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Sample records for albino male mice

  1. Assessment of imidacloprid-induced mutagenic effects in somatic cells of Swiss albino male mice.

    PubMed

    Bagri, Preeti; Kumar, Vinod; Sikka, Anil K

    2016-10-01

    Pesticides are being used for plant protection to increase food protection and to reduce insect-borne diseases worldwide. Exposure to the pesticides may cause genotoxic effects on both the target and nontarget organisms, including man. Therefore, the mutagenicity evaluation of such pesticides has become a priority area of research. Imidacloprid (IMI), a neonicotinoid insecticide, is widely used in agriculture either alone or in combination with other insecticides. A combined approach employing micronucleus test (MNT) and chromosomal aberrations assay (CA) was utilized to assess the mutagenicity of imidacloprid in bone marrow of Swiss albino male mice. IMI suspension was prepared in 3% gum acacia and administered at doses of 5.5, 11 and 22 mg/kg body weight for 7, 14 and 28 days to mice. IMI treatment resulted in a dose and time-dependant increase in the frequencies of micronuclei per cell and chromosomal aberrations in bone marrow cells. A statistically significant increase in chromosomal aberrations and micronuclei/cell was found only after daily treatment of IMI at highest selected dose (22 mg/kg body weight) for longest selected time period (28 days) compared to the control group. Thus, daily exposure of imidacloprid at a dose level of 22 mg/kg body weight for 28 days caused mutagenic effects on the somatic cells of Swiss albino male mice.

  2. Assessment of imidacloprid-induced mutagenic effects in somatic cells of Swiss albino male mice.

    PubMed

    Bagri, Preeti; Kumar, Vinod; Sikka, Anil K

    2016-10-01

    Pesticides are being used for plant protection to increase food protection and to reduce insect-borne diseases worldwide. Exposure to the pesticides may cause genotoxic effects on both the target and nontarget organisms, including man. Therefore, the mutagenicity evaluation of such pesticides has become a priority area of research. Imidacloprid (IMI), a neonicotinoid insecticide, is widely used in agriculture either alone or in combination with other insecticides. A combined approach employing micronucleus test (MNT) and chromosomal aberrations assay (CA) was utilized to assess the mutagenicity of imidacloprid in bone marrow of Swiss albino male mice. IMI suspension was prepared in 3% gum acacia and administered at doses of 5.5, 11 and 22 mg/kg body weight for 7, 14 and 28 days to mice. IMI treatment resulted in a dose and time-dependant increase in the frequencies of micronuclei per cell and chromosomal aberrations in bone marrow cells. A statistically significant increase in chromosomal aberrations and micronuclei/cell was found only after daily treatment of IMI at highest selected dose (22 mg/kg body weight) for longest selected time period (28 days) compared to the control group. Thus, daily exposure of imidacloprid at a dose level of 22 mg/kg body weight for 28 days caused mutagenic effects on the somatic cells of Swiss albino male mice. PMID:26823062

  3. Influence of black gram (Vigna mungo) trypsin inhibitory fraction on the hepatic protein catabolism in male albino mice.

    PubMed

    Kamalakannan, V; Sathyamoorthy, A V; Motlag, D B

    1984-01-01

    The effect of black gram and black gram trypsin inhibitor on the protein catabolism of male albino mice has been investigated. Group 1 was given autoclaved black gram (control), Group II raw black gram and Group III the autoclaved black gram incorporated with 1% black gram trypsin inhibitor. Blood as well as urinary urea and creatine were found to be elevated in Groups II and III. Increased levels of arginase, ornithine transcarbamylase and transaminases were noted in Groups II and III. The results suggested an enhanced catabolism of proteins evoked by the native black gram trypsin inhibitor.

  4. Effect of Olea oleaster and Juniperus procera leaves extracts on thioacetamide induced hepatic cirrhosis in male albino mice.

    PubMed

    Al-Attar, Atef M; Alrobai, Ali A; Almalki, Daklallah A

    2016-05-01

    The effect of Olea oleaster and Juniperus procera leaves extracts and their combination on thioacetamide (TAA)-induced hepatic cirrhosis were investigated in male albino mice. One hundred sixty mice were used in this study and were randomly distributed into eight groups of 20 each. Mice of group 1 served as controls. Mice of group 2 were treated with TAA. Mice of group 3 were exposed to TAA and supplemented with O. oleaster leaves extracts. Mice of group 4 were treated with TAA and supplemented with J. procera leaves extracts. Mice of group 5 were subjected to TAA and supplemented with O. oleaster and J. procera leaves extracts. Mice of groups 6, 7 and 8 were supplemented with O. oleaster, J. procera, and O. oleaster and J. procera leaves extracts respectively. Administration of TAA for six and twelve weeks resulted in a decline in body weight gain and increased the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin. Histopathological evaluations of hepatic sections from mice treated with TAA showed severe alterations including increase of fibrogenesis processes with structural damage. Treatment of mice with these extracts showed a pronounced attenuation in TAA induced hepatic cirrhosis associated with physiological and histopathological alterations. Finally, this study suggests that the supplementation of these extracts may act as antioxidant agents and could be an excellent adjuvant support in the therapy of hepatic cirrhosis.

  5. Effect of Olea oleaster and Juniperus procera leaves extracts on thioacetamide induced hepatic cirrhosis in male albino mice

    PubMed Central

    Al-Attar, Atef M.; Alrobai, Ali A.; Almalki, Daklallah A.

    2015-01-01

    The effect of Olea oleaster and Juniperus procera leaves extracts and their combination on thioacetamide (TAA)-induced hepatic cirrhosis were investigated in male albino mice. One hundred sixty mice were used in this study and were randomly distributed into eight groups of 20 each. Mice of group 1 served as controls. Mice of group 2 were treated with TAA. Mice of group 3 were exposed to TAA and supplemented with O. oleaster leaves extracts. Mice of group 4 were treated with TAA and supplemented with J. procera leaves extracts. Mice of group 5 were subjected to TAA and supplemented with O. oleaster and J. procera leaves extracts. Mice of groups 6, 7 and 8 were supplemented with O. oleaster, J. procera, and O. oleaster and J. procera leaves extracts respectively. Administration of TAA for six and twelve weeks resulted in a decline in body weight gain and increased the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin. Histopathological evaluations of hepatic sections from mice treated with TAA showed severe alterations including increase of fibrogenesis processes with structural damage. Treatment of mice with these extracts showed a pronounced attenuation in TAA induced hepatic cirrhosis associated with physiological and histopathological alterations. Finally, this study suggests that the supplementation of these extracts may act as antioxidant agents and could be an excellent adjuvant support in the therapy of hepatic cirrhosis. PMID:27081362

  6. Oral supplementation of Ocimum basilicum has the potential to improves the locomotory, exploratory, anxiolytic behavior and learning in adult male albino mice.

    PubMed

    Zahra, K; Khan, M A; Iqbal, F

    2015-01-01

    The aim of this project was to determine the effect of 100 mg/ml solvent/kg body weight of Ocimum basilicum leaf extract on neuromuscular co-ordination, exploratory, locomotory and short-term memory formation in male albino mice. Five weeks old, male albino mice were used as the experimental animals in order to demonstrate the effect of O. basilicum's extract on learning and memory. Each male albino mouse was weighted and orally treated either with 100 mg/ml solvent/kg body weight of O. basilicum leaf extract or with commercially available saline solution (Otsuka, Pakistan) for 7 days. Behavioral observations were made by applying a series of neurological tests (Elevated plus maze, Light and dark box, Open field and Rota rod). Dose supplementation continued during neurological testing. It was observed that 100 mg/ml solvent/kg body weight of leaf extract improves neuromuscular co-ordination and male albino mouse performance in open field, light dark box and during novel object test when compared with control group. We concluded that 100 mg/ml solvent/kg body weight of leaf extract has the potential to improve neuromuscular co-ordination, exploratory behavior, object recognition ability and transfer latency in male albino mice and can be safely administrated orally.

  7. Ameliorative Effects of Curcumin on Artesunate-Induced Subchronic Toxicity in Testis of Swiss Albino Male Mice

    PubMed Central

    Rajput, Dhrupadsinh K.; Patel, Pragnesh B.; Highland, Hyacinth N.

    2015-01-01

    India is one of the endemic areas where control of malaria has become a formidable task. Artesunate is the current antimalarial drug used to treat malaria, especially chloroquine resistant. The objective of the present study was to investigate the dose-dependent effect of oral administration of artesunate on the oxidative parameters in testes of adult male Swiss albino mice and ameliorative efficacy of curcumin, a widely used antioxidant. An oral dose of 150 mg/kg body weight (bwt; low dose) and 300 mg/kg bwt (high dose) of artesunate was administered for a period of 45 days to male mice, and ameliorative efficacy of curcumin was also assessed. The results revealed that artesunate caused significant alteration in oxidative parameters in dose-dependent manner. Administration of artesunate brought about significant decrease in activities of superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase, whereas lipid peroxidation and glutathione-S-transferase activity were found to be significantly increased. The results obtained show that oxidative insult is incurred upon the intracellular antioxidant system of testis tissue by artesunate treatment. Further, administration of curcumin at the dose level of 80 mg/kg bwt along with both doses of artesunate attenuated adverse effects in male mice. PMID:26673878

  8. Effect of ammonia on Swiss albino mice

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Casey, C. J.; Furst, A.

    1977-01-01

    Times to incapacitation and death and LC /50/ values were determined for Swiss albino male mice exposed to different concentrations of ammonia in a 4.2 liter hemispherical chamber. The LC/50/ for a 30 minute exposure was 21,430 ppm.

  9. Cognitive and biochemical effects of monosodium glutamate and aspartame, administered individually and in combination in male albino mice.

    PubMed

    Abu-Taweel, Gasem M; A, Zyadah M; Ajarem, Jamaan S; Ahmad, Mohammad

    2014-01-01

    The present study was designed to investigate the in vivo effects of monosodium glutamate (MSG) and aspartame (ASM) individually and in combination on the cognitive behavior and biochemical parameters like neurotransmitters and oxidative stress indices in the brain tissue of mice. Forty male Swiss albino mice were randomly divided into four groups of ten each and were exposed to MSG and ASM through drinking water for one month. Group I was the control and was given normal tap water. Groups II and III received MSG (8 mg/kg) and ASM (32 mg/kg) respectively dissolved in tap water. Group IV received MSG and ASM together in the same doses. After the exposure period, the animals were subjected to cognitive behavioral tests in a shuttle box and a water maze. Thereafter, the animals were sacrificed and the neurotransmitters and oxidative stress indices were estimated in their forebrain tissue. Both MSG and ASM individually as well as in combination had significant disruptive effects on the cognitive responses, memory retention and learning capabilities of the mice in the order (MSG+ASM)>ASM>MSG. Furthermore, while MSG and ASM individually were unable to alter the brain neurotransmitters and the oxidative stress indices, their combination dose (MSG+ASM) decreased significantly the levels of neurotransmitters (dopamine and serotonin) and it also caused oxidative stress by increasing the lipid peroxides measured in the form of thiobarbituric acid-reactive substances (TBARS) and decreasing the level of total glutathione (GSH). Further studies are required to evaluate the synergistic effects of MSG and ASM on the neurotransmitters and oxidative stress indices and their involvement in cognitive dysfunctions.

  10. Effect of aqueous extract of Tinospora cordifolia on functions of peritoneal macrophages isolated from CCl4 intoxicated male albino mice

    PubMed Central

    2011-01-01

    Background The current practice of ingesting phytochemicals for supporting the immune system or fighting infections is based on centuries-old tradition. Macrophages are involved at all the stages of an immune response. The present study focuses on the immunostimulant properties of Tinospora cordifolia extract that are exerted on circulating macrophages isolated from CCl4 (0.5 ml/kg body weight) intoxicated male albino mice. Methods Apart from damaging the liver system, carbon tetrachloride also inhibits macrophage functions thus, creating an immunocompromised state, as is evident from the present study. Such cell functions include cell morphology, adhesion property, phagocytosis, enzyme release (myeloperoxidase or MPO), nitric oxide (NO) release, intracellular survival of ingested bacteria and DNA fragmentation in peritoneal macrophages isolated from these immunocompromised mice. T. cordifolia extract was tested for acute toxicity at the given dose (150 mg/kg body weight) by lactate dehydrogenase (LDH) assay. Results The number of morphologically altered macrophages was increased in mice exposed to CCl4. Administration of CCl4 (i.p.) also reduced the phagocytosis, cell adhesion, MPO release, NO release properties of circulating macrophages of mice. The DNA fragmentation of peritoneal macrophages was observed to be higher in CCl4 intoxicated mice. The bacterial killing capacity of peritoneal macrophages was also adversely affected by CCl4. However oral administration of aqueous fraction of Tinospora cordifolia stem parts at a dose of 40 mg/kg body weight (in vivo) in CCl4 exposed mice ameliorated the effect of CCl4, as the percentage of morphologically altered macrophages, phagocytosis activity, cell adhesion, MPO release, NO release, DNA fragmentation and intracellular killing capacity of CCl4 intoxicated peritoneal macrophages came closer to those of the control group. No acute toxicity was identified in oral administration of the aqueous extract of Tinospora

  11. Studies on Brahma rasayana in male swiss albino mice: Chromosomal aberrations and sperm abnormalities

    PubMed Central

    Guruprasad, K. P.; Mascarenhas, Roshan; Gopinath, P. M.; Satyamoorthy, K.

    2010-01-01

    Ayurveda, the Indian holistic healthcare system encompasses traditional medicines with a principle of creating harmony and maintaining balance within the natural rhythms of the body. Rasayana is one of the branches of Ayurveda frequently used as rejuvenant therapy to overcome many discomforts and prevent diseases. It has been reported that rasayanas have immunomodulatory, antioxidant and antitumor functions. However, the genotoxic potential of many rasayanas remains to be evaluated. The present study was undertaken to assess the role of Brahma rasayana(BR) on genotoxicity in vivo in a mouse test system. The older mice (9 months) were orally fed with rasayana for 8 weeks. The treated groups showed no signs of dose-dependent toxicity at the dosage levels tested. The body weight loss/gain and feed consumption were unaffected at tested doses. Furthermore, sperm abnormalities and chromosomal aberrations were insignificant in the treatment group when compared to controls. However, there was a marginal increase in sperm count in the BR treated animals. These findings clearly indicate that there are no observed adverse genotoxic effects elicited by BR in experimental animals such as mice. PMID:21829300

  12. Effect of sulfur dioxide on Swiss albino mice

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Machado, A. M.

    1977-01-01

    Times to incapacitation and death and LC50 values were determined for male Swiss albino mice exposed to different concentrations of sulfur dioxide in a 4.2 liter hemispherical chamber. The LC50 for a 30 minute exposure was about 3000 ppm SO2.

  13. Effect of nitrogen dioxide on Swiss albino mice

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Machado, A. M.

    1977-01-01

    Times to incapacitation and death and LC50 values were determined for male Swiss albino mice exposed to different concentrations of nitrogen dioxide in a 4.2 liter hemispherical chamber. The LC50 for a 10 minute exposure was about 1000 ppm NO2.

  14. Effect of carbon monoxide on Swiss albino mice

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Cumming, H. J.

    1977-01-01

    Times to incapacitation and death and LC50 values were determined for male Swiss albino mice exposed to different concentrations of carbon monoxide in a 4.2 liter hemispherical chamber. These values are compared to values reported in the literature. The LC50 for a 30 minute exposure was 3570 ppm CO.

  15. Influence of environmental enrichment vs. time-of-day on behavioral repertoire of male albino Swiss mice.

    PubMed

    Loss, Cássio Morais; Binder, Luisa Bandeira; Muccini, Eduarda; Martins, Wagner Carbolin; de Oliveira, Paulo Alexandre; Vandresen-Filho, Samuel; Prediger, Rui Daniel; Tasca, Carla Inês; Zimmer, Eduardo R; Costa-Schmidt, Luiz Ernesto; de Oliveira, Diogo Losch; Viola, Giordano Gubert

    2015-11-01

    Environmental enrichment (EE) is a non-pharmacological manipulation that promotes diverse forms of benefits in the central nervous system of captive animals. It is thought that EE influences animal behavior in a specie-(strain)-specific manner. Since rodents in general present different behaviors during distinct periods of the day, in this study we aimed to investigate the influence of time-of-day on behavioral repertoire of Swiss mice that reared in EE. Forty male Swiss mice (21days old) were housed in standard (SC) or enriched conditions (EC) for 60days. Behavioral assessments were conducted during the light phase (in presence of light) or dark phase (in absence of light) in the following tasks: open field, object recognition and elevated plus maze. First, we observed that the locomotor and exploratory activities are distinct between SC and EC groups only during the light phase. Second, we observed that "self-protective behaviors" were increased in EC group only when mice were tested during the light phase. However, "less defensive behaviors" were not affected by both housing conditions and time-of-day. Third, we showed that the performance of EE animals in object recognition task was improved in both light and dark conditions. Our findings highlight that EE-induced alterations in exploratory and emotional behaviors are just evident during light conditions. However, EE-induced cognitive benefits are remarkable even during dark conditions, when exploratory and emotional behaviors were similar between groups.

  16. Antidepressant Activity of Brahmi in Albino Mice

    PubMed Central

    Kadali, SLDV Ramana Murty; M.C., Das; Rao A.S.R., Srinivasa; Sri G, Karuna

    2014-01-01

    Context: In traditional system of medicine brahmi has been used to enhance memory. Recently it has been reported to have action in psychiatric disorders. With these backgrounds the work has been undertaken to study antidepressant activity of brahmi in albino mice. Aim: To evaluate antidepressant activity of brahmi in experimental models. Materials and Methods: The antidepressant activity was studied in albino mice using forced swimming test (FST), tail suspension test (TST) and shock induced depression (SID). Imipramine (10mg/kg), fluoxetine (30mg/kg) were used as standard drugs and brahmi (10, 20, 30mg/kg) was used as test drug. Results: Brahmi exhibited significant decrease in duration of immobility in FST and reduced the shock induced decrease in activity in SID models. It didn’t show any activity in the TST model. Conclusion: Brahmi has shown antidepressant activity in FST and SID. PMID:24783074

  17. Metabolic rate and thermal insulation in albino and hairless mice

    PubMed Central

    Mount, L. E.

    1971-01-01

    1. Rates of oxygen consumption of albino and hairless mice were measured in a metabolism chamber during periods of approximately 5 or 24 hr. Rectal temperature was measured before and after each period. The chamber temperatures used were 22, 30 and 32° C for both albino and hairless, and in addition 34 and 36° C for the hairless mice. 2. The mean age and body weight of the albino mice were 102 days and 34·6 g; the corresponding values for the hairless mice were 87 days and 32·8 g. 3. The mean minimum rates of oxygen consumption (ml./kg.min) were 31·0 for the albino and 38·8 for the hairless mouse; the corresponding estimated critical temperatures were in the ranges 30-32° C for the albino mouse and 32-34° C for the hairless mouse. 4. The mean values for core-ambient thermal insulation (° C.m2.hr/kcal) were 0·418 and 0·328 for the albino mouse, and 0·275 and 0·221 for the hairless mouse, at 22 and 30° C respectively in each case. PMID:5097602

  18. Bacopa monniera Stabilized Silver Nanoparticles Attenuates Oxidative Stress Induced by Aluminum in Albino Mice.

    PubMed

    Mahitha, B; Deva Prasad Raju, B; Mallikarjuna, K; Durga Mahalakshmi, Ch N; Sushmal, N John

    2015-02-01

    In the recent years usage of nanomedicine plays a promising strategy in the improvement of medical treatment. The ecofriendly synthesized silver nanoparticles has introduced a new opportunity to increase the efficacy of drug by reducing its side effects. In the present study, we investigated the antioxidant property of Bacopa monniera stabilized silver nanoparticles against aluminum induced toxicity in albino mice. Forty male albino mice were randomly divided into five groups. First group was treated as control, second group received aluminum acetate (5 mg/kg b . w), third group received Bacopa monniera extract (5 mg/kg b . w), fourth group received BmSNPs (5 mg/kg b . w), fifth group received aluminum acetate plus BmSNPs. Exposure to aluminum acetate significantly increased lipid peroxidation levels with a significant decrease in the antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase activities in the brain, liver and kidney of mice. Degenerative changes were also observed in brain, liver and kidney of aluminum treated mice. No significant changes in the oxidative stress were observed in the Bacopa monniera and BmSNPs alone treated mice. Whereas, co-administration of BmSNPs to Al treated mice showed a significant decrease in lipid peroxidation levels with a significant increase of SOD, CAT and GPx indicating the antioxidant potential of nanoparticles and in counteracting Al induced oxidative stress and histological response in male albino mice. These findings clearly implicate that BmSNPs are able to eradicate the oxidative stress and prevent the tissue damage in aluminum exposed mice. PMID:26353618

  19. Bacopa monniera Stabilized Silver Nanoparticles Attenuates Oxidative Stress Induced by Aluminum in Albino Mice.

    PubMed

    Mahitha, B; Deva Prasad Raju, B; Mallikarjuna, K; Durga Mahalakshmi, Ch N; Sushmal, N John

    2015-02-01

    In the recent years usage of nanomedicine plays a promising strategy in the improvement of medical treatment. The ecofriendly synthesized silver nanoparticles has introduced a new opportunity to increase the efficacy of drug by reducing its side effects. In the present study, we investigated the antioxidant property of Bacopa monniera stabilized silver nanoparticles against aluminum induced toxicity in albino mice. Forty male albino mice were randomly divided into five groups. First group was treated as control, second group received aluminum acetate (5 mg/kg b . w), third group received Bacopa monniera extract (5 mg/kg b . w), fourth group received BmSNPs (5 mg/kg b . w), fifth group received aluminum acetate plus BmSNPs. Exposure to aluminum acetate significantly increased lipid peroxidation levels with a significant decrease in the antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase activities in the brain, liver and kidney of mice. Degenerative changes were also observed in brain, liver and kidney of aluminum treated mice. No significant changes in the oxidative stress were observed in the Bacopa monniera and BmSNPs alone treated mice. Whereas, co-administration of BmSNPs to Al treated mice showed a significant decrease in lipid peroxidation levels with a significant increase of SOD, CAT and GPx indicating the antioxidant potential of nanoparticles and in counteracting Al induced oxidative stress and histological response in male albino mice. These findings clearly implicate that BmSNPs are able to eradicate the oxidative stress and prevent the tissue damage in aluminum exposed mice.

  20. Retinal compensatory changes after light damage in albino mice

    PubMed Central

    Montalbán-Soler, Luis; Alarcón-Martínez, Luis; Jiménez-López, Manuel; Salinas-Navarro, Manuel; Galindo-Romero, Caridad; Bezerra de Sá, Fabrízio; García-Ayuso, Diego; Avilés-Trigueros, Marcelino; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta

    2012-01-01

    Purpose To investigate the anatomic and functional changes triggered by light exposure in the albino mouse retina and compare them with those observed in the albino rat. Methods BALB/c albino mice were exposed to 3,000 lx of white light during 24 h and their retinas analyzed from 1 to 180 days after light exposure (ALE). Left pupil mydriasis was induced with topical atropine. Retinal function was analyzed by electroretinographic (ERG) recording. To assess retinal degeneration, hematoxylin and eosin staining, the TdT-mediated dUTP nick-end labeling (TUNEL) technique, and quantitative immunohistofluorescence for synaptophysin and protein kinase Cα (PKCα) were used in cross sections. Intravenous injection of horseradish peroxidase and Fluoro-Gold™ tracing were used in whole-mounted retinas to study the retinal vasculature and the retinal ganglion cell (RGC) population, respectively. Results Light exposure caused apoptotic photoreceptor death in the central retina. This death was more severe in the dorsal than in the ventral retina, sparing the periphery. Neither retinal vascular leakage nor retinal ganglion cell death was observed ALE. The electroretinographic a-wave was permanently impaired, while the b-wave decreased but recovered gradually by 180 days ALE. The scotopic threshold responses, associated with the inner retinal function, diminished at first but recovered completely by 14 days ALE. This functional recovery was concomitant with the upregulation of protein kinase Cα and synaptophysin. Similar results were obtained in both eyes, irrespective of mydriasis. Conclusions In albino mice, light exposure induces substantial retinal damage, but the surviving photoreceptors, together with compensatory morphological/molecular changes, allow an important restoration of the retinal function. PMID:22509098

  1. Effect of GABAB receptor antagonist (CGP35348) on learning and memory in albino mice.

    PubMed

    Gillani, Quratulane; Iqbal, Shahid; Arfa, Fatima; Khakwani, Saba; Akbar, Atif; Ullah, Asmat; Ali, Muhammad; Iqbal, Furhan

    2014-01-01

    The present study was designed to demonstrate the potential effect of CGP 35348 (GABAB receptor antagonist) on the learning, memory formation, and neuromuscular coordination in albino mouse. Mice were intrapertoneally injected with 1 mg CGP 35348/mL of distilled water/Kg body weight, while the control animals were injected with equal volume of saline solution. A battery of neurological tests was applied following the intrapertoneal injections. Results of rota rod indicated that CGP 35348 had no effect on neuromuscular coordination in both male (P=0.528) and female (P=0.125) albino mice. CGP 35348 treated females demonstrated poor exploratory behavior during open filed for several parameters (time mobile (P=0.04), time immobile (P=0.04), rotations (P=0.04), and anticlockwise rotations (P=0.038)). The results for Morris water maze (MWM) retention phase indicated that CGP 35348 treated male mice took shorter latency to reach the hidden platform (P=0.04) than control indicating improved memory. This observation was complemented by the swim strategies used by mice during training days in MWM as CGP 35348 treated males used more direct and focal approach to reach the platform as the training proceeded.

  2. Effect of lead acetate toxicity on experimental male albino rat

    PubMed Central

    Ibrahim, Nabil M; Eweis, Esam A; El-Beltagi, Hossam S; Abdel-Mobdy, Yasmin E

    2012-01-01

    Objective To evaluate the effect of different doses of lead acetate (1/20, 1/40 and 1/60 of LD50) on body weight gain, blood picture, plasma protein profile and the function of liver, kidney and thyroid gland. Methods Male albino rats were divided into four groups, the first group represented the health control animals, while the second, third and fourth groups were ingested orally with sub lethal doses of lead acetate (1/20, 1/40 and 1/60) of the oral LD50, respectively. One dose was ingested every two days during the experimental period (14 weeks) including the adaptation time. Blood was collected and used for all analysis. Results The results showed that, the ingestion of Pb2+ induced significant stimulation in glutamic-pyruvic transaminase (ALT) and glutamic-oxalacetic transaminease (AST) activity. Also, total soluble protein and albumin contents of plasma were significantly decreased, while the content of globulin was changed by the Pb2+ treatments. The cholinesterase activity was inhibited, but the activities of alkaline and acid phosphates and lactate dehydrogenase were stimulated, while plasma glucose level was elevated as a result of lead acetate intoxication. In case of blood picture, Pb2+ ingestion reduced the contents of hemoglobin and RBCs count of intoxicated rat's blood and the plasma levels of T3, T4 and blood WBCs count were decreased. Conclusions It can be concluded that lead acetate has harmful effect on experimental male albino rats. Therefore, the present work advises people to prevent exposure to the lead compound to avoid injurious hazard risk. PMID:23569832

  3. Histomorphometric effects of gemcitabine on Swiss albino mice spermatogenesis

    PubMed Central

    Viveka, S; Udyavar, Ajay; Shetty, Balakrishna; Kuriakose, Santhosh; Sudha, M. J

    2015-01-01

    Background: Spermatogenesis is a highly conserved and regulated process and it is sensitive to fluctuations in the physical and chemical environment. Gemcitabine is a novel antimetabolic anticancer drug used frequently in the treatment of many cancers. This study aimed to investigate the histomorphometric effects of gemcitabine on spermatogenesis in Swiss albino mice. Materials and Methods: Gemcitabine in high and low doses (80 and 40 mg/kg) injected intraperitoneally to inbred Swiss albino mice. Gross testicular features and seminiferous tubular histomorphometry was studies at the end of 7th, 14th day and at 2 months sperm shape abnormalities were studied. Results: Seminiferous tubular morphology was altered significantly, showing a reduction in height, perimeter and area in a dose dependent manner. Sertoli cell number decreased. Basement membrane thickness was reduced and it appeared to be permanent, with statistically insignificant changes even after 2 months. There was a reduction of intertubular spaces. Sperms have shown banana heading, decapitation and loss of normal hook of head. The effects were partially reversible at the end of 2 months. Conclusion: It was concluded that gemcitabine affects the process of spermatogenesis adversely in a dose and time dependent manner and the effects are partially reversible. PMID:25709994

  4. Effect of Atorvastatin on Memory in Albino Mice

    PubMed Central

    M.C., Das; Rao A.S.R., Srinivasa; Kadali, SLDV Ramana Murty

    2014-01-01

    Objective: The aim and objective of the present study was to evaluate the effect of atorvastatin on learning and memory in albino mice. Materials and Methods: Thirty Swiss albino mice were divided into 5groups (n=6). In group2, group4 and group5 hyperlipidemia was induced by high fat diet (HFD) orally for 28days. Atrorvastatin was given to group3, group4 and group5 orally for 14 d. Learning and memory was evaluated with Hebb Williams’s maze, Elevated plus maze, Y maze and Step through latency. Continuous data were analyzed by one way ANOVA followed by Scheffe multiple range test, discrete data were analyzed by Kruskal - Wallis test. The level of significance was 5% (p ≤ 0.05). Result and Conclusion: HFD treatment had shown significant increase in body weight, significant impairment in learning and memory (p < 0.05). Only atorvastatin treated group had shown better learning and memory in comparison to HFD group. Atorvastatin 10mg/kg and 20 mg/kg had reversed the HFD induced impairment of learning and memory but there was no significant difference between the doses (p > 0.05). PMID:25584244

  5. Long term creatine monohydrate supplementation, following neonatal hypoxic ischemic insult, improves neuromuscular coordination and spatial learning in male albino mouse.

    PubMed

    Iqbal, Shahid; Ali, Muhammad; Iqbal, Furhan

    2015-04-01

    Creatine is known to rescue animals following brain damage. Present study was designed to demonstrate the effect of long term (15 week) supplementation of 2% creatine monohydrate (Cr), following neonatal hypoxic ischemic insult, on learning and memory formation in male albino mouse. Albino mice pups were subjected to right common carotid artery ligation followed by 8% hypoxia for 25 minutes. Following weaning, animals were separated and grouped on the basis of dietry supplementation for 15 weeks followed by a battery of neurological tests including Morris water maze, open field and rota rod. It was observed that HI mice fed on 2% Cr for 15 weeks performed better than their littermates mice on normal rodent diet during water maze (learning and memory) and rotating rod (neuro-muscular coordination and balance) test while the results of open field test remained unaffected. It was also observed that Cr treated animals had a reduced brain infarct volume than untreated but this difference did not reached statistical significance. We have also observed an overall increase in body weight in Cr treated mice during the study. Over all our results are indicating that long term Cr supplementation is beneficial for male albino following hypoxic ischemic insult.

