and the expression of neuropeptide Y (NPY), the cocaine- and amphetamine-regulated transcript (CART), superoxide dismutase, catalase, ghrelin, acyl ghrelin (AG), ghrelin O-acyltransferase (GOAT) and the ghrelin receptor (GHSR1a) were examined and compared. Results showed that both food intake and the expression of NPY and ghrelin/AG/GOAT/GHSR1a decreased in response to PPA treatment with maximum decrease on Day 2 of the treatment. In contrast, the expression of antioxidants and CART increased, with the maximum increase on Day 2, with the expression opposite to that of NPY and ghrelin. A cerebral infusion of either a GHSR1a antagonist or reactive oxygen species scavenger modulated feeding behavior and NPY, CART, antioxidants and ghrelin system expression, showing the involvement of ghrelin signaling and oxidative stress in regulating PPA-mediated appetite control. We suggest that hypothalamic ghrelin signaling system, with the help of antioxidants, may participate in NPY/CART-mediated appetite control in PPA-treated rats.

  15. Gene expression profiles of hepatocytes treated with La (NO3) 3 of rare earth in rats

    PubMed Central

    Zhao, Hui; Hao, Wei-Dong; Xu, Hou-En; Shang, Lan-Qin; Lu, You-Yong

    2004-01-01

    AIM: To compare the gene expression between La (NO3) 3-exposed and control rats in vivo. METHODS: Rats were fed La (NO3) 3 once daily at a dose of 20 mg/kg for one month by gavage. Gene expression of hepatocytes was detected using mRNA differential display (DD) technique and cDNA microarray and compared between treated and control groups. RESULTS: Six differentially expressed sequence tags were cloned by DD, of which five were up regulated and one was down regulated in treated rats. Two sequences were determined. One band was novel. The other shared 100% sequence homology with AU080263 Sugano mouse brain mncb Mus musculus cDNA clone MNCb-5435 5’. With DNA microarray, 136 differentially expressed genes were identified including 131 over-expressed genes and 5 under-expressed genes. Most of these differentially expressed genes were cell signal and transmission genes, genes associated with metabolism, protein translation and synthesis. CONCLUSION: La (NO3) 3 could change the expression levels of some kinds of genes. Further analysis of the differentially expressed genes would be helpful for understanding the wide biological effect spectrum of rare earth elements. PMID:15162537

  16. Functional changes in piriform cortex pyramidal neurons in the chronic methamphetamine-treated rat.

    PubMed

    Hori, Nobuaki; Kadota, Tomoko; Akaike, Norio

    2015-01-01

    Chronic treatment of rats with methamphetamine (MAP) causes a range of functional changes to the central nervous system (CNS), including a toxicity that is widespread throughout the brain (Frost and Cadet 2000; Fasihpour et al. 2013). In this report, we examined the effect of chronic MAP treatment on pyramidal neurons of the rat piriform cortex, an area involved in sensory processing, associative learning and a model system for studies on synaptic plasticity. MAP treatment significantly depolarized the membrane potential and decreased neuronal input resistance. Furthermore, the voltage-dependence of both AMPA and NMDA responses was disturbed by chronic MAP treatment, and the extent of long-term potentiation (LTP) was decreased. Morphological changes of MAP-treated rat pyramidal neurons were observed as blebbing of the dendrite trees. The changes we observed represent detrimental effects on the function of piriform cortical neurons further illustrating deficits in synaptic plasticity extend beyond the hippocampus. These changes may contribute to behavioural deficits in chronic MAP-treated animals.

  17. Concerning the mechanism of increased thermogenesis in rats treated with dehydroepiandrosterone.

    PubMed

    Bobyleva, V; Kneer, N; Bellei, M; Battelli, D; Lardy, H A

    1993-06-01

    Dehydroepiandrosterone (DHEA) treatment of rats decreases gain of body weight without affecting food intake; simultaneously, the activities of liver malic enzyme and cytosolic glycerol-3-P dehydrogenase are increased. In the present study experiments were conducted to test the possibility that DHEA enhances thermogenesis and decreases metabolic efficiency via transhydrogenation of cytosolic NADPH into mitochondrial FADH2 with a consequent loss of energy as heat. The following results provide evidence which supports the proposed hypothesis: (a) the activities of cytosolic enzymes involved in NADPH production (malic enzyme, cytosolic isocitrate dehydrogenase, and aconitase) are increased after DHEA treatment; (b) cytosolic glycerol-3-P dehydrogenase may use both NAD+ and NADP+ as coenzymes; (c) activities of both cytosolic and mitochondrial forms of glycerol-3-P dehydrogenase are increased by DHEA treatment; (d) cytosol obtained from DHEA-treated rats synthesizes more glycerol-3-P during incubation with fructose-1,6-P2 (used as source of dihydroxyacetone phosphate) and NADP+; the addition of citrate in vitro further increases this difference; (e) mitochondria prepared from DHEA-treated rats more rapidly consume glycerol-3-P added exogenously or formed endogenously in the cytosol in the presence of fructose-1,6-P2 and NADP+.

  18. Efficacy of curcumin to reduce hepatic damage induced by alcohol and thermally treated oil in rats.

    PubMed

    El-Deen, Nasr A M N; Eid, Mohamed

    2010-01-01

    The authors investigated the effect of curcumin on markers of oxidative stress and liver damage in rats that chronically ingested alcohol and heated oil. Nine groups of ten Wistar male rats received combinations of curcumin 100 mg/kg body weight daily, ethanol 5 mg/kg, 15% dietary sunflower oil and 15% heated sunflower oil for 12 weeks. Serum and liver tissue were collected. Groups 4-6, which had received compounds causing oxidative stress, showed increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, triglycerides, low density lipoprotein, very low density lipoprotein and reduced high density lipoprotein, protein and albumin, compared with the controls. Reductions were observed in glutathione peroxidase and reductase gene expression, superoxide dismutase activity, glutathione peroxidase activity, glutathione reductase activity, reduced glutathione concentration and catalase enzyme activity. Groups 7, 8 and 9 which received curcumin with heated oil, ethanol or both, showed lower elevations in serum and oxidative damage markers compared with the corresponding non-curcumin treated groups. It can be concluded that curcumin reduces markers of liver damage in rats treated with heated sunflower oil or ethanol.

  19. Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats.

    PubMed

    Wang, Xiao-Fei; Zhao, Tai-Yun; Su, Rui-Bin; Wu, Ning; Li, Jin

    2016-12-01

    Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hippocampal extracellular glutamate level induced by naloxone (2 mg/kg, i.p.) precipitation. Agmatine (20 mg/kg, s.c.) administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synaptosomes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agmatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors (NMDARs) was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine prevented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including modulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.

  20. Neurotransmitter agonists inhibit inositol phosphate formation in the brain of bupropione-treated rats

    SciTech Connect

    Butler, P.D.; Hungund, B.; Suckow, R.; Barkai, A.I.

    1986-03-05

    Bupropione is a chemically unique antidepressant whose mechanism of action is not known. In this study they have evaluated the effect of chronic treatment with bupropione on the receptor-mediated release of inositol phosphates (IP) from brain slices in rats. Animals were implanted with Alzet osmotic pumps that delivered bupropione at a constant rate (40mg/kg/day) for 2 weeks. Cross-chopped slices of cerebral cortex from control and drug-treated rats were prelabelled with myo-/sup 3/H-inositol in HEPES buffer containing 11 mM LiCl. Accumulation of IP was measured in the presence and absence of the following agonists: Carbamylcholine (100..mu..m); norepinephrine (5..mu..M) and serotonin (10..mu..M). All agonists stimulated release of IP from slices of control animals but appeared to inhibit IP release in bupropione-treated rats. These results indicate that a phospholipase C inhibitor may appear following the activation of this enzyme by the agonist, and that the agonist-induced formation of the apparent inhibitor may be markedly enhanced after treatment with bupropione.

  1. Honey Attenuates the Detrimental Effects of Nicotine on Testicular Functions in Nicotine Treated Wistar Rats.

    PubMed

    Kolawole, T A; Oyeyemi, W A; Adigwe, C; Leko, B; Udeh, C; Dapper, D V

    2015-12-20

    Effect of honey on reproductive functions of male rats exposed to nicotine was examined in this study. Thirty-two adult male wistar rats (n=8/Group) were grouped as Control (distilled water), Nicotine (1.0mg/kg bwt), Honey (100mg/kg bwt) and Nicotine with Honey. The animals were orally treated for 35 days consecutively. Epididymis sperm motility, viability, morphology and counts were estimated, serum Follicle Stimulating Hormone (FSH), Leutinizing Hormone (LH) and Testosterone were assayed using ELISA method and testicular histology were also assessed. Significant reduction in percentage sperm motility, viability, morphology and counts were observed in nicotine group compared to control. Serum FSH, LH and testosterone levels were significantly reduced in nicotine group when compared with the control. There was significant improvement in sperm motility, viability, morphology, counts, FSH, LH and Testosterone in group co-treated with nicotine and honey  relative to nicotine group. Also, the degenerative seminiferous tubule architecture due to nicotine was improved by honey. In conclusion, honey may suppress nicotine toxic effect on reproductive functions in male Wistar rats.

  2. Effects of metabolic syndrome on the ultrastructure of the femoral nerve in aging rats.

    PubMed

    Rodrigues de Souza, Romeu; Gama, Eliane F; El-Razi Neto, Semaan; Maldonado, Diogo

    2015-10-01

    The aim of the present study was to characterize the morphometry of the femoral nerve in aging rats with metabolic syndrome compared to controls. Systolic blood pressure and fasting plasma glucose were measured, and myelinated and unmyelinated fibers in the femoral nerves were quantitatively assessed under electron microscopy. Aging rats exposed to a regimen of metabolic syndrome developed elevation of plasma glucose concentration, mild hypertension and polyneuropathy characterized by a decrease in myelin fiber area, axon diameter, myelin sheath thickness and myelin fiber loss in the femoral nerve. The histogram of size distribution for myelinated fibers and axons from the aging rats of the control group was bimodal. For aging MS animals, the histogram turned out to be unimodal. The ultrastructure of unmyelinated fibers and of Schwann cells in 18-month-old rats was well preserved. Granules of lipofuscin were seen in unmyelinated fiber axons of 18-month-old rats with MS. The damage percentage of the large myelinated fibers has increased significantly in 18-month-old and 18-month-old (MS) rats in relation to the controls. No significant difference was observed among the groups for the g-ratio. Comparing the three groups, the number of neurotubules and neurofilaments in myelinated fibers of 18-month-old rats with MS was significantly smaller than for the groups of 18-month-old and 14-month-old rats. The overall changes seen in the femoral nerve from aging rats seem minor compared to the changes in the aging rats with MS, suggesting that long-term MS accelerates the progressive modifications in peripheral nerves that develop in old age.

  3. Effect of aging and anti-aging caloric restriction on the endocrine regulation of rat liver autophagy.

    PubMed

    Donati, Alessio; Recchia, Gianluca; Cavallini, Gabriella; Bergamini, Ettore

    2008-06-01

    Autophagy is a process that sequesters and degrades altered organelles and macromolecular cytoplasmic constituents for cellular restructuring and repair, and as a source of nutrients for metabolic use in early starvation it may be involved in anti-aging mechanisms of caloric restriction. The effects of 40% daily dietary restriction (DR) and intermittent feeding (EOD) on the age-related changes in the endocrine regulation of autophagic proteolysis were studied by monitoring the rate of valine release from isolated rat liver cells. Results show that in ad libitum-fed rats sensitivity of autophagy to glucagon and insulin declines by one order of magnitude in older rats. Both DR and EOD maintain the sensitivity to glucagon at juvenile levels, whereas only EOD can fully maintain response to insulin. It is concluded that changes in the sensitivity to glucagon may have a role in the aging process.

  4. Oral administration of amino acidic supplements improves protein and energy profiles in skeletal muscle of aged rats: elongation of functional performance and acceleration of mitochondrial recovery in adenosine triphosphate after exhaustive exertion.

    PubMed

    Chen Scarabelli, Carol; McCauley, Roy B; Yuan, Zhaokan; Di Rezze, Justin; Patel, David; Putt, Jeff; Raddino, Riccardo; Allebban, Zuhair; Abboud, John; Scarabelli, Gabriele M; Chilukuri, Karuna; Gardin, Julius; Saravolatz, Louis; Faggian, Giuseppe; Mazzucco, Alessandro; Scarabelli, Tiziano M

    2008-06-02

    Sarcopenia is an inevitable age-related degenerative process chiefly characterized by decreased synthesis of muscle proteins and impaired mitochondrial function, leading to progressive loss of muscle mass. Here, we sought to probe whether long-term administration of oral amino acids (AAs) can increase protein and adenosine triphosphate (ATP) content in the gastrocnemius muscle of aged rats, enhancing functional performance. To this end, 6- and 24-month-old male Fisher 344 rats were divided into 3 groups: group A (6-month-old rats) and group B (24-month-old rats) were used as adult and senescent control group, respectively, while group C (24-month-old rats) was used as senescent treated group and underwent 1-month oral treatment with a mixture of mainly essential AAs. Untreated senescent animals exhibited a 30% reduction in total and fractional protein content, as well as a 50% reduction in ATP content and production, compared with adult control rats (p <0.001). Long-term supplementation with mixed AAs significantly improved protein and high-energy phosphate content, as well as the rate of mitochondrial ATP production, conforming their values to those of adult control animals (p <0.001). The improved availability of protein and high-energy substrates in the gastrocnemius muscle of treated aged rats paralleled a significant enhancement in functional performance assessed by swim test, with dramatic elongation of maximal exertion times compared with untreated senescent rats (p <0.001). In line with these findings, we observed that, after 6 hours of rest following exhaustive swimming, the recovery in mitochondrial ATP content was approximately 70% in adult control rats, approximately 60% in senescent control rats, and normalized in treated rats as compared with animals of the same age unexposed to maximal exertion (p <0.001). In conclusion, nutritional supplementation with oral AAs improved protein and energy profiles in the gastrocnemius of treated rats, enhancing

  5. Morphometric and neurochemical alterations found in l-BMAA treated rats.

    PubMed

    de Munck, Estefanía; Muñoz-Sáez, Emma; Miguel, Begoña G; Solas, M Teresa; Martínez, Ana; Arahuetes, Rosa M

    2015-05-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle paralysis that reflects the motoneurons' degeneration. Several studies support the relationship between β-N-methylamino-l-alanine (l-BMAA), a neurotoxic amino acid produced by cyanobacteria and diatoms, and the sporadic occurrence of ALS and other neurodegenerative diseases. Therefore, the study of its neurotoxicity mechanisms has assumed great relevance in recent years. Recently, our research team has proposed a sporadic ALS animal model by l-BMAA administration in rats, which displays many pathophysiological features of human ALS. In this paper, we deepen the characterization of this model corroborating the occurrence of alterations present in ALS patients such as decreased muscle volume, thinning of the motor cortex, enlarged brain's lateral ventricles, and alteration of both bulbar nuclei and neurotransmitters' levels. Therefore, we conclude that l-BMAA treated rats could be a good model which mimics degenerative features that ALS causes in humans.

  6. Enzymatic activities in brains of diabetic rats treated with vanadyl sulphate and sodium tungstate.

    PubMed

    Lemberg, A; Fernández, M A; Ouviña, G; Rodríguez, R R; Peredo, H A; Susemihl, C; Villarreal, I; Filinger, E J

    2007-12-01

    The hypothesis of the present study was that diabetes mellitus might affect brain metabolism. Streptozotocin (STZ)-induced diabetic rats, treated with vanadyl sulphate (V) and sodium tungstate (T) were employed to observe the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) activities in brain homogenates. Significant increases in AST, ALT and CK activities were found in diabetic brain homogenates against controls, suggesting increments of transamination in brain and/or increases in cell membrane permeability to these enzymes. The increase in brain CK possibly expresses alterations in energy production. The decrease in CK activity caused by V and T treatment in diabetic rats suggests that both agents tend to normalize energy consumption. It is also possible that V and T-induced hypoglycemic effects cause metabolic alterations in brain.

  7. Effect of aluminium on duodenal calcium transport in pregnant and lactating rats treated with bromocriptine.

    PubMed

    Orihuela, Daniel

    2007-09-01

    The aim of present work was to study the effect of oral aluminium (Al) overload on intestinal calcium (Ca) absorption in the critical stages of pregnancy and lactation of rats and to find out possible relationships with prolactin (PRL) and 17beta-estradiol (E2) circulating levels. Adult female Wistar rats were orally treated from day 1 of pregnancy with 0 (control), or 50 mg elemental Al (as chloride)/kg body weight per day. Ca transport was determined by everted duodenal sacs technique using 2 microCi of (45)CaCl(2) as flux marker (JCa(ms)). Al treatment reduced JCa(ms) either in late pregnancy (day 19) or in middle lactation (day 9 postpartum). Oral administration of bromocriptine (BrC), an inhibitor of PRL secretion, at dose of 10 mg/kg body weight given 18 h before JCa(ms) measurements were done, produced a significant decrease in the inhibitory effect of Al on JCa(ms), expressed as percent of control, at day 9 of nursing (vehicle: 51+/-7%, BrC: 28+/-4%, P <0.05). A positive correlation between Al effects on JCa(ms) and the physiological variations of E2 serum levels along pregnancy and lactation in BrC-treated rats was also found (r(2)=0.277, P =0.001). We conclude Al could reduce transcellular Ca absorption in the duodenum by interfering with physiological mechanisms of Ca transport partially mediated by serum level increments of E2 and PRL, observed in late pregnancy and mainly during middle lactation of rats.

  8. HIV-1 transgenic rats display alterations in immunophenotype and cellular responses associated with aging.

    PubMed

    Abbondanzo, Susan J; Chang, Sulie L

    2014-01-01

    Advances in anti-retroviral therapy over the last two decades have allowed life expectancy in patients infected with the human immunodeficiency virus to approach that of the general population. The process of aging in mammalian species, including rats, results in immune response changes, alterations in immunological phenotypes, and ultimately increased susceptibility to many infectious diseases. In order to investigate the immunological pathologies associated with chronic HIV-1 disease, particularly in aging individuals, the HIV-1 transgenic (HIV-1Tg) rat model was utilized. HIV-1Tg rats were challenged with lipopolysaccharide (LPS) to determine immunological alterations during the aging process. LPS is known to cause an imbalance in cytokine and chemokine release, and provides a method to identify changes in immune responses to bacterial infection in an HIV animal model. An immune profile and accompanying cellular consequences as well as changes in inflammatory cytokine and chemokine release related to age and genotype were assessed in HIV-1Tg rats. The percentage of T cells decreased with age, particularly T cytotoxic cells, whereas T helper cells increased with age. Neutrophils and monocytes increased in HIV-1Tg rats during maturation compared to age-matched F344 control rats. Aging HIV-1Tg rats displayed a significant increase in the pro-inflammatory cytokines, IL-6 and TNF-α, along with an increase in the chemokine, KC/GRO, in comparison to age-matched controls. Our data indicate that immunophenotype and immune responses can change during aging in HIV-positive individuals. This information could be important in determining the most beneficial age-dependent therapeutic treatment for HIV patients.

  9. Oestradiol and insulin-like growth factor-1 reduce cell loss after global ischaemia in middle-aged female rats.

    PubMed

    Traub, M L; De Butte-Smith, M; Zukin, R S; Etgen, A M

    2009-12-01

    Whereas the ability of oestradiol and insulin-like growth factor (IGF)-1 to afford neuroprotection against ischaemia-induced neuronal death in young female and male rodents is well established, the impact of IGF-1 in middle-aged animals is largely unknown. The present study assessed the efficacy of oestradiol and IGF-1 with respect to reducing neuronal death after transient global ischaemia in middle-aged female rats after 8 weeks of hormone withdrawal. Rats were ovariohysterectomised and implanted 8 weeks later with an osmotic mini-pump delivering IGF-1 or saline into the lateral ventricle. Some rats also received physiological levels of oestradiol by subcutaneous pellet. Two weeks later, rats were subjected to global ischaemia or sham operation. Surviving hippocampal CA1 neurones were quantified. Ischaemia produced massive CA1 cell death compared to sham-operated animals, which was evident at 14 days. Significantly more neurones survived in animals treated with either oestradiol or IGF-1, but simultaneous treatment produced no additive effect. IGF-1, an endogenous growth factor, may be a clinically useful therapy in preventing human brain injury, with neuroprotective equivalence to oestradiol but without the harmful side-effects.

  10. Age, Dose, and Time-Dependency of Plasma and Tissue Distribution of Deltamethrine in Immature Rats

    EPA Science Inventory

    The major objective of this project was to characterize the systemic disposition of the pyrethroid, deltamethrin (DLT), in immature rats, with emphasis on the age-dependence of target organ (brain) dosimetry. Postnatal day (PND) 10, 21, and 40 male Sprague-Dawley rats received 0...

  11. Ozone Induces Glucose Intolerance and Systemic Metabolic Effects in Young and Aged Brown Norway Rats

    EPA Science Inventory

    Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone could impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in very young and aged rats. Brown Norway (BN) rats, 1,4, 12, and 24 months ol...

  12. Differences in Age-Related Alterations in Muscle Contraction Properties in Rat Tongue and Hindlimb

    ERIC Educational Resources Information Center

    Connor, Nadine P.; Ota, Fumikazu; Nagai, Hiromi; Russell, John A.; Leverson, Glen

    2008-01-01

    Purpose: Because of differences in muscle architecture and biomechanics, the purpose of this study was to determine whether muscle contractile properties of rat hindlimb and tongue were differentially affected by aging. Method: Deep peroneal and hypoglossal nerves were stimulated in 6 young and 7 old Fischer 344-Brown Norway rats to allow…

  13. Effects of a Saturated Fat and High Cholesterol Diet on Memory and Hippocampal Morphology in the Middle-Aged Rat

    PubMed Central

    Granholm, Ann-Charlotte; Bimonte-Nelson, Heather A.; Moore, Alfred B.; Nelson, Matthew E.; Freeman, Linnea R.; Sambamurti, Kumar

    2009-01-01

    Diets rich in cholesterol and/or saturated fats have been shown to be detrimental to cognitive performance. Therefore, we fed a cholesterol (2%) and saturated fat (hydrogenated coconut oil, Sat Fat 10%) diet to 16-month old rats for 8 weeks to explore the effects on the working memory performance of middle-aged rats. Lipid profiles revealed elevated plasma triglycerides, total cholesterol, HDL, and LDL for the Sat-Fat group as compared to an iso-caloric control diet (12% soybean oil). Weight gain and food consumption were similar in both groups. Sat-Fat treated rats committed more working memory errors in the water radial arm maze, especially at higher memory loads. Cholesterol, amyloid-β peptide of 40 (Aβ40) or 42 (Aβ42) residues, and nerve growth factor in cortical regions was unaffected, but hippocampal Map-2 staining was reduced in rats fed a Sat-Fat diet, indicating a loss of dendritic integrity. Map-2 reduction correlated with memory errors. Microglial activation, indicating inflammation and/or gliosis, was also observed in the hippocampus of Sat-Fat fed rats. These data suggest that saturated fat, hydrogenated fat and cholesterol can profoundly impair memory and hippocampal morphology. PMID:18560126

  14. Effect of aging on thyroidal and pituitary T4-5'-deiodinase activity in female rats.

    PubMed

    Correa da Costa, V M; Rosenthal, D

    1996-01-01

    Some alterations in hypothalamo-pituitary-thyroid axis occur during aging. In this study we evaluated the changes induced by aging in pituitary and thyroid iodothyronine-deiodinase (DI) activities, and in serum T4, T3 and TSH. Groups of 6-18 female Dutch-Miranda rats aged 3-5 months (young adults) were studied in parallel with similar groups of old (10-12 months) and senescent (24-30 months) animals. DI activities were determined in the microsomal fraction of pooled pituitary or thyroid glands (6 glands per pool), using T4 as substrate and DTT as cofactor; the T3 formed was measured by specific radioimmunoassay. Serum T3, T4 and TSH were measured by specific radioimmunoassays. Serum T4 was significantly decreased in both groups of aged rats, but serum TSH was unaffected. Serum T3 was just slightly decreased in the senescent rats. Total pituitary DI activity was significantly decreased in the aged rats (10-12 and 24-30 months). Both type I and type II DI activities were affected, although the decrease in type I DI only became significant in the senescent rats. In contrast, to its effect in the pituitary, aging does not decrease, even slightly, the DI activity in the thyroid gland. The thyroid DI activity may contribute to the unaltered serum T3 levels found in aged rats in the present study.

  15. Hippocampal somatostatin receptors and modulation of adenylyl cyclase activity in histamine-treated rats.

    PubMed

    Puebla, L; Rodríguez-Martín, E; Arilla, E

    1996-01-01

    In the present study, the effects of an intracerebroventricular (i.c.v.) dose of histamine (0.1, 1.0 or 10.0 micrograms) on the hippocampal somatostatin (SS) receptor/effector system in Wistar rats were investigated. In view of the rapid onset of histamine action, the effects of histamine on the somatostatinergic system were studied 2 h after its administration. Hippocampal SS-like immunoreactivity (SSLI) levels were not modified by any of the histamine doses studied. SS-mediated inhibition of basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activity was markedly increased in hippocampal membranes from rats treated with 10 micrograms of histamine (23% +/- 1% vs. 17% +/- 1% and 37% +/- 2% vs. 23% +/- 1%, respectively). In contrast, neither the basal nor the FK-stimulated enzyme activities were affected by histamine administration. The functional activity of the hippocampal guanine-nucleotide binding inhibitory protein (Gi protein), as assessed by the capacity of the stable GTP analogue 5'-guanylylimidodiphosphate (Gpp[NH]p) to inhibit FK-stimulated AC activity, was not modified by histamine administration. These data suggest that the increased response of the enzyme to SS was not related to an increased functional activity of Gi proteins. In fact, the increased AC response to SS in hippocampal membranes from histamine (10 micrograms)-treated rats was associated with quantitative changes in the SS receptors. Equilibrium binding data obtained with [125I]Tyr11-SS indicate an increase in the number with specific SS receptors (541 +/- 24 vs. 365 +/- 16 fmol/mg protein, P < 0.001) together with a decrease in their apparent affinity (0.57 +/- 0.04 vs. 0.41 +/- 0.03 nM, P < 0.05) in rat hippocampal membranes from histamine (10 micrograms)-treated rats as compared to control animals. With the aim of determining if these changes were related to histamine binding to its specific receptor sites, the histaminergic H1 and H2 receptor antagonists mepyramine and cimetidine

  16. Hormone replacement with 17β-estradiol plus dihydrotestosterone restores male sexual behavior in rats treated neonatally with clomipramine.