  6. Neuroprotective Effect of Lercanidipine- A Novel Calcium Channel Blocker in Albino Mice

    PubMed Central

    Adhimoolam, Mangaiarkkarasi; Perumal, Deepa Kameswari; Rajamohammed, Meher Ali

    2015-01-01

    Background The available conventional antiepileptics do not afford cure or prophylactic treatment and henceforth there is always a quest to explore new targets for management of convulsions. In this perspective, dihydropyridine calcium channel blockers have been investigated in various animal models of epilepsy. Lercanidipine, a newer dihydropyridine calcium antagonist, is a potential candidate with its favourable lipid profile and longer duration of action. Objective (1) To evaluate the anticonvulsant effect of lercanidipine alone and in combination with standard drug in adult male Swiss albino mice. (2) To evaluate the muscle relaxant and spontaneous locomotor activity of lercanidipine in adult male Swiss albino mice. Materials and Methods Adult male Swiss albino mice weighing 20-30g were used to study the anticonvulsant, muscle relaxant and spontaneous locomotor activity using electroconvulsometer, rotarod and actophotometer apparatus respectively. The mice were divided into six groups of six animals in each group. Group 1 and 2 served as control (vehicle treated) and standard group respectively. Standard drug used to evaluate anticonvulsant effect is phenytoin sodium 25 mg/kg I.P. whereas muscle relaxant activity and locomotor activity is diazepam 4 mg/kg I.P., Group 3 and 4 received lercanidipine 1 and 3 mg/kg I.P., respectively. Anticonvulsant models included group 5 and 6 and they were given combination of phenytoin sodium 12.5 mg/kg I.P., with lercanidipine 1 and 3 mg/kg i.p, respectively. Abolition or reduction of tonic hind limb extension was considered as index of anticonvulsant activity whereas the balancing time of the animals in rod was recorded to asses muscle relaxant activity. The locomotor activity was recorded for 5 minutes. The data were analysed with one-way Analysis of Variance followed by post-hoc ‘Dunnett t-test’. Results Lercanidipine given alone in a dose of 1 and 3 mg/kg had significantly reduced the tonic hind limb extension

  7. Protection against radiation-induced testicular damage in Swiss albino mice by Mentha piperita (Linn.).

    PubMed

    Samarth, Ravindra M; Samarth, Meenakshi

    2009-04-01

    The protective effects of Mentha piperita leaf extract against radiation-induced damage in testis of Swiss albino mice have been studied. Animals (Male Swiss albino mice) were given M. piperita leaf extract orally (1 g/kg body weight/day) for three consecutive days before radiation exposure (8 Gy gamma-radiation). Mice were autopsied at 1, 3, 7, 14, and 30 days after irradiation to evaluate the radiomodulatory effect in terms of histological alterations, lipid peroxidation, and acid and alkaline phosphatases levels in testis. Radiation treatment showed reduction in the testis weight during all days of observation, however, in the M. piperita leaf extract-pretreated irradiated group there was a significant increase in testis weight. Radiation treatment induced moderate to severe testicular atrophy with degeneration of germ cells in seminiferous tubules. The tubules were shrunken and greatly depleted of germ cells. Sertoli cells with few germ cells were observed in the lumen. However, animals pre-treated with M. piperita leaf extract and exposed to radiation showed normal testicular morphology with regular arrangement of germ cells and slight degeneration of seminiferous epithelium. Significant decreases in the lipid peroxidation and acid phosphatase level and increase in level of alkaline phosphatase were observed in testis. The M. piperita leaf extract showed high amount of phenolic content, flavonoids content and flavonols. The results of the present study suggest that M. piperita has a significant radioprotective effect and the amount of phenolic compounds, the content of flavonoids and flavonols of M. piperita leaf extract may be held responsible for radioprotective effect due to their antioxidant and radical scavenging activity.

  8. Patulin in apple juice and its risk assessments on albino mice.

    PubMed

    Al-Hazmi, Mansour A

    2014-07-01

    The contamination of apple juice with patulin mycotoxin is a major risk factor in food safety. This study focuses to assess the biochemical and histopathological effects of patulin in apple juice samples collected from different outlets retailing in Jeddah, Kingdom of Saudi Arabia. On the basis of the selected dose level, 152.5 ppb patulin/ml was administered daily orally for up to 6 weeks to male albino mice. The exposure to contaminated samples revealed significant elevation of all the studied blood parameters (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities as well as creatinine, urea and uric acid contents). On the other hand, and with regard to the accumulated neuronal toxicity of the tested dose level, the toxic signs were recorded as significant increase in the aggressive and locomotor behavioral changes. In addition, the brain areas monoamines concentration revealed variable increased changes. The potential maximal changes in norepinephrine, dopamine and serotonin5-hydroxytryptamine levels attained in cortex, hypothalamus, striatum, hippocampus, midbrain and pons and medulla were assessed. Moreover, the histological examination revealed degeneration and necrosis in liver tissues and degenerated glomeruli and hemorrhage between the tubules of the cortical region in kidney tissues. The study declared that patulin-contaminated (152.5 ppb) apple juice exhibited liver, kidney and neurotoxicological effects in 6 weeks orally administered mice. PMID:23012343

  9. Patulin in apple juice and its risk assessments on albino mice.

    PubMed

    Al-Hazmi, Mansour A

    2014-07-01

    The contamination of apple juice with patulin mycotoxin is a major risk factor in food safety. This study focuses to assess the biochemical and histopathological effects of patulin in apple juice samples collected from different outlets retailing in Jeddah, Kingdom of Saudi Arabia. On the basis of the selected dose level, 152.5 ppb patulin/ml was administered daily orally for up to 6 weeks to male albino mice. The exposure to contaminated samples revealed significant elevation of all the studied blood parameters (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities as well as creatinine, urea and uric acid contents). On the other hand, and with regard to the accumulated neuronal toxicity of the tested dose level, the toxic signs were recorded as significant increase in the aggressive and locomotor behavioral changes. In addition, the brain areas monoamines concentration revealed variable increased changes. The potential maximal changes in norepinephrine, dopamine and serotonin5-hydroxytryptamine levels attained in cortex, hypothalamus, striatum, hippocampus, midbrain and pons and medulla were assessed. Moreover, the histological examination revealed degeneration and necrosis in liver tissues and degenerated glomeruli and hemorrhage between the tubules of the cortical region in kidney tissues. The study declared that patulin-contaminated (152.5 ppb) apple juice exhibited liver, kidney and neurotoxicological effects in 6 weeks orally administered mice.

  10. Naringenin Alleviates Cadmium-Induced Toxicity through the Abrogation of Oxidative Stress in Swiss Albino Mice.

    PubMed

    Das, Avratanu; Roy, Amrita; Das, Ruma; Bhattacharya, Sanjib; Haldar, Pallab Kanti

    2016-01-01

    The present study evaluates the protective potential of the flavonoid naringenin (NRG) against experimentally induced cadmium (Cd) toxicity in Swiss albino mice. NRG (4 and 8 mg/kg) was orally administered to mice 30 min before oral administration of CdCl2 (12 mg/kg) for 11 consecutive days. On the 12th day, we evaluated body and organ weights, hematological profiles, serum biochemical profiles, and hepatic and renal tissue antioxidative parameters including lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase. Cotreatment with NRG markedly and significantly normalized body and organ weights, hematological profiles, and serum biochemical profiles and significantly modulated all of the hepatic and renal tissue biochemical parameters in Cd-intoxicated mice. The present findings show that NRG possesses a remarkable alleviative effect against Cd-induced toxicity in albino mice, mediated by abrogation of Cd-induced oxidative stress by multiple mechanisms. PMID:27481493

  11. Impact of distillery soil leachate on haematology of Swiss albino mice (Mus musculus).

    PubMed

    Sharma, Subhasini; Sharma, Arti; Singh, Pawan Kumar; Soni, Pratima; Sharma, Shweta; Sharma, Pradeep; Sharma, K P

    2007-09-01

    This study reports significant alterations in various haematological parameters such as red and white blood corpuscles counts, haemoglobin content and packed cell volume in adult Swiss albino mice orally administered with diluted distillery soil leachate (5%-20%) for 30 days. Soil leachate also affected red blood cell morphology (poikilocytosis). The haematology of exposed mice improved in the reversal groups. Present study infers contamination potential of distillery soil leachate in the groundwater.

  12. Ultrasonic Songs of Male Mice

    PubMed Central

    2005-01-01

    Previously it was shown that male mice, when they encounter female mice or their pheromones, emit ultrasonic vocalizations with frequencies ranging over 30–110 kHz. Here, we show that these vocalizations have the characteristics of song, consisting of several different syllable types, whose temporal sequencing includes the utterance of repeated phrases. Individual males produce songs with characteristic syllabic and temporal structure. This study provides a quantitative initial description of male mouse songs, and opens the possibility of studying song production and perception in an established genetic model organism. PMID:16248680

  13. Haematological evaluation of ethanolic extract of Allium ascalonicum in male albino rats.

    PubMed

    Owoyele, B V; Alabi, O T; Adebayo, J O; Soladoye, A O; Abioye, A I R; Jimoh, S A

    2004-06-01

    The haematological effect of ethanolic extract of Allium ascalonicum was evaluated in male albino rats during a 21 day administration at the doses of 50, 100 and 200 mg/kg b.w, orally. Parameters evaluated include the serum lipids, red and white cell indices. The results showed that the extract administered decreased most of the parameters relating to red cell and increased most of those parameters relating to white cells. It also decreased the total cholesterol (TCH), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL) with no significant effect on the triglyceride levels.

  14. Effect of tulsi (Ocimum Sanctum Linn.) on sperm count and reproductive hormones in male albino rabbits.

    PubMed

    Sethi, Jyoti; Yadav, Mridul; Sood, Sushma; Dahiya, Kiran; Singh, Veena

    2010-10-01

    Fresh leaves of Ocimum Sanctum (OS) were used to study its effect on male reproductive function (sperm count and reproductive hormones) in male albino rabbits. Animals in the test group received supplementation of 2 g of fresh leaves of OS per rabbit for 30 days, while the control group was maintained on normal diet for the same duration. Sperm count and hormonal estimation [testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH)] were done in serum samples of both groups and compared. A significant decrease was noted in the sperm count in test group rabbits. Serum testosterone levels showed marked increase while FSH and LH levels were significantly reduced in OS-treated rabbits. The results suggest the potential use of OS as an effective male contraceptive agent. PMID:21455446

  15. Effect of tulsi (Ocimum Sanctum Linn.) on sperm count and reproductive hormones in male albino rabbits

    PubMed Central

    Sethi, Jyoti; Yadav, Mridul; Sood, Sushma; Dahiya, Kiran; Singh, Veena

    2010-01-01

    Fresh leaves of Ocimum Sanctum (OS) were used to study its effect on male reproductive function (sperm count and reproductive hormones) in male albino rabbits. Animals in the test group received supplementation of 2 g of fresh leaves of OS per rabbit for 30 days, while the control group was maintained on normal diet for the same duration. Sperm count and hormonal estimation [testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH)] were done in serum samples of both groups and compared. A significant decrease was noted in the sperm count in test group rabbits. Serum testosterone levels showed marked increase while FSH and LH levels were significantly reduced in OS-treated rabbits. The results suggest the potential use of OS as an effective male contraceptive agent. PMID:21455446

  16. Biochemical and immunological changes on oral glutamate feeding in male albino rats

    NASA Astrophysics Data System (ADS)

    Kumar, D.; Bansal, Anju; Thomas, Pauline; Sairam, M.; Sharma, S. K.; Mongia, S. S.; Singh, R.; Selvamurthy, W.

    High altitude stress leads to lipid peroxidation and free radical formation which results in cell membrane damage in organs and tissues, and associated mountain diseases. This paper discusses the changes in biochemical parameters and antibody response on feeding glutamate to male albino Sprague Dawley rats under hypoxic stress. Exposure of rats to simulated hypoxia at 7576 m, for 6 h daily for 5 consecutive days, in an animal decompression chamber at 32+/-2° C resulted in an increase in plasma malondialdehyde level with a concomitant decrease in blood glutathione (reduced) level. Supplementation of glutamate orally at an optimal dose (27 mg/kg body weight) in male albino rats under hypoxia enhanced glutathione level and decreased malondialdehyde concentration significantly. Glutamate feeding improved total plasma protein and glucose levels under hypoxia. The activities of serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) and the urea level remained elevated on glutamate supplementation under hypoxia. Glutamate supplementation increased the humoral response against sheep red blood cells (antibody titre). These results indicate a possible utility of glutamate in the amelioration of hypoxia-induced oxidative stress.

  17. Contraceptive studies of isolated fractions of Cuminum cyminum in male albino rats.

    PubMed

    Saxena, Poonam; Gupta, Rajnish; Gupta, R S

    2015-01-01

    The contraceptive efficacy of Cuminum cyminum isolated fractions (CcFr) in male albino rats was investigated. Oral dose of CcFr at 50 mg/rat/day for 60 days revealed no significant changes in body weight, while marked abnormalities in spermatogenesis were observed with decreased counts (P ≤ 0.001) in round spermatids, preleptotene spermatocytes and secondary spermatocytes. Cross sectional surface area of Sertoli cells as well as number of mature Leydig cell were decreased significantly (P ≤ 0.001). Testicular as well as accessory sex organ biochemical parameters were significantly changed (P ≤ 0.001). Sperm motility, density and morphology were resulted in 100% negative fertility. Testosterone levels were declined significantly. In conclusion, Cuminum cyminum inhibited spermatogenesis in rats, indicating the possibility of developing an herbal male contraceptive.

  18. Differential effects of retinal degeneration on sleep and wakefulness responses to short light-dark cycles in albino mice.

    PubMed

    Hsiao, F-C; Liao, Y-H; Tsai, L-L

    2013-09-17

    This study characterizes the different response patterns of sleep and wakefulness (W) to short light-dark (LD) cycles in albino mice and examines whether retinal degeneration resulting from prolonged bright light treatment and/or rd/rd mutation alters such response patterns. Eight young male Institute for Cancer Research (ICR) mice with normal eyes, seven young male rd/rd Friend Virus B type (FVB) mice, six young ICR and five young rd/rd FVB mice receiving 48-h bright light treatment, and five older rd/rd FVB mice were implanted with skull and muscle electrodes to record sleep and W. All the mice were maintained in 12-h-12-h LD cycles at baseline and received 2 days of short LD cycle treatment, which included 5-min-5-min LD cycles for a total of 24 cycles presented 4h after lights-on and again 4h after lights-off. All the five mouse groups maintained photo-entrainment of sleep and W rhythms at the baseline and showed a preference for paradoxical sleep (PS) occurrence in the 5-min dark period and non-rapid eye movement sleep (NREMS) in the 5-min light period and a brief alerting effect of light onset on experimental days. Retinal degeneration rising from bright light treatment and/or genetic mutation failed to eliminate or reduce the response of PS and NREMS to short LD cycles, although it enhanced the LD contrast of W, i.e., bright light treatment prolonged the alerting effect of light and the rd mutation increased the suppressing effect of the dark on W. These results suggest that sleep responses to short LD cycles and the brief alerting effect of light were independent of the photoreceptors in the outer retina. Furthermore, the residual photoreceptors in the outer retina and/or the photosensitive cells in the inner retina may actively modulate the effect of light and dark signals on W. PMID:23811394

  19. Effect of continuous irradiation with terahertz electromagnetic waves of the NO frequency range on behavioral reactions of male albino rats under stress conditions.

    PubMed

    Kirichuk, V F; Antipova, O N; Krylova, Ya A

    2014-06-01

    We studied the effect of terahertz waves (NO frequency range, 150.176-150.664 GHz) on stress-induced variations in behavioral reactions of male albino rats during hypokinetic stress. THz irradiation was followed by partial or complete normalization of behavioral reactions of male albino rats after hypokinetic stress. The most significant effect was observed after continuous irradiation for 30 min.

  20. Distribution of melanopsin positive neurons in pigmented and albino mice: evidence for melanopsin interneurons in the mouse retina

    PubMed Central

    Valiente-Soriano, Francisco J.; García-Ayuso, Diego; Ortín-Martínez, Arturo; Jiménez-López, Manuel; Galindo-Romero, Caridad; Villegas-Pérez, Maria Paz; Agudo-Barriuso, Marta; Vugler, Anthony A.; Vidal-Sanz, Manuel

    2014-01-01

    Here we have studied the population of intrinsically photosensitive retinal ganglion cells (ipRGCs) in adult pigmented and albino mice. Our data show that although pigmented (C57Bl/6) and albino (Swiss) mice have a similar total number of ipRGCs, their distribution is slightly different: while in pigmented mice ipRGCs are more abundant in the temporal retina, in albinos the ipRGCs are more abundant in superior retina. In both strains, ipRGCs are located in the retinal periphery, in the areas of lower Brn3a+RGC density. Both strains also contain displaced ipRGCs (d-ipRGCs) in the inner nuclear layer (INL) that account for 14% of total ipRGCs in pigmented mice and 5% in albinos. Tracing from both superior colliculli shows that 98% (pigmented) and 97% (albino) of the total ipRGCs, become retrogradely labeled, while double immunodetection of melanopsin and Brn3a confirms that few ipRGCs express this transcription factor in mice. Rather surprisingly, application of a retrograde tracer to the optic nerve (ON) labels all ipRGCs, except for a sub-population of the d-ipRGCs (14% in pigmented and 28% in albino, respectively) and melanopsin positive cells residing in the ciliary marginal zone (CMZ) of the retina. In the CMZ, between 20% (pigmented) and 24% (albino) of the melanopsin positive cells are unlabeled by the tracer and we suggest that this may be because they fail to send an axon into the ON. As such, this study provides the first evidence for a population of melanopsin interneurons in the mammalian retina. PMID:25477787

  1. Antioxidant potential of tea reduces arsenite induced oxidative stress in Swiss albino mice.

    PubMed

    Sinha, D; Roy, S; Roy, M

    2010-04-01

    Environmental arsenic (As) is a potent human carcinogen and groundwater As contamination is a major health concern in West Bengal, India. Oxidative stress has been one of the prime factors in As-induced carcinogenicity. Generation of reactive oxygen species (ROS), beyond the body's endogenous antioxidant balance cause a severe imbalance of the cellular antioxidant defence mechanism. Tea, a popular beverage has excellent chemopreventive and antioxidant properties. In this study it was investigated whether these flavonoids could ameliorate the arsenite (As III) induced oxidative stress in Swiss albino mice. Bio-monitoring with comet assay elicited that the increase in genotoxicity caused by As III was counteracted by both black tea and green tea. Elevated levels of lipid peroxides and protein carbonyl by As III were effectively reduced with green as well as black tea. They also exhibited protective action against the As III induced depletion of antioxidants like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and glutathione (GSH) in mice liver tissue. Thus the tea polyphenols by virtue of their antioxidant potential may be used as an effective agent to reduce the As III induced oxidative stress in Swiss albino mice.

  2. Effect of Tectona grandis Linn. seeds on hair growth activity of albino mice

    PubMed Central

    Jaybhaye, Deepali; Varma, Sushikumar; Gagne, Nitin; bonde, Vijay; Gite, Amol; Bhosle, Deepak

    2010-01-01

    The seeds of Tectona grandis Linn. are traditionally acclaimed as hair tonic in the Indian system of medicine. Studies were therefore undertaken in order to evaluate petroleum ether extract of T. grandis seeds for its effect on hair growth in albino mice. The 5% and 10% extracts incorporated into simple ointment base were applied topically on shaved denuded skin of albino mice. The time required for initiation of hair growth as well as completion of hair growth cycle was recorded. Minoxidil 2% solution was applied topically and served as positive control. The result of treatment with minoxidil 2% is 49% hair in anagenic phase. Hair growth initiation time was significantly reduced to half on treatment with the extracts compared to control animals. The treatment was successful in bringing a greater number of hair follicles (64% and 51%) in anagenic phase than standard minoxidil (49%). The results of treatment with 5% and 10% petroleum ether extracts were comparable to the positive control minoxidil. PMID:21455447

  3. Repeated dose oral toxicity of Trivanga Bhasma in Swiss albino mice

    PubMed Central

    Jamadagni, Pallavi S.; Jamadagni, Shrirang B.; Singh, Rajendrakumar; Gaidhani, Sudesh N.; Upadhyay, Sachchidanand; Hazra, Jayram

    2013-01-01

    Trivanga Bhasma, a metallic preparation containing Bhasmas of Naga (lead), Vanga (tin) and Yashada (zinc), was studied for repeated dose toxicity in Swiss albino mice to estimate No Observed Effect Level (NOEL) or No Observed Adverse Effect Level (NOAEL). A total of 80 Swiss albino mice of either sex with an average body weight of 28-30 g were equally divided into four groups (Group I, II, III, and IV). Group I served as control and was given vehicle (honey: water in 2:3 ratio) Group II, III, and IV received Trivanga Bhasma @ 7.8, 39.5,and 78 mg/kg body weight for 90 consecutive days. The effect of drug was assessed on body weight, feed and water consumption changes, hematological, and histopathological parameters. At the end of the study, all animals were sacrificed and examined for gross pathological changes. Histopathological evaluation was performed for control and high dose group. Trivanga Bhasma was found to be safe. No significant clinical signs were noted in all groups studied. No major alterations were observed during histopathological evaluation. Hence, dose rate of 78 mg/kg body weight was established as NOAEL. It is suggested to carry out a toxicity study at possible higher doses and in a different species so as to establish target organ of toxicity. PMID:24049417

  4. Zinc sulphate and vitamin E alleviate reproductive toxicity caused by aluminium sulphate in male albino rats.

    PubMed

    Rawi, Sayed M; Seif Al Nassr, Fatma M

    2015-03-01

    This study was designed to investigate the reproductive toxicity of aluminium sulphate and the therapeutic effects of administration of zinc sulphate and vitamin E individually or in combination against the toxic effect caused by aluminium (Al) in male albino rats. The animals were divided into five groups: group 1 received distilled water and served as control; group 2 received only aluminium sulphate (50 mg/kg body weight (b.w.)); group 3 received aluminium sulphate (50 mg/kg b.w.) plus zinc sulphate (50 mg/kg b.w.); group 4 received aluminium sulphate (50 mg/kg b.w.) and vitamin E (15 mg/kg b.w.); group 5 received aluminium sulphate plus a combination of zinc sulphate and vitamin E in similar doses as above. Doses were administered orally once daily for 45 consecutive days. The results revealed that aluminium sulphate induced significant decrease in body weight gain and testis weight and significant increase in Al level in both serum and testes of male rats. Biochemical analysis showed significant decrease in serum total protein and phospholipids levels, while serum total lipid was significantly elevated post Al treatment. In addition, significant decrease in total protein, phospholipids and cholesterol levels in the testes of Al-treated rats was recorded. The data also showed significant decrease in the levels of serum testosterone, leutinizing hormone and follicle stimulating hormone and significant increase in the level of serum prolactin in Al-intoxicated rats. Moreover, histological examination showed that aluminium sulphate caused apparent alterations in the testicular structure of the treated animals. Treatment with zinc sulphate and vitamin E individually or in combination ameliorated the harmful effects of Al, which was proved histopathologically by the noticeable improvement in the testicular tissues. We can conclude that the tested dose of aluminium sulphate induced toxic effect on the reproductive system of male albino rats and the treatment with

  5. Evaluation of the aphrodisiac activity of Tribulus terrestris Linn. in sexually sluggish male albino rats

    PubMed Central

    Singh, Surender; Nair, Vinod; Gupta, Yogendra K.

    2012-01-01

    Objectives: To study the effect of acute and repeated dose administration of lyophilized aqueous extract of the dried fruits of Tribulus terrestris (LAET) on sexual function in sexually sluggish male albino rats. Materials and Methods: Aphrodisiac activity of the test drug was evaluated in terms of exhibited sexual behavior. In order to assess the effect of chronic T. terrestris exposure on the hypothalamus--pituitary--gonadal axis, testosterone level estimation and sperm count were carried out. Twenty-eight-day oral toxicity studies were carried out to evaluate the long-term effects of the LAET administration on different body systems. Results: A dose-dependent improvement in sexual behavior was observed with the LAET treatment as characterized by an increase in mount frequency, intromission frequency, and penile erection index, as well as a decrease in mount latency, intromission latency, and ejaculatory latency. The enhancement of sexual behavior was more prominent on chronic administration of LAET. Chronic administration of LAET produced a significant increase in serum testosterone levels with no significant effect on the sperm count. No overt body system dysfunctions were observed in 28-day oral toxicity study. Conclusions: Findings of the present study validate the traditional use of T. terrestris as a sexual enhancer in the management of sexual dysfunction in males. PMID:22368416

  6. Generating Chimeric Mice by Using Embryos from Nonsuperovulated BALB/c Mice Compared with Superovulated BALB/c and Albino C57BL/6 Mice.

    PubMed

    Esmail, Michael Y; Qi, Peimin; Connor, Aurora Burds; Fox, James G; García, Alexis

    2016-01-01

    The reliable generation of high-percentage chimeras from gene-targeted C57BL/6 embryonic stem cells has proven challenging, despite optimization of cell culture and microinjection techniques. To improve the efficiency of this procedure, we compared the generation of chimeras by using 3 different inbred, albino host, embryo-generating protocols: BALB/cAnNTac (BALB/c) donor mice superovulated at 4 wk of age, 12-wk-old BALB/c donor mice without superovulation, and C57BL/6NTac-Tyr(tm1Arte) (albino B6) mice superovulated at 4 wk of age. Key parameters measured included the average number of injectable embryos per donor, the percentage of live pups born from the total number of embryos transferred to recipients, and the number of chimeric pups with high embryonic-stem-cell contribution by coat color. Although albino B6 donors produced significantly more injectable embryos than did BALB/c donors, 12-wk-old BALB/c donor produced high-percentage (at least 70%) chimeras more than 2.5 times as often as did albino B6 mice and 20 times more efficiently than did 4-wk-old BALB/c donors. These findings clearly suggest that 12-wk-old BALB/c mice be used as blastocyst donors to reduce the number of mice used to generate each chimera, reduce the production of low-percentage chimeras, and maximize the generation of high-percentage chimeras from C57BL/6 embryonic stem cells. PMID:27423145

  7. Evaluation of dimethoate-induced implantation delay and nidation by progesterone in albino mice.

    PubMed

    Mahadevaswami, M P; Kaliwal, B B

    2003-01-01

    We investigated the effect of dimethoate, an organophosphorus insecticide, and progesterone on implantation. Virgin pregnant albino mice received dimethoate orally at a dose of 28 mg/kg body wt/d from days 1 to 7. Laparotomy on day 8 showed no implantation sites. Thereafter, graded doses of progesterone, 4, 9, and 12 mg/kg body wt/d, were administered up to day 15. A group of control mice received a similar quantity of distilled water. Autopsy on day 8 revealed that the control mice were pregnant, with a normal number of implantations and 8.08% pre-implantation loss, whereas treatment with dimethoate for 7 days or with dimethoate for 7 days followed by progesterone for 8 days totally abolished implantation, with a 100% pre-implantation loss. In all treated mice, a significant decrease occurred in body weight gain, as well as in the weight of the ovaries, uterus, and liver when compared with those of control mice. No significant changes were found in other organ weights (kidneys, adrenals, spleen, thymus, or thyroid). The observed effect of dimethoate could be due to an imbalance in the estrogen-progesterone ratio essential for implantation. Alternatively, dimethoate treatment could result in blastotoxicity or have an impact on the hypothalamic-pituitary axis.

  8. Effects of a sunscreen formulation on albino hairless mice: a morphological approach.

    PubMed

    Hossy, Bryan Hudson; da Costa Leitão, Alvaro Augusto; Luz, Flávio Barbosa; dos Santos, Elisabete Pereira; Allodi, Silvana; de Pádula, Marcelo; de Oliveira Miguel, Nádia Campos

    2013-08-01

    The purpose of the study was to evaluate the effects of a sunscreen formulation on the skin of albino hairless mice subjected to simulated solar light (SSL) in terms of morphological changes. Young adult albino hairless mice HRS/J (n = 36) were used as an experimental model for determining skin photoaging changes. Mice were irradiated with SSL, and the sunscreen (estimated SPF 30, PF-UVA) was obtained from the Pharmacy College/UFRJ, Brazil. The animals were divided into four groups: non-treated (G1), radiation only (G2), sunscreen-treated (G3) and vehicle + radiation (G4). Animals from groups G2, G3 and G4 were irradiated weekly (5 weeks), with no immobilization. One week after the final exposure, the dorsal skin was observed using a dermatoscopic camera. Biopsies were analyzed in order to quantify neovascularization and to evaluate histological aspects of the skin. Neovascularization was also evaluated with immunohistochemical reactions for the Von Willebrand factor. Animals from G2 displayed classical morphological changes denoting skin photoaging: thickening of the epidermis, increased dermal cellularity, follicular keratosis, sebaceous gland hyperplasia, and angiogenesis. Animals from groups G3 and G1 displayed similar morphological profiles, without these changes. Animals from group G4 showed more morphological changes than group G2, emphasizing the relative importance of the putative photosensitizing components present in the vehicle formulation. The extent of the morphological skin changes suggested that the sunscreen formulation was effective against SSL, and showed the importance of assessing the phototoxicity of vehicle formulations.

  9. Effect of methanolic extract of Dendrophthoe falcata stem on reproductive function of male albino rats.

    PubMed

    Gupta, R S; Kachhawa, J B S; Sharma, A

    2007-01-01

    In spite of the considerable development in contraceptive technology, search for male antifertility agents in plants continues to be a potential area of investigation. Many plants have been known to possess antifertility activity, but limited attempts have been made to scientifically evaluate these claims. Hence the purpose of this study was to evaluate the antifertility and reproductive toxicity potential of Dendrophthoe falcata (Loranthaceae) in male Wistar rats. An oral 70% methanolic extract of stem of D. falcata at a dose level of 100 mg/kg wt/day fed to male albino rats for 60 days did not decrease body weight, while the testes and epididymides were significantly reduced, and the seminal vesicles and ventral prostate also showed a significant reduction (P < 0.01). Treated animals showed a notable depression of spermatogenesis. As a result of 100 mg/kg extract feeding, the preleptotene spermatocytes, secondary spermatocytes, step-19 spermatids and the mature Leydig cells decreased by 74.36%, 80.03%, 79.87%, 32.37%, respectively. At this dose Leydig cell nuclear area and cytoplasmic area, as well as the cross sectional surface area of Sertoli cells, were significantly reduced (P < 0.001) when compared to controls. The reduced sperm count and motility resulted in 100% negative fertility at 100 mg/kg dose level. A significant fall in the total protein and sialic acid content in the testes, epididymides, seminal vesicle and ventral prostate, as well as in the glycogen content of testes was also observed. The level of serum protein, cholesterol, billirubin, SGOT, SGPT, blood urea, and hematological indices were unaltered. In conclusion, Dendrophthoe falcata brought about the inhibition of spermatogenesis.

  10. Antiplasmodial Effect of Anthocleista vogelii on Albino Mice Experimentally Infected with Plasmodium berghei berghei (NK 65)

    PubMed Central

    Gboeloh, Lebari Barine; Okon, Okpok Eta; Udoh, Samuel Effiong

    2014-01-01

    The objective of the present study was to investigate the antiplasmodial effect of the ethanolic stem bark extract of Anthocleista vogelii at different doses in albino mice infected with Plasmodium berghei berghei (NK 65). Thirty-six mice were divided into six groups of six mice each. Five groups (B1–B3, D, and G) were infected with Plasmodium berghei berghei parasitized red blood cells. Groups D, H, and G served as the controls. Six days after infection, mice in groups B1, B2, and B3 were treated orally with 100, 200, and 400 mg/kg body weight of Anthocleista vogelii, respectively, for six executive days. Group D was treated with 5 mg/kg body weight of chloroquine while Group G was given distilled water. Group H was not infected and was not treated. It served as the normal control. The extracts exhibited significant (P < 0.05) dose-dependent chemosuppression of P. berghei. The extract exhibited average chemosuppressive effects of 48.5%, 78.5%, and 86.6% at dose levels of 100, 200, and 400 mg/kg body weight, respectively. Phytochemical screening of the plant extract revealed the presence of saponins, cardiac glycosides, flavonoids, terpenes, alkaloids, and steroid. The acute toxicity (LD50) of the plant was estimated to be 3162 mg/kg body weight. It showed that the stem bark of A. vogelii possesses antiplasmodial property. PMID:24900913

  11. Antitumor and antioxidant status of Terminalia catappa against Ehrlich ascites carcinoma in Swiss albino mice

    PubMed Central

    Pandya, Naitik B.; Tigari, Prakash; Dupadahalli, Kotresha; Kamurthy, Hemalatha; Nadendla, Rama Rao

    2013-01-01

    Objective: The present study was undertaken to evaluate the antitumor and antioxidant status of ethanol extract of Terminalia catappa leaves against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Materials and Methods: The leaves powder was extracted with Soxhlet apparatus and subjected to hot continuous percolation using ethanol (95% v/v). Tumor bearing animals was treated with 50 and 200 mg/kg of ethanol extract. EAC induced in mice by intraperitoneal injection of EAC cells 1 × 106 cells/mice. The study was assed using life span of EAC-bearing hosts, hematological parameters, volume of solid tumor mass and status of antioxidant enzymes such as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) activities. Total phenolics and flavonoids contents from the leaves extract were also determined. Results: Total phenolics and flavonoids contents from the leaves extract were found 354.02 and 51.67 mg/g extract. Oral administration of ethanol extract of T. catappa (50 and 200 mg/kg) increased the life span (27.82% and 60.59%), increased peritoneal cell count (8.85 ± 0.20 and 10.37 ± 0.26) and significantly decreased solid tumor mass (1.16 ± 0.14 cm2) at 200 mg/kg as compared with EAC-tumor bearing mice (P < 0.01). Hematological profile including red blood cell count, white blood cell count, hemoglobin (11.91 ± 0.47 % g) and protein estimation were found to be nearly normal levels in extract-treated mice compared with tumor bearing control mice. Treatment with T. catappa significantly decreased levels of LPO and GSH, and increased levels of SOD and CAT activity (P < 0.01). Conclusion: T. catappa exhibited antitumor effect by modulating LPO and augmenting antioxidant defense systems in EAC bearing mice. The phenolic and flavonoid components in this extract may be responsible for antitumor activity. PMID:24130380

  12. Diuretic activity of leaves of Plectranthus amboinicus (Lour) Spreng in male albino rats

    PubMed Central

    Patel, Roshan; Mahobia, Naveen K.; Gendle, Ravindra; Kaushik, Basant; Singh, Sudarshan K.

    2010-01-01

    The shade-dried powder of leaves of Plectranthus amboinicus (Lour) Spreng was subjected to successive extraction using the various solvents (petroleum ether, chloroform, ethanol and water) in increasing order of polarity. The preliminary phytochemical analyses were carried out for all the extracts. The analyses of the leaves revealed the presence of alkaloids, carbohydrates, glycosides, proteins, amino acids, flavonoids, quinine, tannins, phenolic compounds and terpenoids. Since the phytoconstituents present in the ethanolic and aqueous extracts were similar, both the extracts were selected for further study. The diuretic properties of ethanolic and aqueous extracts were evaluated by determination of urine volume and electrolyte concentration in male albino rats. Furosemide (10 mg/kg) was used as standard while normal saline (0.9%) was used as control. Both ethanolic and aqueous extracts (500 mg/kg) have shown significant increase in the volume of urine and urinary concentration of Na, K and Cl ions. Thus, from the is study it may be concluded that the leaves of P. amboinicus (Lour) Spreng possess diuretic activities. PMID:21808546

  13. Diuretic activity of leaves of Plectranthus amboinicus (Lour) Spreng in male albino rats.

    PubMed

    Patel, Roshan; Mahobia, Naveen K; Gendle, Ravindra; Kaushik, Basant; Singh, Sudarshan K

    2010-03-01

    The shade-dried powder of leaves of Plectranthus amboinicus (Lour) Spreng was subjected to successive extraction using the various solvents (petroleum ether, chloroform, ethanol and water) in increasing order of polarity. The preliminary phytochemical analyses were carried out for all the extracts. The analyses of the leaves revealed the presence of alkaloids, carbohydrates, glycosides, proteins, amino acids, flavonoids, quinine, tannins, phenolic compounds and terpenoids. Since the phytoconstituents present in the ethanolic and aqueous extracts were similar, both the extracts were selected for further study. The diuretic properties of ethanolic and aqueous extracts were evaluated by determination of urine volume and electrolyte concentration in male albino rats. Furosemide (10 mg/kg) was used as standard while normal saline (0.9%) was used as control. Both ethanolic and aqueous extracts (500 mg/kg) have shown significant increase in the volume of urine and urinary concentration of Na, K and Cl ions. Thus, from the is study it may be concluded that the leaves of P. amboinicus (Lour) Spreng possess diuretic activities. PMID:21808546

  14. Neuroprotective effect of grape seed extract against cadmium toxicity in male albino rats.

    PubMed

    El-Tarras, Adel El-Sayed; Attia, Hossam Fouad; Soliman, Mohammed Mohamed; El Awady, Mohammed Abdelhamid; Amin, Adnan Abelghani

    2016-09-01

    Cadmium toxicity can disturb brain chemistry leading to depression, anxiety, and weakened immunity. Cadmium disturbs the neurotransmitter dopamine, resulting in low energy, lack of motivation, and depression, which are predisposing factors for violence. The purpose of this study was to evaluate the ameliorative effect of grape seed extract (GSE) on the brain of 40 male albino rats after exposure to cadmium chloride (Cd) toxicity. The rats were separated into either the control group, the Cd group, the GSE group, or the GSE and Cd mixture (treated) group. The cerebrum showed evidence of degeneration of some nerve fibers and cells. Fibrosis, vacuolations, and congestion in the blood vessels were demonstrated. Satelletosis was located in the capsular cells. Immunohistochemical expression of Bax was strongly positive in the Cd group and decreased in the treated group. These histopathological changes were decreased in the brain tissue of the treated group, but a few blood vessels still had evidence of congestion. Cadmium administration increased the level of MDA and decreased MAO-A, acetylcholinesterase, and glutathione reductase (GR), while the treatment with GSE affected the alterations in these parameters. In addition, cadmium downregulated the mRNA expression levels of GST and GPx, while GSE treatment normalized the transcript levels. The expression of both dopamine and 5-hydroxytryptamine transporter was downregulated in the rats administered cadmium and the addition of GSE normalized the expression of these aggression associated genes. PMID:27271977

  15. Anti-seizure activity of flower extracts of Nepeta bractaeta in Swiss albino mice.

    PubMed

    Bhat, Jalal Uddin; Parray, Shabir Ahmad; Aslam, Mohammad; Ansari, Shahid; Nizami, Qudsia; Khanam, Razia; Siddiqui, Aisha; Ahmad, Mohd Aftab

    2012-01-01

    Epilepsy is a neurological disorder characterized by unprovoked, recurring seizures that disrupts the nervous system and can cause mental and physical dysfunction. Based on the ethno pharmacological information of the plant, the methanolic and aqueous extracts of the flowers of Nepeta bractaeta was evaluated for its antiepileptic activity. The methanolic and aqueous extracts of the flowers of Nepeta bracteata were observed for their antiepileptic activity by increased current Electroshock seizures (ICES) test and Pentylenetetrazole (PTZ) test using Swiss albino mice. Both the extracts showed significant activity in ICES and PTZ induced convulsions in comparison to control. In ICES model, NBAE at higher dose showed 16.7 % and NBME at higher dose showed 33.3 % protection against seizure and in PTZ model, NBME at higher dose showed 33.3 % protection against seizure. From the experiments performed, it can be said that Nepeta bractaeta does possess anticonvulsant property.

  16. Anti-seizure activity of flower extracts of Nepeta bractaeta in Swiss albino mice.

    PubMed

    Bhat, Jalal Uddin; Parray, Shabir Ahmad; Aslam, Mohammad; Ansari, Shahid; Nizami, Qudsia; Khanam, Razia; Siddiqui, Aisha; Ahmad, Mohd Aftab

    2012-01-01

    Epilepsy is a neurological disorder characterized by unprovoked, recurring seizures that disrupts the nervous system and can cause mental and physical dysfunction. Based on the ethno pharmacological information of the plant, the methanolic and aqueous extracts of the flowers of Nepeta bractaeta was evaluated for its antiepileptic activity. The methanolic and aqueous extracts of the flowers of Nepeta bracteata were observed for their antiepileptic activity by increased current Electroshock seizures (ICES) test and Pentylenetetrazole (PTZ) test using Swiss albino mice. Both the extracts showed significant activity in ICES and PTZ induced convulsions in comparison to control. In ICES model, NBAE at higher dose showed 16.7 % and NBME at higher dose showed 33.3 % protection against seizure and in PTZ model, NBME at higher dose showed 33.3 % protection against seizure. From the experiments performed, it can be said that Nepeta bractaeta does possess anticonvulsant property. PMID:27540346

  17. Escherichia coli Braun Lipoprotein (BLP) exhibits endotoxemia – like pathology in Swiss albino mice

    PubMed Central

    Lakshmikanth, Chikkamenahalli Lakshminarayana; Jacob, Shancy Petsel; Kudva, Avinash Kundadka; Latchoumycandane, Calivarathan; Yashaswini, Puttaraju Srikanta Murthy; Sumanth, Mosale Seetharam; Goncalves-de-Albuquerque, Cassiano F.; Silva, Adriana R.; Singh, Sridevi Annapurna; Castro-Faria-Neto, Hugo C.; Prabhu, Sandeep Kumble; McIntyre, Thomas M.; Marathe, Gopal Kedihithlu

    2016-01-01

    The endotoxin lipopolysaccharide (LPS) promotes sepsis, but bacterial peptides also promote inflammation leading to sepsis. We found, intraperitoneal administration of live or heat inactivated E. coli JE5505 lacking the abundant outer membrane protein, Braun lipoprotein (BLP), was less toxic than E. coli DH5α possessing BLP in Swiss albino mice. Injection of BLP free of LPS purified from E. coli DH5α induced massive infiltration of leukocytes in lungs and liver. BLP activated human polymorphonuclear cells (PMNs) ex vivo to adhere to denatured collagen in serum and polymyxin B independent fashion, a property distinct from LPS. Both LPS and BLP stimulated the synthesis of platelet activating factor (PAF), a potent lipid mediator, in human PMNs. In mouse macrophage cell line, RAW264.7, while both BLP and LPS similarly upregulated TNF-α and IL-1β mRNA; BLP was more potent in inducing cyclooxygenase-2 (COX-2) mRNA and protein expression. Peritoneal macrophages from TLR2−/− mice significantly reduced the production of TNF-α in response to BLP in contrast to macrophages from wild type mice. We conclude, BLP acting through TLR2, is a potent inducer of inflammation with a response profile both common and distinct from LPS. Hence, BLP mediated pathway may also be considered as an effective target against sepsis. PMID:27698491

  18. Evaluation of anti-depressant and anxiolytic activity of Rasayana Ghana Tablet (A compound Ayurvedic formulation) in albino mice

    PubMed Central

    Deole, Yogesh S.; Chavan, Sulakshan S.; Ashok, B. K.; Ravishankar, B.; Thakar, A. B.; Chandola, H. M.

    2011-01-01

    In recent years, many Ayurvedic formulations are being researched to provide an effective antidepressant and anxiolytic drug in the field of psycho-pharmacology. The present study was planned to evaluate the anti-depressant and anxiolytic activity of Rasayana Ghana Tablet comprising three herbs Guduchi (Tinospora cordifolia Miers), Aamalaki (Emblica officinalis Garten) (RGT) and Gokshura (Tribulus terrestris Linn). Swiss albino mice were divided into four groups of six animals each, comprising of both male and female in each group. Group I received water served as normal control (WC), group II received vehicle and served as vehicle control (VC), group III received Rasayana Ghana tablet and group IV received standard drug diazepam (2 mg/kg) for anxiolytic study in elevated plus maze and standard antidepressant imipramine (5 mg/kg) for anti-depressant activity in behavior despair test. Rasayana Ghana tablet along with ghee and honey as vehicle is found to be having antidepressant and anxiolytic activity in experimental animals. Thus, this formulation can be used in prevention and treatment of depression and anxiety. PMID:22529654

  19. Effect of honey consumption on intestinal motility in male albino rats.

    PubMed

    Alagwu, E A; Egwurugwu, J N; Nneli, R O; Oguike, F; Osim, E E

    2013-01-01

    This study investigated the effects of honey on intestinal motility and transit using twenty (20) male albino rats of Wistar strain weighing 210-220g. The rats were randomly grouped into control and honey-fed (test) groups of ten (10) rats each. The control group was fed on normal rat chow ( Pfizer Company, Nigeria ) and water while the test group was fed on rat feed, water and honey ( 1 ml of honey to every 10 ml initial drinking water daily) for twenty two (22) weeks after which the rats were starved over night before the experiment and sacrificed by stunning. Laparatomy was immediately performed, proximal and distal portions of the intestine identified, cut and put in aerated tyrode solution. Cut sections of the ileum (2-3cm) were mounted on organ bath instrument for motility experiment with varying concentrations of acetylcholine and carbachol. Contractions were recorded as well as the intestinal transit in each group and lengths of intestine with total mean values calculated. Results obtained showed that honey significantly decreased (p<0.01 ) intestinal transit in the test group (21.15±0.75 ) compared with the control group ( 35.96±1.15); decreased intestinal motility in the test group compared with the control and caused significant percentage reduction of intestinal motility with varied concentrations of acetylcholine and carbachol in the test group ( Ach-75.00±0.75%; Carbachol-79.00±0.28%) compared with the control group (Ach-62.00±0.39%; Carbachol-51.00±0.39%). In conclusion, unprocessed Nigerian honey decreased intestinal transit, caused intestinal smooth muscle inhibition and motility and reduced sensitivity of gastrointestinal tract to cholinergic agents. PMID:24937393

  20. 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

  1. In vivo DNA damaging and apoptotic potential of silver nanoparticles in Swiss albino mice

    PubMed Central

    Al Gurabi, Mohammed A; Ali, Daoud; Alkahtani, Saad; Alarifi, Saud

    2015-01-01

    Nanoparticles can potentially cause adverse effects on organs, tissue, cell levels, and protein levels because of their physicochemical properties. Silver nanoparticles (AgNPs) are being used on a wide scale in world consumer markets; their potential hazards for humans remain largely unknown. This study aimed to investigate the intraperitoneal toxicity of AgNPs (26 mg per kg of body weight, 52 mg per kg of body weight, and 78 mg per kg of body weight) over 72 hours in Swiss albino mice. AgNPs induced a significant increase in serum liver injury markers including alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. Induction of DNA damage was also studied in mice injected with AgNPs. Apoptosis (detected by using the terminal deoxynucleotidyl transferase deoxyuridine triphosphatase nick end labeling assay method) in liver tissue and DNA strand breaks (detected by using the comet assay method) in lymphocytes revealed that a concentration of 78 mg of AgNPs per kg body weight can cause significant apoptosis and DNA damage. The DNA damage and apoptosis raise the concern about the safety associated with application of the AgNPs. Significantly more alterations were induced in the hepatocytes of animals exposed to AgNP doses than in the control animals. The induced histological and apoptotic changes may be due to AgNP toxicity. Immunohistochemical and ultrastructural of AgNP. PMID:25674004

  2. In vivo DNA damaging and apoptotic potential of silver nanoparticles in Swiss albino mice.

    PubMed

    Al Gurabi, Mohammed A; Ali, Daoud; Alkahtani, Saad; Alarifi, Saud

    2015-01-01

    Nanoparticles can potentially cause adverse effects on organs, tissue, cell levels, and protein levels because of their physicochemical properties. Silver nanoparticles (AgNPs) are being used on a wide scale in world consumer markets; their potential hazards for humans remain largely unknown. This study aimed to investigate the intraperitoneal toxicity of AgNPs (26 mg per kg of body weight, 52 mg per kg of body weight, and 78 mg per kg of body weight) over 72 hours in Swiss albino mice. AgNPs induced a significant increase in serum liver injury markers including alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. Induction of DNA damage was also studied in mice injected with AgNPs. Apoptosis (detected by using the terminal deoxynucleotidyl transferase deoxyuridine triphosphatase nick end labeling assay method) in liver tissue and DNA strand breaks (detected by using the comet assay method) in lymphocytes revealed that a concentration of 78 mg of AgNPs per kg body weight can cause significant apoptosis and DNA damage. The DNA damage and apoptosis raise the concern about the safety associated with application of the AgNPs. Significantly more alterations were induced in the hepatocytes of animals exposed to AgNP doses than in the control animals. The induced histological and apoptotic changes may be due to AgNP toxicity. Immunohistochemical and ultrastructural of AgNP.

  3. Antioxidative and radioprotective potential of rutin and quercetin in Swiss albino mice exposed to gamma radiation

    PubMed Central

    Patil, Shrikant L.; Mallaiah, Somashekarappa Hiriyur; Patil, Rajashekar K.

    2013-01-01

    The radioprotective potential of bioflavonoid, rutin (RUT) and quercetin (QRT) was investigated in Swiss albino mice exposed to gamma radiation. The radioprotective potential of RUT and QRT was assessed in pre-treatment group of mice followed on radiation-induced changes in glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPO) levels were also analyzed. Elevation in the GSH, GST, SOD, CAT, and decreased LPO levels were observed in RUT and QRT pretreated group when compared to the irradiated animals. Furthermore, it was observed that RUT and QRT treatment was found to inhibit various free radicals generated in vitro, viz., 2,2-diphenyl-1-picrylhydrazyl(DPPH), O2, 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS)+, and OH in a concentration-dependent manner. This study clearly demonstrates the free radical scavenging action of RUT and QRT, indicating that it may have its potential as a radioprotective agent. Furthermore, the presence of a phenolic group in RUT and QRT is known to contribute to scavenging the radiation-induced free radicals and inhibition of oxidative stress. Present findings demonstrate the potential of RUT and QRT in mitigating radiation-induced oxidative stress, which may be attributed to the inhibition of radiation-induced decline in the endogenous antioxidant levels and scavenging of radiation-induced free radicals. PMID:23776312

  4. Assessment of Immunotoxicity of Dextran Coated Ferrite Nanoparticles in Albino Mice

    PubMed Central

    Syama, Santhakumar; Gayathri, Viswanathan; Mohanan, Parayanthala Valappil

    2015-01-01

    In this study, dextran coated ferrite nanoparticles (DFNPs) of size <25 nm were synthesized, characterized, and evaluated for cytotoxicity, immunotoxicity, and oxidative stress by in vitro and in vivo methods. Cytotoxicity was performed in vitro using splenocytes with different concentrations of DFNPs. Gene expression of selected cytokines (IL-1, IL-10, and TNF β) secretion by splenocytes was evaluated. Also, 100 mg of DFNPs was injected intraperitoneally to 18 albino mice for immunological stimulations. Six animals each were sacrificed at the end of 7, 14, and 21 days. Spleen was subjected to immunotoxic response and liver was analyzed for antioxidant parameters (lipid peroxidation, reduced glutathione, glutathione peroxidase, superoxide dismutase, and glutathione reductase). The results indicated that DFNPs failed to induce any immunological reactions and no significant alternation in antioxidant defense mechanism. Also, mRNA expression of the cytokines revealed an increase in IL-10 expression and subsequent decreased expression of IL-1 and TNF β. Eventually, DNA sequencing of liver actin gene revealed base alteration in nonconserved regions (10–20 bases) of all the treated groups when compared to control samples. Hence, it can be concluded that the DFNPs were nontoxic at the cellular level and nonimmunotoxic when exposed intraperitoneally to mice. PMID:26576301

  5. Protection of swiss albino mice against whole-body gamma irradiation by Mentha piperita (Linn.).

    PubMed

    Samarth, R M; Goyal, P K; Kumar, Ashok

    2004-07-01

    The radioprotective effects of Mentha oil (Mentha piperita Linn.) against radiation induced haematological alterations in peripheral blood and the survival of Swiss albino mice were studied. Mentha oil 40 micro L/animal/day for 3 consecutive days when fed orally prior to whole-body gamma irradiation (8 Gy) showed protection of the animals in terms of the survival percentage and haematological parameters in mice. Fifty per cent of the animals died within 20 days and 100% mortality was observed up to 30 days post-irradiation in the control irradiated group. Whereas only 17% of the mice died within 30 days in the experimental group (Mentha oil pretreated irradiated). The total RBC count decreased maximally at 24 h (3.45 +/- 0.20 x 10(12)/L, p < 0.001), similar observations were obtained for the WBC count, haemoglobin content and haematocrit percentage in the irradiated control animals. However, in irradiated animals pretreated with Mentha oil, although the initial values of haematological components were lower they later showed a remarkable recovery reaching normal at 30 days post-irradiation compared with the irradiated control animals. In general, the recovery of the blood cell number in irradiated animals depends on the survival of stem cells and their derivatives. The results from the present study suggest that the oil of Mentha piperita (Linn.) has a radioprotective role in stimulating/protecting the haematopoietic system. Hence, enhanced survival and an increase in the haematological constituents of peripheral blood of mice against lethal gamma radiation was observed.

  6. Alterations in plasma sodium and potassium levels following chronic oral ingestion of lead, mercury and cadmium in male albino rats.

    PubMed

    Agrawal, R; Chansouria, J P

    1991-08-01

    Adult male albino rats were orally administered 0, 25, 50 and 100 ppm of lead nitrate, mercuric chloride and cadmium chloride for 60, 120 and 180 days. The plasma sodium levels were decreased in rats exposed to varying doses of lead and mercury up to 180 days, while animals which consumed cadmium chloride showed an increase in sodium levels. In lead and mercury treated animals, plasma potassium levels were increased up to 180 days. The levels were decreased in cadmium exposed rats. These observations suggest that chronic exposure to these heavy metals considerably influences plasma sodium and potassium levels depending on the dose and duration of exposure.

  7. Bioassay of Eucalyptus extracts for anticancer activity against Ehrlich ascites carcinoma (eac) cells in Swiss albino mice

    PubMed Central

    Islam, Farhadul; Khatun, Hasina; Ghosh, Soby; Ali, MM; Khanam, JA

    2012-01-01

    Objective To evaluate the antineoplastic activity of Eucalyptus extract (EuE) against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Methods Preliminary examination of four plant extracts (namely Eucalyptus, Costus, Azadirachta, Feronia) has been done by observing the reduction ability of number of EAC cells in previously inoculated Swiss albino mice. Among them as EuE showed maximum capability, the whole study has been conducted with EuE only. Important parameters viz. enhancement of life span, reduction of average tumor weight etc. have been studied. In addition the effects of EuE on hematological parameters in both normal and EAC inoculated mice have been measured. Effect of EuE on normal peritoneal cells has also been studied. Results : EuE reduced tumor burden remarkably. It reduced the tumor growth rate and enhanced the life span of EAC bearing mice noticeably. It reversed back the hematological parameters towards normal, reduced the trasplantability of EAC cells and enhanced the immunomodulatory effects in mice. The host toxic effect of EuE in mice is minimum and mostly reversible with time. All such data have been compared with those obtained by running parallel experiments with bleomycin at dose 0.3 mg/kg (i.p.). Conclusions The Eucalyptus extract may be considered as a potent anticancer agent for advanced researches. PMID:23569937

  8. Radioprotection of Swiss albino mice by Prunus avium with special reference to hematopoietic system.

    PubMed

    Sisodia, Rashmi; Singh, Smita; Mundotiya, Chaturbhuj; Meghnani, Ekta; Srivastava, Preeti

    2011-01-01

    Prunus avium (family Rosaceae) has been used ethnomedicinally for the treatment of many diseases,but its radioprotective efficacy has hardly been explored. Presence of high anthocyanin content and phenolic compound with good antioxidative capacity has been reported by researchers. Its radioprotective effect against 5, 7, 10, and 12 Gygamma radiation was evaluated by 30 day survival assay. Regression analysis yielded LD(50/30) 5.81 and 9.43Gy for irradiated only and (P. avium fruit extract) PAE + radiation groups, respectively. The dose reduction factor was computed as 1.62. For biochemical and hematological studies, Swiss albino mice were divided into four groups: (i) control (vehicle treated), (ii) PAE treated (450 mg kg/day for 15 consequetive days), (iii) irradiated (5 Gy), and (4) PAE + irradiated. The irradiation of animals resulted in a significant elevation of lipid peroxidation and depletion in glutathione and protein levels in blood serum and spleen, which could be significantly checked by administration of PAE. Radiation-induced deficit in blood sugar, cholesterol, and hematological constituents could also be modulated by supplementation of PAE before and after irradiation. The possible prophylactic and therapeutic action noted by P. avium against radiation induced metabolic disorders may be due to synergistic action of various antioxidants, minerals, vitamins, etc., present in the fruit. Further mechanistic studies aimed at identifying the role of major ingredients in the extract are needed. PMID:21609316

  9. Pluchea lanceolata attenuates cadmium chloride induced oxidative stress and genotoxicity in Swiss albino mice.

    PubMed

    Jahangir, Tamanna; Khan, Tajdar Husain; Prasad, Lakshmi; Sultana, Sarwat

    2005-09-01

    Cadmium intoxication induces lipid peroxidation and causes oxidative damage to various tissues by altering antioxidant defence system enzymes. At 24 h after treatment with a single intraperitoneal dose of cadmium chloride (5 mg kg-1), Swiss albino mice showed a significant increase in the levels of malanodialdehyde and xanthine oxidase (P<0.001), and a concomitant depletion of renal glutathione, catalase (P<0.001) and other antioxidant enzymes. CdCl2 also led to a simultaneous increase in micronuclei formation (P<0.001) and chromosomal aberrations (P<0.05) in mouse bone marrow cells. Oral pre-treatment with Pluchea lanceolata extract at doses of 100 and 200 mg kg-1 for 7 consecutive days before CdCl2 intoxication caused a significant reduction in malanodialdehyde formation and xanthine oxidase activity (P<0.001). A significant restoration of the activity of antioxidant defence system enzymes such as catalase, glutathione peroxidase (P<0.05), glutathione-S-transferase and glutathione reductase (P<0.001) was observed. A significant dose-dependent decrease in chromosomal aberrations and micronuclei formation was also observed (P<0.05). The results indicate that pre-treatment with P. lanceolata attenuates cadmium chloride induced oxidative stress and genotoxicity by altering antioxidant enzymes and reducing chromatid breaks and micronuclei formation. PMID:16105241

  10. Clastogenic Effects of Glyphosate in Bone Marrow Cells of Swiss Albino Mice

    PubMed Central

    Prasad, Sahdeo; Srivastava, Smita; Singh, Madhulika; Shukla, Yogeshwer

    2009-01-01

    Glyphosate (N-(phosphonomethyl) glycine, C3H8NO5P), a herbicide, used to control unwanted annual and perennial plants all over the world. Nevertheless, occupational and environmental exposure to pesticides can pose a threat to nontarget species including human beings. Therefore, in the present study, genotoxic effects of the herbicide glyphosate were analyzed by measuring chromosomal aberrations (CAs) and micronuclei (MN) in bone marrow cells of Swiss albino mice. A single dose of glyphosate was given intraperitoneally (i.p) to the animals at a concentration of 25 and 50 mg/kg b.wt. Animals of positive control group were injected i.p. benzo(a)pyrene (100 mg/kg b.wt., once only), whereas, animals of control (vehicle) group were injected i.p. dimethyl sulfoxide (0.2 mL). Animals from all the groups were sacrificed at sampling times of 24, 48, and 72 hours and their bone marrow was analyzed for cytogenetic and chromosomal damage. Glyphosate treatment significantly increases CAs and MN induction at both treatments and time compared with the vehicle control (P < .05). The cytotoxic effects of glyphosate were also evident, as observed by significant decrease in mitotic index (MI). The present results indicate that glyphosate is clastogenic and cytotoxic to mouse bone marrow. PMID:20107585

  11. [EFFICACY OF A NEW MEBENDAZOLE FORMULATION FOR EXPERIMENTAL ECHINOCOCCUS GRANULOSUS LARVAL INVASION IN ALBINO MICE].

    PubMed

    Kovalenko, F P; Kukhaleva, I V; Shkolyar, N A; Legonkov, Yu A; Musaev, G Kh; Bulanova, T E; Samochatova, E I

    2015-01-01

    The problem of echinococcosis has acquired special urgency in Russia in the last 10 years. The dramatically worse epidemiological situation of echinococcosis in the country is suggested by just frequent cases of cystic echinococcosis in the indigenous population of Moscow and its region, including children. Currently, albendazole that is less toxic than mebendazole remains the drug of choice, However, some authors note that E. granulosus larval cysts are moresusceptible to mebendazole than to albendazole. Both drugs mainly show parasitological activity and have no larvicidal effect particularly in larval alveococcosis. Analysis of the results of chemotherapy, with a group of benzimidazole carbamates for echinococcosis in 6 clinical centers from 5 European countries (Italy, Bulgaria, Romania, Greece, and Turkey) over the past 30 years showed that the evaluation of therapeutic effectiveness was overestimated; thus, 40% of all parasitic larval cysts that were considered dead became active again after, 2 years after the treatment. The original oil micronized mebendazole suspension tested by us in albino mice with late-stage larval cystic echinococcosis showed the properties of a highly effective and safe systemic larvicide that caused prompt death in the entire parasite population in the treated animals even in extreme hyperinvasion when the baseline parasite weight was greater than the host's one.

  12. Negative temporal summation of the responses to pairs of tone bursts in albino mice inferior colliculus

    NASA Astrophysics Data System (ADS)

    Bibikov, Nikolay G.; Cai, Chen Qi; Jie, Tang

    2003-10-01

    The extracellular activities of single units in an inferior colliculus of narcotized albino mice have been studied. As a stimuli pairs of best frequency (BF) tone bursts with different duration have been used and forward masking has been studied. The test tone usually has a 40 ms duration at intensity 5 dB above threshold. The intensity and duration of the masker could be changed. It was shown that the forward masking essentially depends upon the duration of the first burst. In many cases, the negative temporal summation can be seen. The increase in the duration of first burst (or masker) leads to the decrease in the whole response. Moreover, the BF tone burst which did not evoke any spike response could inhibit the response to the second (test) tone in some cases. Therefore in many units the inhibitory threshold was lower than the excitatory threshold even at the best frequency. The local application of bicuculline through a multibarrel-electrode increased the pulse activity considerably. However, the effect of forward masking usually left even after an inhibitory antagonist (bicuculline) application. [Work supported by grants 39970251 from NSFC, T010360056 from the Foreign Expert Bureau of the State Council of China, and 02-04-3900 from RFBR-NSFC.

  13. Protection against radiation induced hematopoietic damage in bone marrow of Swiss albino mice by Mentha piperita (Linn).

    PubMed

    Samarth, Ravindra M

    2007-11-01

    The protective effects of Mentha piperita (Linn) extract against radiation induced hematopoietic damage in bone marrow of Swiss albino mice have been studied. Mice were given either double distilled water or leaf extract of M. piperita orally (1 g/kg b.wt./day) once a day for three consecutive days, and after 30 min of treatments on the third day were exposed to 8 Gy gamma radiation. Mice were autopsied at 12, 24, 48 hrs and 5, 10 and 20 days post-irradiation to evaluate the percentage of bone marrow cells, frequency of micronuclei and erythropoietin level in serum. An exposure to gamma radiation resulted in a significant decline in the number of bone marrow cells such as leucoblasts, myelocytes, metamyelocytes, band/stab forms, polymorphs, pronormoblasts and normoblasts, lymphocytes, and megakaryocytes. Pretreatment with leaf extract of M. piperita followed by radiation exposure resulted in significant increases in the numbers of leucoblasts, myelocytes, metamyelocytes, band/stab forms, polymorphs, pronormoblasts and normoblasts, lymphocytes, and megakaryocytes in bone marrow as compared to the control group. Pretreatment with leaf extract of M. piperita followed by radiation exposure also resulted in significant decreases in micronucleus frequencies in bone marrow of Swiss albino mice. A significant increase in erythropoietin level was observed at all the studied intervals in leaf extract of M. piperita pretreated irradiated animals as compared to control animals (radiation alone). The results of the present investigation suggest the protective effects of leaf extract of M. piperita against radiation induced hematopoietic damage in bone marrow may be attributed to the maintenance of EPO level in Swiss albino mice.

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

    PubMed Central

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

    2015-01-01

    Aim: Investigation has been carried out to validate folkloric claim of the potential of Ipomoea digitata (ID) based on reproductive health status in experimentally induced male albino rats. Materials and Methods: Emulsified neem oil fed albino rats were orally administered root powder of ID suspended in water for the doses of 250 and 500 mg/kg body weight for 40 days. Change in organ weight, sperm density and motility, serum hormonal levels and histomorphological changes were evaluated. Results: Significant increase in the sperm density and the sperm motility (P < 0.01) along with increase in the testis, and epididymes weight in neem-oil induced infertile rats treated with ID at both dose levels. This effect is vis-à-vis to serum hormonal levels. Presence of β-sitosterol in the root of ID likely to enhance the process of spermatogenesis as it is evident from histomorphological studies. Conclusion: Results of the present investigation reveal that ID is a good candidate for the management of male infertility. PMID:26401398

  15. Trichosanthes dioica fruit ameliorates experimentally induced arsenic toxicity in male albino rats through the alleviation of oxidative stress.

    PubMed

    Bhattacharya, Sanjib; Haldar, Pallab Kanti

    2012-08-01

    The present work was focused to evaluate the ameliorative property of aqueous extract of Trichosanthes dioica fruit (AQ T. dioica fruit) against arsenic-induced toxicity in male Wistar albino rats. AQ T. dioica fruit was administered orally to rats at 50 and 100 mg/kg body weight for 20 consecutive days prior to oral administration of sodium arsenite (10 mg/kg) for 10 days. Then the rats were sacrificed for the evaluation of body weights, organ weights, hematological profile, serum biochemical profile, and hepatic and renal antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, and DNA fragmentation. Pretreatment with AQ T. dioica fruit at both doses markedly and significantly normalized body weights, organ weights, hematological profiles, and serum biochemical profile in arsenic-treated animals. Further, AQ T. dioica fruit pretreatment significantly modulated all the aforesaid hepatic and renal biochemical perturbations and reduced DNA fragmentation in arsenic-intoxicated rats. Therefore, from the present findings, it can be concluded that T. dioica fruit possessed remarkable value in amelioration of arsenic-induced hepatic and renal toxicity, mediated by alleviation of arsenic-induced oxidative stress by multiple mechanisms in male albino rats.