    PubMed

    Limón-Morales, Ofelia; Soria-Fregozo, Cesar; Arteaga-Silva, Marcela; González, Marisela Hernández; Vázquez-Palacios, Gonzalo; Bonilla-Jaime, Herlinda

    2014-11-01

    Male sexual behavior (MSB) in rodents, in both its consummatory and motivational components, is regulated by hormones such as testosterone, 17β-estradiol and 5-α-dihydrotestosterone. In experiments, neonatal treatment with clomipramine (CMI; a serotonin reuptake inhibitor) reproduces some of the signs of depression in adult age, including reduced sexual behavior manifested in a lower percentage of subjects that mount, intromit and ejaculate, although their testosterone levels were not altered. However, the effect of this treatment on estrogen levels and the consequences of hormone substitution using 17β-estradiol and 5-α-dihydrotestosterone on the expression of male sexual behavior are still unknown. Therefore, the objective of the present study was to analyze the effect of neonatal treatment with CMI on plasma testosterone and 17β-estradiol levels, and the role of testosterone, 17β-estradiol and 5-α-dihydrotestosterone in altering the consummatory and motivational components of sexual behavior in male rats. To this end, it analyzed the copulatory parameters and sexual incentive motivation (SIM) of rats treated with CMI under two conditions: basal and post-hormone replacements. Neonatal treatment with CMI did not affect plasma testosterone or 17β-estradiol concentrations, but did decrease both the consummatory component and sexual motivation according to the results of the SIM test. These aspects were recovered after administering 17β-estradiol +5-α-dihydrotestosterone, but not testosterone.

  17. Lipid Profile and Electrolyte Composition in Diabetic Rats Treated With Leaf Extract of Musa sapientum.

    PubMed

    Adewoye, E O; Ige, A O

    2016-01-01

    Diabetes mellitus affects lipid levels resulting in diabetic dyslipidemia as well as electrolyte loss from the body. Musa sapientum has been reported to possess antidiabetic properties. This study assessed the lipid profile and electrolyte composition in alloxan-induced diabetic rats treated with methanol leaf extract of M. sapientum (cMEMSL). Diabetes was induced with alloxan (120 mg/kg i.p.). Seventy-five male albino rats were divided into 5 groups of 15 rats each. Group 1 was control; groups 2-5 were made diabetic and treated with 0.2 ml 0.9% NaCl, cMEMSL (250 mg/kg and 500 mg/kg), and glibenclamide (5 mg/kg), respectively, for 14 days. Blood samples were obtained from the retro orbital sinus after light anesthesia from 5 animals in each group on days 2, 7, and 14 for lipids and electrolyte analysis. Lipid profile of diabetic treated (cMEMSL and glibenclamide) animals showed significant reduction (p < .05) in total cholesterol, triglyceride, and low density lipoprotein (LDL) levels. The high density lipoprotein (HDL) level in the treatment groups increased significantly (p < .05) compared with diabetic untreated. Sodium, potassium, and phosphate ions significantly increased in all diabetic treatment groups while chloride ion significantly decreased compared with diabetic untreated. There was no significant difference in calcium and bicarbonate ion concentration in all the groups. This study has showed additional properties of Musa sapientum to include its ability to restore electrolyte balance, reduce cholesterol, triglyceride, LDL, and increase the HDL levels in diabetic animals.

  18. Non-specific recognition in phagocytosis: ingestion of aldehyde-treated erythrocytes by rat peritoneal macrophages.

    PubMed Central

    Capo, C; Bongrand, P; Benoliel, A M; Depieds, R

    1979-01-01

    Particles were chemically modified with aldehydes and incubated with rat peritoneal cells for phagocytosis. All dialdehydes and lower monaldehydes tested (methanal, ethanal and propanal) made sheep erythrocytes phagocytosable. Failure of higher monaldehydes to induce phagocytosis of treated erythrocytes was not due to lack of reactivity with red cell membranes. All erythrocytes tested (bird and mammal red cells were used) and rat thymocytes were phagocytosed by rat macrophages after incubation with aldehyde. Treatment of Candida albicans did not induce phagocytosis: this failure was not due to lack of aldehyde binding (as demonstrated with [14C]-methanal) nor to anti-phagocytic properties of the parasite membrane. Sheep erythrocytes were submitted to enzymatic treatment (pronase, trypsin, neuraminidase) or incubated with succinic anhydride (to block free NH2 groups) or iodacetamide (to block free SH groups) before aldehyde treatment: phagocytosis was not decreased, which suggested that aldehydes did not act by altering some definite surface structure of the treated particles. Treatment of erythrocytes with cross-linking compounds such as tetraazotized o-dianisidine (coupling occurs mainly on tyrosine and histidine residues) or l-ethyl(3-dimethyl aminopropyl) carbodiimide (a bivalent reagent binding free COOH groups) did not induce any substantial phagocytosis of erythrocytes. Phagocytosis of aldehyde treated erythrocytes was partly correlated with hydrophobicity of these cells, as measured with a two-phase partition system. It is concluded that aldehyde-mediated phagocytosis of erythrocytes is mainly due to cross-linking of red cell membrane structures, probably involving free OH groups, which must increase local rigidity and thereby modify hydrophobicity of the red cell surface. Images Figure 1 PMID:437841

  19. Non-specific recognition in phagocytosis: ingestion of aldehyde-treated erythrocytes by rat peritoneal macrophages.

    PubMed

    Capo, C; Bongrand, P; Benoliel, A M; Depieds, R

    1979-03-01

    Particles were chemically modified with aldehydes and incubated with rat peritoneal cells for phagocytosis. All dialdehydes and lower monaldehydes tested (methanal, ethanal and propanal) made sheep erythrocytes phagocytosable. Failure of higher monaldehydes to induce phagocytosis of treated erythrocytes was not due to lack of reactivity with red cell membranes. All erythrocytes tested (bird and mammal red cells were used) and rat thymocytes were phagocytosed by rat macrophages after incubation with aldehyde. Treatment of Candida albicans did not induce phagocytosis: this failure was not due to lack of aldehyde binding (as demonstrated with [14C]-methanal) nor to anti-phagocytic properties of the parasite membrane. Sheep erythrocytes were submitted to enzymatic treatment (pronase, trypsin, neuraminidase) or incubated with succinic anhydride (to block free NH2 groups) or iodacetamide (to block free SH groups) before aldehyde treatment: phagocytosis was not decreased, which suggested that aldehydes did not act by altering some definite surface structure of the treated particles. Treatment of erythrocytes with cross-linking compounds such as tetraazotized o-dianisidine (coupling occurs mainly on tyrosine and histidine residues) or l-ethyl(3-dimethyl aminopropyl) carbodiimide (a bivalent reagent binding free COOH groups) did not induce any substantial phagocytosis of erythrocytes. Phagocytosis of aldehyde treated erythrocytes was partly correlated with hydrophobicity of these cells, as measured with a two-phase partition system. It is concluded that aldehyde-mediated phagocytosis of erythrocytes is mainly due to cross-linking of red cell membrane structures, probably involving free OH groups, which must increase local rigidity and thereby modify hydrophobicity of the red cell surface.

  20. n-3 fatty acids effectively improve the reference memory-related learning ability associated with increased brain docosahexaenoic acid-derived docosanoids in aged rats.

    PubMed

    Hashimoto, Michio; Katakura, Masanori; Tanabe, Yoko; Al Mamun, Abdullah; Inoue, Takayuki; Hossain, Shahdat; Arita, Makoto; Shido, Osamu

    2015-02-01

    We investigated whether a highly purified eicosapentaenoic acid (EPA) and a concentrated n-3 fatty acid formulation (prescription TAK-085) containing EPA and docosahexaenoic acid (DHA) ethyl ester could improve the learning ability of aged rats and whether this specific outcome had any relation with the brain levels of EPA-derived eicosanoids and DHA-derived docosanoids. The rats were tested for reference memory errors (RMEs) and working memory errors (WMEs) in an eight-arm radial maze. Fatty acid compositions were analyzed by GC, whereas brain eicosanoid/docosanoids were measured by LC-ESI-MS-MS-based analysis. The levels of lipid peroxides (LPOs) were measured by thiobarbituric acid reactive substances. The administration of TAK-085 at 300 mg·kg⁻¹day⁻¹ for 17 weeks reduced the number of RMEs in aged rats compared with that in the control rats. Both TAK-085 and EPA administration increased plasma EPA and DHA levels in aged rats, with concurrent increases in DHA and decreases in arachidonic acid in the corticohippocampal brain tissues. TAK-085 administration significantly increased the formation of EPA-derived 5-HETE and DHA-derived 7-, 10-, and 17-HDoHE, PD1, RvD1, and RvD2. ARA-derived PGE2, PGD2, and PGF2α significantly decreased in TAK-085-treated rats. DHA-derived mediators demonstrated a significantly negative correlation with the number of RMEs, whereas EPA-derived mediators did not exhibit any relationship. Furthermore, compared with the control rats, the levels of LPO in the plasma, cerebral cortex, and hippocampus were significantly reduced in TAK-085-treated rats. The findings of the present study suggest that long-term EPA+DHA administration may be a possible preventative strategy against age-related cognitive decline.

  1. Age-Stratified Treatment Response Rates in Hospitalized Patients with Clostridium difficile Infection Treated with Metronidazole.

    PubMed

    Pham, Vy P; Luce, Andrea M; Ruppelt, Sara C; Wei, Wenjing; Aitken, Samuel L; Musick, William L; Roux, Ryan K; Garey, Kevin W

    2015-10-01

    Consensus on the optimal treatment of Clostridium difficile infection (CDI) is rapidly changing. Treatment with metronidazole has been associated with increased clinical failure rates; however, the reasons for this are unclear. The purpose of this study was to assess age-related treatment response rates in hospitalized patients with CDI treated with metronidazole. This was a retrospective, multicenter cohort study of hospitalized patients with CDI. Patients were assessed for refractory CDI, defined as persistent diarrhea after 7 days of metronidazole therapy, and stratified by age and clinical characteristics. A total of 242 individuals, aged 60 ± 18 years (Charlson comorbidity index, 3.8 ± 2.4; Horn's index, 1.7 ± 1.0) were included. One hundred twenty-eight patients (53%) had severe CDI. Seventy patients (29%) had refractory CDI, a percentage that increased from 22% to 28% and to 37% for patients aged less than 50 years, for patients from 50 to 70 years, and for patients aged >70 years, respectively (P = 0.05). In multivariate analysis, Horn's index (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.50 to 2.77; P < 0.001), severe CDI (OR, 2.25; 95% CI, 1.15 to 4.41; P = 0.018), and continued use of antibiotics (OR, 2.65; 95% CI, 1.30 to 5.39; P = 0.0072) were identified as significant predictors of refractory CDI. Age was not identified as an independent risk factor for refractory CDI. Therefore, hospitalized elderly patients with CDI treated with metronidazole had increased refractory CDI rates likely due to increased underlying severity of illness, severity of CDI, and concomitant antibiotic use. These results may help identify patients that may benefit from alternative C. difficile treatments other than metronidazole.

  2. [Effect of different light regimens on the development of metabolic syndrome of aging rats].

    PubMed

    Vinogradova, I A

    2007-01-01

    During two years the influence of light regimens (standard lightning--LD, constant lightning--LL, natural lightning of the North-West of Russia--NL) and of melatonin on the development of metabolic syndrome of ageing LIO rats was studied. It was found out that during the process of ageing of rats kept in the conditions of the broken rhythm of day and night, different breaches of metabolism in the form of abdominal obesity, hyperinsulinemia, hypercholesterolemia, hyperglycemia, hyperbetalipoproteinemia and glycosuria occurred. These breaches can be considered to be metabolic syndrome or the syndrome of insulinoresistancy. The use of melatonin at night time starting from the rats' age of four months slowed down the age breaches of metabolism in rats. This fact proves indirectly the lack of this hormone in the conditions of natural lightning of the North-West of Russia.

  3. Effect of Major Royal Jelly Proteins on Spatial Memory in Aged Rats: Metabolomics Analysis in Urine.

    PubMed

    Chen, Di; Liu, Fang; Wan, Jian-Bo; Lai, Chao-Qiang; Shen, Li-Rong

    2017-04-10

    Royal jelly (RJ) produced by worker honeybees is the sole food for the queen bee throughout her life as well as the larvae of worker bees for the first 3 days after hatching. Supplementation of RJ in the diet has been shown to increase spatial memory in rodents. However, the key constituents in RJ responsible for improvement of cognitive function are unknown. Our objective was to determine if the major royal jelly proteins (MRJPs) extracted from RJ can improve the spatial memory of aged rats. The spatial memory assay using the Morris water maze test was administered once to rats after a 14-week feeding. Metabolomics analysis based on quadrupole time-of-flight mass spectrometry was conducted to examine the differences in compounds from urine. Aged male rats fed MRJPs showed improved spatial memory up to 48.5% when compared to the control male aged rats fed distilled water. The metabolite pattern of the MRJPs-fed aged rats was regressed to that of the young rats. Compounds altered by MRJPs were mapped to nicotinate and nicotinamide metabolism, cysteine taurine metabolism, and energy metabolism pathways. In summary, MRJPs may improve spatial memory and possess the potential for prevention of cognitive impairment via the cysteine and taurine metabolism and energy metabolism pathways in aged rats.

  4. Age-Related Changes in Antioxidative Enzyme Capacity in Tongue of Fischer 344 Rats

    PubMed Central

    Baek, Min-Kwan; Kim, Kyung-Ok; Kwon, Hyun-Jin; Kim, Yong-Woo; Woo, Joo-Hyun; Kim, Dong-Young

    2016-01-01

    Objectives Antioxidative enzyme efficiency changes in some organs with age. However, no study has been conducted on age-related antioxidant enzyme changes in tongue. In the present study, the authors investigated the activities of four antioxidative enzymes and their protein expressions in the tongues of young and old Fischer 344 rats. Methods Age-dependent changes in the enzyme activities of total superoxide dismutase (SOD), Mn-SOD, Cu/Zn-SOD, catalase (CAT), and glutathione peroxidase (GPx) were determined using chemical kits, and the protein expressions levels of these enzymes by Western blotting. The study was conducted using rats aged 7 months (the young group, n=8) and 22 months (the old group, n=8). Results Total SOD, Cu/Zn-SOD, and GPx activities in the tongues of old rats were lower than in young rats, and similarly, corresponding protein expressions were downregulated in old rats. On the other hand, although the protein expressions of Mn-SOD and CAT were lower in old rats, their enzyme activities were not. Conclusion The results of this study provide a possible mechanism for the tongue aging process, as in old Fischer 344 rats the antioxidant defense system was diminished with respect to enzyme activity levels and protein abundances. PMID:27334515

  5. Chronic stress induces ageing-associated degeneration in rat Leydig cells

    PubMed Central

    Wang, Fei-Fei; Wang, Qian; Chen, Yong; Lin, Qiang; Gao, Hui-Bao; Zhang, Ping

    2012-01-01

    Several studies have suggested that stress and ageing exert inhibitory effects on rat Leydig cells. In a pattern similar to the normal process of Leydig cell ageing, stress-mediated increases in glucocorticoid levels inhibit steroidogenic enzyme expression that then results in decreased testosterone secretion. We hypothesized that chronic stress accelerates the degenerative changes associated with ageing in Leydig cells. To test this hypothesis, we established a model of chronic stress to evaluate stress-induced morphological and functional alterations in Brown Norway rat Leydig cells; additionally, intracellular lipofuscin levels, reactive oxygen species (ROS) levels and DNA damage were assessed. The results showed that chronic stress accelerated ageing-related changes: ultrastructural alterations associated with ageing, cellular lipofuscin accumulation, increased ROS levels and more extensive DNA damage were observed. Additionally, testosterone levels were decreased. This study sheds new light on the idea that chronic stress contributes to the degenerative changes associated with ageing in rat Leydig cells in vivo. PMID:22609820

  6. Reissner's membrane and the spiral ligament in normal rats and those treated with ethacrynic acid

    NASA Technical Reports Server (NTRS)

    Ross, M. D.

    1981-01-01

    A description is presented of recent ultrastructural findings in Reissner's membrane and the spiral ligament in rats treated daily with ethacrynic acid during the 2nd and 3rd weeks of postnatal life, a period of final maturation of the inner ear and its fluids. A distension of Reissner's membrane in every cochlear turn, indicative of mild endolymphatic hydrops, was found to occur in animals that received a higher dose of ethacrynic acid. Ultrastructurally, the cytoplasm of the epithelial cells of Reissner's membrane showed increased electron density after treatment with ethacrynic acid. This increase was most pronounced in animals treated with a greater quantity of the drug. The epithelial cells had similar ultracellular features throughout except that the cells were much thinner in the region of maximal distension.

  7. Glial glucocorticoid receptors in aged Fisher 344 (F344) and F344/Brown Norway rats

    PubMed Central

    Kasckow, J; Xiao, C; Herman, JP

    2009-01-01

    Glucocorticoid receptors (GR) regulate glial function, and changes in astrocyte gene expression are implicated in age-related pathology. We evaluated changes in astroglial GR expression in two strains of rats – Fisher 344 (F344; 4, 12 and 24 months) and F344/Brown Norway strain (F344/BN; 4, 12 and 30 months). In both strains basal levels of corticosterone were higher in the oldest groups of rats. Age-related increases in GR (+) astrocytes but not the percent of astrocytes expressing GR were observed in the hippocampus CA1 region in F344 rats. Age-related decreases in CA1 GR (+) astrocytes and the percentage of GR (+) astrocytes were observed in the F344/BN strain only. Similar strain-specific changes were observed in the dentate gyrus. In the hypothalamic paraventricular nucleus: 1) F344 rats exhibited significant decreases in the overall number of glial profiles with age, 2) F344/BN rats exhibited decreases in the numbers of GR (+) astrocytes with aging and 3) the proportion of GR (+) astrocytes decreased in older F344/BN, but not F344 rats. Overall, the data demonstrate age- and strain-related alterations in GR astrocytic expression that may explain unique phenotypic differences in brain function observed in both strains. PMID:19249343

  8. Decreases in bone blood flow and bone material properties in aging Fischer-344 rats

    NASA Technical Reports Server (NTRS)

    Bloomfield, Susan A.; Hogan, Harry A.; Delp, Michael D.

    2002-01-01

    The purpose of this study was to quantify precisely aging-induced changes in skeletal perfusion and bone mechanical properties in a small rodent model. Blood flow was measured in conscious juvenile (2 months old), adult (6 months old), and aged (24 months old) male Fischer-344 rats using radiolabeled microspheres. There were no significant differences in bone perfusion rate or vascular resistance between juvenile and adult rats. However, blood flow was lower in aged versus adult rats in the forelimb bones, scapulas, and femurs. To test for functional effects of this decline in blood flow, bone mineral density and mechanical properties were measured in rats from these two age groups. Bone mineral density and cross-sectional moment of inertia in femoral and tibial shafts and the femoral neck were significantly larger in the aged versus adult rats, resulting in increased (+14%-53%) breaking strength and stiffness. However, intrinsic material properties at midshaft of the long bones were 12% to 25% lower in the aged rats. Although these data are consistent with a potential link between decreased perfusion and focal alterations in bone remodeling activity related to clinically relevant bone loss, additional studies are required to establish the mechanisms for this putative relationship.

  9. Accelerated infarct development, cytogenesis and apoptosis following transient cerebral ischemia in aged rats.

    PubMed

    Popa-Wagner, Aurel; Badan, Irina; Walker, Lary; Groppa, Sergiu; Patrana, Nicoleta; Kessler, Christof

    2007-03-01

    Old age is associated with a deficient recovery from stroke, but the cellular mechanisms underlying such phenomena are poorly understood. To address this issue, focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. Aged rats showed a delayed and suboptimal functional recovery in the post-stroke period. Using BrdU-labeling, quantitative immunohistochemistry and 3-D reconstruction of confocal images, we found that aged rats are predisposed to rapidly develop an infarct within the first few days after ischemia. The emergence of the necrotic zone is associated with a high rate of cellular degeneration, premature accumulation of proliferating BrdU-positive cells that appear to emanate from capillaries in the infarcted area, and a large number of apoptotic cells. With double labeling techniques, we were able to identify, for the first time, over 60% of BrdU-positive cells either as reactive microglia (45%), oligodendrocyte progenitors (17%), astrocytes (23%), CD8+ lymphocytes (4%), or apoptotic cells (<1%). Paradoxically, despite a robust reactive phenotype of microglia and astrocytes in aged rats, at 1-week post-stroke, the number of proliferating microglia and astrocytes was lower in aged rats than in young rats. Our data indicate that aging is associated with rapid infarct development and a poor prognosis for full recovery from stroke that is correlated with premature cellular proliferation and increased cellular degeneration and apoptosis in the infarcted area.

  10. Non-steroidal anti-inflammatory drugs attenuate the vascular responses in aging metabolic syndrome rats

    PubMed Central

    Rubio-Ruiz, María Esther; Pérez-Torres, Israel; Diaz-Diaz, Eulises; Pavón, Natalia; Guarner-Lans, Verónica

    2014-01-01

    Aim: Metabolic syndrome (MS) and aging are low-grade systemic inflammatory conditions, and inflammation is a key component of endothelial dysfunction. The aim of this study was to investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) upon the vascular reactivity in aging MS rats. Methods: MS was induced in young male rats by adding 30% sucrose in drinking water over 6, 12, and 18 months. When the treatment was finished, the blood samples were collected, and aortas were dissected out. The expression of COX isoenzymes and PLA2 in the aortas was analyzed using Western blot analysis. The contractile responses of aortic rings to norepinephrine (1 μmol/L) were measured in the presence or absence of different NSAIDs (10 μmol/L for each). Results: Serum levels of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β) in control rats were remained stable during the aging process, whereas serum IL-6 in MS rats were significantly increased at 12 and 18 months. The levels of COX isoenzyme and PLA2 in aortas from control rats increased with the aging, whereas those in aortas from MS rats were irregularly increased with the highest levels at 6 months. Pretreatment with acetylsalicylic acid (a COX-1 preferential inhibitor), indomethacin (a non-selective COX inhibitor) or meloxicam (a COX-2 preferential inhibitor) decreased NE-induced contractions of aortic rings from MS rats at all the ages, with meloxicam being the most potent. Acetylsalicylic acid also significantly reduced the maximum responses of ACh-induced vasorelaxation of aortic rings from MS rats, but indomethacin and meloxicam had no effect. Conclusion: NSAIDs can directly affect vascular responses in aging MS rats. Understanding the effects of NSAIDs on blood vessels may improve the treatment of cardiovascular diseases and MS in the elders. PMID:25263337

  11. Enhancement of memory consolidation by the histone deacetylase inhibitor sodium butyrate in aged rats.

    PubMed

    Blank, Martina; Werenicz, Aline; Velho, Luciana Azevedo; Pinto, Diana F; Fedi, Ana Cláudia; Lopes, Mark William; Peres, Tanara Vieira; Leal, Rodrigo Bainy; Dornelles, Arethuza S; Roesler, Rafael

    2015-05-06

    Here we show that a systemic injection of the histone deacetylase inhibitor (HDACi) sodium butyrate (NaB) immediately after training in a step-down inhibitory avoidance task produced an enhancement of memory consolidation that persisted across consecutive retention tests during 14 days in aged rats, while it did not significantly affect memory in young adults. Control aged and young adult rats showed comparable basal levels of memory retention. Our results suggest that HDACis can display memory-enhancing effects specific for aged animals, even in the absence of age-related memory impairment.

  12. Strontium is incorporated in different levels into bones and teeth of rats treated with strontium ranelate.

    PubMed

    Oliveira, Josianne P; Querido, William; Caldas, Rogério J; Campos, Andrea P C; Abraçado, Leida G; Farina, Marcos

    2012-09-01

    The aim of this study was to evaluate the strontium incorporation into specific bones and teeth of rats treated with strontium ranelate. The relative strontium levels [Sr/(Ca + Sr) ratio] were obtained by synchrotron radiation micro X-ray fluorescence. The incisor teeth were further examined by energy dispersive X-ray spectroscopy (EDS) in a scanning electron microscope. The isolated mineral phase was investigated by EDS in a transmission electron microscope and X-ray diffraction. The strontium content was markedly increased in animals treated with strontium ranelate, with different incorporation levels found among specific bones, regions within the same bone and teeth. The highest strontium levels were observed in the iliac crest, mandible and calvaria, while the lowest were observed in the femoral diaphysis, lumbar vertebrae, rib and alveolar bone. The strontium content was higher in the femoral neck than in the diaphysis. The strontium levels also varied within the alveolar bone. High levels of strontium were found in the incisor tooth, with values similar to those in the iliac crest. Strontium was observed in both enamel and dentin. The strontium content of the molar tooth was negligible. Strontium was incorporated into the mineral substance, with up to one strontium replacing one out of 10 calcium ions within the apatite crystal lattice. The mineral from treated animals presented increased lattice parameters, which might be associated to their bone strontium contents. In conclusion, the incorporation of strontium occurred in different levels into distinct bones, regions within the same bone and teeth of rats treated with strontium ranelate.

  13. Reproductive parameters of female Wistar rats treated with methylphenidate during development.

    PubMed

    Montagnini, Bruno Garcia; Silveira, Kennia Moura; Pierone, Bruna Caroline; de Azevedo Camim, Nathália; Anselmo-Franci, Janete Aparecida; de Fátima Paccola Mesquita, Suzana; Kiss, Ana Carolina Inhasz; Gerardin, Daniela Cristina Ceccatto

    2016-12-01

    Methylphenidate (MPH), a psychoactive agent that acts mainly by blocking the uptake of dopamine, is the main drug used to treat Attention Deficit Hyperactivity Disorder in children and adolescents. During development, important changes in brain architecture and plasticity occur, these changes, sensitive to exposure to stimulant drugs, are important in the control of GnRH secretion, influencing the release of sex hormones throughout the ovarian cycle. This study investigated the effects of repeated treatment with MPH during development on reproductive parameters of adult female rats. Wistar rats received MPH 2.5mg/kg, MPH 5.0mg/kg, or tap water (gavage) from postnatal day (PND) 21 to PND 60. From PND 75, one subgroup of females was selected for evaluation of estrous cycle, estradiol levels, weight of sexual organs, and histomorphological analysis of ovary follicles and uterus. In another subgroup, the sexual and maternal behaviors were evaluated at PND 90 and on lactational day 5, respectively. No significant alterations were observed in the MPH groups. This study demonstrated that repeated administration of MPH during the period corresponding to childhood to early adulthood does not interfere in the reproductive function of female rats in adulthood.

  14. [Effect of cadmium sulphate on the metabolism of carbohydrates in organism of rats of different ages].

    PubMed

    Shepel'ova, I A; Derkach, Ie A; Mel'nykova, N M

    2007-01-01

    The influence of cadmium sulfate on concentration of glucose, lactate, piruvate, alpha-ketoglutarate, malate, oxaloacetate in blood of 3-, 6- and 18-month-old poisoned rats was established the results of our researches. It was found, that poisoning of rats by cadmium sulfate causes the rise of concentration of glucose, metabolites of citric acid cycle and glycolysis in blood of animals of all age groups explored. The research results prove that in blood of 3-month-old poisoned rats the level of glycolysis and citric acid cycle activation is considerably higher in comparison with that of 6- and 18-month-old animals. As a result, a comparison of age-specific dynamics of changes of carbohydrate metabolism indices in the blood of rats, poisoned by cadmium showed that the organism of 3-month-old rats is more sensitive to toxic influence of cadmium.

  15. Glutamatergic signaling and low prodynorphin expression are associated with intact memory and reduced anxiety in rat models of healthy aging

    PubMed Central

    Ménard, Caroline; Quirion, Rémi; Bouchard, Sylvain; Ferland, Guylaine; Gaudreau, Pierrette

    2014-01-01

    The LOU/C/Jall (LOU) rat strain is considered a model of healthy aging due to its increased longevity, maintenance of stable body weight (BW) throughout life and low incidence of age-related diseases. However, aging LOU rat cognitive and anxiety status has yet to be investigated. In the present study, male and female LOU rat cognitive performances (6–42 months) were assessed using novel object recognition and Morris Water Maze tasks. Recognition memory remained intact in all LOU rats up to 42 months of age. As for spatial memory, old LOU rat performed similarly as young animals for learning acquisition, reversal learning, and retention. While LOU rat BW remained stable despite aging, 20-month-old ad-libitum-fed (OAL) male Sprague Dawley rats become obese. We determined if long-term caloric restriction (LTCR) prevents age-related BW increase and cognitive deficits in this rat strain, as observed in the obesity-resistant LOU rats. Compared to young animals, recognition memory was impaired in OAL but intact in 20-month-old calorie-restricted (OCR) rats. Similarly, OAL spatial learning acquisition was impaired but LTCR prevented the deficits. Exacerbated stress responses may favor age-related cognitive decline. In the elevated plus maze and open field tasks, LOU and OCR rats exhibited high levels of exploratory activity whereas OAL rats displayed anxious behaviors. Expression of prodynorphin (Pdyn), an endogenous peptide involved in stress-related memory impairments, was increased in the hippocampus of OAL rats. Group 1 metabotropic glutamate receptor 5 and immediate early genes Homer 1a and Arc expression, both associated with successful cognitive aging, were unaltered in aging LOU rats but lower in OAL than OCR rats. Altogether, our results, supported by principal component analysis and correlation matrix, suggest that intact memory and low anxiety are associated with glutamatergic signaling and low Pdyn expression in the hippocampus of non-obese aging rats. PMID

  16. Age-dependent Muscle Adaptation after Chronic Stretch-shortening Contractions in Rats.

    PubMed

    Rader, Erik P; Layner, KaylaN; Triscuit, Alyssa M; Chetlin, Robert D; Ensey, James; Baker, Brent A

    2016-01-01

    Age-related differences in contraction-induced adaptation have been well characterized especially for young and old rodent models but much less so at intermediate ages. Therefore, additional research is warranted to determine to what extent alterations in adaptation are due to maturation versus aging per se. The purpose of our study was to evaluate muscles of Fisher 344XBrown Norway rats of various ages following one month of exposure to stretch-shortening contractions (SSCs). With exposure, muscles mass increased by ~10% for 27 and 30 month old rats vs. ~20% for 3 and 6 month old rats (P < 0.05). For 3 month old rats, maximum isometric force and dynamic peak force increased by 22 ± 8% and 27 ± 10%, respectively (P < 0.05). For 6 month old rats, these forces were unaltered by exposure and positive work capacity diminished by 27 ± 2% (P = 0.006). By 30 months of age, age-related deficits in maximum isometric force, peak force, negative work, and positive work were apparent and SSC exposure was ineffective at counteracting such deficits. Recovery from fatigue was also tested and exposure-induced improvements in fatigue recovery were indicated for 6 month old rats and to a lesser extent for 3 month old rats whereas no such effect was observed for older rats. Alterations in fatigue recovery were accompanied by evidence of substantial type IIb to IIx fiber type shifting. These results highlight the exceptional adaptive capacity for strength at a young age, the inclination for adaptation in fatigue recovery at early adulthood, and diminished adaptation for muscle performance in general beginning at late adulthood. Such findings motivate careful investigation to determine appropriate SSC exposures at all stages of life.

  17. Methylprednisolone Protects Cardiac Pumping Mechanics from Deteriorating in Lipopolysaccharide-Treated Rats.

    PubMed

    Ko, Ya-Hui; Tsai, Ming-Shian; Chang, Ru-Wen; Chang, Chun-Yi; Wang, Chih-Hsien; Wu, Ming-Shiou; Liang, Jin-Tung; Chang, Kuo-Chu

    2015-01-01

    It has been shown that a prolonged low-dose corticosteroid treatment attenuates the severity of inflammation and the intensity and duration of organ system failure. In the present study, we determined whether low-dose methylprednisolone (a synthetic glucocorticoid) can protect male Wistar rats against cardiac pumping defects caused by lipopolysaccharide-induced chronic inflammation. For the induction of chronic inflammation, a slow-release ALZET osmotic pump was subcutaneously implanted to infuse lipopolysaccharide (1 mg kg(-1) d(-1)) for 2 weeks. The lipopolysaccharide-challenged rats were treated on a daily basis with intraperitoneal injection of methylprednisolone (5 mg kg(-1) d(-1)) for 2 weeks. Under conditions of anesthesia and open chest, we recorded left ventricular (LV) pressure and ascending aortic flow signals to calculate the maximal systolic elastance (E max) and the theoretical maximum flow (Q max), using the elastance-resistance model. Physically, E max reflects the contractility of the myocardium as an intact heart, whereas Q max has an inverse relationship with the LV internal resistance. Compared with the sham rats, the cardiodynamic condition was characterized by a decline in E max associated with the increased Q max in the lipopolysaccharide-treated rats. Methylprednisolone therapy increased E max, which suggests that the drug may have protected the contractile status from deteriorating in the inflamed heart. By contrast, methylprednisolone therapy considerably reduced Q max, indicating that the drug may have normalized the LV internal resistance. In parallel, the benefits of methylprednisolone on the LV systolic pumping mechanics were associated with the reduced cardiac levels of negative inotropic molecules such as peroxynitrite, malondialdehyde, and high-mobility group box 1 protein. Based on these data, we suggested that low-dose methylprednisolone might prevent lipopolysaccharide-induced decline in cardiac intrinsic contractility and LV

  18. Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-β Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus.

    PubMed

    Hong, Yan; Shen, Chao; Yin, Qingqing; Sun, Menghan; Ma, Yingjuan; Liu, Xueping

    2016-05-01

    An increased level of advanced glycation end products (AGEs) is observed in brains of patients with Alzheimer's disease (AD). AGEs and receptor for AGEs (RAGE) play important roles in the pathogenesis of AD. FPS-ZM1 is a high-affinity RAGE-specific blocker that inhibits amyloid-β binding to RAGE, neurological damage and inflammation in the APP(sw/0) transgenic mouse model of AD. FPS-ZM1 is not toxic to mice and can easily cross the blood-brain barrier. In this study, an AGEs-RAGE-activated rat model were established by intrahippocampal injection of AGEs, then these rats were treated with intraperitoneal administration of FPS-ZM1 and the possible neuroprotective effects were investigated. We found that AGEs administration induced an-regulation of Abeta production, inflammation, and oxidative stress, and an increased escape latency of rats in the Morris water maze test, all of these are significantly reduced by FPS-ZM1 treatment. Our results suggest that the AGEs-RAGE pathway is responsible for cognitive deficits, and therefore may be a potential treatment target. FPS-ZM1 might be a novel therapeutic agent to treat AD patients.

  19. Age-related changes in susceptibility of rat brain slice cultures including hippocampus to encephalomyocarditis virus

    PubMed Central

    Su, Weiping; Ueno-Yamanouchi, Aito; Uetsuka, Koji; Nakayama, Hiroyuki; Doi, Kunio

    1999-01-01

    Replication of the D variant of encephalomyocarditis virus (EMC-D) and its cytopathic effects were studied in the brain slice cultures including hippocampus (hippocampal slice) obtained from postnatal 1-, 4-, 7-, 14-, 28-and 56-day-old Fischer 344 rats. At 0, 12, 24, 36 and 48 h after infection, virus titres of the slices and culture media were assayed. Viral replication was observed in cultures from 1-to 28-day-old rats, and the highest titre was recorded in the slice and culture medium from the youngest rat. The peak of virus titre decreased with age and no distinct viral replication was observed in the cultures from 56-day-old rats. Light microscopy revealed that degenerative and necrotic changes appeared in the infected hippocampal slices from 1- to 28-day-old rats, and the changes became less prominent with age. In situ hybridization and indirect immunofluorescence staining showed that positive signals of viral RNA and antigen were prominent in younger rats and decreased with age. These results suggest that an age-related decrease in the susceptibility of rat brain to EMC-D is less related to the maturation of the immune system but possibly to that of the neurone. PMID:10632784

  20. Decreased oral colonization of Streptococcus mutans during aging of Sprague-Dawley rats.

    PubMed

    Van Houte, J; Upeslacis, V N; Edelstein, S

    1977-04-01

    The colonization by streptomycin-resistant Streptococcus mutans strains of the teeth of conventional and ex-germfree Sprague-Dawley rats of various ages fed either a high-sucrose or a high-glucose diet was studied. Bacterial colonization occurred with increasingly greater difficulty as the rats became older. This was observed in studies of the implantation of the test organism after oral inoculation with different cell numbers as well as its transmission between infected and uninfected rats. With rat fed sucrose diet, the effect of age could not be demonstrated until they were age 3 months or older; the results from rats fed a glucose diet suggest that changes may already have occurred early after weaning. Changes in susceptibility to colonization during aging manifested themselves as a decrease in the proportions of rats which became infected as well as lower population levels in infected rats. The possible mechanism(s) involved as well as the possible significance of the findings was discussed.

  1. Acute locomotor effects of fluoxetine, sertraline, and nomifensine in young versus aged Fischer 344 rats.

    PubMed

    Stanford, John A; Currier, Theresa D; Gerhardt, Greg A

    2002-01-01

    Spontaneous locomotor activity was measured in young (6-8 months) and aged (24-26 months) Fischer 344 (F344) rats. Following habituation to the activity monitors, aged rats demonstrated significantly diminished motor activity as quantified by total distance traveled and vertical activity. Movement speed did not differ significantly between the two groups. Following habituation, rats were administered acute doses of fluoxetine, sertraline, or nomifensine (1.0, 3.0, and 10.0 mg/kg). Fluoxetine diminished all three behavioral measures in the young rats, while in the old rats, fluoxetine's effects were limited to a robust attenuation of vertical activity. Sertraline decreased movement speed and vertical activity, but not total distance traveled, in the young rats. Unlike fluoxetine, sertraline produced no significant effects on any of the three behavioral variables in the old rats. Nomifensine increased behavioral scores for both age groups. The results are discussed in relation to acute motor side effects of selective serotonin reuptake inhibitors (SSRIs) in motor-impaired aged individuals, as these effects may influence their eventual use in the clinic.

  2. Gene expression profiling in rat liver treated with compounds inducing phospholipidosis

    SciTech Connect

    Hirode, Mitsuhiro |; Ono, Atsushi |; Miyagishima, Toshikazu; Nagao, Taku; Ohno, Yasuo; Urushidani, Tetsuro |

    2008-06-15

    We have constructed a large-scale transcriptome database of rat liver treated with various drugs. In an effort to identify a biomarker for diagnosis of hepatic phospholipidosis, we extracted 78 probe sets of rat hepatic genes from data of 5 drugs, amiodarone, amitriptyline, clomipramine, imipramine, and ketoconazole, which actually induced this phenotype. Principal component analysis (PCA) using these probes clearly separated dose- and time-dependent clusters of treated groups from their controls. Moreover, 6 drugs (chloramphenicol, chlorpromazine, gentamicin, perhexiline, promethazine, and tamoxifen), which were reported to cause phospholipidosis but judged as negative by histopathological examination, were designated as positive by PCA using these probe sets. Eight drugs (carbon tetrachloride, coumarin, tetracycline, metformin, hydroxyzine, diltiazem, 2-bromoethylamine, and ethionamide), which showed phospholipidosis-like vacuolar formation in the histopathology, could be distinguished from the typical drugs causing phospholipidosis. Moreover, the possible induction of phospholipidosis was predictable by the expression of these genes 24 h after single administration in some of the drugs. We conclude that these identified 78 probe sets could be useful for diagnosis of phospholipidosis, and that toxicogenomics would be a promising approach for prediction of this type of toxicity.

  3. Spinal cord injury in rats treated using bone marrow mesenchymal stem-cell transplantation.

    PubMed

    Chen, Yu-Bing; Jia, Quan-Zhang; Li, Dong-Jun; Sun, Jing-Hai; Xi, Shuang; Liu, Li-Ping; Gao, De-Xuan; Jiang, Da-Wei

    2015-01-01

    The aim of this study was to observe the effects of bone marrow mesenchymal stem-cell transplantation (BMSCs) in repairing acute spinal cord damage in rats and to examine the potential beneficial effects. 192 Wistar rats were randomized into 8 groups. Spinal cord injury was created. Behavior and limb functions were scored. Repairing effects of BMSCs transplantation was evaluated and compared. In vitro 4',6-diamidino-2-phenylindole (DAPI)-tagged BMSCs were observed, and whether they migrated to the area of spinal cord injury after intravenous tail injection was investigated. The expression of neuron-specific protein (NSE) on BMSCs was examined. Fifteen days after transplantation, the BMSCs-treated groups scored significantly higher in limb function tests than the untreated group. Pathological sections of the bone marrow after operation showed significant recovery in treated groups in comparison to the control group. After transplantation, small amounts of fluorescent-tagged BMSCs can be found in the blood vessels in the area of spinal cord injury, and fluorescent-tagged BMSCs were diffused in extravascular tissues, whereas the DAPI-tagged BMSCs could not be detected,and BrdU/NSE double-labeled cells were found in the injured marrow. BMSCs improve behavioral responses and can repair spinal cord injuries by migrating to the injured area, where they can differentiate into neurons.

  4. Insular neural system controls decision-making in healthy and methamphetamine-treated rats

    PubMed Central

    Mizoguchi, Hiroyuki; Katahira, Kentaro; Inutsuka, Ayumu; Fukumoto, Kazuya; Nakamura, Akihiro; Wang, Tian; Nagai, Taku; Sato, Jun; Sawada, Makoto; Ohira, Hideki; Yamanaka, Akihiro; Yamada, Kiyofumi

    2015-01-01

    Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders exhibit altered decision-making patterns, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-treated rats chose a high-risk/high-reward option more frequently and assigned higher value to high returns than control rats, suggestive of changes in decision-making choice strategy. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-treated animals. Pharmacological studies, together with in vivo microdialysis, showed that the insular neural system played a crucial role in decision-making. Moreover, manipulation of INS activation using designer receptor exclusively activated by designer drug technology resulted in alterations to decision-making. Our findings suggest that the INS is a critical region involved in decision-making and that insular neural dysfunction results in risk-taking behaviors associated with altered decision-making. PMID:26150496

  5. In Vivo Evaluation of Transdermal Iodide Microemulsion for Treating Iodine Deficiency Using Sprague Dawley Rats.

    PubMed

    Alayoubi, Alaadin; Sullivan, Ryan D; Lou, Hao; Patel, Hemlata; Mandrell, Timothy; Helms, Richard; Almoazen, Hassan

    2016-06-01

    The objective of this study was to evaluate the transdermal efficiency of iodide microemulsion in treating iodine deficiency using rats as an animal model. Animals were fed either iodine-deficient diet (20 μg/kg iodide) or control diet (200 μg/kg iodide) over a 17-month period. At month 14, iodide microemulsion was applied topically in iodine-deficient group and physiological evaluations of thyroid gland functions were characterized by monitoring the thyroid hormones (T3, T4), thyroid-stimulating hormone (TSH), iodide ion excretion in urine, and the overall rat body weights in both groups. Moreover, morphological evaluations of thyroid gland before and after treatment were performed by ultrasound imaging and through histological assessment. Prior to microemulsion treatment, the levels of T3, T4, and TSH in iodine-deficient group were statistically significant as compared to that in the control group. The levels of T3 and T4 increased while TSH level decreased significantly in iodine-deficient group within the first 4 weeks of treatment. After treatment, iodide concentration in urine increased significantly. There was no statistical difference in weight between the two groups. Ultrasound imaging and histological evaluations showed evidence of hyperplasia in iodine-deficient group. Topical iodide microemulsion has shown a promising potential as a novel delivery system to treat iodine deficiency.

  6. Influence of capsaicin on fluctuation of digoxin pharmacokinetics in lipopolysaccharide-treated rats.

    PubMed

    Kato, Ryuji; Higashitani, Akina; Irie, Takako; Kusukawa, Yugo; Yamamoto, Yu; Nakagawa, Machiko; Urashima, Yoko; Nagata, Makoto; Hayashi, Tetsuya; Ijiri, Yoshio; Tanaka, Kazuhiko

    2012-08-01

    In the present study, we investigated the influence of Cap on digoxin pharmacokinetics in lipopolysaccharide (LPS)-treated rats. After the oral administration of digoxin (0.1 mg/kg), the area under the plasma concentration-time curve (AUC) of digoxin increased significantly until day 3 after LPS treatment. In the LPS + Cap group, the recovery period of AUC was shortened to 3 days. On days 5 and 7, the maximum plasma concentrations decreased significantly as compared to the control group. The bioavailability of digoxin in LPS group was higher than that in the LPS + Cap group. The hepatic cytochrome P450 (CYP) 3A2 content decreased significantly until day 5 after LPS administration, but it returned to the control level until 5 days in the LPS + Cap group. Hepatic CYP3A2 mRNA expression of LPS group decreased significantly until day 3, but it returned to the control level on day 3 and increased significantly until day 7 in the LPS + Cap group. The DNA-binding activity of pregnane X receptor (PXR) was increased on days 3-7 in the Cap and LPS + Cap group. Cap decreased the absorption of digoxin by inducing CYP3A2 mRNA expression via indirect activation of PXR in LPS-treated rats.

  7. The fractionation of isolated liver cells from normal and carcinogen treated rats.

    PubMed Central

    Horsfall, A. C.; Ketterer, B.

    1976-01-01

    Suspensions of isolated cells were obtained from livers of normal rats and rats treated with the hepatocarcinogen N,N-dimethyl-4-aminoazobenzene. Differential centrifugation of dispersed cells yielded a large parenchymal cell fraction and a small non-parencymal cell fraction. By means of rate sedimentation through different concnetrations of Ficoll, parenchymal cells were separated into cells with fast, intermediate and slow rates of sedimentation. Periods of sedimentation were brief and centrifugal forces low in order to retain the best possible state of preservation of cells. DNA, RNA and protein contents, acid phosphatase activity, cell size and nucleocytoplasmic ratios of parenchymal cells sedimenting at fast, intermediate and slow rates were measured. Cell fractions from normal livers had properties suggesting that faster sedimenting cells were derived from the centre and middle of the lobule whereas slowly sedimenting cells were periportal; however, much of the periportal cell population remained in a residue of undissociated tissue. Compared with normal cells, carcinogen treated cells appeared to fractionate according to different physical and chemical criteria and could not be related to their origin within the liver lobule. They were smaller, slower sedimenting, lower in protein and RNA content and acid phosphatase activity. The tissue residue contained abnromal histological structures. PMID:814912

  8. Enhanced feminine sexual behavior and infertility in female rats prenatally treated with an antiestrogen.

    PubMed

    Vega Matuszczyk, Josefa

    2003-07-01

    An attempt to elucidate the possible role of prenatal estrogen on the development of feminine sexual behavior and reproductive function was made by treating females with the antiestrogen CI628 prenatally on days 13-19. Control females were prenatally treated with saline or remained untreated. The animals were delivered by caesarian section on day 22 of pregnancy and placed with foster mothers whose newborn pups had been previously removed. Intact peripubertal females in each treatment group were observed for several reproductive measures, including the capacity to become pregnant. Other females were ovariectomized in adulthood and treated with estradiol benzoate (EB) (1, 1.5, 2 or 4 micro g/rat) and 0.5 mg progesterone and tested for receptivity, proceptivity and sexual partner preference. Two weeks after the completion of these tests, the females were injected daily for 7 days with 0.25 mg testosterone and tested for sexual partner preference and mounting behavior. The results obtained showed accelerated vaginal opening, and infertility in the antiestrogen-treated intact females and enhanced receptivity and proceptivity in response to 1 micro g EB in the antiestrogen ovariectomized females. Sexual partner preference and mounting behavior did not differ between groups. These results suggest an involvement of prenatal estrogen on the development of female reproductive function, but not on behavioral differentiation.

  9. Isolation of pseudoperoxidase-positive astrocyte granules from intact rat brain and cysteamine-treated neuroglial cultures.

    PubMed

    Cissé, S; Schipper, H M

    1993-06-25

    A subpopulation of astrocytes in periventricular regions of aging brain and in cysteamine (CSH)-treated glial cultures contain autofluorescent cytoplasmic granules that exhibit an affinity for Gomori's chrome alum hematoxylin (CAH), and non-enzymatic peroxidase activity. Although shown to be histochemically distinct from lipofuscin, the lack of pure preparations of these glial inclusions has hindered the elucidation of their precise chemical constituents. Using sucrose gradient fractionation and density centrifugation on percoll, we obtained enriched preparations of astrocyte cytoplasmic granules from intact rat brain and CSH-treated astrocyte cultures. The presence and relative purity of these inclusions were confirmed by laser scanning confocal microscopy for red autofluorescent granules, diaminobenzidine histochemistry for non-enzymatic peroxidase activity and chrome alum hematoxylin (Gomori) staining. In the enriched fractions, the smaller granules (0.5-4.0 microns) were spherical and weakly autofluorescent, whereas larger inclusions (5.0-10.0 microns) tended to be intensely autofluorescent and pleomorphic. As in situ, the purified material was argyrophilic and did not stain for lipids. Isolation of these astrocytic inclusions should permit a more thorough characterization of their biochemical contents.

  10. Supplementation of Citrus maxima Peel Powder Prevented Oxidative Stress, Fibrosis, and Hepatic Damage in Carbon Tetrachloride (CCl4) Treated Rats.

    PubMed

    Chowdhury, Mohammed Riaz Hasan; Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah; Hossain, Hemayet; Alam, Md Ashraful

    2015-01-01

    Citrus maxima peel is rich in natural phenolic compounds and has a long use in the traditional medicine. HPLC-DAD analysis on Citrus maxima peel powder exhibited the presence of various phenolic compounds such as caffeic acid and (-)-epicatechin. To determine the plausible hepatoprotective activity of Citrus maxima peel powder, we used carbon tetrachloride (CCl4) treated rat model. Liver damage in rats was confirmed by measuring the AST, ALT, and ALP enzyme activities. In addition, lipid peroxidation products (MDA), nitric oxide, advanced protein oxidation products level (APOP), and catalase activities were also analyzed along with the histological profiling for the inflammatory cell infiltration, collagen, and iron deposition in liver. Dietary supplementation of Citrus maxima peel powder exhibited significant reduction of serum AST, ALT, and ALP activities in carbon tetrachloride treated rats. Moreover, Citrus maxima peel powder also showed a significant reduction of the oxidative stress markers (MDA, NO, and APOP level) and restored the catalase activity in CCl4 treated rats. Histological examination of the liver section revealed reduced inflammatory cells infiltration, collagen, and iron deposition in CCl4 treated rats. The results from this study demonstrated that Citrus maxima peel powder produced significant hepatoprotective action in CCl4 administered rats.