  16. Indian spice curcumin may be an effective strategy to combat the genotoxicity of arsenic in Swiss albino mice.

    PubMed

    Biswas, Jaydip; Roy, Soumi; Mukherjee, Sutapa; Sinha, Dona; Roy, Madhumita

    2010-01-01

    Inorganic arsenic (As) is considered as a human carcinogen because it is associated with cancers of skin, lung, liver and bladder in exposed population. Consumption of As contaminated ground water for long term causes oxidative stress. Generation of reactive oxygen species (ROS), beyond the body's endogenous antioxidant balance results severe imbalance of the cellular antioxidant defense mechanism. The present study was conducted to investigate the antioxidative effect of curcumin against sodium arsenite (As III) induced oxidative damage in Swiss albino mice. Bio-monitoring with comet assay and micronucleus assay revealed that the increase in genotoxicity caused by As III was counteracted when mice were orally administered with 5, 10 and 15 mg curcumin kg-1 bw (body weight) daily. ROS generation, lipid peroxidation and protein carbonyl content, which were elevated by As III, were reduced when treated with curcumin. Curcumin also exhibited protective action against the As III induced depletion of antioxidants like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) and glutathione (GSH) in mice liver tissue. Thus the present work provides a direct evidence for the involvement of curcumin in reducing As III induced oxidative stress in Swiss albino mice by virtue of its antioxidant potential and trapping of free radicals. PMID:20593964

  17. Indian spice curcumin may be an effective strategy to combat the genotoxicity of arsenic in Swiss albino mice.

    PubMed

    Biswas, Jaydip; Roy, Soumi; Mukherjee, Sutapa; Sinha, Dona; Roy, Madhumita

    2010-01-01

    Inorganic arsenic (As) is considered as a human carcinogen because it is associated with cancers of skin, lung, liver and bladder in exposed population. Consumption of As contaminated ground water for long term causes oxidative stress. Generation of reactive oxygen species (ROS), beyond the body's endogenous antioxidant balance results severe imbalance of the cellular antioxidant defense mechanism. The present study was conducted to investigate the antioxidative effect of curcumin against sodium arsenite (As III) induced oxidative damage in Swiss albino mice. Bio-monitoring with comet assay and micronucleus assay revealed that the increase in genotoxicity caused by As III was counteracted when mice were orally administered with 5, 10 and 15 mg curcumin kg-1 bw (body weight) daily. ROS generation, lipid peroxidation and protein carbonyl content, which were elevated by As III, were reduced when treated with curcumin. Curcumin also exhibited protective action against the As III induced depletion of antioxidants like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) and glutathione (GSH) in mice liver tissue. Thus the present work provides a direct evidence for the involvement of curcumin in reducing As III induced oxidative stress in Swiss albino mice by virtue of its antioxidant potential and trapping of free radicals.

  18. Protective effect of Mentha piperita against arsenic-induced toxicity in liver of Swiss albino mice.

    PubMed

    Sharma, Ambika; Sharma, Mukesh Kumar; Kumar, Madhu

    2007-04-01

    The protective role of leaves of Mentha piperita Linn (Mint) was studied in adult Swiss albino mice against arsenic-induced hepatopathy. The animals were divided into four groups. Group I: only vehicle (0.9% NaCl) was administered. Group II: the animals received Mentha leaf extract (1 g/kg body weight per day) orally for 30 days. Group III: animals were treated with sodium arsenite (4 mg/kg body weight) intraperitoneally in 0.9% NaCl. Group IV: animals were given Mentha extract for 10 consecutive days prior to sodium arsenite treatment and continuously for 30 days after sodium arsenite treatment. The animals from the above groups were killed at various time-points, and body weight and liver weight were measured. The biochemical estimation of lipid peroxidation (LPO), reduced glutathione (GSH), lactate dehydrogenase (LDH), acid phosphatase (ACP), and alkaline phosphatase (ALP) in liver and serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) in serum were done. In the arsenic-treated group there was a significant increase in ACP, ALP, SGOT, SGPT and LPO content, whereas a significant decrease was recorded in body weight, liver weight, GSH and LDH activity in liver. Pre- and post-treatment of Mentha with arsenic significantly alters the biochemical parameters in liver. A significant decline in ACP, ALP, SGOT, SGPT and LPO content was observed. However, a significant increase in body weight, liver weight, GSH content and LDH activity in liver was estimated. The results indicate that the Mentha extract may be useful in reducing the side effects of arsenic-induced hepatopathy. PMID:17371529

  19. Protective effect of Mentha piperita against arsenic-induced toxicity in liver of Swiss albino mice.

    PubMed

    Sharma, Ambika; Sharma, Mukesh Kumar; Kumar, Madhu

    2007-04-01

    The protective role of leaves of Mentha piperita Linn (Mint) was studied in adult Swiss albino mice against arsenic-induced hepatopathy. The animals were divided into four groups. Group I: only vehicle (0.9% NaCl) was administered. Group II: the animals received Mentha leaf extract (1 g/kg body weight per day) orally for 30 days. Group III: animals were treated with sodium arsenite (4 mg/kg body weight) intraperitoneally in 0.9% NaCl. Group IV: animals were given Mentha extract for 10 consecutive days prior to sodium arsenite treatment and continuously for 30 days after sodium arsenite treatment. The animals from the above groups were killed at various time-points, and body weight and liver weight were measured. The biochemical estimation of lipid peroxidation (LPO), reduced glutathione (GSH), lactate dehydrogenase (LDH), acid phosphatase (ACP), and alkaline phosphatase (ALP) in liver and serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) in serum were done. In the arsenic-treated group there was a significant increase in ACP, ALP, SGOT, SGPT and LPO content, whereas a significant decrease was recorded in body weight, liver weight, GSH and LDH activity in liver. Pre- and post-treatment of Mentha with arsenic significantly alters the biochemical parameters in liver. A significant decline in ACP, ALP, SGOT, SGPT and LPO content was observed. However, a significant increase in body weight, liver weight, GSH content and LDH activity in liver was estimated. The results indicate that the Mentha extract may be useful in reducing the side effects of arsenic-induced hepatopathy.

  20. Evaluation of antinociceptive and antidiarrhoeal properties of Manilkara zapota leaves in Swiss albino mice.

    PubMed

    Ganguly, Amlan; Al Mahmud, Zobaer; Kumar Saha, Sajal; Abdur Rahman, S M

    2016-08-01

    Context Manilkara zapota (L.). P. Royen. (Sapotaceae) has been used in folk medicine to treat pain, diarrhoea, inflammation, arthralgia, and other disorders. Objective Screening of Manilkara zapota leaves ethanol extract and its different solvent soluble fractions for possible antinociceptive and antidiarrhoeal activities in Swiss albino mice. Materials and methods The extract and various fractions (200 and 400 mg/kg body weight; p.o.) were tested for peripheral and central antinociceptive activity by acetic acid-induced writhing and radiant heat tail-flick method, respectively; castor oil-induced diarrhoeal model was used to evaluate antidiarrhoeal activity at both doses. All the samples were administered once in a day and the duration of study was approximately 5 h. Results Ethanol extract (400 mg/kg), petroleum ether fraction (400 mg/kg), and ethyl acetate fraction (400 mg/kg) showed significant peripheral antinociceptive activity having 59.89, 58.24, and 46.7% (p < 0.001) of writhing inhibition, respectively, which is comparable with that of standard diclofenac (59.34% inhibition). The ethanol extract (400 mg/kg) and petroleum ether fraction (400 mg/kg) also showed promising central analgesic activity having 74.15 and 82.15% (p < 0.001) elongation of reaction time, respectively, at 90 min after administration of sample which is also similar to that obtained by morphine (85.84% elongation). In antidiarrhoeal activity screening, ethanol extract (200 and 400 mg/kg) showed significant inhibition of defecation by 53.57 and 60.71%, respectively (p < 0.001) compared with that of loperamide (71.42%). Discussion and conclusion The findings of the studies demonstrated antinociceptive and antidiarrhoeal activities of M. zapota leaves which could be the therapeutic option against pain and diarrhoeal disease. PMID:26799747

  1. Hair growth promoting activity of Eclipta alba in male albino rats.

    PubMed

    Roy, R K; Thakur, Mayank; Dixit, V K

    2008-08-01

    Alopecia is a dermatological disorder with psychosocial implications on patients with hair loss. Eclipta alba Hassk. is a well-known Ayurvedic herb with purported claims of hair growth promotion. In the reported work attempts were undertaken to evaluate petroleum ether and ethanol extract of E. alba Hassk. for their effect on promoting hair growth in albino rats. The extracts were incorporated into oleaginous cream (water in oil cream base) and applied topically on shaved denuded skin of albino rats. The time (in days) required for hair growth initiation as well as completion of hair growth cycle was recorded. Minoxidil 2% solution was applied topically and served as positive control for comparison. Hair growth initiation time was significantly reduced to half on treatment with the extracts, as compared to control animals. The time required for complete hair growth was also significantly reduced. Quantitative analysis of hair growth after treatment with petroleum ether extract (5%) exhibited greater number of hair follicles in anagenic phase (69 +/- 4) which were higher as compared to control (47 +/- 13). The result of treatment with 2 and 5% petroleum ether extracts were better than the positive control minoxidil 2% treatment. PMID:18478241

  2. Antilithiatic effect of Asparagus racemosus Willd on ethylene glycol-induced lithiasis in male albino Wistar rats.

    PubMed

    Christina, A J M; Ashok, K; Packialakshmi, M; Tobin, G C; Preethi, J; Murugesh, N

    2005-11-01

    The ethanolic extract of Asparagus racemosus Willd. was evaluated for its inhibitory potential on lithiasis (stone formation), induced by oral administration of 0.75% ethylene glycolated water to adult male albino Wistar rats for 28 days. The ionic chemistry of urine was altered by ethylene glycol, which elevated the urinary concentration of crucial ions viz. calcium, oxalate, and phosphate, thereby contributing to renal stone formation. The ethanolic extract, however, significantly (p < 0.05) reduced the elevated level of these ions in urine. Also, it elevated the urinary concentration of magnesium, which is considered as one of the inhibitors of crystallization. The high serum creatinine level observed in ethylene glycol-treated rats was also reduced, following treatment with the extract. The histopathological findings also showed signs of improvement after treatment with the extract. All these observations provided the basis for the conclusion that this plant extract inhibits stone formation induced by ethylene glycol treatment.

  3. Antilithiatic effect of Asparagus racemosus Willd on ethylene glycol-induced lithiasis in male albino Wistar rats.

    PubMed

    Christina, A J M; Ashok, K; Packialakshmi, M; Tobin, G C; Preethi, J; Murugesh, N

    2005-11-01

    The ethanolic extract of Asparagus racemosus Willd. was evaluated for its inhibitory potential on lithiasis (stone formation), induced by oral administration of 0.75% ethylene glycolated water to adult male albino Wistar rats for 28 days. The ionic chemistry of urine was altered by ethylene glycol, which elevated the urinary concentration of crucial ions viz. calcium, oxalate, and phosphate, thereby contributing to renal stone formation. The ethanolic extract, however, significantly (p < 0.05) reduced the elevated level of these ions in urine. Also, it elevated the urinary concentration of magnesium, which is considered as one of the inhibitors of crystallization. The high serum creatinine level observed in ethylene glycol-treated rats was also reduced, following treatment with the extract. The histopathological findings also showed signs of improvement after treatment with the extract. All these observations provided the basis for the conclusion that this plant extract inhibits stone formation induced by ethylene glycol treatment. PMID:16357948

  4. Effect of green tea (Camellia sinensis L.) extract on morphological and functional changes in adult male gonads of albino rats.

    PubMed

    Chandra, Amar K; Choudhury, Shyamosree Roy; De, Neela; Sarkar, Mahitosh

    2011-09-01

    Green tea, prepared from the steamed and dried leaves of the shrub Camellia sinensis, is known for its antioxidant and anti-carcinogenic effects. However, its effects on male gonadal functions have not been explored adequately and the present investigation has been undertaken to evaluate the effect of green tea extract on gonads of adult male albino rats. Results of in vivo studies showed that green tea extract (GTE) at mild (1.25 g%, identical to 5 cups of tea/day), moderate (2.5 g%, identical to 10 cups of tea/day) and high (5.0 g%, identical to 20 cups of tea/day) doses, for a period of 26 days, altered morphology and histology of testis and accessory sex organs. A significant dose-dependent decrease in the sperm counts, inhibited activities of testicular delta(5)3beta-and 17beta-hydroxysteroid dehydrogenase (delta5-3beta3-HSD and 17beta3-HSD respectively) and decreased serum testosterone level were noticed. Significant increase in serum LH level was observed after moderate and high doses; serum FSH level also increased but not significantly. Histopathological examination showed inhibition of spermatogenesis evidenced by preferential loss of matured and elongated spermatids. Results of this study showed that GTE at relatively high dose may cause impairment of both the morphological and normal functional status of testis in rodents and thus its consumption at relatively high doses raises concern on male reproductive function in spite of its other beneficial effects.

  5. Comparison of the acute ultraviolet photoresponse in congenic albino hairless C57BL/6J mice relative to outbred SKH1 hairless mice.

    PubMed

    Konger, Raymond L; Derr-Yellin, Ethel; Hojati, Delaram; Lutz, Cathleen; Sundberg, John P

    2016-09-01

    Hairless albino Crl:SKH1-Hr(hr) mice are commonly utilized for studies in which hair or pigmentation would introduce an impediment to observational studies. Being an outbred strain, the SKH1 model suffers from key limitations that are not seen with congenic mouse strains. Inbred and congenic C57BL/6J mice are commonly utilized for modified genetic mouse models. We compare the acute UV-induced photoresponse between outbred SKH1 mice and an immune competent, hairless, albino C57BL/6J congenic mouse line [B6.Cg-Tyr(c-2J) Hr(hr) /J]. Histologically, B6.Cg-Tyr(c-2J) Hr(hr) /J skin is indistinguishable from that of SKH1 mice. The skin of both SKH1 and B6.Cg-Tyr(c-2J) Hr(hr) /J mice exhibited a reduction in hypodermal adipose tissue, the presence of utricles and dermal cystic structures, the presence of dermal granulomas and epidermal thickening. In response to a single 1500 J/m(2) ultraviolet B dose, the oedema and apoptotic responses were equivalent in both mouse strains. However, B6.Cg-Tyr(c-2J) Hr(hr) /J mice exhibited a more robust delayed sunburn reaction, with an increase in epidermal erosion, scab formation and myeloperoxidase activity relative to SKH1 mice. Compared with SKH1 mice, B6.Cg-Tyr(c-2J) Hr(hr) /J also exhibited an aberrant proliferative response to this single UV exposure. Epidermal Ki67 immunopositivity was significantly suppressed in B6.Cg-Tyr(c-2J) Hr(hr) /J mice at 24 h post-UV. A smaller non-significant reduction in Ki67 labelling was observed in SKH1 mice. Finally, at 72 h post-UV, SKH1 mice, but not B6.Cg-Tyr(c-2J) Hr(hr) /J mice, exhibited a significant increase in Ki67 immunolabelling relative to non-irradiated controls. Thus, B6.Cg-Tyr(c-2J) Hr(hr) /J mice are suitable for photobiology experiments. PMID:27095432

  6. Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice

    SciTech Connect

    Nair, Ramya; Singh, Vikram Jeet; Salian, Sujith Raj; Kalthur, Sneha Guruprasad; D'Souza, Antony Sylvan; Shetty, Pallavi K.; Mutalik, Srinivas; Kalthur, Guruprasad; Adiga, Satish Kumar

    2014-09-15

    Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20 mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5 mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20 mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome. - Highlights: • Methyl parathion induces severe cytoplasmic abnormalities in oocytes. • Inhibits nuclear maturation and spindle damage • Poor blastocyst quality and high DNA

  7. Immunostimulant and chemoprotective effect of vivartana, a polyherbal formulation against cyclophosphamide induced toxicity in Swiss albino mice.

    PubMed

    Gnanasekaran, Sadhana; Sakthivel, Kunnathur Murugesan; Chandrasekaran, Guruvayoorappan

    2015-01-01

    The aim of the study is to develop a technology for cost effective immunomodulator from natural products to combat adverse effects during cancer chemotherapy. In the present study, the immunomodulatory efficacy of Vivartana, a poly herbal formulation in immunosuppressed animal model induced by cyclophosphamide (CTX) and its comparison with standard herbal immunostimulators Chyawanprash and Brahma Rasayana was investigated. The effect of Vivartana (500 mg/kg x bw) (p.o.), Chyawanprash (20 mg/kg.bw) (p.o.) and Brahma Rasayana (20 mg/kg x bw) (p.o.) on hematological parameters, relative organ weight, Bone marrow cellularity and α-esterase activity were determined in Swiss albino mice by using the standard methods. Among the herbal formulations Vivartana showed the maximum number of leukocytes (13150 cells/mm3) on the 15th day. The leukocyte count in Vivartana treated CTX induced group shows significant increase (5375 cells/mm3) when compared with CTX alone induced group (3358 cells/mm3) on the same day. The Vivartana treated CTX induced group shows increase in the hemoglobin level compared with the CTX induced group. Moreover, Vivartana treatment prevented the loss of organ weight in the CTX induced group by the enhancement of spleenocytes on the 7th day and thymocytes on the 11th day. Similarly the lowered bone marrow cellularity and number of α-esterase positive cells in CTX induced group were restored in the Vivartana treatment. Treatment with vivartana also exhibits hepatoprotective activity by regulating the SGOT and SGPT levels in CTX induced group. The study indicates that Vivartana has the considerable potential as an immunostimulant and chemoprotectant against CTX induced immunosuppression in Swiss albino mice.

  8. Modulatory effect of whey proteins in some cytokines involved in wound healing in male diabetic albino rats.

    PubMed

    Abdel-Salam, Bahaa Kenawy Abuel-Hussien

    2014-10-01

    The anti-inflammatory cytokines (interleukin (IL)-4 and IL-10) and the pro-inflammatory cytokines (IL-1β, IL-6, and tumor necroses factor-alpha (TNF-α)) have important functions in wound healing. Thus, the aim of this study was to determine whether dietary supplementation with whey protein could enhance normal inflammatory responses during wound healing in diabetic rats. In this study, male albino rats were divided into a wounded control group, a wounded diabetic group, and a wounded diabetic group supplemented with whey protein orally at a dose of 100 mg/kg body weight. Tested rats showed increasing wound closure in rats treated with whey protein. In addition, after 4 days of wound, modulation in IL-4, IL-10, IL-1β, IL-6, and TNF-α levels were detected. Statistical analysis of data showed significant difference between the whey-protein-treated group and either control or diabetic groups (P < 0.05). Dietary supplementation with whey protein enhances the normal inflammatory responses during wound healing in diabetic rats by modulating the levels of some anti-inflammatory and inflammatory cytokines.

  9. Garlic oil as a modulating agent for oxidative stress and neurotoxicity induced by sodium nitrite in male albino rats.

    PubMed

    Hassan, Hanaa A; Hafez, Hani S; Zeghebar, Fawzia E

    2010-07-01

    In the present study, we investigated the neurobiochemical alterations and oxidative stress induced by food preservative; sodium nitrite (NaNO2) as well as the role of the garlic oil in amelioration of the neurotoxicity in male albino rats. Serum and brain homogenates of the rats received NaNO2 (80 mg/kg body weight) for 3 months exhibited significant decrease in acetylcholine esterase (AChE) activity as well as the levels of phospholipids, total protein and the endogenous antioxidant system (glutathione; GSH and superoxide dismutase; SOD). In contrast, lactic dehydrogenase (LDH) activity, brain thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO) levels were significantly increased. On the other hand, the oral administration of garlic oil (5 ml/kg body weight) daily for 3 months significantly improved the neurobiochemical disorders and inhibited the oxidative stress induced by NaNO2 ingestion. So, this study reveals the neural toxic effects of NaNO2 by exerting oxidative stress and retrograde the endogenous antioxidant system. However, garlic oil has a promising role in attenuating the obtained hazard effects of sodium nitrite by its high antioxidant properties which may eventually be related with the preservation of SOD activity and primary mitochondrial role against nitrite-induced neurotoxicity in rats.

  10. Effect of different doses of monosodium glutamate on the thyroid follicular cells of adult male albino rats: a histological study

    PubMed Central

    Khalaf, Hanaa A; Arafat, Eetmad A

    2015-01-01

    Monosodium glutamate (MSG) is a major flavor enhancer used as a food additive. The present study investigates the effects of different doses of MSG on the morphometric and histological changes of the thyroid gland. 28 male albino rats were used. The rats were divided into four groups: group I control, group II, III and IV treated with MSG (0.25 g/kg, 3 g/kg, 6 g/kg daily for one month) respectively. The thyroid glands were dissected out and prepared for light and electron microscopic examination. Light microscopic examination of thyroid gland of group II revealed increase in follicular epithelial height. Groups III & IV showed decrease in the follicular diameter and irregularity in the shape of some follicles with discontinuity of basement membrane. Follicular hyperplasia was detected in some follicles with appearance of multiple pyknotic nuclei in follicular and interfollicular cells and multiple exfoliated cells in the colloid. In addition, areas of loss of follicular pattern were appeared in group IV. Immunohistochemical examination of BCL2 immunoexpression of the thyroid glands of groups III & IV reveals weak positive reaction in the follicular cells cytoplasm. Ultrathin sections examination of groups III & IV revealed follicular cells with irregular hyperchromatic nuclei, marked dilatation of rER and increased lysosomes with areas of short or lost apical microvilli. In addition, vacuolation of mitochondria was detected in group IV. The results displayed that MSG even at low doses is capable of producing alterations in the body weights and thyroid tissue function and histology. PMID:26884820

  11. Effects of Ocimum sanctum and Camellia sinensis on stress-induced anxiety and depression in male albino Rattus norvegicus

    PubMed Central

    Tabassum, Imrana; Siddiqui, Zeba N.; Rizvi, Shamim J.

    2010-01-01

    Objective: The aim of this study was to study the ameliorative effects of Ocimum sanctum and Camellia sinensis on stress-induced anxiety and depression. Materials and Methods: The study was carried out using male albino rats (200 ± 50 g). The effect of O. sanctum and C. sinensis was evaluated for anxiety and depression using elevated plus maze (EPM) test, open field test (OFT), forced swim test (FST), and tail suspension test (TST). Result: Restraint stress (3 h/day for six consecutive days) induced a significant reduction in both the percentage number of entries and time spent in open arms in EPM, and these changes were reversed with post-treatment of aqueous extract of O. sanctum and C. sinensis (100 mg/kg for 6 days). Restraint stress-induced (a) increased latency and (b) decreased ambulation and rearing were also reversed by O. sanctum and C. sinensis in OFT. A significant increase in immobility period was observed in FST and TST after restraint stress. O. sanctum and C. sinensis significantly reduced the immobility times of rats in FST and TST. Conclusion: O. sanctum and C. sinensis possess anxiolytic and antidepressant activities. PMID:21206619

  12. Cognitive effects of acute restraint stress in male albino rats and the impact of pretreatment with quetiapine versus ghrelin.

    PubMed

    Amin, Shaimaa Nasr; Gamal, Sarah Mahmoud; Esmail, Reham Shehab El Nemr; Aziz, Tarek Mohamed Abdel; Rashed, Laila Ahmed

    2014-12-01

    Stress is any condition that seriously affects the balance of the organism physiologically and psychologically. Stress activates the hypothalamic-pituitary-adrenal (HPA) releasing glucocorticoid hormones that produce generalized effects on different body systems including the nervous system. This study aimed to investigate the effect of acute restraint stress (ARS) on cognitive performance by measuring spatial working memory in Y-maze, behavior (anxiety and exploratory behavior) in open field test, expression of synaptophysin and glial fibrillary acidic protein (GFAP) in the hippocampus by immunohistochemistry, dopaminergic receptors (D2) in the basal ganglia by gene expression and comparing the effect of ghrelin and quetiapine on the previous parameters. 36 adult male albino rats constituted the animal model of this work and have been divided into six groups: control group, control group exposed to ARS, quetiapine group, quetiapine group exposed to ARS, ghrelin group and ghrelin group exposed to ARS. We demonstrated more neuroprotective effect for quetiapine compared to ghrelin on stress response, anxiety behavior and working spatial memory impairment due to ARS. PMID:25391717

  13. Comparative toxicity of /sup 226/Ra, /sup 239/Pu, /sup 241/Am, /sup 249/Cf, and /sup 252/Cf in C57BL/Do black and albino mice

    SciTech Connect

    Taylor, G.N.; Mays, C.W.; Lloyd, R.D.; Gardner, P.A.; TAlbot, L.R.; McFarland, S.S.; Pollard, T.A.; Atherton, D.R.; vanMoorhem, D.; Brammer, D.

    1983-09-01

    Groups of C57BL/Do (black and albino) mice were injected with graded activities of /sup 226/Ra, /sup 239/Pu, /sup 241/Am, /sup 249/Cf, or /sup 252/Cf and were followed throughout life. Bone sarcoma was the principal radiation-induced end point, and the risks associated with average skeletal doses of the four transuranium radionuclides, relative to radium, were determined. The relative biological effectiveness (RBE) was calculated for each emitter by dividing its risk coefficient (bone sarcomas per 10/sup 6/ mouse-rad) by the risk coefficient for /sup 226/Ra. Combined data for males and females in both black and albino mice gave the following values +- SD for the RBE relative to /sup 226/Ra = 1.0: /sup 239/Pu = 15.3 +- 3.9, /sup 241/Am = 4.9 +- 1.4, /sup 249/Cf = 5.0 +- 1.4, and /sup 252/Cf = 2.6 +- 0.8. About 70% of the tumors occurred in the axial skeleton, and the risk coefficient for females averaged about four times higher than for males when all five nuclides were included. The RBE of fission fragment irradiation from /sup 252/Cf for cancer induction, relative to ..cap alpha.. irradiation, for the combined data in all of the animals given /sup 252/Cf and /sup 249/Cf, was 0.02 +- 0.28, in agreement with the calculated theoretical value of 0.03, based on the ratio of summed track lengths in tissue.

  14. Comparative toxicity of /sup 226/Ra, /sup 239/Pu, /sup 241/Am, /sup 249/Cf, and /sup 252/Cf in C57BL/Do black and albino mice

    SciTech Connect

    Taylor, G.N.; Mays, C.W.; Lloyd, R.D.; Gardner, P.A.; Talbot, L.R.; McFarland, S.S.; Pollard, I.A.; Atherton, D.R.; VanMoorhem, D.; Brammer, D.

    1983-09-01

    Groups of C57BL/Do (black and albino) mice were injected with graded activities of /sup 226/Ra, /sup 239/Pu, /sup 241/Am, /sup 249/Cf, or /sup 252/Cf and were followed throughout life. Bone sarcoma was the principal radiation-induced end point, and the risks associated with average skeletal doses of the four transuranium radionuclides, relative to radium, were determined. The relative biological effectiveness (RBE) was calculated for each emitter by dividing its risk coefficient (bone sarcomas per 10(/sup 6/) mouse-rad) by the risk coefficient for /sup 226/Ra. Combined data for males and females in both black and albino mice gave the following values +/- SD for the RBE relative to /sup 226/Ra . 1.0: /sup 239/Pu . 15.3 +/- 3.9, /sup 241/Am . 4.9 +/- 1.4, /sup 249/Cf . 5.0 +/- 1.4, and /sup 252/Cf . 2.6 +/- 0.8. About 70% of the tumors occurred in the axial skeleton, and the risk coefficient for females averaged about four times higher than for males when all five nuclides were included. The RBE of fission fragment irradiation from /sup 252/Cf for cancer induction, relative to alpha irradiation, for the combined data in all of the animals given /sup 252/Cf and /sup 249/Cf, was 0.02 +/- 0.28, in agreement with the calculated theoretical value of 0.03, based on the ratio of summed track lengths in tissue.

  15. Effects of 10-GHz microwaves on hematological parameters in Swiss albino mice and their modulation by Prunus avium.

    PubMed

    Sisodia, Rashmi; Rifat, Faiza; Sharma, Archana; Srivastava, Preeti; Sharma, K

    2013-01-01

    The objective of this study was to investigate the modulatory role of Prunus avium fruit extract (PAE) on several blood parameters after exposure to 10-GHz microwaves. Swiss albino mice from an inbred colony were selected and divided into 3 groups. Mice in group I served as the control; they were placed in a Plexiglas cage (without energizing the system) for 2 hours/day for 30 consecutive days. Group II mice were exposed to 10-GHz microwaves for 2 hours/day for 30 consecutive days. Mice in group III received PAE (500 mg/kg/body weight) orally once daily 1 hour before exposure to 10-GHz microwaves (2 hours/day) for 30 consecutive days. After 30 days of treatment, blood samples were collected from mice in all groups and analyzed. Hemoglobin, monocytes, packed cell volume, red blood cells, mean corpuscular hemoglobin concentration declined significantly (P ≤ 0.01), whereas white blood cells, lymphocytes, erythrocyte sedimentation rate, and mean corpuscular volume increased significantly (P ≤ 0.01) compared to the control group (group I). Cholesterol, alkaline phosphatase, and lipid peroxidation also increased significantly (P ≤ 0.01). Depletion in blood sugar, total protein, acid phosphatase, and glutathione levels was noted after microwave exposure compared with levels in the sham-exposed (control) mice. Histopathological alterations in blood cells also were seen. Signs of improvements in the hematological, biochemical, and histopathological parameters were recorded in group III, where PAE was supplemented before exposure. Exposure to microwaves influences hematological parameters, which could be ameliorated by the supplementation of PAE.

  16. Simple generation of albino C57BL/6J mice with G291T mutation in the tyrosinase gene by the CRISPR/Cas9 system.

    PubMed

    Mizuno, Seiya; Dinh, Tra Thi Huong; Kato, Kanako; Mizuno-Iijima, Saori; Tanimoto, Yoko; Daitoku, Yoko; Hoshino, Yoshikazu; Ikawa, Masahito; Takahashi, Satoru; Sugiyama, Fumihiro; Yagami, Ken-ichi

    2014-08-01

    Single nucleotide mutations (SNMs) are associated with a variety of human diseases. The CRISPR/Cas9 genome-editing system is expected to be useful as a genetic modification method for production of SNM-induced mice. To investigate whether SNM-induced mice can be generated by zygote microinjection of CRISPR/Cas9 vector and single-stranded DNA (ssDNA) donor, we attempted to produce albino C57BL/6J mice carrying the Tyr gene SNM (G291T) from pigmented C57BL/6J zygotes. We first designed and constructed a CRISPR/Cas9 expression vector for the Tyr gene (px330-Tyr-M). DNA cleavage activity of px330-Tyr-M at the target site of the Tyr gene was confirmed by the EGxxFP system. We also designed an ssDNA donor for homology-directed repair (HDR)-mediated gene modification. The px330-Tyr-M vector and ssDNA donor were co-microinjected into the pronuclei of 224 one-cell-stage embryos derived from C57BL/6J mice. We obtained 60 neonates, 28 of which showed the ocular albinism and absence of coat pigmentation. Genomic sequencing analysis of the albino mice revealed that the target of SNM, G291T in the Tyr gene, occurred in 11 mice and one founder was homozygously mutated. The remaining albino founders without Tyr G291T mutation also possessed biallelic deletion and insertion mutants adjacent to the target site in the Tyr locus. Simple production of albino C57BL/6J mice was provided by C57BL/6J zygote microinjection with px330-Tyr-M DNA vector and mutant ssDNA (G291T in Tyr) donor. A combination of CRISPR/Cas9 vector and optional mutant ssDNA could be expected to efficiently produce novel SNM-induced mouse models for investigating human diseases. PMID:24879364

  17. Antifungal efficacy of amphotericin B encapsulated fibrin microsphere for treating Cryptococcus neoformans infection in Swiss albino mice.

    PubMed

    Khan, Azmat Ali; Jabeen, Mumtaz; Alanazi, Amer M; Khan, Abdul Arif

    2016-01-01

    A natural and biocompatible fibrin microsphere is one of the most promising dual delivery vehicle as compared to other traditionally designed delivery modalities. It represents sustained delivery of encapsulated drug and is easily biodegradable in the blood circulation. In the present study, we evaluated the systemic augmentation of the antifungal activity of amphotericin B loaded in fibrin microsphere (AMB-fibrin microsphere) against cryptococcosis in Swiss albino mice. Mice infected with Cryptococcus neoformans were treated with 0.5mg/kg AMB-fibrin microsphere that was given alternately for 7 days. The antifungal potential of AMB-fibrin microsphere was assessed on the basis of reduction of cfu count in the systemic circulation and various vital organs of infected mice. The formulation was found to be highly effective in reducing intracellular pathogen from the experimental animals where fibrin microsphere significantly controlled the release of amphotericin B for longer time duration. The AMB-fibrin microsphere chemotherapy was significantly more effective than free amphotericin B in reducing the fungal burden and showed better survival efficacy (p<0.05). The current study demonstrating the use of novel amphotericin B loaded fibrin microsphere not only imparts protection to the encapsulated amphotericin B but also offers an effective strategy to decrease the drug associated toxicities. PMID:27294976

  18. Protective efficacy of semi purified fraction of high altitude podophyllum hexandrum rhizomes in lethally irradiated Swiss albino mice.