  11. Topical application of dressing with amino acids improves cutaneous wound healing in aged rats.

    PubMed

    Corsetti, Giovanni; D'Antona, Giuseppe; Dioguardi, Francesco Saverio; Rezzani, Rita

    2010-09-01

    The principal goal in treating surgical and non-surgical wounds, in particular for aged skin, is the need for rapid closure of the lesion. Cutaneous wound healing processes involve four phases including an inflammatory response with the induction of pro-inflammatory cytokines. If inflammation develops in response to bacterial infection, it can create a problem for wound closure. Reduced inflammation accelerates wound closure with subsequent increased fibroblast function and collagen synthesis. On the contrary, prolonged chronic inflammation results in very limited wound healing. Using histological and immunohistochemical techniques, we investigated the effects of a new wound dressing called Vulnamin that contains four essential amino acids for collagen and elastin synthesis plus sodium ialuronate (Na-Ial), compared with Na-Ial alone, in closure of experimental cutaneous wounds of aged rats. Our results showed that the application of Vulnamin dressings modulated the inflammatory response with a reduction in the number of inflammatory cells and inducible nitric oxide synthase (iNOS) immunolocalisation, while increasing endothelial nitric oxide synthase (eNOS) and transforming growth factor-beta1 (TGF-beta1) immunolocalisation. Furthermore, the dressing increased the distribution density of fibroblasts and aided the synthesis of thin collagen fibers resulting in a reduction in healing time. The nutritive approach using this new wound dressing can provide an efficacious and safe strategy to accelerate wound healing in elderly subjects, simplifying therapeutic procedures and leading to an improved quality of life.

  12. Growth hormone and melatonin prevent age-related alteration in apoptosis processes in the dentate gyrus of male rats.

    PubMed

    Kireev, R A; Vara, E; Tresguerres, J A F

    2013-08-01

    It has been suggested that the age-related decrease in the number of neurons in the hippocampus that leads to alterations in brain function, may be associated with an increase in apoptosis due to the reduced secretion of growth hormone (GH) and/or melatonin in old animals. In order to investigate this possibility, male Wistar rats of 22 months of age were divided into three groups. One group remained untreated and acted as the control group. The second was treated with growth hormone (hGH) for 10 weeks (2 mg/kg/d sc) and the third was subjected to melatonin treatment (1 mg/kg/d) in the drinking water for the same time. A group of 2-months-old male rats was used as young controls. All rats were killed by decapitation at more than 24 month of age and dentate gyri of the hippocampi were collected. Aging in the dentate gyrus was associated with an increase in apoptosis promoting markers (Bax, Bad and AIF) and with the reduction of some anti-apoptotic ones (XIAP, NIAP, Mcl-1). Expressions of sirtuin 1 and 2 (SIRT1 and 2) as well as levels of HSP 70 were decreased in the dentate gyrus of old rats. GH treatment was able to reduce the pro/anti-apoptotic ratio to levels observed in young animals and also to increase SIRT2. Melatonin reduced also expression of pro-apoptotic genes and proteins (Bax, Bad and AIF), and increased levels of myeloid cell leukemia-1 proteins and SIRT1. Both treatments were able to reduce apoptosis and to enhance survival markers in this part of the hippocampus.

  13. Estrogen administration modulates hippocampal GABAergic subpopulations in the hippocampus of trimethyltin-treated rats

    PubMed Central

    Corvino, Valentina; Di Maria, Valentina; Marchese, Elisa; Lattanzi, Wanda; Biamonte, Filippo; Michetti, Fabrizio; Geloso, Maria Concetta

    2015-01-01

    Given the well-documented involvement of estrogens in the modulation of hippocampal functions in both physiological and pathological conditions, the present study investigates the effects of 17-beta estradiol (E2) administration in the rat model of hippocampal neurodegeneration induced by trimethyltin (TMT) administration (8 mg/kg), characterized by loss of pyramidal neurons in CA1, CA3/hilus hippocampal subfields, associated with astroglial and microglial activation, seizures and cognitive impairment. After TMT/saline treatment, ovariectomized animals received two doses of E2 (0.2 mg/kg intra-peritoneal) or vehicle, and were sacrificed 48 h or 7 days after TMT-treatment. Our results indicate that in TMT-treated animals E2 administration induces the early (48 h) upregulation of genes involved in neuroprotection and synaptogenesis, namely Bcl2, trkB, cadherin 2 and cyclin-dependent-kinase-5. Increased expression levels of glutamic acid decarboxylase (gad) 67, neuropeptide Y (Npy), parvalbumin, Pgc-1α and Sirtuin 1 genes, the latter involved in parvalbumin (PV) synthesis, were also evident. Unbiased stereology performed on rats sacrificed 7 days after TMT treatment showed that although E2 does not significantly influence the extent of TMT-induced neuronal death, significantly enhances the TMT-induced modulation of GABAergic interneuron population size in selected hippocampal subfields. In particular, E2 administration causes, in TMT-treated rats, a significant increase in the number of GAD67-expressing interneurons in CA1 stratum oriens, CA3 pyramidal layer, hilus and dentate gyrus, accompanied by a parallel increase in NPY-expressing cells, essentially in the same regions, and of PV-positive cells in CA1 pyramidal layer. The present results add information concerning the role of in vivo E2 administration on mechanisms involved in cellular plasticity in the adult brain. PMID:26594149

  14. Modifications in Bone Matrix of Estrogen-Deficient Rats Treated with Intermittent PTH

    PubMed Central

    Campos, Jenifer Freitas; Katchburian, Eduardo; de Medeiros, Valquíria Pereira; Nader, Helena Bonciani; Nonaka, Keico Okino; Plotkin, Lilian Irene; Reginato, Rejane Daniele

    2015-01-01

    Bone matrix dictates strength, elasticity, and stiffness to the bone. Intermittent parathyroid hormone (iPTH), a bone-forming treatment, is widely used as a therapy for osteoporosis. We investigate whether low doses of intermittent PTH (1-34) change the profile of organic components in the bone matrix after 30 days of treatment. Forty 6-month-old female Wistar rats underwent ovariectomy and after 3 months received low doses of iPTH administered for 30 days: daily at 0.3 µg/kg/day (PTH03) or 5 µg/kg/day (PTH5); or 3 times per week at 0.25 µg/kg/day (PTH025). After euthanasia, distal femora were processed for bone histomorphometry, histochemistry for collagen and glycosaminoglycans, biochemical quantification of sulfated glycosaminoglycans, and hyaluronan by ELISA and TUNEL staining. Whole tibiae were used to estimate the bone mineral density (BMD). Histomorphometric analysis showed that PTH5 increased cancellous bone volume by 6% over vehicle-treated rats. In addition, PTH5 and PTH03 increased cortical thickness by 21% and 20%, respectively. Tibial BMD increased in PTH5-treated rats and this group exhibited lower levels of chondroitin sulfate; on the other hand, hyaluronan expression was increased. Hormonal administration in the PTH5 group led to decreased collagen maturity. Further, TUNEL-positive osteocytes were decreased in the cortical compartment of PTH5 whereas administration of PTH025 increased the osteocyte death. Our findings suggest that daily injections of PTH at low doses alter the pattern of organic components from the bone matrix, favoring the increase of bone mass. PMID:25695082

  15. Effect of Age, Estrogen Status, and Late-Life GPER Activation on Cardiac Structure and Function in the Fischer344×Brown Norway Female Rat.

    PubMed

    Alencar, Allan K; da Silva, Jaqueline S; Lin, Marina; Silva, Ananssa M; Sun, Xuming; Ferrario, Carlos M; Cheng, Cheping; Sudo, Roberto T; Zapata-Sudo, Gisele; Wang, Hao; Groban, Leanne

    2017-02-01

    Age-associated changes in cardiac structure and function, together with estrogen loss, contribute to the progression of heart failure with preserved ejection fraction in older women. To investigate the effects of aging and estrogen loss on the development of its precursor, asymptomatic left ventricular diastolic dysfunction, echocardiograms were performed in 10 middle-aged (20 months) and 30 old-aged (30 months) female Fischer344×Brown-Norway rats, 4 and 8 weeks after ovariectomy (OVX) and sham procedures (gonads left intact). The cardioprotective potential of administering chronic G1, the selective agonist to the new G-protein-coupled estrogen receptor (GPER), was further evaluated in old rats (Old-OVX+G1) versus age-matched, vehicle-treated OVX and gonadal intact rats. Advanced age and estrogen loss led to decreases in myocardial relaxation and elevations in filling pressure, in part, due to reductions in phosphorylated phospholamban and increases in cardiac collagen deposition. Eight weeks of G-protein-coupled estrogen receptor activation in Old-OVX+G1 rats reversed the adverse effects of age and estrogen loss on myocardial relaxation through increases in sarcoplasmic reticulum Ca(2+) ATPase expression and reductions in interstitial fibrosis. These findings may explain the preponderance of heart failure with preserved ejection fraction in older postmenopausal women and provide a promising, late-life therapeutic target to reverse or halt the progression of left ventricular diastolic dysfunction.

  16. Effects of ageing on the biomechanical properties of rat articular cartilage.

    PubMed

    Wang, L; Kalu, D N; Banu, J; Thomas, J B; Gabriel, N; Athanasiou, K

    2006-05-01

    Previous studies have demonstrated that male Sprague Dawley (SD) rats experience age-related bone loss with the same characteristics as that in ageing men. As articular cartilage, like bone, is a critical component of the health and function of the musculoskeletal system, the authors hypothesized that articular cartilage in the untreated male SD rats could be a suitable model for studying the age-related deterioration of articular cartilage in men. To test this hypothesis, male SD rats were killed at between 6 and 27 months. The right femur of each rat was removed. The effects of ageing on the structural integrity of the distal femoral articular cartilage were studied by biomechanical testing with a creep indentation apparatus. The aggregate modulus, Poisson's ratio, permeability, thickness, and percentage recovery of articular cartilage were determined using finite element/non-linear optimization modelling. No significant differences were observed in these biomechanical properties of the distal femoral articular cartilage as a function of age. Therefore, untreated male SD rats appear to be unsuitable for studying the age-related changes of articular cartilage as they occur in men. However, and more intriguingly, it is also possible that ageing does not affect the biomechanical properties of articular cartilage in the absence of cartilage pathology.

  17. Downregulation of caveolin-1 contributes to the synaptic plasticity deficit in the hippocampus of aged rats

    PubMed Central

    Liu, Yang; Liang, Zhanhua; Liu, Jing; Zou, Wei; Li, Xiaoyan; Wang, Yachen; An, Lijia

    2013-01-01

    Caveolin-1 is involved in the regulation of synaptic plasticity, but the relationship between its pression and cognitive function during aging remains controversial. To explore the relationship be-tween synaptic plasticity in the aging process and changes in learning and memory, we examined caveolin-1 expression in the hippocampus, cortex and cerebellum of rats at different ages. We also examined the relationship between the expression of caveolin-1 and synaptophysin, a marker of synaptic plasticity. Hippocampal caveolin-1 and synaptophysin expression in aged (22–24 month old) rats was significantly lower than that in young (1 month old) and adult (4 months old) rats. pression levels of both proteins were significantly greater in the cortex of aged rats than in that of young or adult rats, and levels were similar between the three age groups in the cerebellum. Linear regression analysis revealed that hippocampal expression of synaptophysin was associated with memory and learning abilities. Moreover, synaptophysin expression correlated positively with caveolin-1 expression in the hippocampus, cortex and cerebellum. These results confirm that caveolin-1 has a regulatory effect on synaptic plasticity, and suggest that the downregulation of hippocampal caveolin-1 expression causes a decrease in synaptic plasticity during physiological aging. PMID:25206583

  18. Taurine enhances the sexual response and mating ability in aged male rats.

    PubMed

    Yang, Jiancheng; Lin, Shumei; Feng, Ying; Wu, Gaofeng; Hu, Jianmin

    2013-01-01

    It has been demonstrated that taurine is abundant in male reproductive organs, and can be biosynthesized by testis, but the taurine concentration will reduce with aging. The levels of serum LH, T, NOS, and NO were found to be obviously increased by taurine supplementation in aged rats in our previous study. In addition, aging will result in a significant decline in sexual response and function, which may be attributed to the androgen deficiency. Furthermore, NO has been proposed as a crucial mediator of penile erection. That makes us hypothesize that there is potential relationship between taurine decline and erection dysfunction in aged males. So the primary aim of the present study was to investigate the effect of taurine on male sexuality in rats. Taurine was offered in water to male aged (20 months old) rats for 110 days. The effects of taurine on the sexual response, mating ability, levels of serum reproductive hormones, and penile NOS and NO levels were investigated. The results showed that taurine can significantly reduce the EL and ML; obviously increase the ERF, MF, IF, and EJF; stimulate the secretion of GnRH, LH, and T; and elevate penis NOS and NO level in aged rats. The results indicated that taurine can enhance the sexual response and mating ability in aged male rats by increasing the level of testosterone and NO, but the exact mechanism of which needs to be further investigated.

  19. Ultrastructural features of sprouted mossy fiber synapses in kindled and kainic acid-treated rats.

    PubMed

    Cavazos, José E; Zhang, Peisu; Qazi, Romena; Sutula, Thomas P

    2003-04-07

    The mossy fiber pathway in the dentate gyrus undergoes sprouting and synaptic reorganization in response to seizures. The types of new synapses, their location and number, and the identity of their postsynaptic targets determine the functional properties of the reorganized circuitry. The goal of this study was to characterize the types and proportions of sprouted mossy fiber synapses in kindled and kainic acid-treated rats. In normal rats, synapses labeled by Timm histochemistry or dynorphin immunohistochemistry were rarely observed in the supragranular region of the inner molecular layer when examined by electron microscopy. In epileptic rats, sprouted mossy fiber synaptic terminals were frequently observed. The ultrastructural analysis of the types of sprouted synapses revealed that 1) in the supragranular region, labeled synaptic profiles were more frequently axospinous than axodendritic, and many axospinous synapses were perforated; 2) sprouted mossy fiber synaptic terminals formed exclusively asymmetric, putatively excitatory synapses with dendritic spines and shafts in the supragranular region and with the soma of granule cells in the granule cell layer; 3) in contrast to the large sprouted mossy fiber synapses in resected human epileptic hippocampus, the synapses formed by sprouted mossy fibers in rats were smaller; and 4) in several cases, the postsynaptic targets of sprouted synapses were identified as granule cells, but, in one case, a sprouted synaptic terminal formed a synapse with an inhibitory interneuron. The results demonstrate that axospinous asymmetric synapses are the most common type of synapse formed by sprouted mossy fiber terminals, supporting the viewpoint that most sprouted mossy fibers contribute to recurrent excitation in epilepsy.

  20. DNA microarray unravels rapid changes in transcriptome of MK-801 treated rat brain

    PubMed Central

    Kobayashi, Yuka; Kulikova, Sofya P; Shibato, Junko; Rakwal, Randeep; Satoh, Hiroyuki; Pinault, Didier; Masuo, Yoshinori

    2015-01-01

    AIM: To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions. METHODS: Rats were treated with an intraperitoneal injection of MK-801 [0.08 (low-dose) and 0.16 (high-dose) mg/kg] or NaCl (vehicle control). In a first series of experiment, the frontoparietal electrocorticogram was recorded 15 min before and 60 min after injection. In a second series of experiments, the whole brain of each animal was rapidly removed at 40 min post-injection, and different regions were separated: amygdala, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum on ice followed by DNA microarray (4 × 44 K whole rat genome chip) analysis. RESULTS: Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline gamma frequency (30-80 Hz) oscillations in the frontoparietal electroencephalogram. DNA microarray analysis showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose (0.08 mg/kg) of MK-801. Under high-dose (0.16 mg/kg), ventral striatum (811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region. CONCLUSION: Acute MK-801 treatment increases synchrony of baseline gamma oscillations, and causes very early changes in gene expressions in six individual rat brain regions, a first report. PMID:26629322

  1. Does Swimming Exercise Affect Experimental Chronic Kidney Disease in Rats Treated with Gum Acacia?

    PubMed Central

    Ali, Badreldin H.; Al-Salam, Suhail; Al Za'abi, Mohammed; Al Balushi, Khalid A.; Ramkumar, Aishwarya; Waly, Mostafa I.; Yasin, Javid; Adham, Sirin A.; Nemmar, Abderrahim

    2014-01-01

    Different modes of exercise are reported to be beneficial in subjects with chronic kidney disease (CKD). Similar benefits have also been ascribed to the dietary supplement gum acacia (GA). Using several physiological, biochemical, immunological, and histopathological measurements, we assessed the effect of swimming exercise (SE) on adenine –induced CKD, and tested whether SE would influence the salutary action of GA in rats with CKD. Eight groups of rats were used, the first four of which were fed normal chow for 5 weeks, feed mixed with adenine (0.25% w/w) to induce CKD, GA in the drinking water (15% w/v), or were given adenine plus GA, as above. Another four groups were similarly treated, but were subjected to SE during the experimental period, while the first four groups remained sedentary. The pre-SE program lasted for four days (before the start of the experimental treatments), during which the rats were made to swim for 5 to 10 min, and then gradually extended to 20 min per day. Thereafter, the rats in the 5th, 6th, 7th, and 8th groups started to receive their respective treatments, and were subjected to SE three days a week for 45 min each. Adenine induced the typical signs of CKD as confirmed by histopathology, and the other measurements, and GA significantly ameliorated all these signs. SE did not affect the salutary action of GA on renal histology, but it partially improved some of the above biochemical and physiological analytes, suggesting that addition of this mode of exercise to GA supplementation may improve further the benefits of GA supplementation. PMID:25048380

  2. 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.

  3. Growth hormone-releasing peptide-6 inhibits cerebellar cell death in aged rats.

    PubMed

    Pañeda, Covadonga; Arroba, Ana I; Frago, Laura M; Holm, Anne Mette; Rømer, John; Argente, Jesús; Chowen, Julie A

    2003-08-26

    Insulin-like growth factor (IGF)-I is essential for cerebellar granule neuron survival and a decline in IGF-I is implicated in various age-dependent processes. Here we show that IGF-I mRNA levels are decreased in the cerebellum of old rats compared with young rats and this was associated with increased cell death and activation of caspases 3 and 9. Growth hormone-releasing peptide (GHRP)-6, a synthetic ligand for the ghrelin receptor, increased IGF-I mRNA levels, decreased cell death and inhibited caspase 3 and 9 activation in the cerebellum of aged rats. These results suggest that increasing IGF-I expression in the cerebellum can decrease cell death in aged rats via inhibition of caspase 3 and 9 activation.

  4. Spatial reference memory in normal aging Fischer 344 × Brown Norway F1 hybrid rats.

    PubMed

    McQuail, Joseph A; Nicolle, Michelle M

    2015-01-01

    Fischer 344 × Brown Norway F1 (F344 × BN-F1) hybrid rats express greater longevity with improved health relative to aging rodents of other strains; however, few behavioral reports have thoroughly evaluated cognition across the F344 × BN-F1 lifespan. Consequently, this study evaluated spatial reference memory in F344 × BN-F1 rats at 6, 18, 24, or 28 months of age in the Morris water maze. Reference memory decrements were observed between 6 and 18 months and 18 and 24 months. At 28 months, spatial learning was not worse than 24 months, but swim speed was significantly slower. Reliable individual differences revealed that ∼50% of 24- to 28-month-old rats performed similarly to 6 months, whereas others were spatial learning impaired. Aged rats were impaired at learning within daily training sessions but not impaired at retaining information between days of training. Aged rats were also slower to learn to escape onto the platform, regardless of strategy. In summary, these data clarify the trajectory of cognitive decline in aging F344 × BN-F1 rats and elucidate relevant behavioral parameters.

  5. Exercise-induced changes of the capillaries in the cortex of middle-aged rats.

    PubMed

    Huang, C-X; Qiu, X; Wang, S; Wu, H; Xia, L; Li, C; Gao, Y; Zhang, L; Xiu, Y; Chao, F; Tang, Y

    2013-03-13

    Previous studies have shown that running exercise could increase regional cerebral blood flow. There have been previous studies investigating the effects of running exercise on capillary density in the brain and showing that running exercise could induce brain angiogenesis. However, there have been no studies investigating the effects of running exercise on the total volume, total length and total surface area of the capillaries in the cortex. Moreover, sex differences in the effects of running exercise on the capillaries of the cortex have not previously been investigated. The current study was designed to investigate the effects of running exercise on the capillaries in the cortex of middle-aged rats using the new unbiased stereological methods. The present study found that the total length and total surface area of the capillaries in the cortex of running middle-aged female rats were significantly increased, compared to control rats. Our results also reveal that there are sex differences in the effects of running exercise on the capillaries in the cortex of middle-aged rats. These results demonstrate that exercise-induced increases of the capillaries in the female rat cortex might be one of the structural bases for the exercise-induced improvement in the spatial learning capacity of middle-aged female rats. These results provide a baseline for further studies that search for strategies to delay the deleterious effects of brain aging.

  6. Age and altitude tolerance in rats - Temperature, plasma enzymes, and corticosterone

    SciTech Connect

    Altland, P.D.; Rattner, B.A.

    1981-02-01

    The influence of age on altitude tolerance in rats is investigated on the basis of changes in body weight and temperature, plasma enzyme levels and corticosterone concentration as indicators of condition. Immature (24-34 days), young adult (130-140 days) and old (600-625 days) rats were exposed to simulated altitudes from 6096 to 8230 m for four hours, and plasma activities of aspartate amino transferase (AsAT), fructose diphosphate aldolase (FDA), lactate dehydrogenase (LDH) and creatine kinase were determined, along with body weight and temperature and corticosterone. A critical survival threshold of 8230 m is obtained for the immature rats, while mortality was observed in some young adult and old rats at 7620 m, indicating the greater altitude tolerance of the immature animals. The degree of hypothermia and corticosterone elevation induced by altitude exposure in immature rats, but not young adult or old rats, is found to be directly related to the severity of hypoxia. Plasma enzyme activities are found to be relatively unchanged in immature rats, but AsAT and LDH activities in old rats, as well as FDA in young adults, were elevated at the critical survival threshold. Results thus indicate the usefulness of body temperature and plasma corticosterone in determining the altitude tolerance of immature rats, and enzyme activities for tolerance assessment in young adult and old rats.

  7. Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat

    PubMed Central

    Khojah, Sohair M.; Payne, Anthony P.; McGuinness, Dagmara; Shiels, Paul G.

    2016-01-01

    There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16Ink4a, Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16INK4a expression was significantly higher in AS/AGU animals compared to age-matched AS controls (p < 0.001) and displayed segmental expression across various brain regions. The age-related expression of sirtuins similarly showed differences between strains and between brain regions. Our data clearly show segmental aging processes within the rat brain, and that these are accelerated in the AS/AGU mutant. The accelerated aging, Parkinsonian phenotype, and disruption to dopamine signalling in the basal ganglia in AS/AGU rats, suggests that this rat strain represents a useful model for studies of development and progression of Parkinson’s disease in the context of biological aging and may offer unique mechanistic insights into the biology of aging. PMID:27763519

  8. The effect of age on digoxin pharmacokinetics in Fischer-344 rats

    SciTech Connect

    Evans, R.L.; Owens, S.M.; Ruch, S.; Kennedy, R.H.; Seifen, E. )

    1990-01-01

    Digoxin protein binding and pharmacokinetics were studied in 4-, 14-, and 25-month-old male Fischer-344 rats to determine if there were age-dependent changes in digoxin disposition. Serum protein binding did not differ among age groups. The average percentage unbound digoxin for all animals was 61.3 {plus minus} 5.3% (means {plus minus} SD, n = 15). For pharmacokinetic studies, ({sup 3}H)digoxin and 1 mg/kg unlabeled digoxin were administered as an intravenous bolus dose to animals from each age group. The ({sup 3}H)digoxin terminal elimination half-life was 2.0, 2.3, and 2.5 hr, respectively. The steady-state volume of distribution in the three age groups was 1.51, 1.49, and 1.27 liters/kg, respectively. Total body clearance for the three age groups was 14.2, 12.1, and 7.5 ml/min/kg, respectively. Analysis of variance of these data followed by Duncan's multiple range test indicated a significant decrease in clearance in the aged rats (25-month-old, p less than 0.05). This age-dependent decrease in clearance suggested that digoxin pharmacokinetics could be a significant factor in age-related alterations in digoxin cardiotoxicity in the rat, as it is in humans, and that the Fischer-344 rat could be a useful model for studies of digoxin pharmacokinetic changes with age.

  9. Exercise induces age-dependent changes on epigenetic parameters in rat hippocampus: a preliminary study.

    PubMed

    Elsner, Viviane Rostirola; Lovatel, Gisele Agustini; Moysés, Felipe; Bertoldi, Karine; Spindler, Christiano; Cechinel, Laura Reck; Muotri, Alysson Renato; Siqueira, Ionara Rodrigues

    2013-02-01

    Regular exercise improves learning and memory, including during aging process. Interestingly, the imbalance of epigenetic mechanisms has been linked to age-related cognitive deficits. However, studies about epigenetic alterations after exercise during the aging process are rare. In this preliminary study we investigated the effect of aging and exercise on DNA methyltransferases (DNMT1 and DNMT3b) and H3-K9 methylation levels in hippocampus from 3 and 20-months aged Wistar rats. The animals were submitted to two exercise protocols: single session or chronic treadmill protocol. DNMT1 and H3-K9 methylation levels were decreased in hippocampus from aged rats. The single exercise session decreased both DNMT3b and DNMT1 levels in young adult rats, without any effect in the aged group. Both exercise protocols reduced H3-K9 methylation levels in young adult rats, while the single session reversed the changes on H3-K9 methylation levels induced by aging. Together, these results suggest that an imbalance on DNMTs and H3-K9 methylation levels might be linked to the brain aging process and that the outcome to exercise seems to vary through lifespan.