    PubMed

    Gupta, M L; Tyagi, S; Flora, S J S; Agrawala, P K; Choudhary, P; Puri, S C; Sharma, A; Devi, M; Haksar, A; Qazi, G N; Tripathi, R P

    2007-05-30

    A fraction of high altitude Podophyllum hexandrum rhizome, REC-2006, was evaluated for its radioprotective efficacy against lethal gamma-irradiation (10 Gy, whole body) in Swiss albino mice. The maximum tolerated dose (MTD) and LD50 of this fraction were found to be 45 mg/kg b.w. and 74 mg/kg b.w. respectively. Pre-irradiation (- 2 h, ) administration (i.p.) of 6 or 8 mg/kg b.w. of REC-2006 rendered > 90% survival in lethally irradiated mice. The dose reduction factor was calculated to be 1.62 considering survival as the end point. REC-2006 treatment marked in significant increase in endogenous spleen colony forming units. In REC-2006 treated group, super oxide dismutase activity was increased significantly compared to the radiation control group (Liver, p = 0.00, Jejunum p = 0.00). The extract also inhibited radiation induced lipid peroxidation in liver (p = 0.00) at 24 h. REC-2006 administration (100-200 microg/ml) significantly reduced the halo diameter in mice thymocytes. Nearly 10 fold difference between the effective dose (6 mg/kg b.w.) and LD50 and the high degree of whole body survival (> 90% against 10 Gy irradiation) indicates REC-2006 to be safe and highly promising to achieve significant radioprotection against lethal radiation. Further purification and identification of active molecules and their efficacy studies in higher animals therefore demand attention.

  19. Histopathology effects of nickel nanoparticles on lungs, liver, and spleen tissues in male mice

    NASA Astrophysics Data System (ADS)

    Ajdari, Marziyeh; Ziaee Ghahnavieh, Marziyeh

    2014-09-01

    Because of the classification of the nickel compounds as carcinogenic substances, there is a need for in vivo tests to nickel nanoparticles (NiNPs) for observing their effects on health experimentally. Spherical NiNPs with 10 nm in diameter and 75 ppm concentration were applied for investigating their toxicities within male albino mice as an in vivo model. We randomly made sham group, control group, and 75 ppm group (with five animals in each group). Then, the nanoparticles were injected into mice intraperitonealy for 7 days and after that their lungs, liver, and spleen were removed for histopathological observations. At the end of the test, section microscopic observations of liver, spleen, and lung in sham and control groups showed normal tissues but these tissues underwent significant abnormal effects in 75 ppm group. NiNPs can cause undesirable effects in lungs, liver, and spleen tissues with same condition of this study.

  20. ANTI-INFLAMMATORY, ANALGESIC AND ANTIPYRETIC ACTIVITIES OF THE AQUEOUS METHANOLIC EXTRACT OF BERBERIS CALLIOBOTRYS IN ALBINO MICE.

    PubMed

    Alamgeer; Naz, Huma; Rasool, Shadid; Raza, Sayed Atif; Ahmad, Taseer; Ahsan, Haseeb; Mushtaq, Muhammad Naveed; Asif, Hira; Khan, Zahid; Noor, Nabeela; Utra, Ambreen Malik; Umme-Habiba-Hassan

    2016-01-01

    The aqueous methanolic extract of stem part of Berberis calliobotiys (AMEBC) was evaluated for anti-inflammatory, analgesic and antipyretic activities in albino mice. Anti-inflammatory activity was evaluated by using carrageenan and albumin induced paw edema, while the analgesic effect was assessed by using formalin-induced paw licking and acetic acid induced abdominal writhing in mice. The brewer's yeast-induced pyrexia model was used for antipyretic investigation. Ibuprofen (40 mg/kg) was used as a standard drug in all the three models. The aqueous methanolic extract at both (250 mg/kg and 500 mg/kg) doses, showed highly significant (p < 0.001) reduction in paw edema induced by carrageenan and albumin. Moreover, the aqueous methanolic extract also highly significantly (p < 0.001) reduced (87%) the formalin-induced paw licking at 500 mg/kg. The highly significant (p < 0.001) reductions (24.48% and 37.9%) was also observed in the number of writhings. Furthermore, aqueous methanolic extract also demonstrated significant (p < 0.001) antipyretic activity against yeast induced pyrexia. The maximum effect was observed in all the three parameters at 500 mg/kg dose. The results suggest a potential benefit of the aqueous methanolic extract of Berbeis calliobotrys in treating conditions associated with inflammation, pain and fever. PMID:27505907

  1. Depletion by styrene of glutathione in plasma and bronchioalveolar lavage fluid of non-Swiss albino (NSA) mice.

    PubMed

    Carlson, Gary P

    2010-01-01

    Styrene is a widely used chemical, but it is known to produce lung and liver damage in mice. This may be related to oxidative stress associated with the decrease in the levels of reduced glutathione (GSH) in the target tissues. The purpose of this study was to investigate the effect of styrene and its primary metabolites R-styrene oxide (R-SO) and S-styrene oxide (S-SO) on GSH levels in the lung lumen, as determined by amounts of GSH in bronchioalveolar lavage fluid (BALF) and in plasma. When non-Swiss albino (NSA) mice were administered styrene (600 mg/kg, ip), there was a significant fall in GSH levels in both BALF and plasma within 3 h. These returned to control levels by 12 h. The active metabolite R-SO (300 mg/kg, ip) also produced significant decreases in GSH in both BALF and plasma, but S-SO was without marked effect. Since GSH is a principal antioxidant in the lung epithelial lining fluid, this fall due to styrene may exert a significant influence on the ability of the lung to buffer oxidative damage.

  2. ANTI-INFLAMMATORY, ANALGESIC AND ANTIPYRETIC ACTIVITIES OF THE AQUEOUS METHANOLIC EXTRACT OF BERBERIS CALLIOBOTRYS IN ALBINO MICE.

    PubMed

    Alamgeer; Naz, Huma; Rasool, Shadid; Raza, Sayed Atif; Ahmad, Taseer; Ahsan, Haseeb; Mushtaq, Muhammad Naveed; Asif, Hira; Khan, Zahid; Noor, Nabeela; Utra, Ambreen Malik; Umme-Habiba-Hassan

    2016-01-01

    The aqueous methanolic extract of stem part of Berberis calliobotiys (AMEBC) was evaluated for anti-inflammatory, analgesic and antipyretic activities in albino mice. Anti-inflammatory activity was evaluated by using carrageenan and albumin induced paw edema, while the analgesic effect was assessed by using formalin-induced paw licking and acetic acid induced abdominal writhing in mice. The brewer's yeast-induced pyrexia model was used for antipyretic investigation. Ibuprofen (40 mg/kg) was used as a standard drug in all the three models. The aqueous methanolic extract at both (250 mg/kg and 500 mg/kg) doses, showed highly significant (p < 0.001) reduction in paw edema induced by carrageenan and albumin. Moreover, the aqueous methanolic extract also highly significantly (p < 0.001) reduced (87%) the formalin-induced paw licking at 500 mg/kg. The highly significant (p < 0.001) reductions (24.48% and 37.9%) was also observed in the number of writhings. Furthermore, aqueous methanolic extract also demonstrated significant (p < 0.001) antipyretic activity against yeast induced pyrexia. The maximum effect was observed in all the three parameters at 500 mg/kg dose. The results suggest a potential benefit of the aqueous methanolic extract of Berbeis calliobotrys in treating conditions associated with inflammation, pain and fever.

  3. Histopathological evaluation of gastro protective effect of Berberis vulgaris (Zereshk) seeds against aspirin induced ulcer in albino mice.

    PubMed

    Majeed, Wafa; Aslam, Bilal; Javed, Ijaz; Khaliq, Tanweer; Muhammad, Faqir; Ali, Asghar; Raza, Ahmed

    2015-11-01

    The present study was carried out to investigate the antiulcer activity of Berberis vulgaris (Zereshk) seeds in albino mice. After acclimatization, animals were divided into six equal groups. Aspirin 150 mg/kg was used to induce gastric ulcer in all groups except normal control. Omeprazole 20mg/kg was used as synthetic anti ulcer drug in study. Three dose levels of B. vulgaris seed powder 300 mg/kg, 600 mg/kg and 900 mg/kg were used respectively orally. Histopathological analysis was carried out to evaluate the gastroprotective activity of B. vulgaris seed powder. Results of the study showed that in case of aspirin treated mice gastric luminal mucosa villi were decreased in height or were absent. In the glandular region there was connective tissue proliferation and also infiltration of cells. Similar infiltration of cells was present on muscularis mucosa. In esophageal region tumor cells were present. However three dose levels of B. vulgaris significantly reduced the tissue proliferation, infiltration of cells and sloughing induced by aspirin. Highest dose of B. vulgaris (900 mg/kg) showed similar results as synthetic antiulcer drug omeprazole.

  4. Effects of lithium chloride on testicular steroidogenic and gametogenic functions in mature male albino rats

    SciTech Connect

    Ghosh, D.; Chaudhuri, A.; Biswas, N.M.; Ghosh, P.K. )

    1990-01-01

    The present study was undertaken to evaluate the effects of lithium, on steroidogenic and gametogenic functions of testis in the rat. Adult male rats of Wistar strain were injected with lithium chloride at the dose of 0.1 mg, 0.2 mg, and 0.4 mg/100 g body weight/day for 21 days. All the treated animals along with the vehicle treated controls were sacrificed 24 hours after the last injections. Testicular steroidogenic activity was evaluated by measuring the activities of two steroidogenic key enzymes, {Delta}{sup 5}-3{beta} hydroxysteriod dehydrogenase ({Delta}{sup 5} -3{beta}-HSD) and 17{beta} hydroxysteroid dehydrogenase (17{beta} -HSD). Gametogenic capacity was determined by counting the number of germ cells at stage VII of seminiferous cycle. Plasma levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and testosterone (T) were measured by radioimmunoassay (RIA). Administration of lithium chloride at a dose of 0.1 mg/100g body wt. for 21 days led to insignificant changes of plasma FSH, LH, PRL and T along with unaltered activities of testicular {Delta}5 -3{beta}-HSD, 17 {beta}-HSD activities and gametogenesis.

  5. Biosynthesis of silver nanoparticles from Premna serratifolia L. leaf and its anticancer activity in CCl4-induced hepato-cancerous Swiss albino mice

    NASA Astrophysics Data System (ADS)

    Arockia John Paul, J.; Karunai Selvi, B.; Karmegam, N.

    2015-11-01

    In this study, we report the biosynthesis of silver nanoparticles using the ethanolic leaf powder extract of Premna serratifolia L. and its anticancer activity in carbon tetra chloride (CCl4)-induced liver cancer in Swiss albino mice (Balb/c). The synthesized silver nanoparticles were characterized by SEM, FTIR and XRD analyses. The Debye-Scherrer equation was used to calculate particle size and the average size of silver nanoparticles synthesized from P. serratifolia leaf extract was 22.97 nm. The typical pattern revealed that the sample contained cubic structure of silver nanoparticles. FTIR analysis confirmed that the bioreduction of silver ions to silver nanoparticles is due to reduction by capping material of the plant extract. The silver nanoparticles of P. serratifolia leaf extract were effective in treating liver cancer in Swiss albino mice when compared with P. serratifolia leaf extract with isoleucine.

  6. Antiproliferative and antioxidant potential of hesperetin against benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice.

    PubMed

    Bodduluru, Lakshmi Narendra; Kasala, Eshvendar Reddy; Barua, Chandana C; Karnam, Kalyani Chowdary; Dahiya, Vicky; Ellutla, Maheswara

    2015-12-01

    Lung cancer is the foremost cause of cancer mortality and is a growing economic burden worldwide. Chemoprevention, employing the use of natural, dietary or synthetic agents has become an appealing strategy to combat the increasing cases of cancers worldwide. The present study was designed to investigate the mechanism-based chemopreventive nature of hesperetin (HSP) against B[a]P induced lung carcinogenesis in Swiss albino mice. We analyzed the chemopreventive potential of HSP by estimating the status of lipid peroxidation (LPO), enzymic (SOD, CAT, GPx, GR, and GST), nonenzymic antioxidants (GSH, Vit C and Vit E), proinflammatory cytokine (TNF-α), western blotting (CYP1A1, PCNA, Nrf2 and NF-κB expression) and histopathology of lung tissues of control and experimental mice. Administration of B[a]P (50 mg/kg, p.o.) resulted in an increase in lung weight, LPO with concomitant decrease in body weight, enzymic (SOD, CAT, GPx, GR, and GST) and non-enzymic (GSH, Vit C and Vit E) antioxidants. Histological examination of lungs revealed severe alveolar and bronchiolar damages in B[a]P-induced mice. Further, elevated levels of TNF-α along with activated expression of NF-κB, PCNA and CYP1A1, and downregulation of Nrf2 was observed in B[a]P intoxicated animals. Pre- and post-treatment with HSP effectively suppressed B[a]P induced lung carcinoma and the associated preneoplastic lesions by alleviating LPO, modulating antioxidants and decreasing the expression of NF-κB, PCNA and CYP1A1. These findings demonstrate that HSP possesses a potential chemopreventive activity against B[a]P induced lung cancer and this is attributed to its free radical scavenging, antioxidant, anti-inflammatory and antiproliferative properties.

  7. Prophylactic Role of Averrhoa carambola (Star Fruit) Extract against Chemically Induced Hepatocellular Carcinoma in Swiss Albino Mice

    PubMed Central

    Singh, Ritu; Sharma, Jyoti; Goyal, P. K.

    2014-01-01

    Liver cancer remains one of the severe lethal malignancies worldwide and hepatocellular carcinoma (HCC) is the most common form. The current study was designed to evaluate the prophylactic role of the fruit of Averrhoa carambola (star fruit or Kamrak) on diethylnitrosamine- (DENA-) induced (15 mg/kg b.wt.; single i.p. injection) and CCl4-promoted (1.6 g/kg b.wt. in corn oil thrice a week for 24 weeks) liver cancer in Swiss albino mice. Administration of ACE was made orally at a dose of 25 mg/kg b.wt/day for 5 consecutive days and it was withdrawn 48 hrs before the first administration of DENA (preinitiational stage). CCl4 was given after 2 weeks of DENA administration. A cent percent tumor incidence was noted in carcinogen treated animals while ACE administration resulted in a considerable reduction in tumor incidence, tumor yield, and tumor burden. Further, ACE treatment brings out a significant reduction in lipid peroxidation (P < 0.001) along with an elevation in the activities of enzymatic antioxidants (superoxide dismutase, P < 0.001, and catalase, P < 0.001), nonenzymatic antioxidant (reduced glutathione, P < 0.001), and total proteins (P < 0.001) when compared to the carcinogen treated control. These results demonstrate that ACE prevents the DENA/CCl4 induced adverse physical and biochemical alterations during hepatic carcinogenesis in mice. This study suggests the prophylactic role of Averrhoa carambola against hepatocellular carcinoma in mice; therefore, it could be employed for the further screening as a good chemopreventive natural supplement against cancer. PMID:24696677

  8. Prophylactic Role of Averrhoa carambola (Star Fruit) Extract against Chemically Induced Hepatocellular Carcinoma in Swiss Albino Mice.

    PubMed

    Singh, Ritu; Sharma, Jyoti; Goyal, P K

    2014-01-01

    Liver cancer remains one of the severe lethal malignancies worldwide and hepatocellular carcinoma (HCC) is the most common form. The current study was designed to evaluate the prophylactic role of the fruit of Averrhoa carambola (star fruit or Kamrak) on diethylnitrosamine- (DENA-) induced (15 mg/kg b.wt.; single i.p. injection) and CCl4-promoted (1.6 g/kg b.wt. in corn oil thrice a week for 24 weeks) liver cancer in Swiss albino mice. Administration of ACE was made orally at a dose of 25 mg/kg b.wt/day for 5 consecutive days and it was withdrawn 48 hrs before the first administration of DENA (preinitiational stage). CCl4 was given after 2 weeks of DENA administration. A cent percent tumor incidence was noted in carcinogen treated animals while ACE administration resulted in a considerable reduction in tumor incidence, tumor yield, and tumor burden. Further, ACE treatment brings out a significant reduction in lipid peroxidation (P < 0.001) along with an elevation in the activities of enzymatic antioxidants (superoxide dismutase, P < 0.001, and catalase, P < 0.001), nonenzymatic antioxidant (reduced glutathione, P < 0.001), and total proteins (P < 0.001) when compared to the carcinogen treated control. These results demonstrate that ACE prevents the DENA/CCl4 induced adverse physical and biochemical alterations during hepatic carcinogenesis in mice. This study suggests the prophylactic role of Averrhoa carambola against hepatocellular carcinoma in mice; therefore, it could be employed for the further screening as a good chemopreventive natural supplement against cancer.

  9. Protective effects of oat oil on deltamethrin-induced reprotoxicity in male mice.

    PubMed

    Ben Halima, Nihed; Ben Slima, Ahlem; Moalla, Imen; Fetoui, Hamadi; Pichon, Chantal; Gdoura, Radhouane; Abdelkafi, Slim

    2014-09-01

    Oats (Avena sativa L.), which are used in foods, are a potential economically viable source of oil. The purpose of this study was to determine the efficiency of oats oil to alleviate oxidative damage of testis induced by deltamethrin, which is a pyrethroid pesticide that exerts a wide range of effects on non-targeted organisms. The reprotoxicity caused by orally administered deltamethrin (DEL) to mice can be effectively antagonized by the beneficial effects of oats oil (OO) as an antioxidant. Thirty-two male albino mice were divided into four equal groups: a control group, a group of mice given deltamethrin (5 mg per kg b.w.), a group administered deltamethrin after receiving oats oil (6 g per kg b.w.), and a group receiving only OO. Exposure to deltamethrin at a dose of 5 mg per kg b.w. per day caused oxidative stress in testis, proven by a decrease in the epididymal sperm count and motility, an increase in the number of abnormal morphologies in spermatozoa and a significant increase of lipid peroxidation (LP) in the testis when compared to control animals. Co-administration of oats oil to the DEL-treated mice ameliorated the testicular biochemical parameters as well as the histological impairments in testis. We concluded that oats oil ameliorated the toxic effects of deltamethrin in testis explored by reduced LP and improved total sperm density, motility and morphology in mice spermatozoa, suggesting its role as a potential antioxidant.

  10. The effect of mycotoxins found in some herbal plants on biochemical parameters in blood of female albino mice.

    PubMed

    Alwakeel, Suaad S

    2009-04-15

    In this study, twenty five samples ofwell-known herbs in Riyadh, Saudi Arabia were collected and analyzed for Total Fungi Count (TFC). Mycotoxins were extracted and screened using SMKY liquid medium. One hundred and thirty adult female albino mice were grouped into three wherein one group (n = 110) was fed with an aqueous extract from herbal plants. The second group (n = 15) was fed with an aqueous extract of the isolated fungal species. The third group comprised the control group which was given water only (n = 5). All mice were fed with mice breeding diet by Pillsbury, UK. After 5 weeks, mice were fasted and blood was withdrawn for biochemical analysis including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), serum creatinine and urea. Calligonum comosum with 2 x 10(5) cfu g(-1) fungus spore, grained mixed herbs (24 x 10(3) cfu g(-1)) and Salvia officinalis (23 x 10(3) cfu g(-1)) were the most contaminated samples. The genus Aspergillus was the most dominant genus recovered (142 isolates) followed by Penicillium (14 isolates) and these two genera were found in 85.0 and 11.0% of the samples analyzed. Aspergillus fumigatus, Aspergillus flavus and Aspergillus ochraceus were the most dominant and frequently isolated (47.3, 46.5 and 18.1%, respectively), followed by Aspergillus citrinum (11.0%). Aspergillus ochraceus had 21.7 microg kg(-1) of Aflatoxin B2 and 7.25 microg kg(-1) of ochratoxin A, whereas Aspergillus flavus had 7.45 microg kg(-1) of Aflatoxin B2 and Aspergillus fumigatus had 3.5 microg kg(-1) of Aflatoxin B2 and 3.8 microg kg(-1) of ochratoxin A. Mean creatinine, urea, ALT, AST and GGT were higher in mice fed or treated with herbal and fungal extracts group than the control group. This study confirms previous studies demonstrating the predominance of Aspergillus species in herbal and medicinal plants and its capability in the production of aflatoxin with induction of nephrotoxicity and hepatoxicity in

  11. Protective effects of Mentha piperita Linn on benzo[a]pyrene-induced lung carcinogenicity and mutagenicity in Swiss albino mice.

    PubMed

    Samarth, R M; Panwar, Meenakshi; Kumar, Madhu; Kumar, Ashok

    2006-01-01

    The chemopreventive and antimutagenic effects of an aqueous extract of Mentha piperita leaves were evaluated by using 9 week medium term model of benzo[a]pyrene (BP)-induced lung tumors. Lung tumors were induced by a single subcutaneous injection in the scapular region with BP in newborn Swiss albino mice (<24 h old). The oral administration of Mentha extract (ME) showed a significant reduction in the number of lung tumors from an incidence of 67.92% in animals given only BP to 26.31%. The inhibition rate was 61.26% in ME treated group with respect to reference group (BP-alone). However, tumor multiplicity was reduced from 0.83 in the BP-alone group to 0.31 in the BP+ME group. Also, ME treatment reduced the frequency of BP-induced chromosomal aberrations and micronuclei in bone marrow cells and decreased the levels of lipoperoxides and increased sulfhydryl groups in liver as well as lung. In cell-free assays, ME showed strong scavenging activity for both the DPPH* and ABTS*+ radicals. ME had an IC50 value of 272 microg/ml in the DPPH* assay. The chemopreventive action and antimutagenic effects observed in the present study is attributed to the antioxidative and radical scavenging properties of ME.

  12. Phytochemical Screening and Acute Toxicity of Aqueous Extract of Leaves of Conocarpus erectus Linnaeus in Swiss Albino Mice.

    PubMed

    Nascimento, Dayane K D; Souza, Ivone A DE; Oliveira, Antônio F M DE; Barbosa, Mariana O; Santana, Marllon A N; Pereira, Daniel F; Lira, Eduardo C; Vieira, Jeymesson R C

    2016-09-01

    Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae) known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE). The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5.

  13. Ganoderma lucidum total triterpenes attenuate DLA induced ascites and EAC induced solid tumours in Swiss albino mice.

    PubMed

    Smina, T P; Mathew, J; Janardhanan, K K

    2016-01-01

    G. lucidum total triterpenes were assessed for its apoptosis-inducing and anti-tumour activities. The ability of the total triterpenes to induce apoptosis was evaluated in Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines. Total triterpenes were found to be highly cytotoxic to DLA and EAC cell lines with IC50 values 5 ± 0.32 and 7.9 ± 0.2 µg/ml respectively. Total triterpenes induced apoptosis in both cell lines which is evident from the DNA fragmentation assay. Anti-tumour activity was accessed using DLA induced solid and EAC induced ascites tumour models in Swiss albino mice. Administration of 10, 50 and 100 mg/kg b. wt. total triterpenes showed 11.86, 27.27 and 40.57% increase in life span of animals in ascites tumour model. Treatment with 10, 50 and 100 mg/kg b. wt. total triterpenes exhibited 76.86, 85.01 and 91.03% inhibition in tumour volume and 67.96, 72.38 and 77.90% inhibition in tumour weight respectively in the solid tumour model. The study reveals the significant dose-dependent anti-tumour activity of total triterpenes in both models. Total triterpenes were more active against the solid tumour than the ascites tumour. The anti-oxidant potential and ability to induce cell-specific apoptosis could be contributing to its anti-tumour activities. PMID:27188870

  14. Assessment of chromosomal aberration in the bone marrow cells of Swiss Albino mice treated by 4-methylimidazole.

    PubMed

    Norizadeh Tazehkand, Mostafa; Topaktas, Mehmet; Yilmaz, Mehmet Bertan

    2016-01-01

    4-Methylimidazole (4-MEI) is formed during the production of certain caramel coloring agents used in many food and drink products. It may also be formed during the cooking, roasting, or other processing of some foods and beverages. So it was unintentionally consumed in worldwide. This study was aimed to investigate the genotoxic and cytotoxic effects of 4-MEI using chromosome aberration (CA) and mitotic index (MI) in Swiss Albino mice. In this research, CA and MI of the mouse bone marrow cells were analyzed after treating the animals with 4-MEI (100, 130 and 160 mg/kg) for 12 h and 24 h treatment times. All data were analyzed using statistical methods. 4-MEI significantly increased the percentage of CAs at all concentrations for 12 h and at highest concentration for 24 h treatment periods. 4-MEI at highest concentration for 12 h and at all concentrations for 24 h decreased the MI in comparison with control. Genotoxic and cytotoxic effects of 4-MEI at 24 h treatment periods were concentration dependent. Consequently, it can be said that 4-MEI have genotoxic and cytotoxic effect in mouse. PMID:26634952

  15. Phytochemical Screening and Acute Toxicity of Aqueous Extract of Leaves of Conocarpus erectus Linnaeus in Swiss Albino Mice.

    PubMed

    Nascimento, Dayane K D; Souza, Ivone A DE; Oliveira, Antônio F M DE; Barbosa, Mariana O; Santana, Marllon A N; Pereira, Daniel F; Lira, Eduardo C; Vieira, Jeymesson R C

    2016-09-01

    Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae) known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE). The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5. PMID:27508993

  16. Hypoglycemic Effect of Aqueous and Methanolic Extract of Artemisia afra on Alloxan Induced Diabetic Swiss Albino Mice.

    PubMed

    Issa, Idris Ahmed; Hussen Bule, Mohammed

    2015-01-01

    Diabetes mellitus is metabolic syndrome that causes disability, early death, and many other complications. Currently insulin and many synthetic drugs are used in diabetes treatment. However, these pharmaceutical drugs are too expensive particularly for sub-Saharan population in addition to their undesirable side effects. The present study was aimed to evaluate antidiabetic effect and toxicity level of Artemisia afra which was collected from its natural habitat in Bale Zone, around Goba town, 455 km southeast of Addis Ababa. Air dried aerial parts of Artemisia afra were separately extracted with both distilled water and 95% methanol. Oral acute toxicity test was conducted on healthy Swiss albino mice. Antidiabetic effect of the aqueous and methanolic extracts of Artemisia afra was separately evaluated on alloxan induced diabetic mice at doses of 500, 750, and 1000 mg/Kg body weight orally. The results indicate that mean lethal dose (LD50) for aqueous extract of Artemisia afra was 9833.4 mg/Kg. Blood glucose level was significantly decreased by 24% (p < 0.005) and 56.9% (p < 0.0004) in groups that received aqueous extract of Artemisia afra at dose of 500 mg/Kg and 750 mg/Kg, respectively. The methanolic extract of Artemisia afra also significantly lowered blood glucose by 49.8% (p < 0.0001) at doses of 1000 mg/kg on the 5th hr. Aqueous extract of Artemisia afra was regarded as nontoxic and safe since its LD50 was found above 5000 mg/Kg. Aqueous extract showed higher effect at relatively lower dose as compared to methanolic extract. The aqueous extract was screened positive for phytochemicals like flavonoids, polyphenols, and tannins that were reported to have antioxidant activity. PMID:26345313

  17. Effect of fenugreek seeds extract on cyclophosphamide-induced histomorphometrical, ultrastructural and biochemical changes in testes of albino mice.

    PubMed

    Sakr, Saber A; Mahran, Hoda A; Abo-El-Yazid, Samah M

    2012-04-01

    Cyclophosphamide (CPA) is an anticancer drug used in the treatment of a variety of neoplastic lesions. On the other hand, treatment with CPA was accompanied by different toxic effects on different body organs. The present work was conducted to study the effect of fenugreek seed extract on histomorphometrical and ultrastructural changes induced by CPA in testes of albino mice. Twenty animals were given CPA (7.0 mg/kg body weight) three times/week orally for 8 weeks and were killed after 4 and 8 weeks. Testis of CPA-treated mice showed many histological alterations including appearance of irregular seminiferous tubules, reduction in the number of all spermatogenic cells, degeneration of Leydig cells and appearance of intertubular hemorrhage. Concerning the ultrastructural changes, abnormalities in spermatogonia (A and B), spermatocytes, round and elongated spermatids were observed. Degenerated Sertoli cells and degenerated interstitial tissue with abnormal Leydig cells were also seen. Moreover, administration of CPA to animals significantly increased malondialdehyde (MDA, lipid peroxidation marker) and decreased superoxide dismutase (SOD) and catalase (CAT). These changes were time-dependent. Treating animals with CPA and fenugreek seed extract (0.4 g/kg body weight) led to an improvement in the histological and ultrastructural pictures of the testis together with reduction in the level of serum MDA and increase in the activities of serum SOD and CAT. In conclusion, the results of the present work indicated that fenugreek had ameliorative effect against testis damage induced by CPA and this may be mediated by its potent antioxidant activities.

  18. [Experimental infection caused by Machupo virus in intact and immunosuppressed albino mice].

    PubMed

    Orlova, S V; Votiakov, V I

    1989-01-01

    Features of the course of experimental infection in white mice caused by Machupo virus in relation to their age, route of virus inoculation, and under conditions of normal and suppressed immune response created by antithymocyte globulin (ATG) were studied. The effect of different ATG doses and intervals of its administration on the experimental infection were demonstrated.

  19. Attenuation of hepatotoxicity and oxidative stress in diabetes STZ-induced type 1 by biotin in Swiss albino mice.

    PubMed

    Aldahmash, Badr Abdullah; El-Nagar, Doaa Mohamed; Ibrahim, Khalid Elfakki

    2016-03-01

    Diabetes mellitus is one of the major health problems. This study was designed to investigate the effect of biotin to regulate blood glucose level, reduced toxicity and oxidative stress in liver of diabetic mice STZ-induced type 1. Male mice were divided into three groups, the first one served as the control group, the second and the third groups received single ip dose of 150 mg/kg of STZ, the second group served as the untreated diabetic group, the third group received daily oral dose of 15 mg/kg of biotin, livers and liver index showed insignificant difference among groups. Blood glucose level showed a significant decrease in treated diabetic mice compared to untreated diabetic mice. Biochemical analysis showed a significant decrease in liver enzymes AST and ALT compared to the control group. Histopathological examination showed severe changes in untreated diabetic liver tissue manifested by dilated portal vein, leukocytic infiltration, fatty degeneration and moderate to severe histopathological score, whereas, treated diabetic mice with biotin showed reduction in hepatotoxicity represented by appearance of relative healthy hepatocytes and normal histopathological score. Immunohistochemistry of acrolein showed intense immunoreactions in liver section of untreated diabetic mice and faint immunoreactions in treated diabetic mice with biotin as evidence to oxidative stress reduction. PMID:26981014

  20. Attenuation of hepatotoxicity and oxidative stress in diabetes STZ-induced type 1 by biotin in Swiss albino mice

    PubMed Central

    Aldahmash, Badr Abdullah; El-Nagar, Doaa Mohamed; Ibrahim, Khalid Elfakki

    2015-01-01

    Diabetes mellitus is one of the major health problems. This study was designed to investigate the effect of biotin to regulate blood glucose level, reduced toxicity and oxidative stress in liver of diabetic mice STZ-induced type 1. Male mice were divided into three groups, the first one served as the control group, the second and the third groups received single ip dose of 150 mg/kg of STZ, the second group served as the untreated diabetic group, the third group received daily oral dose of 15 mg/kg of biotin, livers and liver index showed insignificant difference among groups. Blood glucose level showed a significant decrease in treated diabetic mice compared to untreated diabetic mice. Biochemical analysis showed a significant decrease in liver enzymes AST and ALT compared to the control group. Histopathological examination showed severe changes in untreated diabetic liver tissue manifested by dilated portal vein, leukocytic infiltration, fatty degeneration and moderate to severe histopathological score, whereas, treated diabetic mice with biotin showed reduction in hepatotoxicity represented by appearance of relative healthy hepatocytes and normal histopathological score. Immunohistochemistry of acrolein showed intense immunoreactions in liver section of untreated diabetic mice and faint immunoreactions in treated diabetic mice with biotin as evidence to oxidative stress reduction. PMID:26981014

  1. Squaraine PDT induces oxidative stress in skin tumor of swiss albino mice

    NASA Astrophysics Data System (ADS)

    Cibin, T. R.; Gayathri, Devi D.; Ramaiah, D.; Abraham, Annie

    2010-02-01

    Photodynamic Therapy (PDT) using a sensitizing drug is recognized as a promising medical technique for cancer treatment. It is a two step process that requires the administration of a photosensitizer followed by light exposure to treat a disease. Following light exposure the photosensitizer is excited to a higher energy state which generates free radicals and singlet oxygen. The present study was carried out to assess the oxidative damage induced by bis (3, 5-diiodo-2, 4, 6- trihydroxyphenyl) squaraine in skin tumor tissues of mice with/ without light treatment. Skin tumor was induced using 7, 12-Dimethyl Benz(a)anthracene and croton oil. The tumor bearing mice were given an intraperitoneal injection with the squaraine dye. After 24h, the tumor area of a few animals injected with the dye, were exposed to visible light from a 1000 W halogen lamp and others kept away from light. All the mice were sacrificed one week after the PDT treatment and the oxidative profile was analyzed (TBARS, SOD, catalase, GSH, GPx and GR) in tumor/ skin tissues. The dye induces oxidative stress in the tumor site only on illumination and the oxidative status of the tumor tissue was found to be unaltered in the absence of light. The results of the study clearly shows that the tumor destruction mediated by PDT using bis (3, 5-diiodo-2, 4, 6-trihydroxyphenyl) squaraine as a photosensitizer is due to the generation of reactive oxygen species, produced by the light induced changes in the dye.