  10. Long-term intermittent feeding restores impaired GR signaling in the hippocampus of aged rat.

    PubMed

    Tesic, Vesna; Perovic, Milka; Lazic, Divna; Kojic, Snezana; Smiljanic, Kosara; Ruzdijic, Sabera; Rakic, Ljubisav; Kanazir, Selma

    2015-05-01

    Diminished glucocorticoid signaling is associated with an age-related decline in hippocampal functioning. In this study we demonstrate the effect of intermittent, every other day (EOD) feeding on the glucocorticoid hormone/glucocorticoid receptor (GR) system in the hippocampus of middle-aged (18-month-old) and aged (24-month-old) Wistar rats. In aged ad libitum-fed rats, a decrease in the level of total GR and GR phosphorylated at Ser(232) (pGR) was detected. Conversely, aged rats subjected to EOD feeding, starting from 6 months of age, showed an increase in GR and pGR levels and a higher content of hippocampal corticosterone. Furthermore, prominent nuclear staining of pGR was observed in CA1 pyramidal and DG granule neurons of aged EOD-fed rats. These changes were accompanied by increased Sgk-1 and decreased GFAP transcription, pointing to upregulated transcriptional activity of GR. EOD feeding also induced an increase in the expression of the mineralocorticoid receptor. Our results reveal that intermittent feeding restores impaired GR signaling in the hippocampus of aged animals by inducing rather than by stabilizing GR signaling during aging.

  11. Imipramine-induced c-Fos expression in the medial prefrontal cortex is decreased in the ACTH-treated rats.

    PubMed

    Li, Bingjin; Suemaru, Katsuya; Kitamura, Yoshihisa; Gomita, Yutaka; Araki, Hiroaki; Cui, Ranji

    2013-11-01

    Previous studies have shown that the antidepressive-like effect of tricyclic antidepressants is blocked by repeated treatments with adrenocorticotropic hormone (ACTH). However, little is known about the neuroanatomy underlying the mechanism of the imipramine treatment-resistant depression model. In the present study, first experimental evidence showed no significant difference of the serum imipramine concentrations between the saline and ACTH-treated rats. In further study, imipramine produced significant increases in the c-Fos expression in the medial prefrontal cortex (mPFC), the dentate gyrus of the hippocampus (DGH), and the central nucleus of the amygdala (CeA), in rats repeatedly treated with saline. The imipramine-increased c-Fos immunoreactivity was suppressed in the mPFC of rats repeatedly treated with ACTH. However, there was no significant difference in c-Fos expression in the DGH and CeA between ACTH- and saline-treated rats. These results suggest that the mPFC is maybe involved in effects of the imipramine in the ACTH-treated rats.

  12. Protective effect of heat-treated cucumber (Cucumis sativus L.) juice on alcohol detoxification in experimental rats.

    PubMed

    Bajpai, Vivek K; Kim, Na-Hyung; Kim, Ji-Eun; Kim, Kangmin; Kang, Sun Chul

    2016-05-01

    In this study, heat-treated cucumber juice was assessed for its protective effect on blood alcohol levels and hepatic alcohol metabolic enzyme system in experimental rats. Initially, during detoxification of alcohol, all groups were orally dosed to 22% alcohol (6ml/kg body weight) along with different concentrations of heat-treated cucumber juice (10, 100 and 500mg/kg) and commercial goods for hangover-removal on sale (2ml/kg). Cucumber juice was dosed before 30 min, and simultaneously after 30min of alcohol administration, and its hepatoprotective effect on blood alcohol levels and hepatic alcohol metabolic enzyme system in experimental rats was evaluated. As a result, after 7h, remarkable reduction was found in the blood alcohol levels for all concentrations of cucumber juice treatment. Treatment with cucumber juice resulted in increasing dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) enzymatic activities in rat liver at 9h after alcohol administration thereby stimulated blood alcohol metabolism as compared with control group. The effect of heat-treated cucumber juice on alcohol detoxification was observed only in the rats treated before 30min from alcohol administration. These findings indicate that heat-treated cucumber juice has significant protective effect on alcohol detoxification in experimental rats, suggesting its usefulness in the treatment of liver injury caused by alcohol consumption.

  13. Comorbidity, age and mortality among adults treated intensively for acute myeloid leukemia (AML)

    PubMed Central

    Tawfik, Bernard; Pardee, Timothy; Isom, Scott; Sliesoraitis, Sarunas; Winter, Allison; Lawrence, Julia; Powell, Bayard L.; Klepin, Heidi D.

    2015-01-01

    Introduction Our goal was to characterize comorbidities among adults receiving intensive therapy for AML, and investigate their association with outcomes. Methods We retrospectively analyzed 277 consecutive patients with newly diagnosed AML treated intensively at the Comprehensive Cancer Center of Wake Forest University from 2002–2009. Pretreatment comorbidities were identified by ICD-9 codes and chart review. Comorbidity burden (modified Charlson Comorbidity Index [CCI]) and specific conditions were analyzed individually. Outcomes were overall survival (OS), remission, and 30-day mortality. Covariates included age, gender, cytogenetic characteristics, hemoglobin, white cell count, lactate dehydrogenase, body mass index, and insurance type. Cox proportional hazards models were used to evaluate OS; logistic regression was used for remission and 30-day mortality. Results In this series, 144 patients were ≥60 years old (median age 70 years, median survival 8.7 months) and 133 were <60 years (median age 47 years, median survival 23.1 months). Older patients had a higher comorbidity burden (CCI≥1 58% versus 26%, p<0.001). Prevalent comorbid conditions differed by age (diabetes 19.2% versus 7.5%; cardiovascular disease 12.5% versus 4.5%, for older versus younger patients, respectively). The CCI was not independently associated with OS or 30-day mortality in either age group. Among older patients, diabetes was associated with higher 30-day mortality (33.3% vs. 12.0% in diabetic vs. non diabetic patients, p =0.006). Controlling for age, cytogenetic characteristics and other comorbidities, the presence of diabetes increased the odds of 30-day mortality by 4.9 (CI 1.6–15.2) times. Discussion Diabetes is adversely associated with 30-day survival in older AML patients receiving intensive therapy. PMID:26527394

  14. Anti-inflammatory Effect of Isaria sinclairii Glycosaminoglycan in an Adjuvant-treated Arthritis Rat Model

    PubMed Central

    Jee, Sang Duck; Hwang, Jae Sam; Yun, Eun Young; Ahn, Kwang Seok; Kim, Yeong Shik

    2013-01-01

    The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund’s adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin® as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-κB activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin E2-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-α production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin® (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future. PMID:24386520

  15. The effects of acute alcohol on motor impairments in adolescent, adult, and aged rats.

    PubMed

    Ornelas, Laura C; Novier, Adelle; Van Skike, Candice E; Diaz-Granados, Jaime L; Matthews, Douglas B

    2015-03-01

    Acute alcohol exposure has been shown to produce differential motor impairments between aged and adult rats and between adolescent and adult rats. However, the effects of acute alcohol exposure among adolescent, adult, and aged rats have yet to be systematically investigated within the same project using a dose-dependent analysis. We sought to determine the age- and dose-dependent effects of acute alcohol exposure on gross and coordinated motor performance across the rodent lifespan. Adolescent (PD 30), adult (PD 70), and aged (approximately 18 months) male Sprague-Dawley rats were tested on 3 separate motor tasks: aerial righting reflex (ARR), accelerating rotarod (RR), and loss of righting reflex (LORR). In a separate group of animals, blood ethanol concentrations (BEC) were determined at multiple time points following a 3.0 g/kg ethanol injection. Behavioral tests were conducted with a Latin square repeated-measures design in which all animals received the following doses: 1.0 g/kg or 2.0 g/kg alcohol or saline over 3 separate sessions via intraperitoneal (i.p.) injection. During testing, motor impairments were assessed on the RR 10 min post-injection and on ARR 20 min post-injection. Aged animals spent significantly less time on the RR when administered 1.0 g/kg alcohol compared to adult rats. In addition, motor performance impairments significantly increased with age after 2.0 g/kg alcohol administration. On the ARR test, aged rats were more sensitive to the effects of 1.0 g/kg and 2.0 g/kg alcohol compared to adolescents and adults. Seven days after the last testing session, animals were given 3.0 g/kg alcohol and LORR was examined. During LORR, aged animals slept longer compared to adult and adolescent rats. This effect cannot be explained solely by BEC levels in aged rats. The present study suggests that acute alcohol exposure produces greater motor impairments in older rats when compared to adolescent and adult rats and begins to establish a

  16. [11C]PBR28 PET imaging is sensitive to neuroinflammation in the aged rat

    PubMed Central

    Walker, Matthew D; Dinelle, Katherine; Kornelsen, Rick; Lee, Nathan V; Miao, Qing; Adam, Mike; Takhar, Christine; Mak, Edwin; Schulzer, Michael; Farrer, Matthew J; Sossi, Vesna

    2015-01-01

    Neuroinflammation in the aging rat brain was investigated using [11C]PBR28 microPET (positron emission tomography) imaging. Normal rats were studied alongside LRRK2 p.G2019S transgenic rats; this mutation increases the risk of Parkinson's disease in humans. Seventy [11C]PBR28 PET scans were acquired. Arterial blood sampling enabled tracer kinetic modeling and estimation of VT. In vitro autoradiography was also performed. PBR28 uptake increased with age, without differences between nontransgenic and transgenic rats. In 12 months of aging (4 to 16 months), standard uptake value (SUV) increased by 56% from 0.44 to 0.69 g/mL, whereas VT increased by 91% from 30 to 57 mL/cm3. Standard uptake value and VT were strongly correlated (r=0.52, 95% confidence interval (CI)=0.31 to 0.69, n=37). The plasma free fraction, fp, was 0.21±0.03 (mean±standard deviation, n=53). In vitro binding increased by 19% in 16 months of aging (4 to 20 months). The SUV was less variable across rats than VT; coefficients of variation were 13% (n=27) and 29% (n=12). The intraclass correlation coefficient for SUV was 0.53, but was effectively zero for VT. These data show that [11C]PBR28 brain uptake increases with age, implying increased microglial activation in the aged brain. PMID:25833342

  17. Age-related changes in growth hormone-immunoreactive cells in the anterior pituitary gland of Jcl: Wistar-TgN (ARGHGEN) 1Nts rats (Mini rats).

    PubMed

    Matsumoto, Yoshiki; Tsukamoto, Yasuhiro; Miki, Takanori; Ogawa, Kazushige; Lee, Kyoung-Youl; Yokoyama, Toshifumi; Satriotomo, Irawan; Li, Hong-Peng; Gu, He; Wang, Zhi-Yu; Karasawa, Shigeru; Ueda, Susumu; Sasaki, Fumihiko; Takeuchi, Yoshiki

    2006-12-01

    Rats of the Jcl: Wistar-TgN (ARGHGEN) 1Nts strain (Mini rats) are transgenic animals carrying an antisense RNA transgene for rat growth hormone (GH); they show poor somatic growth and a low blood GH level compared to age-matched wild-type Wistar (non-Mini) rats. The purpose of the present study was to investigate age-related changes in growth hormone-immunoreactive (GH-IR) cells in the anterior pituitary gland (AP) of Mini rats at four, six, and eight weeks of age. The body weight and size of the GH-IR cells of Mini rats was significantly lower than that of non-Mini rats at six and eight weeks of age; however, this difference was not observed at four weeks of age. The AP volume and the number of GH-IR cells in Mini rats were significantly smaller than those of the age-matched non-Mini rats at the three ages. These results suggest that the abnormal development of GH-IR cells in the AP induced by the GH antisense RNA transgene is responsible for the poor somatic growth and the low blood GH levels in Mini rats.

  18. Age-related Changes in the Fracture Resistance of Male Fischer F344 Rat Bone

    PubMed Central

    Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J.; Does, Mark D.; Nyman, Jeffry S.

    2015-01-01

    In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Both Raman spectroscopy and reference point indentation detected differences in tissue properties with age, though the trends did not necessarily match observations from human tissue. PMID:26610688

  19. Age-related changes in the fracture resistance of male Fischer F344 rat bone.

    PubMed

    Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J; Does, Mark D; Nyman, Jeffry S

    2016-02-01

    In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Raman spectroscopy analysis of embedded cross-sections of the tibia mid-shaft detected an increase in carbonate subsitution with advanced aging for both inner and outer tissue.

  20. Pulmonary arterial hypertension in rats due to age-related arginase activation in intermittent hypoxia.

    PubMed

    Nara, Akina; Nagai, Hisashi; Shintani-Ishida, Kaori; Ogura, Sayoko; Shimosawa, Tatsuo; Kuwahira, Ichiro; Shirai, Mikiyasu; Yoshida, Ken-ichi

    2015-08-01

    Pulmonary arterial hypertension (PAH) is prevalent in patients with obstructive sleep apnea syndrome (OSAS). Aging induces arginase activation and reduces nitric oxide (NO) production in the arteries. Intermittent hypoxia (IH), conferred by cycles of brief hypoxia and normoxia, contributes to OSAS pathogenesis. Here, we studied the role of arginase and aging in the pathogenesis of PAH in adult (9-mo-old) and young (2-mo-old) male Sprague-Dawley rats subjected to IH or normoxia for 4 weeks and analyzed them with a pressure-volume catheter inserted into the right ventricle (RV) and by pulsed Doppler echocardiography. Western blot analysis was conducted on arginase, NO synthase isoforms, and nitrotyrosine. IH induced PAH, as shown by increased RV systolic pressure and RV hypertrophy, in adult rats but not in young rats. IH increased expression levels of arginase I and II proteins in the adult rats. IH also increased arginase I expression in the pulmonary artery endothelium and arginase II in the pulmonary artery adventitia. Furthermore, IH reduced pulmonary levels of nitrate and nitrite but increased nitrotyrosine levels in adult rats. An arginase inhibitor (N(ω)-hydroxy-nor-1-arginine) prevented IH-induced PAH and normalized nitrite and nitrate levels in adult rats. IH induced arginase up-regulation and PAH in adult rats, but not in young rats, through reduced NO production. Our findings suggest that arginase inhibition prevents or reverses PAH.

  1. The Anti-Aging Effect of Erythropoietin via the ERK/Nrf2-ARE Pathway in Aging Rats.

    PubMed

    Wu, Haiqin; Zhao, Jiaxin; Chen, Mengyi; Wang, Huqing; Yao, Qingling; Fan, Jiaxin; Zhang, Meng

    2017-03-01

    Erythropoietin (EPO) has a neuroprotective effect and can resist aging, which most likely occur through EPO increasing the activity of antioxidant enzymes and scavenging free radicals. In this study, we verified the anti-aging function of EPO and discussed the mechanism occurring through the extracellular signal-regulated kinase (ERK)/NF-E2-related factor 2 (Nrf2)-ARE pathway. A rat model of aging was induced by the continuous subcutaneous injection of 5 % D-galactose for 6 weeks. At the beginning of the sixth week, physiological saline or EPO was administered twice per day through a lateral ventricle system for a total of 7 days. In one group, 2 μl PD98059 was administered 30 min before EPO. Learning and memory ability were analyzed with the Morris water maze system. HE staining was used to observe the morphological changes in the neurons in the hippocampus, and immunohistochemical staining as well as Western blots were carried out to detect the expression of ERK for each group of rats and the expression of phosphorylated-ERK (P-ERK), Nrf2, and superoxide dismutase (SOD). Real-Time PCR was carried out to detect the amount of Nrf2 mRNA and the KEAP1 mRNA expression. EPO can significantly improve learning and memory ability in aging rats and can provide protection against aging by improving the hippocampus morphology. Immunohistochemical staining and Western blots showed P-ERK, Nrf2, and Cu-Zn SOD decreases in aging rats compared to the normal group, while the expression for those proteins increased after EPO intervention. PD98059 inhibited the enhanced expression of P-ERK, Nrf2, and Cu-Zn SOD induced by EPO. Real-Time PCR results suggested that the trend of Nrf2mRNA expression was the same as that for the proteins, which confirmed that the enhancement occurred at the gene level. As such, EPO can significantly resist or delay aging and protect the brain by reducing oxidative stress. The most likely mechanism is that EPO can promote the ERK/Nrf2-ARE pathway in

  2. Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution

    PubMed Central

    Herrera-Pérez, José Jaime; Fernández-Guasti, Alonso; Martínez-Mota, Lucía

    2013-01-01

    In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT) expression associated with low testosterone (T) levels. The objectives of this study were to establish (1) if brain SERT expression is reduced by aging and (2) if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months) and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population. PMID:26317087

  3. UNDERNUTRITION IN EARLY LIFE DOES NOT IMPAIR LEARNING IN YOUNG OR AGING RATS.

    EPA Science Inventory

    Prenatal undernutrition is associated with increased incidence of obesity, heart disease, diabetes. Effects of pre- and post-natal undernutrition on nervous system function in middle-aged and aging male SD rats were examined. Intrauterine growth retardation (IUGR) was induced by ...

  4. Effect of Tongue Exercise on Protrusive Force and Muscle Fiber Area in Aging Rats

    ERIC Educational Resources Information Center

    Connor, Nadine P.; Russell, John A.; Wang, Hao; Jackson, Michelle A.; Mann, Laura; Kluender, Keith

    2009-01-01

    Purpose: Age-related changes in tongue function may contribute to dysphagia in elderly people. The authors' purpose was to investigate whether aged rats that have undergone tongue exercise would manifest increased protrusive tongue forces and increased genioglossus (GG) muscle fiber cross-sectional areas. Method: Forty-eight young adult,…

  5. Carcinogenically relevant split dose repair increased with age in rat skin model.

    NASA Astrophysics Data System (ADS)

    Burns, Fredric; Tang, Moon-Shong Eric; Wu, Feng; Uddin, Ahmed

    2012-07-01

    These experiments utilize cancer induction to evaluate cancer-relevant repair during the interval between dose fractions. Low LET electron radiation(LET ~ 0.34 keV/u) were utilized in experiments that involved exposing rat dorsal skin to 2 equal 8 Gy dose fractions separated at various intervals from 0.25 h to 24 h. Cancer onset was established for 80 weeks after the exposures and only histologically verified cancers were included in the analysis. This experiment involved a total of 540 rats and 880 induced cancers. In the youngest rats (irradiated at 28 days of age) the cancer yield declined with a halftime of approximately 3.5 hrs. In 113 day old rats the cancer yield halftime was shortened to 1.3 hrs. In the oldest rats (182 days of age), the halftime could not be established quantitatively, because it was less than the shortest interval (15 min) utilized in the protocol (best estimate ~5 min). In the oldest rats the cancer yields for all fractionated exposures dropped essentially to the expected level of 2 single fractions, below which theoretically no further reduction is possible. The follow-up times for obtaining cancer yields were the same for all exposure groups in spite of the differing ages at exposure. These results indicate that repair of carcinogenically-relevant damage accelerates with age of the rat. No information is available on the possible mechanistic basis for this finding, although the model might be useful for delineating which of the many postulated split dose repair pathways is the correct one. The finding indicates that older rats should be less susceptible to the carcinogenic action of single doses of low LET radiation in comparison to younger rats, which has been verified in separate studies.

  6. Effects of the continuous administration of an Agaricus blazei extract to rats on oxidative parameters of the brain and liver during aging.

    PubMed

    de Sá-Nakanishi, Anacharis B; Soares, Andréia A; Natali, Maria R M; Comar, Jurandir Fernando; Peralta, Rosane M; Bracht, Adelar

    2014-11-13

    An investigation of the effects of an aqueous extract of Agaricus blazei, a medicinal mushroom, on the oxidative state of the brain and liver of rats during aging (7 to 23 months) was conducted. The treatment consisted in the daily intragastric administration of 50 mg/kg of the extract. The A. blazei treatment tended to maintain the ROS contents of the brain and liver at lower levels, but a significant difference was found only at the age of 23 months and in the brain. The TBARS levels in the brain were maintained at lower levels by the A. blazei treatment during the whole aging process with a specially pronounced difference at the age of 12 months. The total antioxidant capacity in the brain was higher in treated rats only at the age of 12 months. Compared with previous studies in which old rats (21 months) were treated during a short period of 21 days with 200 mg/kg, the effects of the A. blazei extract in the present study tended to be less pronounced. The results also indicate that the long and constant treatment presented a tendency of becoming less effective at ages above 12 months.

  7. Procognitive effect of AC-3933 in aged mice, and synergistic effect of combination with donepezil in scopolamine-treated mice.

    PubMed

    Hashimoto, Takashi; Hatayama, Yuki; Nakamichi, Keiko; Yoshida, Naoyuki

    2014-12-15

    We have previously reported that AC-3933, a newly developed benzodiazepine receptor partial inverse agonist, facilitates acetylcholine release in the hippocampus and ameliorates scopolamine-induced memory deficits in rats. To further confirm the procognitive effect of AC-3933, we assessed in this study the beneficial effects of this compound in aged mice using the Y-maze and object recognition tests. In addition, we investigated the synergistic effect of AC-3933 and donepezil, a cholinesterase inhibitor, on scopolamine-induced memory impairment in mice. In aged mice, oral administration of AC-3933 at doses of 0.05-0.1 mg/kg and 0.05 mg/kg significantly improved spatial working memory and episodic memory, respectively. In scopolamine-treated mice, both AC-3933 and donepezil significantly ameliorated memory deficits in the Y-maze test at doses of 0.3-3 mg/kg and 10-15 mg/kg, respectively. The beneficial effect of AC-3933, but not that of donepezil, on scopolamine-induced memory impairment was antagonized by flumazenil, a benzodiazepine receptor antagonist, indicating that the procognitive action of AC-3933 arises via a mechanism different from that of donepezil. Co-administration of donepezil at the suboptimal dose of 3 mg/kg with AC-3933 at doses of 0.1-1 mg/kg significantly ameliorated scopolamine-induced memory impairment, suggesting that AC-3933 potentiates the effect of donepezil on memory impairment induced by cholinergic hypofunction. These findings indicate that AC-3933 not only has good potential as a cognitive enhancer by itself, but also is useful as a concomitant drug for the treatment of Alzheimer׳s disease.

  8. Age-related histological changes in kidneys of Brown Norway rat.

    PubMed

    Yabuki, Akira; Yoneshige, Shinichiro; Tanaka, Shin; Tsujio, Masashi; Mitani, Sawane; Yamato, Osamu

    2014-03-01

    In this study, age-dependent histological changes in the kidneys of Brown Norway rat, a strain useful for conducting aging research, were evaluated. Examination was performed at 3, 12, 18, 24 and 30 months of age. Sclerotic and hypertrophic changes of the glomeruli were observed, and quantitative scores of these changes persistently increased with age. A marginal increase in scores was observed for glomerular cystic changes and tubulointerstitial damage. Further, urothelial hyperplasia was observed in the renal papillae, particularly at 30 months of age. In conclusion, the findings of the present study demonstrate that the Brown Norway strain exhibits persistent, but mild progression of age-dependent renal histological changes.

  9. Age-dependent inhibition of pentobarbital sleeping time by ozone in mice and rats

    SciTech Connect

    Canada, A.T.; Calabrese, E.J.; Leonard, D.

    1986-09-01

    The effect of age on the metabolism of pentobarbital in mice and rats was investigated following exposure to 0.3 ppm of ozone for 3.75 hr. Young animals were 2.5 months of age and the mature were 18 months. The pentobarbital sleeping time was significantly prolonged following the ozone exposure in both the mice and rats when compared with an air control. No ozone effect on sleeping time was found in the young animals. The results indicate that there may be an age-related sensitivity to the occurrence of ozone-related inhibition of pentobarbital metabolism.

  10. Methanolic Extract of Dill Leaves Inhibits AGEs Formation and Shows Potential Hepatoprotective Effects in CCl4 Induced Liver Toxicity in Rat.

    PubMed

    Oshaghi, Ebrahim Abbasi; Khodadadi, Iraj; Mirzaei, Fatemeh; Khazaei, Mozafar; Tavilani, Heidar; Goodarzi, Mohammad Taghi

    2017-01-01

    The research was aimed at evaluating the antiglycation, antioxidant, and hepatoprotective properties of methanolic extract of Anethum graveolens (dill). The antioxidant properties, photochemical characteristics, and antiglycation effects of dill extract were measured. Carbon tetrachloride-induced hepatotoxic rats were used to show the hepatoprotective activity of dill leaves. Different concentration of dill extract (0.032, 0.065, 0.125, 0.25, 0.5, and 1 mg/mL) showed potential antioxidant ability. The extract of dill leaves significantly reduced AGEs formation and also fructosamine and protein carbonyl levels in rats' liver. Thiol groups' oxidation, amyloid cross-β, and protein fragmentation (P < 0.001) significantly reduced in treated rats. Liver damage markers significantly reduced in dill-treated animals (P < 0.05). Dill with potential antioxidant, antiglycation, and hepatoprotective effects can be suggested for treatment of diabetes complications.