  2. Protective effect of kombucha mushroom (KM) tea on phenol-induced cytotoxicity in albino mice.

    PubMed

    Yapar, Kursad; Cavusoglu, Kultigin; Oruc, Ertan; Yalcin, Emine

    2010-09-01

    The present study was carried out to evaluate the protective role of kombucha mushroom (KM) tea on cytotoxicity induced by phenol (PHE) in mice. We used weight gain and micronucleus (MN) frequency as indicators of cytotoxicity and supported these parameters with pathological findings. The animals were randomly divided into seven groups: (Group I) only tap water (Group II) 1000 microl kg(-1) b. wt KM-tea, (Group III) 35 mg kg(-1) body wt. PHE (Group IV) 35 mg kg(-1) body wt. PHE + 250 microl kg(-1) b. wt KM-tea (Group V) 35 mg kg(-1) b. wt PHE + 500 microl kg(-1) b. wt KM-tea (Group VI) 35 mg kg(-1) b. wt PHE + 750 microl kg(-1) b. wt KM-tea, (Group VII) 35 mg kg(-1) b. wt PHE + 1000 microl kg(-1) b. wt KM-tea, for 20 consecutive days by oral gavage. The results indicated that all KM-tea supplemented mice showed a lower MN frequency than erythrocytes in only PHE-treated group. There was an observable regression on account of lesions in tissues of mice supplemented with different doses of KM-tea in histopathological observations. In conclusion, the KM-tea supplementation decreases cytotoxicity induced by PHE and its protective role is dose-dependent.

  3. Effects of glycowithanolides on lipid peroxidation and lipofuscinogenesis in male reproductive organs of mice

    PubMed Central

    Walvekar, Madhuri; Shaikh, Nilofar; Sarvalkar, Priti

    2013-01-01

    Background: Glycowithanolides (Withaferin A), is one of the main withanolides active principle isolated from plant Withania somnifera and is claimed that it possess the aphrodisiac, sedative, rejuvenate and life prolonging properties. Objective: In the present investigation, antioxidant activity of active principles of Withania somnifera was tested against D-galactose induced oxidative stress in mouse testes, epididymis and seminal vesicle. Materials and Methods: For the present investigation Swiss male albino mice Mus musculus (Linn) were used. They were grouped in to control (I), D-galactose treated (II), protective (III) and curative groups (IV). Oxidative stress was induced in six month old mice by injecting a low dose of D-galactose. Antioxidant effect of plant extract was studied in testes, epididymis, and seminal vesicle of oxidative stressed mice on Lipid peroxidation (LPO) and fluorescence product. Results: In the present study, both total as well as mitochondrial lipid peroxidation and fluorescence product in testes, epididymis and seminal vesicle were increased in D-galactose induced mice. After the treatment of glycowithanolides there was significantly decrease in total as well as mitochondrial lipid peroxidation and fluorescence product in protective and curative groups. Conclusion: Our results indicate that Withania somnifera has a capability of preventing oxidative stress and also combating stress induced infertility. PMID:24639810

  4. Antiplasmodial activity of certain medicinal plants against chloroquine resistant Plasmodium berghei infected white albino BALB/c mice.

    PubMed

    Rajendran, C; Begam, M; Kumar, Dharmendra; Baruah, Indra; Gogoi, H K; Srivastava, R B; Veer, Vijay

    2014-06-01

    In the present study of antimalarial efficacy, aqueous extracts of leaves and unripe fruits of Psidium guajava, leaves of Ocimum sanctum and leaves of Murraya koenigii are evaluated against Plasmodium berghei (chloroquine resistant NK65 strain) infected white albino BALB/c mice. A 7 days oral administration was adopted with different dosage viz., 350 mg, 750 mg and 1,000 mg/kg body weight as treatment schedule along with parasite (Group I) and drug control with Chloroquine, 50 mg/kg body weight (Group II). All the parts were extracted based on the decoction method, which is commonly seen among the villagers/tribes as their usual method of preparation of decoction for most of the ailments. The antimalarial activities were evaluated from the giemsa stained blood smears collected from different treated groups of mice used in this experiment. The antiplasmodial effect that is percent parasitaemia and percent suppression (values in parenthesis) showed by the treated groups of mice at 350 mg/kg b. wt. by the aqueous extracts of P. guajava leaves (Group III) was 19.8 ± 1.22 (73.7 %), P. guajava unripe fruits (Group IV) was 52.7 ± 2.19 (30.0 %), leaves of O. sanctum (Group V) was 64.0 ± 0.73 (15.1 %) and leaves of M. koenigii (Group VI) was 28.9 ± 0.81 (61.6 %) whereas at 750 mg/kg b. wt., it all showed 10.3 ± 0.7 (80.2 %), 26.3 ± 0.52 (65.1 %), 42.0 ± 0.47 (44.2 %) and 14.9 ± 0.46 (71.5 %) whereas at 1,000 mg/kg b. wt. dose, it all showed 9.2 ± 0.39 (85.8 %), 25.6 ± 0.40 (62.0 %), 41.8 ± 0.29 (35.5 %) and 14.0 ± 0.42 (76.9 %) respectively.

  5. Antiplasmodial activity of certain medicinal plants against chloroquine resistant Plasmodium berghei infected white albino BALB/c mice.

    PubMed

    Rajendran, C; Begam, M; Kumar, Dharmendra; Baruah, Indra; Gogoi, H K; Srivastava, R B; Veer, Vijay

    2014-06-01

    In the present study of antimalarial efficacy, aqueous extracts of leaves and unripe fruits of Psidium guajava, leaves of Ocimum sanctum and leaves of Murraya koenigii are evaluated against Plasmodium berghei (chloroquine resistant NK65 strain) infected white albino BALB/c mice. A 7 days oral administration was adopted with different dosage viz., 350 mg, 750 mg and 1,000 mg/kg body weight as treatment schedule along with parasite (Group I) and drug control with Chloroquine, 50 mg/kg body weight (Group II). All the parts were extracted based on the decoction method, which is commonly seen among the villagers/tribes as their usual method of preparation of decoction for most of the ailments. The antimalarial activities were evaluated from the giemsa stained blood smears collected from different treated groups of mice used in this experiment. The antiplasmodial effect that is percent parasitaemia and percent suppression (values in parenthesis) showed by the treated groups of mice at 350 mg/kg b. wt. by the aqueous extracts of P. guajava leaves (Group III) was 19.8 ± 1.22 (73.7 %), P. guajava unripe fruits (Group IV) was 52.7 ± 2.19 (30.0 %), leaves of O. sanctum (Group V) was 64.0 ± 0.73 (15.1 %) and leaves of M. koenigii (Group VI) was 28.9 ± 0.81 (61.6 %) whereas at 750 mg/kg b. wt., it all showed 10.3 ± 0.7 (80.2 %), 26.3 ± 0.52 (65.1 %), 42.0 ± 0.47 (44.2 %) and 14.9 ± 0.46 (71.5 %) whereas at 1,000 mg/kg b. wt. dose, it all showed 9.2 ± 0.39 (85.8 %), 25.6 ± 0.40 (62.0 %), 41.8 ± 0.29 (35.5 %) and 14.0 ± 0.42 (76.9 %) respectively. PMID:24808642

  6. Toxicity and inflammatory response in Swiss albino mice after intraperitoneal and oral administration of polyurethane nanoparticles.

    PubMed

    Silva, Adny H; Locatelli, Claudriana; Filippin-Monteiro, Fabíola B; Martin, Philip; Liptrott, Neill J; Zanetti-Ramos, Betina G; Benetti, Luana C; Nazari, Evelize M; Albuquerque, Cláudia A C; Pasa, André A; Owen, Andrew; Creczynski-Pasa, Tânia B

    2016-03-30

    In this work in vivo experiments were conducted in order to characterize the biocompatibility of polyurethane nanoparticles (PU-NPs) after intraperitoneal (i.p.) and oral administration. Additionally, ex vivo assays were performed to assess human blood compatibility as well as in vitro assays to assess protein binding. Our results indicated that administration of three different concentrations of PU-NPs induced a significant increase in visceral fat accumulation after oral dosing. In addition, fat tissue of mice intraperitoneally treated with the highest concentration of nanoparticles showed diffuse mononuclear inflammatory infiltrate in the fat tissue. Histopathological assessment showed inflammatory infiltrate and hepatocyte vacuolization in the liver, inflammatory infiltration and vascular congestion in the lung and glomerular necrosis in the kidney. Hepatic enzymes related with liver function were significantly increased in both groups of mice treated with PU-NPs. The PU-NPs did not affect the human blood cells number as well as coagulation time but showed a susceptibility to bind in proteins commonly found in the blood stream. In addition, increased amounts of pro inflammatory cytokines in vivo, as well as ex vivo in human cells were observed. Further studies to establish the consequences of long-term exposure to PU-NPs are warranted.

  7. Effect of helium-neon laser irradiation on hair follicle growth cycle of Swiss albino mice.

    PubMed

    Shukla, S; Sahu, K; Verma, Y; Rao, K D; Dube, A; Gupta, P K

    2010-01-01

    We report the results of a study carried out to investigate the effect of helium-neon (He-Ne) laser (632.8 nm) irradiation on the hair follicle growth cycle of testosterone-treated and untreated mice. Both histology and optical coherence tomography (OCT) were used for the measurement of hair follicle length and the relative percentage of hair follicles in different growth phases. A positive correlation (R = 0.96) was observed for the lengths of hair follicles measured by both methods. Further, the ratios of the lengths of hair follicles in the anagen and catagen phases obtained by both methods were nearly the same. However, the length of the hair follicles measured by both methods differed by a factor of 1.6, with histology showing smaller lengths. He-Ne laser irradiation (at approximately 1 J/cm(2)) of the skin of both the control and the testosterone-treated mice was observed to lead to a significant increase (p < 0.05) in % anagen, indicating stimulation of hair growth. The study also demonstrates that OCT can be used to monitor the hair follicle growth cycle, and thus hair follicle disorders or treatment efficacy during alopecia. PMID:20016249

  8. Presence of toll like receptor-2 in spleen, lymph node and thymus of Swiss albino mice and its modulation by Staphylococcus aureus and bacterial lipopolysaccharide. .

    PubMed

    Ghosh, Chandrayee; Prakash, Nune Ravi; Manna, Sunil Kumar; Bishayi, Biswadev

    2015-02-01

    Toll-like receptors (TLR) are a family of pattern recognition receptors identifying pathogen associated molecular patterns (PAMPs). They play a critical role in the innate immune response during the initial interaction between the infecting microorganism and phagocytic cells. Here, we verified the presence of TLR-2 in spleen, lymph node and thymus of Swiss albino mice and their modulation after infection with Staphylococcus aureus and Lipopolysaccharide (LPS) challenge. It was seen that TLR-2 gene transcribed to its respective mRNA on S. aureus infection, in thymus, spleen and lymph node of mice but their levels and mode of expression varied. When challenged with LPS no prominent changes in the expression of TLR-2 receptor was observed but its expression increased gradually with time in the thymus, spleen and lymph node of S. aureus infected mice. TLR-2 expression was also found enhanced in infected splenic macrophages. By studying the serum cytokine profile the functionality of the receptor was measured. The results indicate the presence of TLR-2 in thymus, spleen and lymph node of Swiss albino strain of mice and that they are modulated by S. aureus.

  9. Anti-neoplastic activities of sepia officinalis ink and coelatura aegyptiaca extracts against Ehrlich ascites carcinoma in Swiss albino mice

    PubMed Central

    Soliman, Amel M; Fahmy, Sohair R; El-Abied, Salma A

    2015-01-01

    Objectives: With the development of sophisticated instruments for the isolation and elucidation of natural products structures from marine and freshwater organisms, major advances have been made in the discovery of aquatic derived therapeutics. Present investigations were carried out to evaluate cuttlefish (Sepia officinalis) ink extract (IE) and freshwater clam (Coelatura aegyptiaca) extract (CE) for their anticancer and antioxidant activities as compared to 5-flurouracil (5-Fu), in Ehrlich ascites carcinoma (EAC). Methods: Sixty female Swiss albino mice were divided into five groups (n = 12). All groups except group I received EAC cells (5 × 106 cells/mouse i.p.) and this was taken as the 0th day. Group I served as saline control (5 ml/kg 0.9% NaCl w/v p.o). Group II served as EAC control. Rats of groups III, IV and V received IE, CE (200 mg/kg body weight i.p.), and reference drug (5-Fu, 20 mg/kg body weight i.p.), respectively. Results: The reduction in tumor volume, packed cell volume, tumor cell counts and increase in median survival time and percentage increase in life span in treated animals were observed. There was a significant increase in RBC count; Hb content in treated animals and reduction in total WBC count. There was a significant decrease in AST, ALT, ALP and liver MDA levels and increase in GSH, SOD and NO levels were observed in all treated animals. Conclusion: Both IE and CE were effective in inhibiting the tumor growth in ascitic tumor models. The biochemical, antioxidants and histopathological studies were also supported their antitumor properties. PMID:26097537

  10. Chemopreventive effects of cardamom (Elettaria cardamomum L.) on chemically induced skin carcinogenesis in Swiss albino mice.

    PubMed

    Qiblawi, Samir; Al-Hazimi, Awdah; Al-Mogbel, Mohammed; Hossain, Ashfaque; Bagchi, Debasis

    2012-06-01

    The chemopreventive potential of cardamom was evaluated on 7,12-dimethylbenz[a]anthracene-initiated and croton oil-promoted mouse skin papillomagenesis. A significant reduction in the values of tumor incidence, tumor burden, and tumor yield and the cumulative number of papillomas was observed in mice treated orally with 0.5 mg of cardamom powder in suspension continuously at pre-, peri-, and post-initiational stages of papillomagenesis compared with the control group. The average weight and diameter of tumors recorded were also comparatively lower in the cardamom-treated mouse group. Treatment of cardamom suspension by oral gavage for 15 days resulted in a significant decrease in the lipid peroxidation level of the liver (P < .01). In addition, the reduced glutathione level was significantly elevated in comparison with the control group (P < .05) following cardamom suspension treatment. Taken together, these findings indicate the potential of cardamom as a chemopreventive agent against two-stage skin cancer.

  11. Protective effects of fruit extracts of Hippophae rhamnoides L. against arsenic toxicity in Swiss albino mice.

    PubMed

    Gupta, R; Flora, S J S

    2006-06-01

    Seabuckthorn (Hippophae rhamnoides L.) berry has a long history of applications as a food and medicinal ingredient in eastern countries. The present study was carried out to investigate the effect of different fruit extracts of H. rhamnoides on altered biochemical parameters indicative of haematological alterations, tissue oxidative stress, and arsenic concentration in arsenic-exposed mice (2.5 mg/kg body weight, intraperitoneally). Two aqueous extracts (at room temperature and under reflux condition) and an ethanolic extract of H. rhamnoides at a dose of 500 mg/kg body weight were co-administered daily during arsenic exposure in mice for 3 weeks. Exposure to arsenic led to a significant inhibition of blood delta-aminolevulinic acid dehydratase (ALAD) activity, suggesting disturbed haem synthesis pathway. Arsenic also caused significant depletion of reduced hepatic glutathione (GSH) level, glutathione S-transferase (GST) and glutathione peroxidase and catalase activities, while it increased the level of thiobarbituric acid reactive substance (TBARS), suggesting liver oxidative stress. Most of the altered biochemical variables responded favorably to the co-supplementation of H. rhamnoides, particularly the aqueous fruit extract, extracted at room temperature (HF-WRT). However, arsenic concentration in blood and tissues remained unchanged, suggesting the lack of chelating property of fruit extract of H. rhamnoides. The present study, thus, led us to conclude that the fruit extract of H. rhamnoides has a significant protective role against arsenic-induced oxidative injury. However, it lacks the ability to remove arsenic from the binding sites, suggesting that the herbal extract could be co-administered with a chelating agent of known efficacy during treatment of arsenic to achieve the optimum effect of chelation treatment.

  12. Acute inhalation toxicity of smoke of fentanyl and its 1-substituted analogs in Swiss albino mice.

    PubMed

    Yadav, S K; Swami, D; Kumar, P; Meena, M K; Maurya, C K; Gupta, P K; Ganesan, K; Jain, A K; Bhattacharya, R

    2014-01-01

    Fentanyl (N-(1-phenethyl-4-piperidinyl)propionanilide) is a synthetic, potent narcotic analgesic agent. However, it is known to have several side effects, which led to synthesis and evaluation of its new analogs for the management of pain. We have earlier reported the comparative bioassay of fentanyl and its eight 1-substituted analogs (1-8) in mice. Three compounds, viz., N-(1-(2-phenoxyethyl)-4-piperidinyl)propionanilide (2), N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6) were found to be more effective and less toxic compared to fentanyl. The present study reports the comparative acute inhalation toxicity of smoke of fentanyl and its three analogs, viz., 2, 5, and 6 in mice. Animals were exposed to different concentrations of smoke generated by heating the compounds. Exposure was performed in a head only all glass static exposure assembly for 15 min to determine the median lethal concentration (LC50). The breathing pattern and various respiratory parameters of the animals were also monitored online using a polygraph. Out of three compounds tested, analog 5 was found to be most toxic (LC50 = 2820 mg/m3) while 2 was least toxic (LC50 = >8000 mg/m3). All the compounds caused long lasting respiratory depression in a dose-dependent manner, which did not completely resolve even after discontinuation of exposure. Aerodynamic median diameter and geometric standard deviation of smoke particles was determined employing eight-stage Andersen sampler. The particles were found to be within the respirable range. The study, however, concludes that due to possible decomposition of the compounds by heating or its poor absorption by the alveolar surface, the present inhalation technique cannot be employed to generate smoke of fentanyl and its analogs for any medical or surreptitious use. PMID:25208041

  13. Anti-tumor activity of Aloe vera against DMBA/croton oil-induced skin papillomagenesis in Swiss albino mice.

    PubMed

    Saini, M; Goyal, Pradeep Kumar; Chaudhary, Geeta

    2010-01-01

    Human populations are increasingly exposed to various carcinogens such as chemicals, radiation, and viruses in the environment. Chemopreventive drugs of plant origin are a promising strategy for cancer control because they are generally nontoxic or less toxic than synthetic che-mopreventive agents, and can be effective at different stages of carcinogenesis. The present investigation was undertaken to explore the antitumor activity of topical treatment with aloe vera (Aloe vera) gel, oral treatment with aloe vera extract, and topical and oral treatment with both gel and extract in stage-2 skin carcinogenesis in Swiss albino mice induced by 7,12-dim ethylbenz(a)anthracene (DMBA) and promoted croton (Croton tiglium) oil. The animals were randomly divided into 4 groups and treated as follows: Group I, DMBA + croton oil only (controls); Group II, DMBA + croton oil + topical aloe vera gel; Group III, DMBA + croton oil + oral aloe vera extract; Group I V, DMBA + croton oil + topical aloe vera gel + oral aloe vera extract. Results showed that body weight was significantly increased from 78.6% in the control group (Group I) to 92.5%, 87.5%, and 90.0% in Groups II, III, and I V, respectively. A 100% incidence of tumor development was noted in Group I, which was decreased to 50%, 60%, and 40% in Groups II, III, and I V, respectively. Also in Groups II, III, and IV, the cumulative number of papillomas was reduced significantly from 36 to 12, 15, and 11; tumor yield from 3.6 to 1.2, 1.5, and 1.1; and tumor burden from 3.6 to 2.4, 2.50, and 2.75, respectively, after treatment with aloe vera. Conversely, the average latent period increased significantly from 4.9 (Group I) to 5.23, 5.0, and 6.01 weeks in Groups II, III, and I V, respectively. We conclude that aloe vera protects mice against DMBA/croton oil-induced skin papillomagenesis, likely due to the chemopreventive activity of high concentrations of antioxidants such as vitamins A, C, and E; glutathione peroxidase; several

  14. Chemopreventive effects of cardamom (Elettaria cardamomum L.) on chemically induced skin carcinogenesis in Swiss albino mice.

    PubMed

    Qiblawi, Samir; Al-Hazimi, Awdah; Al-Mogbel, Mohammed; Hossain, Ashfaque; Bagchi, Debasis

    2012-06-01

    The chemopreventive potential of cardamom was evaluated on 7,12-dimethylbenz[a]anthracene-initiated and croton oil-promoted mouse skin papillomagenesis. A significant reduction in the values of tumor incidence, tumor burden, and tumor yield and the cumulative number of papillomas was observed in mice treated orally with 0.5 mg of cardamom powder in suspension continuously at pre-, peri-, and post-initiational stages of papillomagenesis compared with the control group. The average weight and diameter of tumors recorded were also comparatively lower in the cardamom-treated mouse group. Treatment of cardamom suspension by oral gavage for 15 days resulted in a significant decrease in the lipid peroxidation level of the liver (P < .01). In addition, the reduced glutathione level was significantly elevated in comparison with the control group (P < .05) following cardamom suspension treatment. Taken together, these findings indicate the potential of cardamom as a chemopreventive agent against two-stage skin cancer. PMID:22404574

  15. In-vivo characterization of endogenous porphyrin fluorescence from DMBA-treated Swiss Albino mice skin carcinogenesis for measuring tissue transformation

    NASA Astrophysics Data System (ADS)

    Ganesan, Singaravelu; Ebenezar, Jeyasingh; Hemamalini, Srinivasan; Aruna, Prakasa R.

    2002-05-01

    Steady state fluorescence spectroscopic characterization of endogenous porphyrin emission from DMBA treated skin carcinogenesis in Swiss albino mice was carried out. The emission of endogenous porphyrin from normal and abnormal skin tissues was studied both in the presence and absence of exogenous ALA to compare the resultant porphyrin emission characterictics. The mice skin is excited at 405nm and emission spectra are scanned from 430 to 700nm. The average fluorescence emission spectra of mice skin at normal and various tissues transformation conditions were found to be different. Two peaks around 460nm and 636nm were observed and they may be attributed to NADH, Elastin and collagen combination and endogenous porphyrin emission. The intensity at 636nm increases as the stage of the cancer increases. Although exogenous ALA enhances the PPIX level in tumor, the synthesis of PPIX was also found in normal surrounding skin, in fact, with higher concentration than that of tumor tissues.

  16. Baclofen prevents the elevated plus maze behavior and BDNF expression during naloxone precipitated morphine withdrawal in male and female mice.

    PubMed

    Pedrón, Valeria T; Varani, André P; Balerio, Graciela N

    2016-05-01

    In previous studies we have shown that baclofen, a selective GABAB receptor agonist, prevents the somatic expression and reestablishes the dopamine and μ-opioid receptors levels, modified during naloxone-precipitated morphine withdrawal syndrome in male and female mice. There are no previous reports regarding sex differences in the elevated plus maze (EPM) and the expression of BDNF in morphine-withdrawn mice. The present study analyses the behavioral and biochemical variations during morphine withdrawal in mice of both sexes, and whether these variations are prevented with baclofen. Swiss-Webster albino prepubertal mice received morphine (2 mg/kg, i.p.) twice daily, for 9 consecutive days. On the 10th day, one group of morphine-treated mice received naloxone (opioid receptor antagonist; 6 mg/kg, i.p.) 1 h after the last dose of morphine to precipitate withdrawal. A second group received baclofen (2 mg/kg, i.p.) before naloxone administration. The EPM behavior was measured during 15 min after naloxone injection. The expression of BDNF-positive cells was determined by immunohistochemistry. Withdrawn male mice showed a higher percentage of time spent and number of entries to the open arms compared to withdrawn female mice. Baclofen prevented this behavior in both sexes. BDNF expression decreased in the AcbC, BNST, CeC, and CA3 of the hippocampus while increased in the BLA of morphine withdrawn male. Baclofen pretreatment prevented the BDNF expression observed in morphine withdrawn male mice in all the brain areas studied except in the CeC. Baclofen prevention of the EPM behavior associated to morphine withdrawal could be partially related to changes in BDNF expression.

  17. Analysis of male aggressive and sexual behavior in mice.

    PubMed

    Kikusui, Takefumi

    2013-01-01

    Pheromone and odor signals play a pivotal role in male mouse reproductive behaviors, such as sexual and aggressive behavior. There are several methods used to assess male behaviors, each of which examines a unique aspect of the biological function of mice. There are two major ways of assessing male aggressive behavior in mice, one is using isolation-induced aggression, and the other is territorial aggression in pair-housed males. To analyze male sexual behavior, a female mouse that is hormone-primed with estradiol and progesterone is usually introduced into a male home range, and mounting, intromission, and ejaculation behaviors are observed for 1 h. Here, we summarize the detailed protocols for assessing male behaviors.

  18. Lactobacillus rhamnosus GG supplementation during critical windows of gestation influences immune phenotype in Swiss albino mice offspring.

    PubMed

    Himaja, N; Hemalatha, R; Narendra Babu, K; Shujauddin, M

    2016-01-01

    Probiotic supplementation during critical windows of gestation might have a significant influence on the infant's immune phenotype. Swiss albino mice (F0 generation) aged 31 days were supplemented orally with probiotic Lactobacillus rhamnosus GG (LGG); and the supplementation was continued throughout mating, gestation and lactation. The pups (F1 generation) born to them were separated post weaning and received either the same probiotic supplementation as their mothers or were denied supplementation postnatally. Neutrophil phagocytic ability, splenocyte proliferation, immunoglobulins and cytokines were determined in both F0 and F1 pups. In addition, antibody response against hepatitis-B surface antigen (HBsAg) was determined in F1 pups. Probiotic supplementation had no effect on the neutrophil phagocytic ability and splenocyte proliferation index. The serum immunoglobulin G (IgG) and secretory IgA (s-IgA) among the probiotic supplemented group of F0 generation were significantly (P<0.05) higher compared to the controls. Similarly, the mean concentration of interleukin (IL)-10, IL-17 and interferon gamma (IFN-γ) among F0 probiotic group were significantly higher (P<0.05) compared to the control. Prenatal and postnatal probiotic supplementation in F1 pups led to similar results as F0 dams. Prenatal probiotic supplementation in F1 pups led to significantly (P<0.05) higher serum IgG (55.15 ± 1.35 ng/ml) and intestinal s-IgA (77.9 ± 2.86 ng/mg protein) concentration when compared to the control. Similarly, IFN-γ concentration increased (P<0.05) with prenatal probiotic supplementation compared to the control. However, IL-10 and IL-17 concentrations of prenatal probiotic supplemented F1 pups were comparable to the control. As for the antibody response to HBsAg, prenatal probiotic supplementation led to enhanced HBsAg antibody response (471.4 ± 3.97 U/ml) compared to the control. LGG affected the immune regulation and immune responses favourably in mothers and

  19. Functional and morphological effects of laser-induced ocular hypertension in retinas of adult albino Swiss mice

    PubMed Central

    Salinas-Navarro, Manuel; Alarcón-Martínez, Luis; Valiente-Soriano, Francisco Javier; Ortín-Martínez, Arturo; Jiménez-López, Manuel; Avilés-Trigueros, Marcelino; Villegas-Pérez, María Paz; de la Villa, Pedro

    2009-01-01

    Purpose To investigate the effects of laser photocoagulation (LP)-induced ocular hypertension (OHT) on the survival and retrograde axonal transport of retinal ganglion cells (RGC), as well as on the function of retinal layers. Methods Adult albino Swiss mice (35–45 g) received laser photocoagulation of limbal and episcleral veins in the left eye. Mice were sacrificed at 8, 17, 35, and 63 days. Intraocular pressure (IOP) in both eyes was measured with a Tono-Lab before LP and at various days after LP. Flash electroretinogram (ERG) scotopic threshold response (STR) and a- and b-wave amplitudes were recorded before LP and at various times after LP. RGCs were labeled with 10% hydroxystilbamidine methanesulfonate (OHSt) applied to both superior colliculi before sacrifice and in some mice, with dextran tetramethylrhodamine (DTMR) applied to the ocular stump of the intraorbitally transected optic nerve. Retinas were immunostained for RT97 or Brn3a. Retinas were prepared as whole-mounts and photographed under a fluorescence microscope. Labeled RGCs were counted using image analysis software, and an isodensity contour plot was generated for each retina. Results IOP increased to twice its basal values by 24 h and was maintained until day 5, after which IOP gradually declined to reach basal values by 1 wk. Similar IOP increases were observed in all groups. The mean total number of OHSt+ RGCs was 13,428±6,295 (n=12), 10,456±14,301 (n=13), 12,622±14,174 (n=21), and 10,451±13,949 (n=13) for groups I, II, III, and IV, respectively; these values represented 28%, 23%, 26%, and 22% of the values found in their contralateral fellow retinas. The mean total population of Brn3a+ RGCs was 24,343±5,739 (n=12) and 10,219±8,887 (n=9), respectively, for groups I and III; these values represented 49% and 20%, respectively, of the values found in their fellow eyes. OHT retinas showed an absence of OHSt+ and DTMR+ RGCs in both focal wedge-shaped and diffuse regions of the retina. By 1

  20. Biochemical and histopathological effects on liver due to acute oral toxicity of aqueous leaf extract of Ecliptaalba on female Swiss albino mice

    PubMed Central

    Singh, Tanuja; Sinha, Nivedita; Singh, Anjali

    2013-01-01

    Background: Limited data is available about the toxicity of herbal remedies used for self-medication. Since a popular medicinal plant Ecliptaalba contains various bioactive molecules, the present study aimed to observe the biochemical and histological changes in liver associated with acute oral toxicity (LD50) of aqueous extract of E. alba (L.) Hassk. in female Swiss albino mice. Materials and Methods: For the acute oral toxicity study, the animals were divided into six groups of 6 mice each. Group– I was normal control and the treatment groups were administered aqueous leaf extract of E. alba orally at different doses of 500 mg (group – I),1750 mg (group–III), 2000 mg (group- IV), 2500 mg (group- V) and 3000 mg/ kg/b.wt.(group- VI) for seven consecutive days. The mice were sacrificed on the eighth day and blood was collected for the analysis of ALP (alkaline phosphatase), SGPT (serum glutamic pyruvic transferase), total protein and albumin. The liver was dissected, weighed, and processed for histopathological analysis. Results: The LD50 was found to be 2316.626 mg/kg /body weight in female mice. Serum SGPT, total protein and albumin increased in treated group- IV (P < 0.05), V (P < 0.01), and VI (P < 0.01) as compared to the control (group- I). ALP level significantly decreased in the treated group- IV (P < 0.05), V (P < 0.01) and VI (P < 0.01). Histopathological changes were observed at dose of 2000 mg (group- IV), 2500 mg (group- V) and 3000 mg (group- VI). Conclusion: It was concluded that oral administration of aqueous leaf extract of E. alba had detrimental effects on biochemical parameters and induced histopathological alterations in liver of female Swiss albino mice at doses higher than 2000 mg/kg/day indicating that its indiscriminate use should be avoided. PMID:23543876

  1. Behavioral characterization of non-copulating male mice.

    PubMed

    Portillo, W; Antonio-Cabrera, E; Camacho, F J; Díaz, N F; Paredes, R G

    2013-06-01

    Non-copulating (NC) males are those animals that do not mate in spite of repeated testing with sexually receptive females. They have been observed in several species including rats and mice. The present experiment was designed to perform a detailed behavioral characterization of NC male mice. Thus, we evaluated their sexual incentive motivation for a sexually receptive female or a sexually active male, olfactory preference for volatile and non-volatile odors from females or males, and olfactory discrimination between female and male volatile odors and food related odors (milk versus vinegar). We compared the activity of the accessory olfactory system (AOS) in copulating (C) and NC males in response to estrous bedding using the induction of Fos-immunoreactivity (Fos-IR) as a measure of neuronal activation. We also determined if estradiol or dopamine treatment could induce sexual behavior in NC males. Finally, we compared the testis weight and the number of penile spines in C, NC, and gonadectomized males. In the sexual incentive motivation test C males spend significantly more time in the female incentive zone than in the male incentive zone. On the other hand, NC males spend the same amount of time in both incentive zones. In tests of olfactory preference, NC males spent less time investigating estrous odors than C males. As well, NC males discriminate urine from conspecifics but they spend less time smelling these odors than C males. In addition, no increase in Fos expression is observed in NC males when they are exposed to odors from estrous females. Our data also suggest that the deficits observed in NC males are not due to lower circulating levels of gonadal hormones, because estradiol supplementation does not induce sexual behavior in these animals, and their testis weight and the number of penile spines are normal. The results suggest that NC males are not sexually motivated by the receptive females and their odors.