  11. Methanolic Extract of Dill Leaves Inhibits AGEs Formation and Shows Potential Hepatoprotective Effects in CCl4 Induced Liver Toxicity in Rat

    PubMed Central

    Khodadadi, Iraj; Mirzaei, Fatemeh; Khazaei, Mozafar; Tavilani, Heidar

    2017-01-01

    The research was aimed at evaluating the antiglycation, antioxidant, and hepatoprotective properties of methanolic extract of Anethum graveolens (dill). The antioxidant properties, photochemical characteristics, and antiglycation effects of dill extract were measured. Carbon tetrachloride-induced hepatotoxic rats were used to show the hepatoprotective activity of dill leaves. Different concentration of dill extract (0.032, 0.065, 0.125, 0.25, 0.5, and 1 mg/mL) showed potential antioxidant ability. The extract of dill leaves significantly reduced AGEs formation and also fructosamine and protein carbonyl levels in rats' liver. Thiol groups' oxidation, amyloid cross-β, and protein fragmentation (P < 0.001) significantly reduced in treated rats. Liver damage markers significantly reduced in dill-treated animals (P < 0.05). Dill with potential antioxidant, antiglycation, and hepatoprotective effects can be suggested for treatment of diabetes complications. PMID:28182107

  12. Glutamate co-transmission from developing medial nucleus of the trapezoid body - Lateral superior olive synapses is cochlear dependent in kanamycin-treated rats

    SciTech Connect

    Lee, Jae Ho; Pradhan, Jonu; Maskey, Dhiraj; Park, Ki Sup; Hong, Sung Hwa; Suh, Myung-Whan; Kim, Myeung Ju; Ahn, Seung Cheol

    2011-02-11

    Research highlights: {yields} Glutamate co-transmission is enhanced in kanamycin-treated rats. {yields} VGLUT3 expression is increased in kanamycin-treated rats. {yields} GlyR expression is decreased in kanamycin-treated rats. {yields} GlyR, VGLUT3 expression patterns are asymmetric in unilaterally cochlear ablated rat. -- Abstract: Cochlear dependency of glutamate co-transmission at the medial nucleus of the trapezoid body (MNTB) - the lateral superior olive (LSO) synapses was investigated using developing rats treated with high dose kanamycin. Rats were treated with kanamycin from postnatal day (P) 3 to P8. A scanning electron microscopic study on P9 demonstrated partial cochlear hair cell damage. A whole cell voltage clamp experiment demonstrated the increased glutamatergic portion of postsynaptic currents (PSCs) elicited by MNTB stimulation in P9-P11 kanamycin-treated rats. The enhanced VGLUT3 immunoreactivities (IRs) in kanamycin-treated rats and asymmetric VGLUT3 IRs in the LSO of unilaterally cochlear ablated rats supported the electrophysiologic data. Taken together, it is concluded that glutamate co-transmission is cochlear-dependent and enhanced glutamate co-transmission in kanamycin-treated rats is induced by partial cochlear damage.

  13. Sevoflurane induces endoplasmic reticulum stress mediated apoptosis in hippocampal neurons of aging rats.

    PubMed

    Chen, Gang; Gong, Ming; Yan, Min; Zhang, Xiaoming

    2013-01-01

    Elderly patients are more likely to suffer from postoperative memory impairment for volatile anesthetics could induce aging neurons degeneration and apoptosis while the mechanism was still elusive. Therefore we hypothesized that ER stress mediated hippocampal neurons apoptosis might play an important role in the mechanism of sevoflurane-induced cognitive impairment in aged rats. Thirty 18-month-old male Sprague-Dawley rats were divided into two groups: the sham anesthesia group (exposure to simply humidified 30-50% O2 balanced by N2 in an acrylic anesthetizing chamber for 5 hours) and the sevoflurane anesthesia group (received 2% sevoflurane in the same humidified mixed air in an identical chamber for the same time). Spatial memory of rats was assayed by the Morris water maze test. The ultrastructure of the hippocampus was observed by transmission electron microscopy (TEM). The expressions of C/EBP homologous protein (CHOP) and caspase-12 in the hippocampus were observed by immunohistochemistry and real-time PCR analysis. The apoptosis neurons were also assessed by TUNEL assay. The Morris water maze test showed that sevoflurane anesthesia induced spatial memory impairment in aging rats (P<0.05). The apoptotic neurons were condensed and had clumped chromatin with fragmentation of the nuclear membrane, verifying apoptotic degeneration in the sevoflurane group rats by TEM observation. The expressions of CHOP and caspase-12 increased, and the number of TUNEL positive cells of the hippocampus also increased in the sevoflurane group rats (P<0.05). The present results suggested that the long time exposure of sevoflurane could induce neuronal degeneration and cognitive impairment in aging rats. The ER stress mediated neurons apoptosis may play a role in the sevoflurane-induced memory impairment in aging rats.

  14. Effects of age on recovery of body weight following REM sleep deprivation of rats.

    PubMed

    Koban, Michael; Stewart, Craig V

    2006-01-30

    Chronically enforced rapid eye (paradoxical) movement sleep deprivation (REM-SD) of rats leads to a host of pathologies, of which hyperphagia and loss of body weight are among the most readily observed. In recent years, the etiology of many REM-SD-associated pathologies have been elucidated, but one unexplored area is whether age affects outcomes. In this study, male Sprague-Dawley rats at 2, 6, and 12 months of age were REM sleep-deprived with the platform (flowerpot) method for 10-12 days. Two-month-old rats resided on 7-cm platforms, while 10-cm platforms were used for 6- and 12-month-old rats; rats on 15-cm platforms served as tank controls (TCs). Daily changes in food consumption (g/kg(0.67)) and body weight (g) during baseline, REM-SD or TCs, and post-experiment recovery in home cages were determined. Compared to TCs, REM-SD resulted in higher food intake and decreases in body weight. When returned to home cages, food intake rapidly declined to baseline levels. Of primary interest was that rates of body weight gain during recovery differed between the age groups. Two-month-old rats rapidly restored body weight to pre-REM-SD mass within 5 days; 6-month-old rats were extrapolated by linear regression to have taken about 10 days, and for 12-month-old rats, the estimate was about 35 days. The observation that restoration of body weight following its loss during REM-SD may be age-dependent is in general agreement with the literature on aging effects on how mammals respond to stress.

  15. Histomorphologic and ultrastructural recovery of myopathy in rats treated with low-level laser therapy.

    PubMed

    Servetto, Natalia; Cremonezzi, David; Simes, Juan Carlos; Di Pietro, Antonio; Campana, Vilma R

    2017-03-09

    The purpose of the present work was to study the effect of low-level laser therapy (LLLT): helium-neon (He-Ne) and gallium arsenide (Ga-As) laser on the histomorphology of muscle and mitochondria in experimental myopathy in rats. Thirty Suquía strain female rats were distributed in groups: (A) control (intact), (B) injured, (C) injured and treated with He-Ne laser, (D) injured and treated with Ga-As laser, (E) irradiated with He-Ne laser on the non-injured muscle, and (F) irradiated with Ga-As laser on the non-injured muscle. Myopathy was induced by injecting 0.05 mg/rat/day of adrenaline in the left gastrocnemius muscle at the same point on five consecutive days, in groups B, C, and D. LLLT was applied with 9.5 J cm(-2) daily for seven consecutive days in groups C, D, E, and F. The muscles were examined with optic and electronic microscopy. The inflammation was classified as absent, mild, and intense and the degree of mitochondrial alteration was graded I, II, III, and IV. Categorical data were statistically analyzed by Chi-square and the Fisher-Irwin Bilateral test, setting significant difference at p < 0.05. The damage found in muscle and mitochondria histomorphology in animals with induced myopathy (B) was intense or severe inflammation with grade III or IV of mitochondrial alteration. They underwent significant regression (p < 0.001) compared with the groups treated with He-Ne (C) and Ga-As (D) laser, in which mild or moderate inflammation was seen and mitochondrial alteration grades I and II, recovering normal myofibrillar architecture. No differences were found between the effects caused by the two lasers, or between groups A, E, and F. Group A was found to be different from B, C, and D (p < 0.001). LLLT in experimental myopathy caused significant muscular and mitochondrial morphologic recovery.

  16. Estradiol valerate and tibolone: effects upon brain oxidative stress and blood biochemistry during aging in female rats.

    PubMed

    de Aguiar, R B; Dickel, O E; Cunha, R W; Monserrat, J M; Barros, D M; Martinez, P E

    2008-10-01

    Estrogen compounds have been described as important brain protectors. This study investigated the effects of estradiol valerate (EV--0.3 mg/kg) and two concentrations of tibolone (TB1=0.5 mg/kg and TB2=1 mg/kg) on brain oxidative stress parameters and blood biochemistry in ovariectomized female rats, of three different age groups (young--2 months, adult--8 months, and old--20 months). In the brain cortex, young and old TB2-treated and old no-hormone-replacement (NR) females showed lower lipid hydroperoxide (LPO) levels compared to young Sham and adult TB1 animals (P<0.05). Also in the cortex, both tibolone doses produced higher (P<0.05) total antioxidant capacity (TOSC) levels compared to EV-treated adult females. Ovariectomized adult females (NR, EV, TB1 and TB2) showed lower (P<0.05) TOSC levels in the hippocampus compared to the Sham control. Reactive oxygen species (ROS) were higher (P<0.05) in old females compared to all younger ones. TB2-treated adults showed higher plasma glucose (P<0.05) levels compared to old animals. Regardless of age, TB2 treatment increased female (P<0.05) LDL levels compared to Sham and EV-treated animals. In old females, TB2 significantly increased HDL levels compared to Sham controls, and decreased triglyceride levels were shown in EV, TB1 and TB2 compared to Sham old females. The Atherogenic Index of Plasma was higher (P<0.05) in adult tibolone-treated females compared to both young and old TB2-treated females. These results suggest that the effects of gonad steroid on brain and blood physiology change significantly with aging, and that evaluating hormonal treatment types and doses could be the key factor in the potential use of a specific hormone therapy.

  17. Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats.

    PubMed

    Kitagawa, Kouhei; Kitamura, Yoshihisa; Miyazaki, Toshiaki; Miyaoka, Junya; Kawasaki, Hiromu; Asanuma, Masato; Sendo, Toshiaki; Gomita, Yutaka

    2009-07-01

    The dopamine D2/D3 receptor agonist pramipexole has clinically been proven to improve depression or treatment-resistant depression. However, the involvement of the dopamine receptor system on the effect of pramipexole on depression remains unclear. We examined the influence of pramipexole on the duration of immobility during the forced swim test in normal and adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which pramipexole acts in this model was explored specifically in relation to the site of action through the use of microinjections into the intramedial prefrontal cortex and nucleus accumbens. Pramipexole (0.3-1 mg/kg) significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by L-741,626, a D2 receptor antagonist, and nafadotride, a D3 receptor antagonist, in normal rats. Furthermore, infusions of pramipexole into the intranucleus accumbens, but not the medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Taken together, the results of these experiments suggested that pramipexole, administered into the intranucleus accumbens rather than the medial prefrontal cortex, exerted an antidepressant-like effect on ACTH-treated rats via the dopaminergic system. The immobility-decreasing effect of pramipexole may be mediated by dopamine D2 and D3 receptors.

  18. Microvesicles from brain-extract—treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke

    PubMed Central

    Lee, Ji Yong; Kim, Eiru; Choi, Seong-Mi; Kim, Dong-Wook; Kim, Kwang Pyo; Lee, Insuk; Kim, Han-Soo

    2016-01-01

    Transplantation of mesenchymal stem cells (MSCs) was reported to improve functional outcomes in a rat model of ischemic stroke, and subsequent studies suggest that MSC-derived microvesicles (MVs) can replace the beneficial effects of MSCs. Here, we evaluated three different MSC-derived MVs, including MVs from untreated MSCs (MSC-MVs), MVs from MSCs treated with normal rat brain extract (NBE-MSC-MVs), and MVs from MSCs treated with stroke-injured rat brain extract (SBE-MSC-MVs), and tested their effects on ischemic brain injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. NBE-MSC-MVs and SBE-MSC-MVs had significantly greater efficacy than MSC-MVs for ameliorating ischemic brain injury with improved functional recovery. We found similar profiles of key signalling proteins in NBE-MSC-MVs and SBE-MSC-MVs, which account for their similar therapeutic efficacies. Immunohistochemical analyses suggest that brain-extract—treated MSC-MVs reduce inflammation, enhance angiogenesis, and increase endogenous neurogenesis in the rat brain. We performed mass spectrometry proteomic analyses and found that the total proteomes of brain-extract—treated MSC-MVs are highly enriched for known vesicular proteins. Notably, MSC-MV proteins upregulated by brain extracts tend to be modular for tissue repair pathways. We suggest that MSC-MV proteins stimulated by the brain microenvironment are paracrine effectors that enhance MSC therapy for stroke injury. PMID:27609711

  19. Memory impairment in rats after desflurane anesthesia is age and dose dependent.

    PubMed

    Callaway, Jennifer K; Jones, Nigel C; Royse, Alistair G; Royse, Colin F

    2015-01-01

    Post-operative cognitive dysfunction (POCD) predominantly affects the elderly who suffer memory and concentration deficits after anesthesia and surgery. Animal studies have demonstrated anesthetic alone may contribute to POCD but results are variable and little is known about common anesthetics other than isoflurane. The present study investigated dose-dependence of desflurane anesthesia in young adult and aged rats. We hypothesize higher concentrations of desflurane will result in memory impairment in the water maze and that impairment will be worse in aged rats. Effects of anesthesia (1 or 1.5 MAC, 4 h) desflurane, or sham exposure on cognition were investigated in young adult (3 months) and aged (20-24 months) rats at 1, 4, and 12 weeks post-exposure. The Morris water maze was used to assess acquisition and retention of spatial reference memory. Latency to find the hidden platform and swimming speed were compared between treatments. Aged rats showed significant impairment in task acquisition after exposure to 1.5 MAC, but not 1.0 MAC desflurane anesthetic when tested 1 week following exposure. Latency to find the platform and distance travelled were significantly longer in aged rats given 1.5 MAC desflurane (latency: F(1,108) = 19.71, p < 0.0001; distance: F(1,108) = 5.79, p = 0.018). Deficits were not long-lasting and were no longer present at 4 or 12 weeks. In contrast, young adult rats performed equally as well as sham-exposed control rats irrespective of desflurane dose. This study showed the effects of desflurane on learning and memory in the water maze are age and dose dependent and are brief in duration.

  20. Insulin-Like Growth Factor (IGF)-I Modulates Endothelial Blood-Brain Barrier Function in Ischemic Middle-Aged Female Rats

    PubMed Central

    Bake, Shameena; Okoreeh, Andre K.; Alaniz, Robert C.

    2016-01-01

    In comparison with young females, middle-aged female rats sustain greater cerebral infarction and worse functional recovery after stroke. These poorer stroke outcomes in middle-aged females are associated with an age-related reduction in IGF-I levels. Poststroke IGF-I treatment decreases infarct volume in older females and lowers the expression of cytokines in the ischemic hemisphere. IGF-I also reduces transfer of Evans blue dye to the brain, suggesting that this peptide may also promote blood-brain barrier function. To test the hypothesis that IGF-I may act at the blood-brain barrier in ischemic stroke, 2 approaches were used. In the first approach, middle-aged female rats were subjected to middle cerebral artery occlusion and treated with IGF-I after reperfusion. Mononuclear cells from the ischemic hemisphere were stained for CD4 or triple-labeled for CD4/CD25/FoxP3 and subjected to flow analyses. Both cohorts of cells were significantly reduced in IGF-I–treated animals compared with those in vehicle controls. Reduced trafficking of immune cells to the ischemic site suggests that blood-brain barrier integrity is better maintained in IGF-I–treated animals. The second approach directly tested the effect of IGF-I on barrier function of aging endothelial cells. Accordingly, brain microvascular endothelial cells from middle-aged female rats were cultured ex vivo and subjected to ischemic conditions (oxygen-glucose deprivation). IGF-I treatment significantly reduced the transfer of fluorescently labeled BSA across the endothelial monolayer as well as cellular internalization of fluorescein isothiocyanate–BSA compared with those in vehicle-treated cultures, Collectively, these data support the hypothesis that IGF-I improves blood-brain barrier function in middle-aged females. PMID:26556536

  1. [Multiple hepatic cysts in rat rendered diabetic by streptozotocin and treated by islets of Langerhans grafts: the role of streptozotocin].

    PubMed

    Viatettes, B; Barrat, E; Lassmann, V; Guidon, J; Altomare, E; Simon, C; Vague, P

    1978-01-01

    This study is based on the investigation by light and electron microscopy of hepatic biopsies from 14 rats rendered diabetic by streptozotocin and treated by portal embolization of islets of Langerhans. Macroscopically, voluminous projecting cysts were observed, sometimes occupying a whole lobe. By light microscopy, the cysts were lined with canalicular-type epithelium. Ultrastructural studies confirmed the canalicular nature of these cells and cilia were frequently observed. The presence of identical cysts in rats rendered diabetic by streptozotocin but not treated by embolization proves that this product is the agent responsible for the induction of this adenomatosis.

  2. Effect of exercise training on ethanol-induced oxidative damage in aged rats.

    PubMed

    Mallikarjuna, K; Nishanth, K; Hou, Chien-Wen; Kuo, Chia-Hua; Sathyavelu Reddy, K

    2009-02-01

    It is well known that lipid peroxidation increases with age, and alcohol drinking further exacerbates this damage. The present study determined the effect of regular exercise training on alcohol-induced oxidative damage and antioxidant status in the liver of aged animals. The age-matched Wistar albino rats (3 months young, n=24; 18 months old, n=24) were evenly divided into four groups: control (C), exercise trained (Ex), ethanol drinking (Et), and exercise plus ethanol drinking (Ex+Et). With ethanol drinking, hepatic malondialdehyde (MDA) level was significantly elevated above control (P<.001), whereas glutathione (GSH) and ascorbic acid (vitamin C) contents were significantly decreased below control. These changes were found to be greater in the aged rats than those of the young rats. For both age groups, exercise training significantly reversed the increase in MDA and decreases in GSH and ascorbic acid induced by ethanol drinking. The present study showed that ethanol-induced deterioration in lipid peroxidation and reduction in antioxidant status in the liver were exacerbated with age. Here, we found that exercise training significantly reversed the adverse conditions that were caused by ethanol in aged rats.

  3. Estradiol impairs response inhibition in young and middle-aged, but not old rats

    PubMed Central

    Wang, Victor C.; Neese, Steven L.; Korol, Donna L.; Schantz, Susan L.

    2011-01-01

    Estrogens have been shown to have a strong influence on such cognitive domains as spatial memory, response learning, and several tasks of executive function, including both working memory and attention. However, the effects of estrogens on inhibitory control and timing behavior, both important aspects of executive function, have received relatively little attention. We examined the effects of estradiol on inhibitory control and timing using a differential reinforcement of low rates of responding (DRL) task. Ovariectomized young (3 month), middle-aged (12 month), and old (18 month) Long-Evans rats received 5% or 10% 17β-estradiol in cholesterol vehicle or cholesterol vehicle alone via Silastic implants and were tested on a DRL task requiring them to wait 15 seconds between lever presses to receive a food reinforcer. The ratio of reinforced to non-reinforced lever presses did not differ across age in the cholesterol vehicle group. Conversely, 17β-estradiol impaired learning of the DRL task in young and middle-aged rats, but the learning of old rats was not impaired relative to vehicle controls following either 5% or 10% 17β-estradiol treatment. Overall, old rats also made fewer lever presses than both the young and middle-aged rats. These results provide new evidence that estrogens impair inhibitory control, an important aspect of self regulation, and add to existing evidence that estrogens differentially affect cognition at different ages. PMID:21281713

  4. Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

    SciTech Connect

    Schindler, Matthew K. Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

    2008-03-01

    Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals.

  5. Chronic infusions of GABA into the medial prefrontal cortex induce spatial alternation deficits in aged rats.

    PubMed

    Meneses, S; Galicia, O; Brailowsky, S

    1993-10-21

    It has been proposed that functions associated with the prefrontal cortex could change as a consequence of aging. Previous experiments in young rats have demonstrated that anatomical lesions or chronic GABA infusions into this area produce deficits in spatial delayed alternation tasks. The present study examines the effect of chronic (7 days) GABA or saline infusion into the prefrontal cortex on the performance of delayed alternation task in old rats (24 months). The results suggested that aged rats needed more sessions to acquire the delayed alternation task. GABA infusions into the prefrontal cortex produced deficits in spatial alternation tasks similar to those previously observed in young rats. Performance rapidly recovered after the infusion period. Histological analysis showed similar lesion size in both groups. The results suggest that aged prefrontal cortex and/or related areas participating in the acquisition of the delayed alternation task are more sensitive to aging processes. Furthermore, the prefrontal cortex is important for the retention of a previously learned spatial delayed alternation task. The structures involved in functional recovery from these deficits appear to be fully functional in aged rats.

  6. BQ123 Stimulates Skeletal Muscle Antioxidant Defense via Nrf2 Activation in LPS-Treated Rats

    PubMed Central

    Jeleń, Agnieszka; Żebrowska, Marta; Balcerczak, Ewa; Gorąca, Anna

    2016-01-01

    Little is understood of skeletal muscle tissue in terms of oxidative stress and inflammation. Endothelin-1 is an endogenous, vasoconstrictive peptide which can induce overproduction of reactive oxygen species and proinflammatory cytokines. The aim of this study was to evaluate whether BQ123, an endothelin-A receptor antagonist, influences the level of TNF-α, IL-6, SOD-1, HO-1, Nrf2 mRNA, and NF-κB subunit RelA/p65 mRNA in the femoral muscle obtained from endotoxemic rats. Male Wistar rats were divided into 4 groups (n = 6) and received iv (1) saline (control), (2) LPS (15 mg/kg), (3) BQ123 (1 mg/kg), (4) BQ123 (1 mg/kg), and LPS (15 mg/kg, resp.) 30 min later. Injection of LPS led to significant increase in levels of RelA/p65 mRNA, TNF-α, and IL-6, while content of SOD-1, HO-1, and Nrf2 mRNA was unchanged. Administration of BQ123 prior to LPS challenge resulted in a significant reduction in RelA/p65 mRNA, TNF-α, and IL-6 levels, as well as markedly elevated concentrations of SOD-1, HO-1, and Nrf2 mRNA. BQ123 appears to enhance antioxidant defense and prevent production of TNF-α and IL-6 in skeletal muscle of LPS-treated rat. In conclusion, endothelin-A receptor antagonism exerts significant impact on the skeletal muscle favouring anti-inflammatory effects and protection against oxidative stress. PMID:26823945

  7. Kidney injury biomarkers in hypertensive, diabetic, and nephropathy rat models treated with contrast media.

    PubMed

    Rouse, Rodney L; Stewart, Sharron R; Thompson, Karol L; Zhang, Jun

    2013-01-01

    Contrast-induced nephropathy (CIN) refers to a decline in renal function following exposure to iodinated contrast media (CM). The present study was initiated to explore the role of known human risk factors (spontaneous hypertension, diabetes, protein-losing nephropathy) on CIN development in rodent models and to determine the effect of CM administration on kidney injury biomarkers in the face of preexisting kidney injury. Spontaneously hypertensive rats (hypertension), streptozotocin-treated Sprague Dawley rats (diabetes), and Dahl salt-sensitive rats (protein-losing nephropathy) were given single intravenous injections of the nonionic, low osmolar contrast medium, iohexol. Blood urea nitrogen (BUN), serum creatinine (sCr), and urinary biomarkers; albumin, lipocalin 2 (Lcn-2), osteopontin (Opn), kidney injury molecule 1 (Kim-1), renal papillary antigen 1 (Rpa-1), α-glutathione S-transferase (α-Gst), µ-glutathione S-transferase (µ-Gst), and beta-2 microglobulin (β2m) were measured in disease models and appropriate controls to determine the response of these biomarkers to CM administration. Each disease model produced elevated biomarkers of kidney injury without CM. Preexisting histopathology was exacerbated by CM but little or no significant increases in biomarkers were observed. When 1.5-fold or greater sCr increases from pre-CM were used to define true positives, receiver-operating characteristic curve analysis of biomarker performance showed sCr was the best predictor of CIN across disease models. β2m, Lcn-2, and BUN were the best predictors of histopathology defined kidney injury.

  8. Effect of dual-type oligosaccharides on constipation in loperamide-treated rats

    PubMed Central

    Han, Sung Hee; Hong, Ki Bae; Kim, Eun Young; Ahn, So Hyun

    2016-01-01

    BACKGROUND/OBJECTIVES Constipation is a condition that can result from intestinal deformation. Because humans have an upright posture, the effects of gravity can cause this shape deformation. Oligosaccharides are common prebiotics and their effects on bowel health are well known. However, studies of the physiological functionality of a product that contains both lactulose and galactooligosaccharides are insufficient. We investigated the constipation reduction effect of a dual-type oligosaccharide, Dual-Oligo, in loperamide-treated rats. MATERIALS/METHODS Dual-Oligo consists of galactooligosaccharides (15.80%) and lactulose (51.67%). Animals were randomly divided into four groups, the normal group (normal), control group (control), low concentration of Dual-Oligo (LDO) group, and high concentration of Dual-Oligo (HDO) group. After 7 days of oral administration, fecal pellet amount, fecal weight, water content of fecal were measured. Blood chemistry, short-chain fatty acid (SCFA), gastrointestinal transit ratio and length and intestinal mucosa were analyzed. RESULTS Dual-Oligo increased the fecal weight, and water content of feces in rats with loperamide-induced constipation. Gastrointestinal transit ratio and length and area of intestinal mucosa significantly increased after treatment with Dual-Oligo in loperamide-induced rats. A high concentration of Dual-Oligo tended to produce more acetic acid than that observed for the control group, and Dual-Oligo affected the production of total SCFA. Bifidobacteria concentration of cecal contents in the high-concentration oligosaccharide (HDO) and low-concentration oligosaccharide (LDO) groups was similar to the result of the normal group. CONCLUSIONS These results showed that Dual-Oligo is a functional material that is derived from a natural food product and is effective in ameliorating constipation. PMID:27909555

  9. Effect of propofol on brain-derived neurotrophic factor and tyrosine kinase receptor B in the hippocampus of aged rats with chronic cerebral ischemia.

    PubMed

    Chen, Gang; Fu, Qiang; Cao, Jiangbei; Mi, Weidong

    2012-07-25

    We intraperitoneally injected 10 and 50 mg/kg of propofol for 7 consecutive days to treat a rat model of chronic cerebral ischemia. A low-dose of propofol promoted the expression of brain-derived neurotrophic factor, tyrosine kinase receptor B, phosphorylated cAMP response element binding protein, and cAMP in the hippocampus of aged rats with chronic cerebral ischemia, but a high-dose of propofol inhibited their expression. Results indicated that the protective effect of propofol against cerebral ischemia in aged rats is related to changes in the expression of brain-derived neurotrophic factor and tyrosine kinase receptor B in the hippocampus, and that the cAMP-cAMP responsive element binding protein pathway is involved in the regulatory effect of propofol on brain-derived neurotrophic factor expression.

  10. Cofactor metals and antioxidant enzymes in cisplatin-treated rats: effect of antioxidant intervention.

    PubMed

    Sabuncuoglu, Suna; Eken, Ayse; Aydin, Ahmet; Ozgunes, Hilal; Orhan, Hilmi

    2015-10-01

    We explored the association between the activities of antioxidant enzymes and their metallic cofactors in rats treated with cisplatin. The antioxidant effects of aminoguanidine, and a combination of vitamins E and C were investigated. Plasma platin was significantly lower than liver and kidney. Cisplatin treatment caused significant increase in plasma Se-glutathione peroxidase activity. Activities of Se-glutathione peroxidase, glutathione S-transferase, catalase and Cu,Zn-superoxide dismutase have been found to be significantly decreased in liver and kidney compared to controls. Zn levels in these organs were diminished upon cisplatin treatment, while levels of Cu were unaffected. Interestingly, levels of iron, the cofactor of catalase, were found to be significantly increased in liver and kidney. Intervention with aminoguanidine or vitamins was generally prevented cisplatin-caused changes in the activity of enzymes and in the tissue levels of cofactor metals. These observations suggest that relation between activities of enzymes and levels of cofactor metals is multifactorial.

  11. Kinetics of changes in the crypts of the jejunal mucosa of dimethylhydrazine-treated rats.

    PubMed Central

    Sunter, J. P.; Appleton, D. R.; Wright, N. A.; Watson, A. J.

    1978-01-01

    When symmetrical 1,2 dimethylhydrazine was administered to rats by weekly s.c. injection, 37% of the animals had developed small intestinal carcinomas after 21-27 weeks. These lesions were largely localized to duodenum and upper jejunum. At the same time there was a diffuse crypt hyperplasia in the jejunum which affected all the treated animals, not just those with neoplasms. This marked hyperplasia was preceded by a modest sustained crypt elongation which was seen soon after DMH injections began. In these hyperplastic jejunal crypts the absolute size of the proliferative compartment was increased, but the growth fraction calculated from labelling studies appeared to fall, probably by reduction in relative size of the proliferating population within the proliferative compartment. No convincing alteration in actual cell-cycle time was observed in the abnormal crypts. There was a slight (25%) increase in cell-production rate in the abnormal crypts. Images Fig. 1 PMID:656298

  12. Demonstration of direct lineage between hepatocytes and hepatocellular carcinoma in diethylnitrosamine-treated rats.

    PubMed

    Bralet, Marie-Pierre; Pichard, Virginie; Ferry, Nicolas

    2002-09-01

    The question whether hepatocellular carcinoma (HCC) arises from dedifferentiation of mature hepatocytes or from proliferation of liver stem cells is still debated. In the present study, we used retroviral-mediated genetic labeling to investigate the fate of mature hepatocytes in rats after administration of diethylnitrosamine (DEN). Mature hepatocytes were genetically labeled by intravenous injection of retroviral vectors containing the Escherichia coli beta-galactosidase gene coupled to a nuclear localization signal (nls-LacZ) 1 day after partial hepatectomy. Liver biopsies performed after completion of hepatic regeneration showed that 18.3% of hepatocytes expressed the nls-LacZ transgene. Rats were then treated with DEN in drinking water for 12 weeks and sacrificed between 98 and 151 days after the onset of DEN administration. Clones of beta-galactosidase positive cells were observed, half of which (53%) also expressed the placental form of glutathione-S-transferase (GSTp), a marker of preneoplastic cells. HCCs of various sizes expressing GSTp were present in all animals. Careful examination of 90 HCCs revealed that 16 (17.7%) also expressed nls-LacZ. This figure precisely matched the proportion of labeled hepatocytes before DEN treatment (18.3%). In conclusion, a random clonal origin of HCC from mature hepatocytes is seen in the DEN model of hepatocarcinogenesis.

  13. Effect of retinyl acetate on transglutaminase 2 activity in carcinogen treated rat liver.

    PubMed

    Aydin, O; Akyuz, F; Tekin, N; Ustuner, Mc; Degirmenci, I; Burukoglu, D; Ozden, H

    2016-07-01

    Transglutaminase 2 (TG2) has been implicated in wound healing, cellular differentiation, apoptosis and cell survival. TG2 activity increases following acute and chronic liver injury; however, the role of TG2 in tumors, is controversial. TG2 is a retinoid-inducible enzyme. We investigated the effects of retinyl acetate (RA) on the activity and levels of TG2 during the initiation and promotion stages of liver cancer. p-Dimethylaminoazobenzene (p-DAB) was used as initiator and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) was used as promoter in our model of carcinogenesis. Rats were divided into four groups of 24: control, corn oil control, p-DAB + TCDD, and p-DAB + TCDD + RA. Six rats from each group were sacrificed at days 30, 60, 90 and 120. TG2 activity decreased in the p-DAB + TCDD treated group, but TG2 immunostaining scores did not change by days 90 and 120. Neither TG2 enzyme activity nor the immunostaining score of TG2 protein changed in the tissues of the p-DAB + TCDD + RA group by days 90 and 120. TG2 activity was not be ameliorated by RA during the initiation or promotion stages of carcinogen induced liver cancer.

  14. Effects of fermented Cordyceps sinensis on oxidative stress in doxorubicin treated rats

    PubMed Central

    Wu, Rong; Gao, Jian-Ping; Wang, Hui-Lin; Gao, Yan; Wu, Qian; Cui, Xiao-Hua

    2015-01-01

    Background: Cordyceps sinensis (CS) is one of the rare traditional Chinese herbs, only a very limited amount of natural CS is produced. Fermented CS, as a substitute for natural CS, is widely used in the field of supplementary medical treatment and health products. Its antagonistic effect on oxidative stress (OS) in vivo has not been investigated. Objective: Our aim was to investigate the antagonistic effect of fermented CS on OS in doxorubicin (DOX) treated rats and to compare the anti-OS effects in heart and liver tissues. Materials and Methods: OS rats were induced by tail-intravenous injection of DOX (total of 7.5 mg/kg), and then administered intragastrically with fermented CS (1.5 g/kg) for 4 weeks. At the end of the experiment, heart, liver and serum samples were taken for and biochemical analyses. Results: Fermented CS significantly increased the activities of glutathione peroxidase and catalase and the scavenging activity of O2− in serum, and the total superoxide dismutase activity in cardiac tissue; reduced the malondialdehyde content in liver and cardiac tissues. Conclusion: Fermented CS can inhibit DOX-induced OS reactions, and the anti-OS effects have high selectivity to heart and liver, especially to heart. Thus, fermented CS may be a candidate used for the prevention against various cardiac diseases induced by OS. PMID:26600716

  15. Lipid peroxidation and antioxidant system in rats acutely treated with acetone.

    PubMed

    Mathias, M G; Almeida, B B de; Bueno, J E; Portari, G V; Jordao, A A

    2010-06-01

    Cascades of metabolic changes leading to acetone production are induced in states of energy catabolism such as starvation or the use of a ketogenic diet. The reduced capacity for cell detoxification or the increased generation of free radicals is responsible for the toxic effect of acetone. The objective of the present study was to determine the effects of acute treatment (AT) with acetone on the oxidative and metabolic status of rats. The AT group (n=16) was treated by gavage with a single administration of 7.0 g acetone/kg body weight at a concentration of 25% (m/v). Eight rats were euthanized 6 h later (AT6) and eight 24 h later (AT24). Acetone levels were determined in blood and urine and oxidative parameters were analyzed by determining thiobarbituric acid reactive species (TBARS, indicators of lipid peroxidation) and reduced glutathione (GSH) and vitamin E as antioxidant parameters. Serum glucose, blood cholesterol and triglycerieds and hepatic fat were also determined. The results indicated a significant difference in the hepatic oxidative parameters, serum glucose and in plasma triglycerides between the groups. Thus, we conclude that the administration of acute acetone doses can promote changes in some biochemical parameters and in the hepatic oxidative profile.

  16. Age- and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

    EPA Pesticide Factsheets

    Differences in various mitochondrial bioenergetics parameters in different brain regions in different age groups.This dataset is associated with the following publication:Pandya, J.D., J. Royland , R.C. McPhail, P.G. Sullivan, and P. Kodavanti. Age-and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats. NEUROBIOLOGY OF AGING. Elsevier Science Ltd, New York, NY, USA, 42: 25-34, (2016).

  17. Metabolomic profiling reveals severe skeletal muscle group-specific perturbations of metabolism in aged FBN rats.

    PubMed

    Garvey, Sean M; Dugle, Janis E; Kennedy, Adam D; McDunn, Jonathan E; Kline, William; Guo, Lining; Guttridge, Denis C; Pereira, Suzette L; Edens, Neile K

    2014-06-01

    Mammalian skeletal muscles exhibit age-related adaptive and pathological remodeling. Several muscles in particular undergo progressive atrophy and degeneration beyond median lifespan. To better understand myocellular responses to aging, we used semi-quantitative global metabolomic profiling to characterize trends in metabolic changes between 15-month-old adult and 32-month-old aged Fischer 344 × Brown Norway (FBN) male rats. The FBN rat gastrocnemius muscle exhibits age-dependent atrophy, whereas the soleus muscle, up until 32 months, exhibits markedly fewer signs of atrophy. Both gastrocnemius and soleus muscles were analyzed, as well as plasma and urine. Compared to adult gastrocnemius, aged gastrocnemius showed evidence of reduced glycolytic metabolism, including accumulation of glycolytic, glycogenolytic, and pentose phosphate pathway intermediates. Pyruvate was elevated with age, yet levels of citrate and nicotinamide adenine dinucleotide were reduced, consistent with mitochondrial abnormalities. Indicative of muscle atrophy, 3-methylhistidine and free amino acids were elevated in aged gastrocnemius. The monounsaturated fatty acids oleate, cis-vaccenate, and palmitoleate also increased in aged gastrocnemius, suggesting altered lipid metabolism. Compared to gastrocnemius, aged soleus exhibited far fewer changes in carbohydrate metabolism, but did show reductions in several glycolytic intermediates, fumarate, malate, and flavin adenine dinucleotide. Plasma biochemicals showing the largest age-related increases included glycocholate, heme, 1,5-anhydroglucitol, 1-palmitoleoyl-glycerophosphocholine, palmitoleate, and creatine. These changes suggest reduced insulin sensitivity in aged FBN rats. Altogether, these data highlight skeletal muscle group-specific perturbations of glucose and lipid metabolism consistent with mitochondrial dysfunction in aged FBN rats.

  18. Effects of age on aneural regeneration of soleus muscle in rat.

    PubMed Central

    Lewis, D M; Schmalbruch, H

    1995-01-01

    1. The ability of autografted soleus muscles to regenerate without innervation was investigated in young (two groups: 17 days or 35 g and 5 weeks or 100 g) and old (10 weeks or 300 g and 19 months or 700 g) rats. 2. Tetanic force and fibre area of the regenerated muscles were followed in 35, 100 and 300 g rats and found to reach a maximum 10-15 days after the operation and then declined. 3. Maximal tetanic force and fibre area were greater in old than in young rats; the largest increase was seen between 100 and 300 g rats. The relaxation phase of the twitch became shorter in the 700 g animals. The force per cross-sectional area appeared to fall with age. The length of the new fibres, inferred from the width of the length-force curve, increased only slightly with age. 4. Ten days after grafting, autophagocytosis of necrotic fibres was completed in young but not in old rats. The new fibres in young rats had one central nucleus per cross-section and fibre size was unimodally distributed; fibres in old rats had multiple internal nuclei and the size distribution was bimodal due to the presence of large fibres. 5. Previous results indicating greater muscle regeneration in young than in old rats may reflect more vigorous reinnervation in young animals rather than a greater myogenic potential. Increased fibre size of regenerated muscles of old compared with young rats may be attributed to the larger amount of necrotic material which is mitogenic for satellite cells, or to age-dependent changes of the expression of cell adhesion molecules. Enhanced lateral fusion of myotubes would give rise to large fibres with multiple internal nuclei. Images Figure 3 Figure 4 PMID:8568686

  19. Dialysable and non-dialysable hydroxyproline in the rat's urine: age related and diurnal variations

    PubMed Central

    Gaggi, Renato; Gianni, Anna Maria; Montanaro, Nicola

    1982-01-01

    1. Urinary dialysable and non-dialysable hydroxyproline, which are considered good indices of bone resorption and neoformation respectively, were determined in rats under conditions that modify skeleton metabolism, such as body growth and parathyroid or calcitonin administration. It was also investigated whether dialysable and non-dialysable hydroxyproline excretions showed significant circadian fluctuations in rats of different ages. 2. Dialysable hydroxyproline excretion sharply decreased from the first to the fifth months of age and underwent further gradual reduction up to the fourteenth month of life. Non-dialysable hydroxyproline excretion followed a smoother decrease up to the fifth month, then remained constant. Urinary excretion of non-dialysable hydroxyproline expressed as a percentage of the total hydroxyprolinuria (n.d.%) slowly increased with advancing rat age. 3. In 2-, 4- and 6-month old rats, dialysable hydroxyproline excretion showed significant circadian fluctuations with minima and maxima at the end of the dark and light fraction of the cycle respectively. Daily fluctuations were greater in young and adult rats (50-65% of the respective average levels) than in 4-month old rats (25%). Non-dialysable hydroxyproline excretion followed similar but less pronounced patterns. Significant circadian fluctuations of n.d.% were detectable only in 2- and 4-month old rats, with peaks at 04.00-05.00 hr, thus indicating that the bone formation/resorption ratio increased in the nocturnal fraction of the cycle. 4. Young rats administered with calcitonin exhibited reduced levels of urinary dialysable but not of non-dialysable hydroxyproline when the hormone was given at 13.30 hr. No changes were observed when calcitonin was injected at 19.30 hr. On the contrary, both diurnal and nocturnal parathyroid hormone administration to young rats caused increased levels of dialysable and non-dialysable hydroxyproline of the same magnitude. PMID:7202048

  20. Changes in calcium status in aged rats fed Lactobacillus GG and Bifidobacterium lactis and oligofructose-enriched inulin.

    PubMed

    Naughton, Violetta; McSorley, Emeir; Naughton, Patrick J

    2011-02-01

    In this study we hypothesized that an increase in numbers of beneficial bacteria in the large intestine can affect calcium (Ca) status in the elderly. Adult and aged rats were fed a diet with or without synbiotics for 21 days. Synbiotics increased the numbers of lactobacilli and bifidobacteria in large intestine in both adult and aged rats. The plasma Ca concentration was significantly increased while osteocalcin concentration was significantly decreased only in aged rats fed synbiotics.

  1. Reduced RANKL expression impedes osteoclast activation and tooth eruption in alendronate-treated rats.

    PubMed

    Bradaschia-Correa, Vivian; Moreira, Mariana M; Arana-Chavez, Victor E

    2013-07-01

    The creation of the eruption pathway requires the resorption of the occlusal alveolar bone by osteoclasts and signaling events between bone and dental follicle are necessary. The aim of the present study has been to evaluate the effect of alendronate on osteoclastogenesis and the expression of the regulator proteins of osteoclast activation, namely RANK, RANKL and OPG, in the bone that covers the first molar germ. Newborn Wistar rats were treated daily with 2.5 mg/kg alendronate for 4, 8, 14, 21 and 28 days, whereas controls received sterile saline solution. At the time points cited, maxillae were fixed, decalcified and processed for light and electron microscopic analysis. TRAP histochemistry was performed on semi-serial sections and the osteoclasts in the occlusal half of the bony crypt surface were counted. TUNEL analysis was carried out on paraffin sections. The occlusal bone that covers the upper first molar was removed in additional 4- and 8-day-old alendronate-treated and control rats in which the expression of RANK, RANKL and OPG was analyzed by SDS-polyacrylamide gel electrophoresis and Western blotting. TRAP-positive osteoclasts were more numerous in the alendronate group at all time points, despite their unactivated phenotype and the presence of apoptotic cells. RANKL expression in the alendronate specimens was inhibited at all time points, unlike in controls. Our findings indicate that the expression of RANKL in the occlusal portion of the bony crypt is unrelated to osteoclast recruitment and differentiation but is crucial to their activation during the creation of the eruption pathway.

  2. Glutamate co-transmission from developing medial nucleus of the trapezoid body--lateral superior olive synapses is cochlear dependent in kanamycin-treated rats.

    PubMed

    Lee, Jae Ho; Pradhan, Jonu; Maskey, Dhiraj; Park, Ki Sup; Hong, Sung Hwa; Suh, Myung-Whan; Kim, Myeung Ju; Ahn, Seung Cheol

    2011-02-11

    Cochlear dependency of glutamate co-transmission at the medial nucleus of the trapezoid body (MNTB)--the lateral superior olive (LSO) synapses was investigated using developing rats treated with high dose kanamycin. Rats were treated with kanamycin from postnatal day (P) 3 to P8. A scanning electron microscopic study on P9 demonstrated partial cochlear hair cell damage. A whole cell voltage clamp experiment demonstrated the increased glutamatergic portion of postsynaptic currents (PSCs) elicited by MNTB stimulation in P9-P11 kanamycin-treated rats. The enhanced VGLUT3 immunoreactivities (IRs) in kanamycin-treated rats and asymmetric VGLUT3 IRs in the LSO of unilaterally cochlear ablated rats supported the electrophysiologic data. Taken together, it is concluded that glutamate co-transmission is cochlear-dependent and enhanced glutamate co-transmission in kanamycin-treated rats is induced by partial cochlear damage.

  3. Soluble Milk Protein Supplementation with Moderate Physical Activity Improves Locomotion Function in Aging Rats

    PubMed Central

    Lafoux, Aude; Baudry, Charlotte; Bonhomme, Cécile; Le Ruyet, Pascale; Huchet, Corinne

    2016-01-01

    Aging is associated with a loss of muscle mass and functional capacity. Present study was designed to compare the impact of specific dairy proteins on muscular function with or without a low-intensity physical activity program on a treadmill in an aged rat model. We investigated the effects of nutritional supplementation, five days a week over a 2-month period with a slow digestible protein, casein or fast digestible proteins, whey or soluble milk protein, on strength and locomotor parameters in sedentary or active aged Wistar RjHan rats (17–19 months of age). An extensive gait analysis was performed before and after protein supplementation. After two months of protein administration and activity program, muscle force was evaluated using a grip test, spontaneous activity using an open-field and muscular mass by specific muscle sampling. When aged rats were supplemented with proteins without exercise, only minor effects of different diets on muscle mass and locomotion were observed: higher muscle mass in the casein group and improvement of stride frequencies with soluble milk protein. By contrast, supplementation with soluble milk protein just after physical activity was more effective at improving overall skeletal muscle function in old rats compared to casein. For active old rats supplemented with soluble milk protein, an increase in locomotor activity in the open field and an enhancement of static and dynamic gait parameters compared to active groups supplemented with casein or whey were observed without any differences in muscle mass and forelimb strength. These results suggest that consumption of soluble milk protein as a bolus immediately after a low intensity physical activity may be a suitable nutritional intervention to prevent decline in locomotion in aged rats and strengthen the interest to analyze the longitudinal aspect of locomotion in aged rodents. PMID:27973615

  4. Increased myogenic repressor Id mRNA and protein levels in hindlimb muscles of aged rats.

    PubMed

    Alway, Stephen E; Degens, Hans; Lowe, Dawn A; Krishnamurthy, Gururaj

    2002-02-01

    The objective of this study was to determine if levels of repressors to myogenic regulatory factors (MRFs) differ between muscles from young adult and aged animals. Total RNA from plantaris, gastrocnemius, and soleus muscles of Fischer 344 x Brown Norway rats aged 9 mo (young adult, n = 10) and 37 mo (aged, n = 10) was reverse transcribed and then amplified by PCR. To obtain a semiquantitative measure of the mRNA levels, PCR signals were normalized to cyclophilin or 18S signals from the corresponding reverse transcription product. Normalization to cyclophilin and 18S gave similar results. The mRNA levels of MyoD and myogenin were approximately 275-650% (P < 0.001) and approximately 500-1,100% (P < 0.001) greater, respectively, in muscles from aged compared with young adults. In contrast, the protein levels were lower in plantaris and gastrocnemius muscles and similar in the soleus muscle of aged vs. young adult rats. Id repressor mRNA levels were approximately 300-900% greater in fast and slow muscles of aged animals (P < or = 0.02), and Mist 1 mRNA was approximately 50% greater in the plantaris and gastrocnemius muscles (P < 0.01). The mRNA level of Twist mRNA was not significantly affected by aging. Id-1, Id-2, and Id-3 protein levels were approximately 17-740% greater (P < 0.05) in hindlimb muscles of aged rats compared with young adult rats. The elevated levels of Id mRNA and protein suggest that MRF repressors may play a role in gene regulation of fast and slow muscles in aged rats.

  5. Mitochondrial dysfunction in rat brain with aging Involvement of complex I, reactive oxygen species and cardiolipin.

    PubMed

    Petrosillo, G; Matera, M; Casanova, G; Ruggiero, F M; Paradies, G

    2008-11-01

    Reactive oxygen species (ROS) are considered a key factor in brain aging process. Mitochondrial respiration is an important site of ROS production and hence a potential contributor to brain functional changes with aging. In this study we examined the effect of aging on complex I activity, oxygen consumption, ROS production and phospholipid composition in rat brain mitochondria. The activity of complex I was reduced by 30% in brain mitochondria from 24 months aged rats relative to young animals. These changes in complex I activity were associated with parallel changes in state 3 respiration. H(2)O(2) generation was significantly increased in mitochondria isolated from aged rats. The mitochondrial content of cardiolipin, a phospholipid required for optimal activity of complex I, decreased by 31% as function of aging, while there was a significant increase in the level of peroxidized cardiolipin. The age-related decrease in complex I activity in brain mitochondria could be reversed by exogenously added cardiolipin. This effect of cardiolipin could not be replaced by other phospholipids. It is proposed that aging causes brain mitochondrial complex I dysfunction which can be attributed to ROS-induced cardiolipin oxidation. These findings may prove useful in elucidating the mechanism underlying mitochondrial dysfunction associated with brain aging.

  6. Benefits of caloric restriction in the myenteric neuronal plasticity in aging rats.

    PubMed

    Pereira, Joice N B; Mari, Renata B; Stabille, Sandra R; de Faria, Haroldo G; Mota, Thais F M; Ferreira, Walter M

    2014-09-01

    Aging is a biologic process characterized by progressive damage of structures and functions of organic systems. In gastrointestinal tract, it can involve enteric nervous system, which plays an important role in digestion and absorption of nutrients, causing hastening of intestinal transit thus reducing its absorptive function. Caloric restriction has been used in several studies with the intention of delaying deleterious effects of aging. This study aimed to evaluate the effects of caloric restriction on myenteric neurons of ileum by aging in rats. 30 Wistar rats were grouped as follows: GI (animals aged 6 months fed with normal diet), GII (animals aged 18 months fed with normal diet) and GIII (animals aged 18 months subject to 31% of caloric restriction). The rats of the GI group were euthanized at 6 months of age and after experimental period of 12 months animals of the group GII and GIII were euthanized, the ileum of all groups were collected, measured and processed by NADPH-dp and Acetylcholinesterase. Quantitative analysis of neurons revealed that aging promotes the increasing of myenteric neurons NADPH-dp and reduces Acetylcholinesterase neuronal population. However, in the cellular profile area, were not observed significant differences between the groups. The caloric restriction has been efficient and can be used preventively because it minimizes quantitative changes associated with aging on ileum myenteric plexuses.

  7. Age-related change of endocytic receptors megalin and cubilin in the kidney in rats.

    PubMed

    Odera, Keiko; Goto, Sataro; Takahashi, Ryoya

    2007-10-01

    Megalin and cubilin are the major endocytic receptors responsible for resorption of glomerular filtrate proteins, particularly albumin, in the renal proximal tubule. In order to better understand the mechanism of the development of albuminuria with age in rats, we investigated age-related change of the amount and cellular localization of both receptors in the kidney. Immunoblot analysis of the kidney extracts showed that the amount of megalin significantly decreased with age. Although there was no age-related change in the amount of intact cubilin, the amount of cubilin fragments increased with age. Immunohistochemical study revealed that megalin and cubilin were predominantly localized in brush border membrane of proximal tubular cells in young rats, but the receptors tended to diffuse into the cytoplasm in the old rats. Interestingly, low but significant amounts of megalin and cubilin were present in the glomerular cells in addition to the proximal tubular cells. The quantity of receptors progressively increased in the glomerulus with age. This age-related increase might be to compensate for the age-related defect of the uptake of albumin by the proximal tubules. Thus, although it is unclear whether megalin and cubilin in the glomerulus contribute to the uptake of albumin in primary urine, the age-related increase in the amount of albumin in urine might at least partly be due to quantitative and qualitative alterations of both receptors in the proximal tubule.