  2. Effect of Drug Alprazolam on Restrained Stress Induced Alteration of Serum Cortisol and Antioxidant Vitamins (Vitamin C and E) in Male Albino Rats

    PubMed Central

    Kori, Rohini Sharanappa; Aladakatti, Ravindranath H.; Desai, S.D.

    2016-01-01

    Introduction Stress can cause harmful effects in the body that induce a wide range of biochemical and behavioural changes. As anti-stress drugs are routinely used to combat stress hence study is needed to assess the contraindication of these drugs in the physiological systems. Aim To investigate the effect of alprazolam on restrained stress induced alteration of serum cortisol, and antioxidant vitamin levels in male albino rats. Materials and Methods Adult male albino rats (body weight 175-225g) were divided into four groups of six animals in each. Group I (control), kept undisturbed in the metabolic cage throughout the 42 days experimental period. Group II (stress) rats were kept in a wire mesh restrainer for 6 hr/day for 42 days. Group III (stress+ withdrawal) rats were stressed for 21 days and withdrawal of stress for remaining 21 days (total 42 days). Group IV (stress + alprazolam) rats were only stressed for 21 days and treated with drug alprazolam (5mg/kg body weight, intraperitoneal) in continuation with stress for remaining 21 days (total period is 42 days). At the end of 42 days all the rats were sacrificed and serum cortisol, vitamin C and E levels were estimated. Results Group II (stressed) showed a significant increase in serum cortisol level with concomitant decrease of serum vitamin C and E levels. Group III (withdrawal) and Group IV (+alprazolam) rats showed significant reduction of serum cortisol along with subsequent increase of serum vitamin C and E concentrations. Conclusion Results indicate a possible antioxidant effect of alprazolam on restrained stress induced alteration of serum cortisol and antioxidant vitamin levels. PMID:27656428

  3. Delineating the antigenotoxic and anticytotoxic potentials of 4-methylimidazole against ethyl methanesulfonate toxicity in bone marrow cell of swiss albino mice.

    PubMed

    Norizadeh Tazehkand, M; Topaktas, M; Yilmaz, M B; Hajipour, O; Valipour, E

    2016-01-01

    4-Methylimidazole (4-MEI) is mostly used in beverages and coloring food, dark beers and common brands of cola drinks, which may contain more than 100 μg of this compound per 12-ounce serving. This study was aimed to investigate the antigenotoxic and anticytotoxic effects of 4-MEI (100, 130 and 160 mg/kg) against ethyl methanesulfonate (240 mg/kg) using chromosome aberrations (CAs) and Mitotic index (MI) tests in bone marrow cells of Swiss Albino Mice at 12 h and 24 h treatment periods. So, the t-test was used for the statistical analysis.In this research, 4-MEI at all concentrations for 12 h treatment period reduced chromosomal aberrations and at 130 and 160 mg/kg concentrations for 24 h treatment period increased chromosomal aberrations induced by EMS (240 mg/kg), but th ese reductions and increases were not significant. Also, intraperitoneal injection of 4-MEI at doses of 100, 130 and 160 mg/kg combined with EMS (240 mg/kg) showed that the mitotic index was decreased at 100 and 130 mg/kg for 12h and 130 mg/kg for 24 h treatment periods, when compared to positive sample (EMS), but did not show any statistically difference from the EMS treated group. It can be concluded that 4-MEI might not be antigenotoxic and protective effects in bone marrow cells of Swiss Albino Mice, because 4-MEI could not reduce the chromosomal aberrations induced by EMS. PMID:27215965

  4. Antagonistic role of tea against sodium arsenite-induced oxidative DNA damage and inhibition of DNA repair in Swiss albino mice.

    PubMed

    Sinha, Dona; Roy, Madhumita

    2011-01-01

    Arsenic (As) contamination in groundwater is of increasing health concern in West Bengal, India. Arsenic has been associated with various human cancers, but the precise mechanism of its co-carcinogenic action is not clearly elucidated. Oxidative stress and defective repair mechanisms may promote accumulation of mutations and may be a stepping stone for carcinogenesis. Prevention of arsenic-induced oxidative stress and repair inhibition may reduce the chances of initiation of cancer. Tea polyphenols are reported to have excellent chemopreventive properties against cancer. This study aimed to elucidate the role of tea against arsenic-induced formation of 8-hydroxy-2'-deoxyguanosine (8OHdG) and arsenic-suppressed DNA repair in Swiss albino mice. Both green and black tea gave fruitful results in the reduction of 8OHdG and 8-oxoguanine DNA glycosylase (OGG1) in Swiss albino mice administered sodium arsenite (As III). DNA repair enzymes--such as PARP1, DNA β-polymerase, XRCC1, DNA ligase III, DNA protein kinase (catalytic subunit), XRCC 4, DNA ligase IV, and DNA topoisomerase IIβ--were induced by the phytochemicals at both the protein and genetic levels. Thus, tea polyphenols may prove effective in treating arsenic-induced carcinogenesis.

  5. Female mice ultrasonically interact with males during courtship displays

    PubMed Central

    Neunuebel, Joshua P; Taylor, Adam L; Arthur, Ben J; Egnor, SE Roian

    2015-01-01

    During courtship males attract females with elaborate behaviors. In mice, these displays include ultrasonic vocalizations. Ultrasonic courtship vocalizations were previously attributed to the courting male, despite evidence that both sexes produce virtually indistinguishable vocalizations. Because of this similarity, and the difficulty of assigning vocalizations to individuals, the vocal contribution of each individual during courtship is unknown. To address this question, we developed a microphone array system to localize vocalizations from socially interacting, individual adult mice. With this system, we show that female mice vocally interact with males during courtship. Males and females jointly increased their vocalization rates during chases. Furthermore, a female's participation in these vocal interactions may function as a signal that indicates a state of increased receptivity. Our results reveal a novel form of vocal communication during mouse courtship, and lay the groundwork for a mechanistic dissection of communication during social behavior. DOI: http://dx.doi.org/10.7554/eLife.06203.001 PMID:26020291

  6. Vitamin E attenuates liver injury induced by exposure to lead, mercury, cadmium and copper in albino mice

    PubMed Central

    Al-Attar, Atef M.

    2011-01-01

    Water pollution is the contamination of water resources by harmful wastes or toxins. Both community and private sources of drinking water are susceptible to a myriad of chemical contaminants. Heavy metals pollution of surface water can create health risks. The present study was aimed to investigate the effect of vitamin E supplementation on male mice exposed to a mixture of some heavy metals (lead, mercury, cadmium and copper) in their drinking water for seven weeks. Significant increases of blood alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) were detected in heavy metals-treated mice. Histopathologically, the liver sections from heavy metals-treated mice showed severe changes including disarrangement of hepatic strands, rupture in hepatocytes, advanced hepatocellular necrosis, dilation and congestion of blood vessels with hemorrhage, dense lymphocytic infiltration round the central vein and dark stained hepatocytic nuclei indicating cell pycnosis. Administration of vitamin E at a dose of 50 IU/kg body weight, five times weekly improved the observed biochemical and histopathological changes induced by these heavy metals intoxication. Hence, the results of this study suggest that vitamin E protects against these heavy metals-induced liver injury and the attenuating effect of vitamin E may be due to its antioxidant activity. PMID:23961152

  7. Vitamin E attenuates liver injury induced by exposure to lead, mercury, cadmium and copper in albino mice.

    PubMed

    Al-Attar, Atef M

    2011-10-01

    Water pollution is the contamination of water resources by harmful wastes or toxins. Both community and private sources of drinking water are susceptible to a myriad of chemical contaminants. Heavy metals pollution of surface water can create health risks. The present study was aimed to investigate the effect of vitamin E supplementation on male mice exposed to a mixture of some heavy metals (lead, mercury, cadmium and copper) in their drinking water for seven weeks. Significant increases of blood alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) were detected in heavy metals-treated mice. Histopathologically, the liver sections from heavy metals-treated mice showed severe changes including disarrangement of hepatic strands, rupture in hepatocytes, advanced hepatocellular necrosis, dilation and congestion of blood vessels with hemorrhage, dense lymphocytic infiltration round the central vein and dark stained hepatocytic nuclei indicating cell pycnosis. Administration of vitamin E at a dose of 50 IU/kg body weight, five times weekly improved the observed biochemical and histopathological changes induced by these heavy metals intoxication. Hence, the results of this study suggest that vitamin E protects against these heavy metals-induced liver injury and the attenuating effect of vitamin E may be due to its antioxidant activity. PMID:23961152

  8. Antiplasmodial activity of eco-friendly synthesized palladium nanoparticles using Eclipta prostrata extract against Plasmodium berghei in Swiss albino mice.

    PubMed

    Rajakumar, Govindasamy; Rahuman, Abdul Abdul; Chung, Ill-Min; Kirthi, Arivarasan Vishnu; Marimuthu, Sampath; Anbarasan, Karunanithi

    2015-04-01

    Malaria is an infectious disease caused by the Plasmodium parasite that continues to be a health issue for humans. It is one of the most common pathogenic factors of morbidity and mortality. Palladium nanoparticles (Pd NPs) have been used as target antimicrobial compounds, as a catalyst to manufacture pharmaceuticals, degrade harmful environmental pollutants, and as sensors for the detection of various analyses. The aim of this study was to investigate the antiplasmodial activity of synthesized Pd NPs by using leaf aqueous extract of Eclipta prostrata against Plasmodium berghei in Swiss albino mice. The synthesized Pd NPs were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR), Scanning electron microscopy (SEM) with Energy dispersive X-ray spectroscopy (EDX), and High-resolution transmission electron microscope (HRTEM) with the Selected area (electron) diffraction (SAED). The XRD peaks appeared at 35.61°, 44.27°, 56.40°, and 74.51°, which correspond to (111), (200), (220), and (311) planes for palladium, respectively. The FTIR spectra that were carried out to identify the potential biomolecule of synthesized Pd NPs showed the peaks at 3361, 1540, 1399, 1257, 1049, and 659 in the region of 4000-500 cm(-1). The SEM images showed aggregation of NPs with an average size of 63 ± 1.4. The HRTEM images of the precipitated solid phase obtained after termination of the reaction of E. prostrata aqueous leaf extract were in the range from 18 to 64 nm with an average size of 27 ± 1.3 nm. The in vivo antiplasmodial assay was carried out as per Peters' 4-day suppressive test, and the synthesized Pd NP-treated mice group showed reduction of parasitemia by 78.13% with an inhibitory concentration (IC)50 value of 16.44 mg/kg/body weight. The growth inhibition of E. prostrata aqueous leaf extract, palladium acetate, and synthesized Pd NPs showed the IC20, IC50, and IC90 values of 1.90, 10.29, and 64.11; 4.49, 9.84, and 23.04; and 4.34, 8

  9. Modulatory effects of Mentha piperita on lung tumor incidence, genotoxicity, and oxidative stress in benzo[a]pyrene-treated Swiss albino mice.

    PubMed

    Samarth, R M; Panwar, Meenakshi; Kumar, Ashok

    2006-04-01

    Mentha piperita or peppermint is currently used for alleviating nausea, flatulence, and vomiting. In the present investigation, we evaluated the chemopreventive, antigenotoxic, and antioxidative effects of an aqueous extract of Mentha piperita leaves. One-day-old Swiss albino mice were treated with a single subcutaneous injection of 0.5 mg benzo[a]pyrene (BP) and then given either water or a Mentha extract (ME; 1 g/kg body weight) by gavage starting at 3 weeks of age (weaning). The mice were killed at 9 weeks of age and tested for lung tumor incidence (chemoprevention); bone marrow micronucleus and chromosome aberration frequency (antigenotoxicity); and levels of liver and lung sulfhydral groups, superoxide dismutase (SOD) and catalase (CAT) activity, and lipid peroxidation (LPO) (antioxidative properties). The ME treatment resulted in a significant reduction in the number of lung adenomas from an incidence of 67.92% in animals given only BP to 26.31%, an inhibition of 61.26%. Tumor multiplicity was 1.22 in the BP-alone group and 1.15 in the BP + ME group. In addition, compared with the animals in the BP-alone group, ME reduced the frequency of chromosomal aberrations and micronuclei in bone marrow cells and decreased the levels of LPO and increased reduced glutathione content, and SOD and CAT activities in liver as well as lung. The results of this study indicate that ME is chemopreventive and antigenotoxic when given subsequent to an initiating dose of BP in newborn Swiss albino mice. The chemopreventive action and antigenotoxic effects observed in the present study may be due to the antioxidative properties of ME.

  10. Proteomic Analysis of Pachytene Spermatocytes of Sterile Hybrid Male Mice.

    PubMed

    Wang, Lu; Guo, Yueshuai; Liu, Wenjing; Zhao, Weidong; Song, Gendi; Zhou, Tao; Huang, Hefeng; Guo, Xuejiang; Sun, Fei

    2016-09-01

    Incompatibilities in interspecific hybrids, such as reduced hybrid fertility and lethality, are common features resulting from reproductive isolation that lead to speciation. Subspecies crosses of house mice produce offspring in which one sex is infertile or absent, yet the molecular mechanisms of hybrid sterility are poorly understood. In this study, we observed extensive asynapsis of chromosomes and disturbance of the sex body in pachytene spermatocytes of sterile F1 males (PWK/Ph female × C57BL/6J male). We report the high-confidence identification of 4005 proteins in the pachytene spermatocytes of fertile F1 males (PWK/Ph male × C57BL/6J female) and sterile F1 males (PWK/Ph female × C57BL/6J male), of which 215 were upregulated and 381 were downregulated. Bioinformatics analysis of the proteome led to the identification of 43 and 59 proteins known to be essential for male meiosis and spermatogenesis in mice, respectively. Characterization of the proteome of pachytene spermatocytes associated with hybrid male sterility provides an inventory of proteins that is useful for understanding meiosis and the mechanisms of hybrid male infertility.

  11. Vomeronasal neuroepithelium and forebrain Fos responses to male pheromones in male and female mice.

    PubMed

    Halem, H A; Cherry, J A; Baum, M J

    1999-05-01

    Male urinary pheromones modulate behavioral and neuroendocrine function in mice after being detected by sensory neurons in the vomeronasal organ (VNO) neuroepithelium. We used nuclear Fos protein immunoreactivity (Fos-IR) as a marker of changes in neuronal activity to examine the processing of male pheromones throughout the VNO projection pathway to the hypothalamus. Sexually naive male and female Balb/c mice were gonadectomized and treated daily with estradiol benzoate (EB) or oil vehicle for 3 weeks. Subjects were then exposed to soiled bedding from gonadally intact Balb/c males or to clean bedding for 90 min prior to sacrifice and processing of their VNOs and forebrains for Fos-IR. Male pheromones induced similar numbers of Fos-IR cells in the VNO neuroepithelium of oil-treated male and female subjects; however, EB-treated females had significantly more Fos-IR neurons in the VNO than any other group. There was an equivalent neuronal Fos response to male odors in the mitral and granule cells of the anterior and posterior accessory olfactory bulb of males and females, regardless of hormone treatment. In central portions of the VNO projection pathway (i.e., bed nucleus of the stria terminalis, medial preoptic area) neuronal Fos responses to male pheromones were present in female but absent in male subjects, regardless of hormone treatment. In a separate experiment, mating induced neuronal Fos-IR in these brain regions at levels in gonadally intact male subjects which were equal to or greater than those seen in ovariectomized females primed with estrogen and progesterone. This suggests that neurons in the central portions of the male's VNO pathway are capable of expressing Fos. Our results suggest that sexually dimorphic central responses to pheromones exist in mice that may begin in the VNO neuroepithelium.

  12. Comparative study of the hepatotoxic, genotoxic and carcinogenic effects of praziquantel distocide & the natural myrrh extract Mirazid on adult male albino rats.

    PubMed

    Omar, Ahmed; Elmesallamy, Ghada El-Said; Eassa, Shereen

    2005-04-01

    Praziquantel (PZQ) is widely and effectively used in the control of bilharziasis which constitutes a major endemic health problem in Egypt. However, recent studies recommended that the drug must be re-evaluated because of its potential carcinogenicity and genotoxicity. Mirazid is a new natural anti-schistosomal drug formed of myrrh extract and considered to be a safe drug. This work was conducted to evaluate and compare hepatotoxic, genotoxic and carcinogenic effects of PZQ and Mirazid on adult male albino rats by assessment of serum levels of ALT, AST and bilirubin, histopathological study of the liver and cytogenetic study of bone marrow cells. 100 adult male albino rats were equally divided into 4 groups: (I): negative control, (II): control rats received distilled water, (III): received weekly single oral dose of PZQ (1500 mg/kg) for 6 weeks, (IV): received daily oral dose of Mirazid (500 mg/kg) for 6 weeks. At the end of the study 10 rats of each group were investigated by assessment of the levels of AST, ALT, & Bilirubin. After scarification, liver sections were examined by light microscopy. Another 10 rats of each group were submitted to cytogenetic examination. It was found that praziquantel induced a significant increase in the mean values of AST, ALT and bilirubin with areas of hyaline degeneration, fatty changes, dysplasia and necrosis in the liver sections. It also induced a significant increase in the incidence of chromosomal aberrations as polyploidy, fragment, deletion and ring chromosome as compared with control group. Mirazid induced a non significant increase in the mean values of AST, ALT and bilirubin, with a normal hepatic tissue, and a non significant increase in the incidence of chromosomal aberrations, as compared with the control group. On comparing both drugs, praziquantel induced a significant hepatotoxic, genotoxic and carcinogenic effects. It was concluded that, Praziquantel is considered to be a hepatotoxic, genotoxic and carcinogenic

  13. Sexual attractiveness of male chemicals and vocalizations in mice.

    PubMed

    Asaba, Akari; Hattori, Tatsuya; Mogi, Kazutaka; Kikusui, Takefumi

    2014-01-01

    Male-female interaction is important for finding a suitable mating partner and for ensuring reproductive success. Male sexual signals such as pheromones transmit information and social and sexual status to females, and exert powerful effects on the mate preference and reproductive biology of females. Likewise, male vocalizations are attractive to females and enhance reproductive function in many animals. Interestingly, females' preference for male pheromones and vocalizations is associated with their genetic background, to avoid inbreeding. Moreover, based on acoustic cues, olfactory signals have significant effects on mate choice in mice, suggesting mate choice involves multisensory integration. In this review, we synopsize the effects of both olfactory and auditory cues on female behavior and neuroendocrine functions. We also discuss how these male signals are integrated and processed in the brain to regulate behavior and reproductive function.

  14. Sexual attractiveness of male chemicals and vocalizations in mice

    PubMed Central

    Asaba, Akari; Hattori, Tatsuya; Mogi, Kazutaka; Kikusui, Takefumi

    2014-01-01

    Male-female interaction is important for finding a suitable mating partner and for ensuring reproductive success. Male sexual signals such as pheromones transmit information and social and sexual status to females, and exert powerful effects on the mate preference and reproductive biology of females. Likewise, male vocalizations are attractive to females and enhance reproductive function in many animals. Interestingly, females' preference for male pheromones and vocalizations is associated with their genetic background, to avoid inbreeding. Moreover, based on acoustic cues, olfactory signals have significant effects on mate choice in mice, suggesting mate choice involves multisensory integration. In this review, we synopsize the effects of both olfactory and auditory cues on female behavior and neuroendocrine functions. We also discuss how these male signals are integrated and processed in the brain to regulate behavior and reproductive function. PMID:25140125

  15. Bioefficacy of hydromethanolic extract of tuber of Chlorophytum borivilianum (Safed Musli) for the management of male infertility in cyproterone acetate-treated albino rats.

    PubMed

    Ray, S; Chatterjee, K; De, D; Ghosh, D

    2014-08-01

    Increase in male sexual dysfunction, and its treatment with conventional aphrodisiac drugs with side effects lead to investigate the spermatogenesis and androgenesis augmentative efficacy of hydromethanolic (40 : 60) extract of root of Chlorophytum borivilianum (family - Liliaceae) against cyproterone acetate-induced subfertility in Wistar strain male albino rat. For this purpose, experimental rats were divided into three treatment groups: vehicle (received distilled water), cyproterone acetate (gastric intubation at 250 mg kg(-1) twice daily for 35 days) and cyproterone acetate plus root extract of C. borivilianum (gastric intubation at 250 mg kg(-1) plus 400 mg kg(-1) with an interval of 20 min twice daily for 35 days). After 35-day treatment, all rats were euthanised. Reproductive deviations towards negative side were investigated by screening the spermatogenic and steroidogenic biosensors. Oxidative stress profile in reproductive organs and sperm pellet was evaluated by biochemical assessment of antioxidative enzyme activities and level of end products of the lipid peroxidation. Apoptosis profile was evaluated by Western blot study, TUNEL assay and DNA fragmentation study of testicular tissues. Evaluation of toxicity profile was included for experimental investigation. After cyproterone acetate treatment, the pituitary-testicular axis was deviated towards the negative side and its tuning system was affected by oxidative stress and apoptosis-mediated process, which reduced the quality of semen and finally led to subfertility. Co-administration of C. borivilianum root extract enhanced male reproductive potentiality and prevented the negative deviations after the treatment with cyproterone acetate by means of increasing oxidative defence and maintaining homeostasis in testicular apoptosis process.

  16. Amelioration Effect of Zinc and Iron Supplementation on Selected Oxidative Stress Enzymes in Liver and Kidney of Cadmium-Treated Male Albino Rat

    PubMed Central

    Jamakala, Obaiah; Rani, Usha A.

    2015-01-01

    Cadmium (Cd) is a highly toxic, nonessential heavy metal with many industrial uses that can contribute to a well-defined spectrum of diseases in animals as well as in humans. The present study examines the effect of zinc (Zn) and iron (Fe) supplementation on oxidative stress enzymes in Cd-treated rats. Wistar strain male albino rats were treated with cadmium chloride (CdCl2) at a dose of 1/10th LD50/48 h, that is, 22.5 mg/kg body weight for 7, 15, and 30 days (d) time intervals. The 15d Cd-treated rats were divided into three groups. The first group received Zn (12 mg/kg), second group Fe (40 mg/kg) alone, and third group supplemented with both Zn and Fe and observed for 7, 15, and 30d. After the specific time intervals, rats were decapitated and oxidative stress enzymes like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were assayed in liver and kidney. Simultaneously lipid peroxidation (LPO) levels were also measured. A significant elevation in LPO levels with decreased activity levels of CAT, SOD, GPx, and GST were observed during Cd intoxication. With Zn and/or Fe supplementation, a significant reversal in the oxidative stress enzymes was observed. Our study reveals that combination of Zn and Fe supplementation is effective in detoxifying the Cd body burden from the test tissues. PMID:26862254

  17. Amelioration Effect of Zinc and Iron Supplementation on Selected Oxidative Stress Enzymes in Liver and Kidney of Cadmium-Treated Male Albino Rat.

    PubMed

    Jamakala, Obaiah; Rani, Usha A

    2015-01-01

    Cadmium (Cd) is a highly toxic, nonessential heavy metal with many industrial uses that can contribute to a well-defined spectrum of diseases in animals as well as in humans. The present study examines the effect of zinc (Zn) and iron (Fe) supplementation on oxidative stress enzymes in Cd-treated rats. Wistar strain male albino rats were treated with cadmium chloride (CdCl2) at a dose of 1/10(th) LD50/48 h, that is, 22.5 mg/kg body weight for 7, 15, and 30 days (d) time intervals. The 15d Cd-treated rats were divided into three groups. The first group received Zn (12 mg/kg), second group Fe (40 mg/kg) alone, and third group supplemented with both Zn and Fe and observed for 7, 15, and 30d. After the specific time intervals, rats were decapitated and oxidative stress enzymes like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were assayed in liver and kidney. Simultaneously lipid peroxidation (LPO) levels were also measured. A significant elevation in LPO levels with decreased activity levels of CAT, SOD, GPx, and GST were observed during Cd intoxication. With Zn and/or Fe supplementation, a significant reversal in the oxidative stress enzymes was observed. Our study reveals that combination of Zn and Fe supplementation is effective in detoxifying the Cd body burden from the test tissues.

  18. Amelioration Effect of Zinc and Iron Supplementation on Selected Oxidative Stress Enzymes in Liver and Kidney of Cadmium-Treated Male Albino Rat.

    PubMed

    Jamakala, Obaiah; Rani, Usha A

    2015-01-01

    Cadmium (Cd) is a highly toxic, nonessential heavy metal with many industrial uses that can contribute to a well-defined spectrum of diseases in animals as well as in humans. The present study examines the effect of zinc (Zn) and iron (Fe) supplementation on oxidative stress enzymes in Cd-treated rats. Wistar strain male albino rats were treated with cadmium chloride (CdCl2) at a dose of 1/10(th) LD50/48 h, that is, 22.5 mg/kg body weight for 7, 15, and 30 days (d) time intervals. The 15d Cd-treated rats were divided into three groups. The first group received Zn (12 mg/kg), second group Fe (40 mg/kg) alone, and third group supplemented with both Zn and Fe and observed for 7, 15, and 30d. After the specific time intervals, rats were decapitated and oxidative stress enzymes like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were assayed in liver and kidney. Simultaneously lipid peroxidation (LPO) levels were also measured. A significant elevation in LPO levels with decreased activity levels of CAT, SOD, GPx, and GST were observed during Cd intoxication. With Zn and/or Fe supplementation, a significant reversal in the oxidative stress enzymes was observed. Our study reveals that combination of Zn and Fe supplementation is effective in detoxifying the Cd body burden from the test tissues. PMID:26862254

  19. Effects of monosodium-L-glutamate administration on serum levels of reproductive hormones and cholesterol, epididymal sperm reserves and testicular histomorphology of male albino rats.

    PubMed

    Ochiogu, Izuchukwu S; Ogwu, David; Uchendu, Chukwuka N; Okoye, Chidozie N; Ihedioha, John I; Mbegbu, Edmund C

    2015-03-01

    This study investigated the effects of administration of monosodium L-glutamate (MSG) on serum gonadotrophin-releasing hormone (GnRH), luteinising hormone (LH), testosterone and total cholesterol (TC), cauda epididymal sperm reserves (CESR) and testicular histomorphology of adult male albino rats. Eighty-four rats, randomly assigned to 7 groups of 12 rats each, were used for the study. Varying low doses (0.25, 0.50 or 1.00 g/kg body weight) of MSG were administered orally or subcutaneously at 48-h intervals for six weeks. Serum GnRH, LH, testosterone and TC, and CESR were evaluated on days 14, 28 and 42 of MSG administration. Testicular histomorphology was evaluated on day 42. The results showed that the mean serum GnRH, LH and testosterone levels, and the CESR of all the treated groups were significantly (P < 0.05) lower than those of the untreated control on days 14, 28 and 42 of MSG administration. The mean serum TC levels of all the treated groups were also significantly (P < 0.05) lower than those of the control group on days 14 and 28. No lesions were observed on sections of the testes. It was concluded that MSG administration for 14, 28 and 42 days led to significantly lower serum levels of GnRH, LH, testosterone and TC, and significantly lower CESR. PMID:25655420

  20. Genetics and evolution of hybrid male sterility in house mice.

    PubMed

    White, Michael A; Stubbings, Maria; Dumont, Beth L; Payseur, Bret A

    2012-07-01

    Comparative genetic mapping provides insights into the evolution of the reproductive barriers that separate closely related species. This approach has been used to document the accumulation of reproductive incompatibilities over time, but has only been applied to a few taxa. House mice offer a powerful system to reconstruct the evolution of reproductive isolation between multiple subspecies pairs. However, studies of the primary reproductive barrier in house mice-hybrid male sterility-have been restricted to a single subspecies pair: Mus musculus musculus and Mus musculus domesticus. To provide a more complete characterization of reproductive isolation in house mice, we conducted an F(2) intercross between wild-derived inbred strains from Mus musculus castaneus and M. m. domesticus. We identified autosomal and X-linked QTL associated with a range of hybrid male sterility phenotypes, including testis weight, sperm density, and sperm morphology. The pseudoautosomal region (PAR) was strongly associated with hybrid sterility phenotypes when heterozygous. We compared QTL found in this cross with QTL identified in a previous F(2) intercross between M. m. musculus and M. m. domesticus and found three shared autosomal QTL. Most QTL were not shared, demonstrating that the genetic basis of hybrid male sterility largely differs between these closely related subspecies pairs. These results lay the groundwork for identifying genes responsible for the early stages of speciation in house mice.

  1. Protective role of diet supplements Spirulina and Tamarind fruit pulp on kidney in sodium fluoride exposed Swiss albino mice: Histological and biochemical indices.

    PubMed

    Yadav, N; Sharma, Shweta; Sharma, K p; Pandey, A; Pareek, P; Sharma, Subhasini

    2016-01-01

    Fluoride toxicity through potable water, particularly ground water, is not uncommon in countries such as India, China, Iran, Iraq, Turkey, parts of Africa and Afghanistan. Kidney being the main organ involved in fluoride removal, it accumulates considerable amount of fluoride. Here, we report toxic effects of oral exposure of Swiss albino mice to fluoride (sub-acute: 190 mg/kg body wt. for 7 days; and sub-chronic: 94 mg/kg body wt. for 90 days) and recovery of sub-chronic fluoride exposed mice after 90 days of sodium fluoride (NaF) withdrawal. The role of diet supplements (Spirulina and tamarind fruit pulp @ 230 mg/kg body wt. independently as well as in combination) in amelioration of fluoride toxicity has also been screened. Compared with controls, feed intake decreased from 3-43%, body wt. 4-18%, and kidney wt. 5-12% in treated mice (except diet supplement groups of sub-chronic exposure) while their water intake increased from 4-43%. Histopathological changes in the cortical region of kidney in fluoride treated mice were as follows: dilation of bowman's capsule and thickening of its parietal and visceral layer; alterations in glomeruli size and their sclerotization; increase in bowman's space; proliferation of mesangial cells; reduction in podocyte counts; and dilation of proximal and distal tubules. Fluoride exposure altered tissue biochemistry (protein, acid phosphatase and alkaline phosphatase content) and increased urea (23-58%) and creatinine content (14-127%) in the serum. Sub-acute exposure was found more toxic. The diet modulation not only reduced fluoride toxicity but also led to better recovery of treated mice after withdrawal, especially in combination. PMID:26891552

  2. Protective role of diet supplements Spirulina and Tamarind fruit pulp on kidney in sodium fluoride exposed Swiss albino mice: Histological and biochemical indices.

    PubMed

    Yadav, N; Sharma, Shweta; Sharma, K p; Pandey, A; Pareek, P; Sharma, Subhasini

    2016-01-01

    Fluoride toxicity through potable water, particularly ground water, is not uncommon in countries such as India, China, Iran, Iraq, Turkey, parts of Africa and Afghanistan. Kidney being the main organ involved in fluoride removal, it accumulates considerable amount of fluoride. Here, we report toxic effects of oral exposure of Swiss albino mice to fluoride (sub-acute: 190 mg/kg body wt. for 7 days; and sub-chronic: 94 mg/kg body wt. for 90 days) and recovery of sub-chronic fluoride exposed mice after 90 days of sodium fluoride (NaF) withdrawal. The role of diet supplements (Spirulina and tamarind fruit pulp @ 230 mg/kg body wt. independently as well as in combination) in amelioration of fluoride toxicity has also been screened. Compared with controls, feed intake decreased from 3-43%, body wt. 4-18%, and kidney wt. 5-12% in treated mice (except diet supplement groups of sub-chronic exposure) while their water intake increased from 4-43%. Histopathological changes in the cortical region of kidney in fluoride treated mice were as follows: dilation of bowman's capsule and thickening of its parietal and visceral layer; alterations in glomeruli size and their sclerotization; increase in bowman's space; proliferation of mesangial cells; reduction in podocyte counts; and dilation of proximal and distal tubules. Fluoride exposure altered tissue biochemistry (protein, acid phosphatase and alkaline phosphatase content) and increased urea (23-58%) and creatinine content (14-127%) in the serum. Sub-acute exposure was found more toxic. The diet modulation not only reduced fluoride toxicity but also led to better recovery of treated mice after withdrawal, especially in combination.