  8. Effect of chronic treatments with GH, melatonin, estrogens, and phytoestrogens on oxidative stress parameters in liver from aged female rats.

    PubMed

    Kireev, R A; Tresguerres, A F; Vara, E; Ariznavarreta, C; Tresguerres, J A F

    2007-10-01

    The aging theory postulates that this process may be due to the accumulation of oxidative damage in cells and molecules. The present study has investigated the effect of castration in old female rats on various parameters related to the antioxidant properties of several cellular fractions obtained from the liver, and the influence of several chronic treatments on it, both in intact and castrated animals. Sixty-one 22-month-old Wistar female rats, were used. About 21 intact animals were divided into three groups and treated for 10 weeks with GH, melatonin or saline, and 40 ovariectomized (at 12 months of age) animals were divided into five groups and treated for the same time with GH, melatonin, estrogens (Eos), phytoestrogens (Phyt) or saline. All animals were sacrificed at 24 months of age by decapitation. The activity of glutathione peroxidase (GPx) in cytosolic fraction, glutathione-S-transferase (GST) in cytosol and microsomal fractions, and the levels of nitric oxide (NO) and cytochrome C in mitochondrial and cytosol fractions of liver were determined. A decrease in GST activity was detected in cytosol and in the microsomal fraction in ovariectomized animals as compared to intact rats. The activity of GPx was also decreased in ovariectomized as compared with the intact group. NO level was increased and cytochrome C decreased in the mitochondrial fraction of the liver in ovariectomized females as compared with the intact group, respectively. No significant changes after melatonin or GH treatments were found in GPx, GST activity and NO level in mitochondrial fraction in the intact group. Administration of GH, melatonin, Eos and Phyt in the ovariectomized groups significantly increased the GPx, and GST activity in the cytosol and microsomal fraction and decreased the level of NO in the mitochondrial fraction as compared with the untreated rats. A significant increase in the level of cytochrome C in the mitochondrial fraction and a decrease in the cytosol fraction

  9. Endothelium-dependent relaxation in pulmonary arteries of L-NAME-treated Wistar and stroke-prone spontaneously hypertensive rats.

    PubMed

    Sekiguchi, Fumiko; Yamamoto, Kazuo; Matsuda, Kyoko; Kawata, Kyoko; Negishi, Maki; Shinomiya, Kazuaki; Shimamur, Keiichi; Sunano, Satoru

    2002-10-01

    To evaluate whether the elevated blood pressure induced by chronic treatment with N(omega)-nitro-L-arginine methyl ester (L-NAME) contributes to an impairment of endothelium-dependent relaxation (EDR), the effects of chronic treatment of Wistar rats with L-NAME on systolic blood pressure, pulmonary arterial blood pressure and EDR of the pulmonary arteries were studied and compared with those of stroke-prone spontaneously hypertensive rats (SHRSP). While the systolic blood pressure (SBP) of Wistar rats was increased above that of controls by chronic treatment with L-NAME, it was still significantly lower than that of SHRSP. Chronic treatment with L-NAME did not affect pulmonary arterial blood pressure. On the other hand, the pulmonary arterial blood pressure of SHRSP was slightly but significantly higher than that of the control normotensive Wistar Kyoto rats (WKY). EDR in response to acetylcholine in the pulmonary artery of L-NAME-treated rats was significantly smaller than that in control Wistar rats. The EDR markedly increased in the presence of L-arginine and completely disappeared in the presence of N(omega)-nitro-L-arginine. Indomethacin hardly affected EDR. In preparations from SHRSP, the EDR was not different from that in those from WKY. Relaxation induced by sodium nitroprusside was identical in all preparations. Elevation of SBP and the impairment of EDR observed in L-NAME-treated rats recovered two weeks following cessation of treatment. These results suggest that the impaired EDR in the pulmonary artery of L-NAME-treated rats is not due to an L-NAME-induced increase in blood pressure but due to the inhibition of nitric oxide synthase by the drug remaining in the endothelium.

  10. Hepato- and nephroprotective effects of bradykinin potentiating factor from scorpion (Buthus occitanus) venom on mercuric chloride-treated rats

    PubMed Central

    Salman, Muhammad M. A.; Kotb, Ahmed M.; Haridy, Mohie A. M.; Hammad, Seddik

    2016-01-01

    Bioactive peptides such as bradykinin potentiating factor (BPF), have, anti-oxidative, anti-inflammatory, immunomodulatory and ameliorative effects in chronic diseases and play a potential role in cancer prevention. It is known that the liver and kidney accumulate inorganic mercury upon exposure, which often leads to mercury intoxication in these organs. In this study, we investigated the effect of bradykinin potentiating factor (BPF), a scorpion venom peptide, on mercuric chloride-induced hepatic and renal toxicity in rats. We used 20 adult male Albino rats divided into four equal groups: the first group was injected with saline (control); the second group was administered daily with mercuric chloride (HgCl2) for 2 weeks; the third group was administered with BPF twice weekly for 2 successive weeks, while the fourth group was exposed to BPF followed by HgCl2. We observed that HgCl2 treated rats had a significant increase in serum ALT, AST, ALP, creatinine and urea levels compared to control. Furthermore, HgCl2 treated rats showed a marked decrease in total proteins, albumin and uric acids compared to control. The previously studied parameters were not significantly changed in BPF pretreated rats compared to control. Moreover, a significant decrease in the activities of glutathione perioxidase (GSH), superoxide dismutase (SOD), and catalase (CAT), in addition to a significant increase in the level of malondialdehyde (MDA) were observed in hepatic and renal tissues of rats after HgCl2 treatment. In contrast, the HgCl2/BPF treated rats showed a significant elevation in the activity of GSH, SOD, and CAT accompanied with a significant regression in the level of MDA compared to the HgCl2 exposed rats. We conclude that treatment with BPF is a promising prophylactic approach for the management of mercuric chloride-induced hepato- and nephro-toxicities. PMID:28337111

  11. Age-related ultrastructural and monoamine oxidase changes in the rat optic nerve.

    PubMed

    Taurone, S; Ripandelli, G; Minni, A; Lattanzi, R; Miglietta, S; Pepe, N; Fumagalli, L; Micera, A; Pastore, F S; Artico, M

    2016-01-01

    The aim of this paper is to study the morphology and the distribution of the monoamine oxidase enzymatic system in the optic nerve of 4 month-old Wistar (young) and 28 month-old Wistar (old) rats. The optic nerve was harvested from 20 young and old rats. The segment of optic nerve was divided longitudinally into two pieces, each 0.1 mm in length. The first piece was used for transmission electron microscopy. The second piece was stained with histochemical reaction for monoamine oxidase. The agerelated changes in the optic nerve of rats include micro-anatomical details, ultrastructure and monoamine oxidase histochemical staining. A strong decrease of the thin nerve fibers and a swelling of the thick ones can be observed in optic nerve fibers of old rats. Increased monoamine oxidase histochemical staining of the optic nerve of aged rats is well demonstrated. The increase of meningeal shealth and the decrease of thin nerve fibers of the optic nerve in old rats are well documented. Morphological, ultrastructural and histochemical changes observed in optic nerve fibers of the old rats show a close relation with aging.

  12. Protein Synthesis Inhibitors Did Not Interfere with Long-Term Depression Induced either Electrically in Juvenile Rats or Chemically in Middle-Aged Rats

    PubMed Central

    2016-01-01

    In testing the hypothesis that long-term potentiation (LTP) maintenance depends on triggered protein synthesis, we found no effect of protein synthesis inhibitors (PSIs) on LTP stabilization. Similarly, some studies reported a lack of effect of PSIs on long-term depression (LTD); the lack of effect on LTD has been suggested to be resulting from the short time recordings. If this proposal were true, LTD might exhibit sensitivity to PSIs when the recording intervals were enough long. We firstly induced LTD by a standard protocol involving low frequency stimulation, which is suitable for eliciting NMDAR-LTD in CA1 area of hippocampal slices obtained from juvenile Sprague-Dawley rats. This LTD was persistent for intervals in range of 8–10 h. Treating slices with anisomycin, however, did not interfere with the magnitude and persistence of this form of LTD. The failure of anisomycin to block synaptic-LTD might be relied on the age of animal, the type of protein synthesis inhibitors and/or the inducing protocol. To verify whether those variables altogether were determinant, NMDA or DHPG was used to chemically elicit LTD recorded up to 10 h on hippocampal slices obtained from middle-aged rats. In either form of LTD, cycloheximide did not interfere with LTD stabilization. Furthermore, DHPG application did show an increase in the global protein synthesis as assayed by radiolabeled methodology indicating that though triggered protein synthesis can occur but not necessarily required for LTD expression. The findings confirm that stabilized LTD in either juvenile, or middle-aged rats can be independent of triggered protein synthesis. Although the processes responsible for the independence of LTD stabilization on the triggered protein synthesis are not yet defined, these findings raise the possibility that de novo protein synthesis is not universally necessary. PMID:27517693

  13. Protein Synthesis Inhibitors Did Not Interfere with Long-Term Depression Induced either Electrically in Juvenile Rats or Chemically in Middle-Aged Rats.

    PubMed

    Abbas, Abdul-Karim

    2016-01-01

    In testing the hypothesis that long-term potentiation (LTP) maintenance depends on triggered protein synthesis, we found no effect of protein synthesis inhibitors (PSIs) on LTP stabilization. Similarly, some studies reported a lack of effect of PSIs on long-term depression (LTD); the lack of effect on LTD has been suggested to be resulting from the short time recordings. If this proposal were true, LTD might exhibit sensitivity to PSIs when the recording intervals were enough long. We firstly induced LTD by a standard protocol involving low frequency stimulation, which is suitable for eliciting NMDAR-LTD in CA1 area of hippocampal slices obtained from juvenile Sprague-Dawley rats. This LTD was persistent for intervals in range of 8-10 h. Treating slices with anisomycin, however, did not interfere with the magnitude and persistence of this form of LTD. The failure of anisomycin to block synaptic-LTD might be relied on the age of animal, the type of protein synthesis inhibitors and/or the inducing protocol. To verify whether those variables altogether were determinant, NMDA or DHPG was used to chemically elicit LTD recorded up to 10 h on hippocampal slices obtained from middle-aged rats. In either form of LTD, cycloheximide did not interfere with LTD stabilization. Furthermore, DHPG application did show an increase in the global protein synthesis as assayed by radiolabeled methodology indicating that though triggered protein synthesis can occur but not necessarily required for LTD expression. The findings confirm that stabilized LTD in either juvenile, or middle-aged rats can be independent of triggered protein synthesis. Although the processes responsible for the independence of LTD stabilization on the triggered protein synthesis are not yet defined, these findings raise the possibility that de novo protein synthesis is not universally necessary.

  14. Beneficial effect of Boswellia serrata gum resin on spatial learning and the dendritic tree of dentate gyrus granule cells in aged rats

    PubMed Central

    Hosseini-Sharifabad, Mohammad; Kamali-Ardakani, Razieh; Hosseini-Sharifabad, Ali

    2016-01-01

    Objective: The hippocampal formation, particularly the dentate gyrus (DG), shows age-related morphological changes that could cause memory decline. It is indicated that Boswellia resins attenuates memory deficits and the major component of Boswellia serrata (Bs) gum resin, beta boswellic acid increased neurite outgrowth and branching in hippocampal neurons. This study was designed to investigate the effect of Boswellia treatment on spatial learning performance and the morphology of dentate granule cells in aged rats. Materials and Methods: Sixteen male Wistar rats (24 months old) were divided into experimental and control groups. Experimental group was intragastrically administered with the aqueous extract of Bs (100 mg/kg/d for 8 weeks) and control group received a similar volume of water. Spatial learning performance of rats was tested using Morris water maze task. At the end of experiment, the brain was removed and the right hippocampus was serially sectioned for morphometric analysis. The Cavalieri principle was employed to estimate the volume of the DG. A quantitative Golgi study was used to analyze the dendritic trees of dentate granule cells. Results: Chronic treatment with Bs improved spatial learning capability during the three acquisition days. Comparisons also revealed that Bs-treated aged rat had greater DG with increased dendritic complexity in the dentate granule cells than control rats. Hippocampal granule cells of Bs-treated aged rats had more dendritic segments, larger arbors, more numerical branching density and more dendritic spines in comparison to control animals. Conclusion: This study provided a neuro-anatomical basis for memory improvement due to chronic treatment with Bs. PMID:27222832

  15. Spontaneous malignant craniopharyngioma in an aged Wistar rat

    PubMed Central

    Heinrichs, Martin; Ernst, Heinrich

    2016-01-01

    Craniopharyngiomas are extremely rare epithelial tumors of the sellar region in human beings and domestic and laboratory animals. A craniopharyngioma, 0.6 cm in diameter, was observed grossly in the sellar and parasellar regions of an untreated 23-month-old male Wistar-derived rat sacrificed moribund. The tumor was composed of cords, columns, and nests of neoplastic stratified squamous epithelium with marked hyperkeratosis and parakeratosis. Neoplastic cells formed solid or cystic areas, infiltrating the base of the skull, brain, and pituitary gland. Immunocytochemical evaluation revealed a strong cytoplasmic reaction for pan-cytokeratin in all tumor cells. Malignant craniopharyngioma should be considered a differential diagnosis in the rat when a tumor with stratified squamous epithelial features and a locally aggressive growth pattern is observed in the sellar or suprasellar region. PMID:27559246

  16. Arginine-deficient diets alter plasma and tissue amino acids in young and aged rats.

    PubMed

    Gross, K L; Hartman, W J; Ronnenberg, A; Prior, R L

    1991-10-01

    Blood and urine metabolites were measured in two experiments for young (2-mo-old) and aged (20-mo-old) male Sprague-Dawley rats fed arginine-devoid diets made isonitrogenous to a control 1.12% arginine diet by adding alanine or glycine. Diet, fed for 7 or 13 d, had little effect on urinary or plasma ammonia and urea. Urinary orotate excretion was more than 40-fold higher in rats fed the arginine-deficient diets (P less than 0.01) in both experiments. Source of nonessential N (alanine or glycine) in the arginine-deficient diets did not alter orotic acid excretion or plasma or urine ammonia or urea. Changes in plasma arginine, alanine and glycine concentrations reflected the levels of these amino acids in the diet. Tissue ornithine levels reflected dietary arginine level, but tissue citrulline was unaffected by dietary arginine. Glutamate and glutamine were greater in the plasma and liver of rats fed arginine-deficient diets. Plasma concentrations of glutamate and glutamine were positively correlated with urinary orotic acid excretion (P less than 0.05) and ornithine and arginine were negatively correlated with orotic acid excretion (P less than 0.01). Increased tissue glutamine may be related to the greater orotate excretion in rats fed arginine-devoid diets. The metabolic responses to dietary arginine deficiency were similar in young and aged rats. In general, concentrations of amino acids in plasma, liver and spleen were higher in aged rats.

  17. Daily supplementation with mushroom (Agaricus bisporus) improves balance and working memory in aged rats.

    PubMed

    Thangthaeng, Nopporn; Miller, Marshall G; Gomes, Stacey M; Shukitt-Hale, Barbara

    2015-12-01

    Decline in brain function during normal aging is partly due to the long-term effects of oxidative stress and inflammation. Several fruits and vegetables have been shown to possess antioxidant and anti-inflammatory properties. The present study investigated the effects of dietary mushroom intervention on mobility and memory in aged Fischer 344 rats. We hypothesized that daily supplementation of mushroom would have beneficial effects on behavioral outcomes in a dose-dependent manner. Rats were randomly assigned to receive a diet containing either 0%, 0.5%, 1%, 2%, or 5% lyophilized white button mushroom (Agaricus bisporus); after 8 weeks on the diet, a battery of behavioral tasks was given to assess balance, coordination, and cognition. Rats on the 2% or 5% mushroom-supplemented diet consumed more food, without gaining weight, than rats in the other diet groups. Rats in the 0.5% and 1% group stayed on a narrow beam longer, indicating an improvement in balance. Only rats on the 0.5% mushroom diet showed improved performance in a working memory version of the Morris water maze. When taken together, the most effective mushroom dose that produced improvements in both balance and working memory was 0.5%, equivalent to about 1.5 ounces of fresh mushrooms for humans. Therefore, the results suggest that the inclusion of mushroom in the daily diet may have beneficial effects on age-related deficits in cognitive and motor function.

  18. Melatonin Counteracts at a Transcriptional Level the Inflammatory and Apoptotic Response Secondary to Ischemic Brain Injury Induced by Middle Cerebral Artery Blockade in Aging Rats.

    PubMed

    Paredes, Sergio D; Rancan, Lisa; Kireev, Roman; González, Alberto; Louzao, Pedro; González, Pablo; Rodríguez-Bobada, Cruz; García, Cruz; Vara, Elena; Tresguerres, Jesús A F

    2015-01-01

    Aging increases oxidative stress and inflammation. Melatonin counteracts inflammation and apoptosis. This study investigated the possible protective effect of melatonin on the inflammatory and apoptotic response secondary to ischemia induced by blockade of the right middle cerebral artery (MCA) in aging male Wistar rats. Animals were subjected to MCA obstruction. After 24 h or 7 days of procedure, 14-month-old nontreated and treated rats with a daily dose of 10 mg/kg melatonin were sacrificed and right and left hippocampus and cortex were collected. Rats aged 2 and 6 months, respectively, were subjected to the same brain injury protocol, but they were not treated with melatonin. mRNA expression of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), Bcl-2-associated death promoter (BAD), Bcl-2-associated X protein (BAX), glial fibrillary acidic protein (GFAP), B-cell lymphoma 2 (Bcl-2), and sirtuin 1 was measured by reverse transcription-polymerase chain reaction. In nontreated animals, a significant time-dependent increase in IL-1β, TNF-α, BAD, and BAX was observed in the ischemic area of both hippocampus and cortex, and to a lesser extent in the contralateral hemisphere. Hippocampal GFAP was also significantly elevated, while Bcl-2 and sirtuin 1 decreased significantly in response to ischemia. Aging aggravated these changes. Melatonin administration was able to reverse significantly these alterations. In conclusion, melatonin may ameliorate the age-dependent inflammatory and apoptotic response secondary to ischemic cerebral injury.

  19. Sodium-, potassium-, chloride-, and bicarbonate-related effects on blood pressure and electrolyte homeostasis in deoxycorticosterone acetate-treated rats.

    PubMed

    Ziomber, Agata; Machnik, Agnes; Dahlmann, Anke; Dietsch, Peter; Beck, Franz-Xaver; Wagner, Hubertus; Hilgers, Karl F; Luft, Friedrich C; Eckardt, Kai-Uwe; Titze, Jens

    2008-12-01

    Na(+) loading without Cl(-) fails to increase blood pressure in the DOCA model. We compared the changes in the total body (TB) effective Na(+), K(+), Cl(-), and water (TBW) content as well as in intracellular (ICV) or extracellular (ECV) volume in rats receiving DOCA-NaCl, DOCA-NaHCO(3), or DOCA-KHCO(3). We divided 42 male rats into 5 groups. Group 1 was untreated, group 2 received 1% NaCl, and groups 3, 4, and 5 were treated with DOCA and received 1% NaCl, 1.44% NaHCO(3), or 1.7% KHCO(3) to drink. We measured mean arterial blood pressure (MAP) directly after 3 wk. Tissue electrolyte and water content was measured by chemical analysis. Compared with control rats, DOCA-NaCl increased MAP while DOCA-NaHCO(3) and DOCA-KHCO(3) did not. DOCA-NaCl increased TBNa(+) 26% but only moderately increased TBW. DOCA-NaHCO(3) led to similar TBNa(+) excess, while TBW and ICV, but not ECV, were increased more than in DOCA-NaCl rats. DOCA-KHCO(3) did not affect TBNa(+) or volume. At a given TB(Na(+)+K(+)) and TBW, MAP in DOCA-NaCl rats was higher than in control, DOCA-NaHCO(3), and DOCA-KHCO(3) rats, indicating that hypertension in DOCA-NaCl rats was not dependent on TB(Na(+)+K(+)) and water mass balance. Skin volume retention was hypertonic compared with serum and paralleled hypertension in DOCA-NaCl rats. These rats had higher TB(Na(+)+K(+))-to-TBW ratio in accumulated fluid than DOCA-NaHCO(3) rats. DOCA-NaCl rats also had increased intracellular Cl(-) concentrations in skeletal muscle. We conclude that excessive cellular electrolyte redistribution and/or intracellular Na(+) or Cl(-) accumulation may play an important role in the pathogenesis of salt-sensitive hypertension.

  20. Yield Behavior of Solution Treated and Aged Ti-6Al-4V

    NASA Technical Reports Server (NTRS)

    Ring, Andrew J.; Baker, Eric H.; Salem, Jonathan A.; Thesken, John C.

    2014-01-01

    Post yield uniaxial tension-compression tests were run on a solution treated and aged (STA), titanium 6-percent aluminum 4-percent vanadium (Ti-6Al-4V) alloy to determine the yield behavior on load reversal. The material exhibits plastic behavior almost immediately on load reversal implying a strong Bauschinger effect. The resultant stress-strain data was compared to a 1D mechanics model and a finite element model used to design a composite overwrapped pressure vessel (COPV). Although the models and experimental data compare well for the initial loading and unloading in the tensile regime, agreement is lost in the compressive regime due to the Bauschinger effect and the assumption of perfect plasticity. The test data presented here are being used to develop more accurate cyclic hardening constitutive models for future finite element design analysis of COPVs.

  1. Evaluation of hyperdiploidy in the bladder epithelial cells of male F344 rats treated with ortho-phenylphenol.

    PubMed

    Balakrishnan, S; Eastmond, D A

    2003-05-09

    Ortho-phenylphenol (OPP) is a broad-spectrum fungicide and anti-bacterial agent that has been shown to cause bladder cancer in male F344 rats. An earlier study to investigate the potential role of aneuploidy in OPP-induced bladder carcinogenicity, failed to detect increases in frequencies of hyperdiploidy/polyploidy in treated animals, presumably due to the presence of polyploid cells in the bladder. To overcome this problem, we utilized a novel approach to determine increases in numerical alterations in the slowly dividing replicating cells of the rat bladder following treatment with OPP. Collagenase digestion of the bladder was used to enrich for actively-dividing cells and FISH in conjunction with BrdU was employed to detect hyperdiploidy in the replicating interphase cells. Initial studies were performed using FISH with a chromosome 4 probe. Follow-up studies were conducted with OPP and a positive control, vinblastine sulfate using probes for chromosomes 4 and 19. No significant increases in hyperdiploidy/polyploidy were seen in the replicating bladder cells of the OPP-treated rats using FISH with either the chromosome 4 or 19 probes. As expected, no significant increases in hyperdiploidy were seen in the non-replicating cells. In contrast, highly significant increases in hyperdiploidy/polyploidy, as detected using FISH with probes for either chromosome 4 or 19, were seen in the replicating cells from rats treated with a combination of OPP and vinblastine. The inability to detect increases in hyperdiploidy/polyploidy in the bladder of OPP-treated rats indicates that chromosome gain is unlikely to play a major role in the early genotoxic effects of OPP. However, the increase in hyperdiploidy/polyploidy induced by vinblastine sulfate in OPP-treated rats, clearly demonstrates that this approach using FISH in combination with BrdU is capable of detecting changes in chromosome number even in slowly-dividing tissues, such as the urinary bladder.

  2. Effects of exposure to heavy particles and aging on object recognition memory in rats

    NASA Astrophysics Data System (ADS)

    Rabin, Bernard; Joseph, James; Shukitt-Hale, Barbara; Carrihill-Knoll, Kirsty; Shannahan, Ryan; Hering, Kathleen

    Exposure to HZE particles produces changes in neurocognitive performance. These changes, including deficits in spatial learning and memory, object recognition memory and operant responding, are also observed in the aged organism. As such, it has been proposed that exposure to heavy particles produces "accelerated aging". Because aging is an ongoing process, it is possible that there would be an interaction between the effects of exposure and the effects of aging, such that doses of HZE particles that do not affect the performance of younger organisms will affect the performance of organisms as they age. The present experiments were designed to test the hypothesis that young rats that had been exposed to HZE particles would show a progressive deterioration in object recognition memory as a function of the age of testing. Rats were exposed to 12 C, 28 S or 48 Ti particles at the N.A.S.A. Space Radiation Laboratory at Brookhaven National Laboratory. Following irradiation the rats were shipped to UMBC for behavioral testing. HZE particle-induced changes in object recognition memory were tested using a standard procedure: rats were placed in an open field and allowed to interact with two identical objects for up to 30 sec; twenty-four hrs later the rats were again placed in the open field, this time containing one familiar and one novel object. Non-irradiated control animals spent significantly more time with the novel object than with the familiar object. In contrast, the rats that been exposed to heavy particles spent equal amounts of time with both the novel and familiar object. The lowest dose of HZE particles which produced a disruption of object recognition memory was determined three months and eleven months following exposure. The threshold dose needed to disrupt object recognition memory three months following irradiation varied as a function of the specific particle and energy. When tested eleven months following irradiation, doses of HZE particles that did

  3. Androgen-mediated development of irradiation-induced thyroid tumors in rats: dependence on animal age during interval of androgen replacement in castrated males

    SciTech Connect

    Hofmann, C.; Oslapas, R.; Nayyar, R.; Paloyan, E.

    1986-07-01

    When male Long-Evans rats at age 8 weeks were radiation treated (40 microCi Na131I), thyroid follicular adenomas and carcinomas were observed at age 24 months with a high incidence of 94%. Castration of males prior to irradiation significantly reduced this tumor incidence to 60%. When testosterone (T) was replaced in castrated, irradiated male rats, differentially increased incidences of thyroid tumors occurred. Immediate (age 2-6 mo) or early (age 6-12 mo) T replacem