  3. Protective effect of curcumin against experimentally induced aflatoxicosis on the renal cortex of adult male albino rats: a histological and immunohisochemical study

    PubMed Central

    El-Mahalaway, Abeer M

    2015-01-01

    Background: Aflatoxin contamination of foods is a worldwide problem. Chronic aflatoxin exposure is associated with kidney damage. Curcumin is a herbal agent, used in medicine with a wide range of beneficial therapeutic effects. Objective: to evaluate the effect of curcumin against experimentally induced aflatoxicosis on the renal cortex of adult male albino rats. Materials and methods: Forty adult male rats were included and they were divided equally into 4 groups (10 rats each): Group I (control group), group II (Curcumin group): The rats received curcumin (200 mg/kg b.w.) orally by gastric tube for 5 days/week, group III (Aflatoxin B1 group): The rats received aflatoxin B1 (250 μg/kg b.w./day) orally by gastric tube 5 days/week for 4 weeks, group IV (Aflatoxin B1 and Curcumin group): The rats received aflatoxin and curcumin orally by gastric tube 5 days/week for 4 weeks. Kidney specimens were prepared and sections were stained with hematoxylin and eosin, Masson’s trichrome, Periodic acid Schiff, immunohistochemical detection of desmin and Bcl2. Results: The tubules of group III showed degenerative and necrotic changes with disruption of basal lamina. There was a significant decrease Bcl2 expression in the tubules, but the glomeruli showed an enlargement with dilation of their capillaries lumina in some areas, while the other areas showed glomerular atrophy with obliteration of their capillaries lumina. There was a significant increase in desmin expression in the glomerular cells. The interstitium showed hemorrhage and cellular infiltration. Group IV showed improvement of the histological and immunohistochemical changes described before. Conclusion: Aflatoxin B1 has deleterious effects of on the histological structure of the rat’s renal cortex and curcumin minimized these effects as it has antioxidant, anti-inflammatory and antiapoptotic activities. We advise eating nutritious diets that contain sufficient amounts of curcumin and regulation must implement to

  4. Effect of chrysotile asbestos fibers on germ cells of mice

    SciTech Connect

    Rita, P.; Reddy, P.P.

    1986-10-01

    An Indian form of chrysotile asbestos procured from a local asbestos factory (Hyderabad) was tested for its toxic effects on spermatocytes and sperm of mice. Swiss albino male mice were fed orally with chrysotile asbestos suspended in water. The concentration tested was 20 mg/kg/day. Chronic oral administration of chrysotile failed to induce chromosomal aberrations and abnormal sperms in mice.

  5. Phenolic Profiling and Evaluation of Contraceptive Effect of the Ethanolic Extract of Salsola imbricata Forssk. in Male Albino Rats

    PubMed Central

    Shehab, Naglaa Gamil

    2014-01-01

    Reported researches dealing with either composition or bioactivity of Salsola imbricata are limited. This study was conducted aiming to investigate the phenolic composition of the plant and evaluate its efficacy as male contraceptive. Polyphenols, namely, phenolic acids and flavonoids, were qualitatively and quantitatively analysed by RP-HPLC in the hydrolysed methanol extract using two different wavelengths, 280 and 330 nm. The efficiency of different solvents in extracting the plant phenolics was assessed via spectrophotometric determination of the total phenolic and flavonoid contents. Acute toxicity study was carried out on the ethanolic extract to ascertain its safety prior to biological evaluation. The contraceptive effect was assessed, in male rats, by oral administration of the extract at two doses (250 and 500 mg/kg b. wt.), over a period of 65 days. HPLC analyses allowed the identification and quantification of a total of 13 and 8 components in the hydrolysed-methanol extract; the overall phenolic composition was dominated by quercitrin (12.692%) followed by coumaric acid (4.251%). Prolonged oral administration of the ethanolic extract caused slight reduction in the testis weight only. A significant decrease in the sperm count was observed (P < 0.01) in the two treated groups while significant decrease in the epididymal sperm motility was only observed in the high dose group. Morphological abnormalities were observed in sperms of treated animals. No distinct change in serum FSH, LH, and testosterone concentration was recorded. The histopathological findings supported to a high extent these results. The male contraceptive activity of Salsola imbricata could be ascribed to its phenolic components, especially quercitrin. PMID:25587346

  6. Effect of green tea (camellia sinensis l.) leaf extract on reproductive system of adult male albino rats

    PubMed Central

    Das, Shyamal Kanti; Karmakar, Soumendra Nath

    2015-01-01

    Green tea leaf extract (GTLE), used in this experiment has shown great influence on male reproductive system functionally as well as morphologically. The extract was prepared according to the method of Wei. H. et al. The extract was given to two different experimental animal groups with two different doses during 26 consecutive days. After treatment it was found that, the weight of the testis was markedly reduced instead of normal weight gain of all the animals. The sperm count and motility were reduced for the treated groups as compared with control animal group. The enzymes like SGPT and SGOT were as usual and other blood parameters like glucose and protein were also as usual comparing with controlled group. Testosterone level was reduced in the treated groups. FSH and LH levels were also altered accordingly in treated groups. Histological examination showed inhibition of spermatogenesis as evidenced by disintegration of seminiferous tubules of testis. Result of this study showed that GTLE has potent castrative effect on male reproductive system in dose dependent manner. PMID:27073594

  7. Repeated positive fighting experience in male inbred mice.

    PubMed

    Kudryavtseva, Natalia N; Smagin, Dmitry A; Kovalenko, Irina L; Vishnivetskaya, Galina B

    2014-11-01

    Repeated aggression is a frequent symptom of many psychiatric and neurological disorders, including obsessive-compulsive and attention deficit hyperactivity disorders, bipolar and post-traumatic stress disorders, epilepsy, autism, schizophrenia and drug abuse. However, repeated aggression is insufficiently studied because there is a lack of adequate models in animals. The sensory contact model (SCM), widely used to study the effects of chronic social defeat stress, can also be used to investigate the effects of repeated aggression. Mice with repeated positive fighting experience in daily agonistic interactions in this model develop pronounced aggressiveness, anxiety and impulsivity, disturbances in motivated and cognitive behaviors, and impairments of sociability; they also demonstrate hyperactivity, attention-deficit behavior, motor dysfunctions and repetitive stereotyped behaviors, such as jerks, rotations and head twitches. In this protocol, we describe how to apply the SCM to study repeated aggression in mice. Severe neuropathology develops in male mice after 20-21 d of agonistic interactions.

  8. Repeated positive fighting experience in male inbred mice.

    PubMed

    Kudryavtseva, Natalia N; Smagin, Dmitry A; Kovalenko, Irina L; Vishnivetskaya, Galina B

    2014-11-01

    Repeated aggression is a frequent symptom of many psychiatric and neurological disorders, including obsessive-compulsive and attention deficit hyperactivity disorders, bipolar and post-traumatic stress disorders, epilepsy, autism, schizophrenia and drug abuse. However, repeated aggression is insufficiently studied because there is a lack of adequate models in animals. The sensory contact model (SCM), widely used to study the effects of chronic social defeat stress, can also be used to investigate the effects of repeated aggression. Mice with repeated positive fighting experience in daily agonistic interactions in this model develop pronounced aggressiveness, anxiety and impulsivity, disturbances in motivated and cognitive behaviors, and impairments of sociability; they also demonstrate hyperactivity, attention-deficit behavior, motor dysfunctions and repetitive stereotyped behaviors, such as jerks, rotations and head twitches. In this protocol, we describe how to apply the SCM to study repeated aggression in mice. Severe neuropathology develops in male mice after 20-21 d of agonistic interactions. PMID:25340443

  9. [Efficacy of cefixime and cefepime vs. other cephalosporins in experimental plague of albino mice due to variants FI+ and FI- of the plague microbe].

    PubMed

    Ryzhko, I V; Shcherbaniuk, A I; Moldavan, I A; Tsuraeva, R I; Anisimov, B I; Trishina, A V

    2007-01-01

    Efficacy of cefixime and cefepime vs. ceftriaxone, cefotaxime, ceftazidime and cefoperazone was studied in vitro and in the treatment of experimental plague of albino mice due to natural, antigen complete strains of the plague microbe and the pathogen variants deprived of the ability to produce the capsule antigen fraction I (FI- phenotype). The MICs of cefixime and cefepime for 20 FI+ and 20 FI- strains of the plague microbe were 0.02-0.08 mg/l, that corresponded to the MICs of ceftriaxone, cefotaxime and ceftazidime. The MICs of cefoperazone were somewhat higher (0.1-0.2 mg/l). The ED50 values of cefixime and cefepime for prevention and treatment of experimental plague in mice statistically did not significantly differ from the ED50 values of ceftriaxone, cefotaxime, ceftazidime and cefoperazone. The efficacy indices (EIs) of cefixime and cefepime were > 10(4) independent of the infective strain phenotype (FI+ or FI-) and did not differ from those of ceftriaxone and ceftazidime. The efficacy of cefotaxime and cefoperazone was somewhat lower (EIs 1.7 x 10(3)-8.9 x 10(3)). Both the antibacterials were shown to provide high protective and therapeutic efficacy (80-100% of the survivors) independent of the phenotype (FI+ or FI-) of the pathogen infective strain. The results allowed to consider the antibiotics prospective in prevention and treatment of plague.

  10. Mitigating role of baicalein on lysosomal enzymes and xenobiotic metabolizing enzyme status during lung carcinogenesis of Swiss albino mice induced by benzo(a)pyrene.

    PubMed

    Naveenkumar, Chandrashekar; Raghunandakumar, Subramanian; Asokkumar, Selvamani; Binuclara, John; Rajan, Balan; Premkumar, Thandavamoorthy; Devaki, Thiruvengadam

    2014-06-01

    The lungs mainly serve as a primary site for xenobiotic metabolism and constitute an important defense mechanism against inhalation of carcinogens. Our current study aimed to evaluate the chemotherapeutic efficacy of baicalein (BE) in Swiss albino mice exposed to tobacco-specific carcinogen benzo(a)pyrene [B(a)P] for its ability to mitigate pulmonary carcinogenesis. Here, we report that altered activities/levels of lysosomal enzymes (cathepsin-D, cathepsin-B, acid phosphatase, β-D-galactosidase, β-D-glucuronidase, and β-D-N-acetyl glucosaminidase), phase I biotransformation enzymes (cytochrome P450, cytochrome b5, NADPH-cytochrome P450 reductase, and NADH-cytochrome b5 reductase), and phase II enzymes (glutathione S-transferase, UDP-glucuronyl transferase, and DT-diaphorase) were observed in the B(a)P-induced mice. Treatment with BE significantly restored back the activities/levels of lysosomal enzymes, phase I and phase II biotransformation enzymes. Moreover, assessment of lysosomal abnormalities by transmission electron microscopic examination revealed that BE treatment effectively counteract B(a)P-induced oxidative damages. Protein expression levels studied by immunohistochemistry, immunofluorescence, and immunoblot analysis of CYP1A1 revealed that BE treatment effectively negate B(a)P-induced upregulated expression of CYP1A1. Further analysis of scanning electron microscopic studies in lung was carried out to substantiate the anticarcinogenic effect of BE. The overall data suggest that BE treatment significantly inhibits lysosomal and microsomal dysfunction, thus revealing its potent anticarcinogenic effect.

  11. Creatine monohydrate supplementation for 10 weeks mediates neuroprotection and improves learning/memory following neonatal hypoxia ischemia encephalopathy in female albino mice.

    PubMed

    Allah Yar, Razia; Akbar, Atif; Iqbal, Furhan

    2015-01-21

    Currently there are no uniform standard treatments for newborn suffering from cerebral hypoxia-ischemia (HI) and to find new and effective strategies for treating the HI injury remains a key direction for future research. Present study was designed to demonstrate that optimal dose (1 or 3%) of creatine monohydrate (Cr) for the treatment of neonatal HI in female albino mice. On postnatal day 10, animals were subjected to left carotid artery ligation followed by 8% hypoxia for 25 minutes. Following weaning on postnatal day 20, mice were divided into three treatments on the basis of diet supplementation (Normal rodent diet, 1% and 3% creatine supplemented diet) for 10 week. A battery of neurological tests (Rota rod, open field and Morris water maze) was used to demonstrate effect of Cr supplementation on neurofunction and infarct size following HI. Open field test results indicated that Cr supplementation had significantly improved locomotory and exploratory behavior in subjects. It was observed that Cr treated mice showed better neuromuscular coordination (rota rod) and improved spatial memory (Morris Water Maze test). A significant affect of creatine supplementation in reducing infarct size was also observed. Post hoc analysis of post hoc multiple comparisons revealed that mice supplemented with 3% Cr for 10 weeks performed better during Morris water maze test while 1% Cr supplementation improved the exploratory behavior and gain in body weight than control group indicating that Cr supplementation has the potential to improve the neurofunction following neonatal brain damage. This article is part of a Special Issue entitled SI: Brain and Memory.

  12. The possible counteractive effect of gold nanoparticles against streptozotocin-induced type 1 diabetes in young male albino rats.

    PubMed

    Selim, Manar E; Hendi, Awatif A; Alfallaj, Ebtesam

    2016-05-01

    The current study was performed to study the effect of biologically synthesised gold nanoparticles (AuNPs) to control hyperglycaemic conditions in streptozotocin (STZ)-induced diabetic mice. In this study, the rats were divided into four groups: Group I normal control rats (non-diabetic, untreated); Group II diabetes-induced rats used as diabetic controls DC (diabetic, untreated). Group III diabetes-induced rats treated with AuNPs DT; Group IV normal rats treated with AuNPs NT. Diabetes was induced by administering an intraperitoneal injection of a freshly prepared solution of STZ (50mg/kg body weight (bw)). The glucose level was significantly increased in the diabetic control rats compared with the controls (P<0.001). Decreased liver function and kidney function were detected in the diabetic treated rats and normal treated rats after AuNP administration compared with the controls. The present study is the first to demonstrate that AuNPs significantly enhance antioxidant production in STZ-induced diabetic rats, a recognised model of type 1 diabetes mellitus (T1DM). PMID:27166528

  13. Citronellal ingestion decreases the appeal of male mouse urinary pheromone for female mice.

    PubMed

    Osada, Kazumi; Hanawa, Masaaki; Tsunoda, Kenji; Izumi, Hiroshi

    2012-01-01

    To determine whether ingestion of citronellal decreases the attractive power of the male mouse urinary odor, female mice were used in preference tests. A series of tests revealed that the female mice preferred voided urine odors from aged mice over those from younger adult mice. However, exogenous citronellal directly inhibited the advantage of the aged males with regard to attraction.

  14. Effects of lead on the male reproductive system in mice.

    PubMed

    Wadi, S A; Ahmad, G

    1999-04-01

    The effect of environmental lead on the male reproductive system has been a major area of concern for several years. Lead toxicity to the male reproductive system of sexually mature male CF-1 mice was investigated by administering two concentrations of lead (0.25% and 0.5%) via drinking water for 6 wk. The low lead dose significantly reduced the number of sperm within the epididymis, while the high dose reduced both the sperm count and percentage of motile sperm and increased the percentage of abnormal sperm within the epididymis. There was no significant effect on testis weight; however, the high-dose treatment significantly decreased the epididymis and seminal vesicle weights as well as overall body weight gain. Plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) levels were not affected by lead administration indicating that in adult male CF-1 mice, lead targets testicular spermatogenesis and sperm within the epididymis to produce reproductive toxicity rather than acting at other sites within the hypothalamic-pituitary-testicular axis.

  15. Sphingomyelin Synthase 1 Is Essential for Male Fertility in Mice

    PubMed Central

    Scherthan, Harry; Horsch, Marion; Beckers, Johannes; Fuchs, Helmut; Gailus-Durner, Valerie; Hrabě de Angelis, Martin; Ford, Steven J.; Burton, Neal C.; Razansky, Daniel; Trümbach, Dietrich; Aichler, Michaela; Walch, Axel Karl; Calzada-Wack, Julia; Neff, Frauke; Wurst, Wolfgang; Hartmann, Tobias; Floss, Thomas

    2016-01-01

    Sphingolipids and the derived gangliosides have critical functions in spermatogenesis, thus mutations in genes involved in sphingolipid biogenesis are often associated with male infertility. We have generated a transgenic mouse line carrying an insertion in the sphingomyelin synthase gene Sms1, the enzyme which generates sphingomyelin species in the Golgi apparatus. We describe the spermatogenesis defect of Sms1-/- mice, which is characterized by sloughing of spermatocytes and spermatids, causing progressive infertility of male homozygotes. Lipid profiling revealed a reduction in several long chain unsaturated phosphatidylcholins, lysophosphatidylcholins and sphingolipids in the testes of mutants. Multi-Spectral Optoacoustic Tomography indicated blood-testis barrier dysfunction. A supplementary diet of the essential omega-3 docosahexaenoic acid and eicosapentaenoic acid diminished germ cell sloughing from the seminiferous epithelium and restored spermatogenesis and fertility in 50% of previously infertile mutants. Our findings indicate that SMS1 has a wider than anticipated role in testis polyunsaturated fatty acid homeostasis and for male fertility. PMID:27788151

  16. Isolation-induced facilitation of male sexual behavior in mice.

    PubMed

    de Catanzaro, D; Gorzalka, B B

    1979-04-01

    Sexual performance of male mice housed individually or in groups of 3 or 12 was compared. Experiment 1 examined naive males presented at weekly intervals with ovariectomized, estrogen-primed, progesterone-treated females. Performance in isolates was consistently superior and reached an asymptote that was twice that of grouped animals. Reversal of housing conditions reversed performance. Experiment 2 varied intervals of isolation among subjects, finding facilitation at several intervals. Experiment 3 compared animals under different population densities. Density did not alter the effects of isolation and grouping. In all experiments, additional tests with target males indicated that aggressive and sexual performance were moderately correlated and responded similarly to parametric manipulations. These results parallel and extend studies of isolation-induced aggression. PMID:572378

  17. Effect of N′-nitrosodimethylamine on red blood cell rheology and proteomic profiles of brain in male albino rats

    PubMed Central

    Ahmad, Areeba; Fatima, Ravish; Maheshwari, Veena; Ahmad, Riaz

    2011-01-01

    We investigated the effects of N'-nitrosodimethylamine (NDMA) induced toxicity on red blood cell rheology in male rats and identified bands in proteomic profiles of brain which can be used as novel markers. Polyacrylamide gel electrophoresis (PAGE) profiles exhibited constitutive as well as induced expression of the polypeptides. Remarkably, the molecular weight range of the polypeptides (8–150 kDa) corresponded to that of the family of heat shock proteins. Our results revealed significant changes in blood parameters and showed the presence of acanthocytes, tear drop cells, spicules and cobot rings in the treated categories. Lactate dehydrogenase and esterase zymograms displayed a shift to anaerobic metabolism generating hypoxia-like conditions. This study strongly suggests that NDMA treatment causes acute toxicity leading to cell membrane destruction and alters protein profiles in rats. It is therefore recommended that caution should be exercised in using NDMA to avoid risks, and if at all necessary strategies should be designed to combat such conditions. PMID:22058653

  18. Agmatine blocks ethanol-induced locomotor hyperactivity in male mice.

    PubMed

    Ozden, Onder; Kayir, Hakan; Ozturk, Yusuf; Uzbay, Tayfun

    2011-05-20

    Ethanol-induced locomotor activity is associated to rewarding effects of ethanol and ethanol dependence. Agmatine is a novel endogenous ligand at α2-adrenoceptors, imidazoline and N-methyl-d-aspartate (NMDA) receptors, as well as a nitric oxide synthase (NOS) inhibitor. There is no evidence presented for the relationship between the acute locomotor stimulating effect of ethanol and agmatine. Thus, the present study investigated the effects of agmatine on acute ethanol-induced locomotor hyperactivity in mice. Adult male Swiss-Webster mice (26-36g) were used as subjects. Locomotor activity of the mice was recorded for 30min immediately following intraperitoneal administration of ethanol (0.5, 1 and 2g/kg) or saline (n=8 for each group). Agmatine (5, 10 and 20mg/kg) or saline was administered intraperitoneally to another four individual groups (n=8 for each group) of the mice 20min before the ethanol injection. In these groups, locomotor activity was also recorded immediately following ethanol (0.5g/kg) injection for 30min. Ethanol (0.5g/kg) produced some significant increases in locomotor activity of the mice. Agmatine (5-20mg/kg) significantly blocked the ethanol (0.5g/kg)-induced locomotor hyperactivity. These doses of agmatine did not affect the locomotor activity in naive mice when they were administered alone. Our results suggest that agmatine has an important role in ethanol-induced locomotor hyperactivity in mice. There may be a relationship between the addictive psychostimulant effects of the ethanol and central agmatinergic system.

  19. Effect of Potassium Bromate on the Liver of Adult Male Albino Rat and A Possible Protective Role of Vitamin C: Histological, Immunohistochemical, and Biochemical Study.

    PubMed

    Bayomy, Naglaa A; Soliman, Gehan M; Abdelaziz, Eman Z

    2016-09-01

    Potassium bromate (KBrO3 ) is a food additive which is used primarily as a maturing agent for flour. It is proved as a toxic agent with significant reduction in the activities of antioxidant capacity. The therapeutic efficacy of vitamin C as antioxidant may provide a possible solution to KBrO3 mediated oxidative damage. Twenty four adult male albino rats were used to evaluate the protective role of vitamin C against KBrO3 induced hepatotoxicity and divided into four groups; Group 1 (control), Group 2: received 30 mg/Kg/day vitamin C orally for 4 weeks, Group 3: received 20 mg/Kg/dose KBrO3 orally twice weekly for 4 weeks and Group 4: received both KBrO3 and vitamin C. Liver specimens were processed for histological study by light and electron microscopes and stained immunohistochemically to detect glial fibriller acidic protein (GFAP). Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were estimated as well as the levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities in all dissected tissues were determined. KBrO3 induced histological alterations in the form of degeneration, cellular infiltration and significant increase in collagen deposition in portal tracts with a significant increase in immunoexpression of GFAP. Significant rise in serum levels of AST, ALT, and MDA in liver tissues were recorded. However, levels of GSH and SOD were significantly decreased. Most of these changes were improved by vitamin C treatment. In conclusion, vitamin C ameliorates the histological and biochemical alterations of the liver induced by KBrO3 . Anat Rec, 299:1256-1269, 2016. © 2016 Wiley Periodicals, Inc.

  20. Histological Study on Effect of Mesenchymal Stem Cell Therapy on Experimental Renal Injury Induced by Ischemia/Reperfusion in Male Albino Rat

    PubMed Central

    Sadek, Eman Mostafa; Afifi, Noha Mohamed; Elfattah, Lamiaa Ibrahim Abd; Mohsen, Manal Ali Abd-El

    2013-01-01

    Background and Objectives Acute kidney injury (AKI) represents a major clinical problem with high mortality and limited treatment protocols. This study was planned to evaluate the therapeutic effectiveness of bone marrow - derived mesenchymal stem cells (BM-MSCs) in a rat model of ischemia/reperfusion (I/R) AKI. Methods and Results This study was carried out on thirty adult male albino rats. Animals were divided equally into three groups. Group I (control sham-operated group) (n=10), were subdivided equally into two subgroups; Ia and Ib. The experimental group (n=20) were all subjected to I/R injury by clamping both renal pedicles for 40 minutes. Half of the I/R animals did not receive MSC therapy (group II) [non-MSC treated group]. The other half of the I/R animals received single intravenous injection of PKH26 labelled BM-MSCs immediately after removal of the clamps and visual confirmation of reflow (group III) [MSC treated group]. Animals were sacrificed 24 hrs (subgroups IIa & IIIa) and 72 hrs (subgroups IIb & IIIb) after intervention. Serological measurements included serum urea and creatinine. Kidney specimens were processed for H&E, PAS and PCNA. Mean % of renal corpuscles with affected glomeruli, mean % of affected tubules, mean area % of PAS-positive reaction and mean area % of PCNA immunoreactivity were measured by histomorphometric studies and statistically compared. MSCs-treated group exhibited protection against renal injury serologically and histologically. Conclusions Results of the present study suggest a potential reno-protective capacity of MSCs which could be of considerable therapeutic promise for cell-based management of clinical AKI. PMID:24298374

  1. Effect of Potassium Bromate on the Liver of Adult Male Albino Rat and A Possible Protective Role of Vitamin C: Histological, Immunohistochemical, and Biochemical Study.

    PubMed

    Bayomy, Naglaa A; Soliman, Gehan M; Abdelaziz, Eman Z

    2016-09-01

    Potassium bromate (KBrO3 ) is a food additive which is used primarily as a maturing agent for flour. It is proved as a toxic agent with significant reduction in the activities of antioxidant capacity. The therapeutic efficacy of vitamin C as antioxidant may provide a possible solution to KBrO3 mediated oxidative damage. Twenty four adult male albino rats were used to evaluate the protective role of vitamin C against KBrO3 induced hepatotoxicity and divided into four groups; Group 1 (control), Group 2: received 30 mg/Kg/day vitamin C orally for 4 weeks, Group 3: received 20 mg/Kg/dose KBrO3 orally twice weekly for 4 weeks and Group 4: received both KBrO3 and vitamin C. Liver specimens were processed for histological study by light and electron microscopes and stained immunohistochemically to detect glial fibriller acidic protein (GFAP). Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were estimated as well as the levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities in all dissected tissues were determined. KBrO3 induced histological alterations in the form of degeneration, cellular infiltration and significant increase in collagen deposition in portal tracts with a significant increase in immunoexpression of GFAP. Significant rise in serum levels of AST, ALT, and MDA in liver tissues were recorded. However, levels of GSH and SOD were significantly decreased. Most of these changes were improved by vitamin C treatment. In conclusion, vitamin C ameliorates the histological and biochemical alterations of the liver induced by KBrO3 . Anat Rec, 299:1256-1269, 2016. © 2016 Wiley Periodicals, Inc. PMID:27373450

  2. Responses of Male C57BL/6N Mice to Observing the Euthanasia of Other Mice.

    PubMed

    Boivin, Gregory P; Bottomley, Michael A; Grobe, Nadja

    2016-01-01

    The AVMA Panel on Euthanasia recommends that sensitive animals should not be present during the euthanasia of others, especially of their own species, but does not provide guidelines on how to identify a sensitive species. To determine if mice are a sensitive species we reviewed literature on empathy in mice, and measured the cardiovascular and activity response of mice observing euthanasia of conspecifics. We studied male 16-wk-old C57BL/6N mice and found no increase in cardiovascular parameters or activity in the response of the mice to observing CO2 euthanasia. Mice observing decapitation had an increase in all values, but this was paralleled by a similar increase during mock decapitations in which no animals were handled or euthanized. We conclude that CO2 euthanasia of mice does not have an impact on other mice in the room, and that euthanasia by decapitation likely only has an effect due to the noise of the guillotine. We support the conceptual idea that mice are both a sensitive species and display empathy, but under the controlled circumstances of the euthanasia procedures used in this study there was no signaling of stress to witnessing inhabitants in the room. PMID:27423146

  3. Antiepileptic and Antioxidant Effect of Hydroalcoholic Extract of Ferula Assa Foetida Gum on Pentylentetrazole- induced Kindling in Male Mice

    PubMed Central

    Kiasalari, Zahra; Khalili, Mohsen; Roghani, Mehrdad; Heidari, Hamid; Azizi, Yaser

    2013-01-01

    Introduction Considering the prevalence of epilepsy and the failure of available treatments for many epileptic patients, finding more effective drugs in the treatment of epilepsy seems necessary. Oxidative stress has a special role in the pathogenesis of epileptic syndrome. Therefore, in the present study, we have examined the anti-epileptic and anti-oxidant properties of the Ferula Assa Foetida gum extract, using the pentylentetrazole (PTZ) kindling method. In this experimental study, sixty male Albino mice weighing 25-30 g were selected and were randomly divided into 6 groups. 1- the control group, 2- PTZ-kindled mice, 3- positive control group which received valproate (100 mg/kg) as anti-convulsant drug, 4-5 & 6- the groups of kindled mice that pretreated with 25, 50 and 100 mg/kg doses of Ferula Assa Foetida gum extract. Methods Kindling has been induced in all groups, except for the control group via 11 PTZ injections (35 mg /kg; ip) every other day for 22 days. In the 24th day, the PTZ challenge dose was injected (75 mg / kg) to all groups except the control group. The intensity of seizures were observed and noted until 30 minutes after PTZ injection. At list, the mice were decapitated and the brains of all the mice were removed.. and their biochemical factors levels including malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) were determined. Results Results of this study show that Ferula Assa Foetida gum extract is able to reduce seizure duration and its intensity. In addition, this extract has reduced MDA and NO levels and increased the level of SOD in the brain tissue compared to the PTZ- kindled mice. Discussion It can be concluded that Ferula Assa Foetida gum extract, in specific doses, is able to show an anti-epileptic effect because of its antioxidant properties, probably acting through an enzyme activity mechanism. PMID:25337361

  4. Lipopolysaccharide Cross-Tolerance Delays Platelet-Activating Factor-Induced Sudden Death in Swiss Albino Mice: Involvement of Cyclooxygenase in Cross-Tolerance.

    PubMed

    Jacob, Shancy Petsel; Lakshmikanth, Chikkamenahalli Lakshminarayana; Chaithra, Vyala Hanumanthareddy; Kumari, Titus Ruth Shantha; Chen, Chu-Huang; McIntyre, Thomas M; Marathe, Gopal Kedihitlu

    2016-01-01

    Lipopolysaccharide (LPS) signaling through Toll-like receptor-4 (TLR-4) has been implicated in the pathogenesis of many infectious diseases. Some believe that TLR-mediated pathogenicity is due, in part, to the lipid pro-inflammatory mediator platelet-activating factor (PAF), but this has been questioned. To test the direct contribution of PAF in endotoxemia in murine models, we injected PAF intraperitoneally into Swiss albino mice in the presence and absence of LPS. PAF alone (5 μg/mouse) caused death within 15-20 min, but this could be prevented by pretreating mice with PAF-receptor (PAF-R) antagonists or PAF-acetylhydrolase (PAF-AH). A low dose of LPS (5 mg/kg body wt) did not impair PAF-induced death, whereas higher doses (10 or 20 mg/kg body wt) delayed death, probably via LPS cross-tolerance. Cross-tolerance occurred only when PAF was injected simultaneously with LPS or within 30 min of LPS injection. Tolerance does not appear to be due to an abundant soluble mediator. Histologic examination of lungs and liver and measurement of circulating TNF-α and IL-10 levels suggested that the inflammatory response is not diminished during cross-tolerance. Interestingly, aspirin, a non-specific cyclooxygenase (COX) inhibitor, partially blocked PAF-induced sudden death, whereas NS-398, a specific COX-2 inhibitor, completely protected mice from the lethal effects of PAF. Both COX inhibitors (at 20 mg/kg body wt) independently amplified the cross-tolerance exerted by higher dose of LPS, suggesting that COX-derived eicosanoids may be involved in these events. Thus, PAF does not seem to have a protective role in endotoxemia, but its effects are delayed by LPS in a COX-sensitive way. These findings are likely to shed light on basic aspects of the endotoxin cross-tolerance occurring in many disease conditions and may offer new opportunities for clinical intervention. PMID:27064683

  5. Lipopolysaccharide Cross-Tolerance Delays Platelet-Activating Factor-Induced Sudden Death in Swiss Albino Mice: Involvement of Cyclooxygenase in Cross-Tolerance

    PubMed Central

    Jacob, Shancy Petsel; Lakshmikanth, Chikkamenahalli Lakshminarayana; Chaithra, Vyala Hanumanthareddy; Kumari, Titus Ruth Shantha; Chen, Chu-Huang; McIntyre, Thomas M.; Marathe, Gopal Kedihitlu

    2016-01-01

    Lipopolysaccharide (LPS) signaling through Toll-like receptor-4 (TLR-4) has been implicated in the pathogenesis of many infectious diseases. Some believe that TLR-mediated pathogenicity is due, in part, to the lipid pro-inflammatory mediator platelet-activating factor (PAF), but this has been questioned. To test the direct contribution of PAF in endotoxemia in murine models, we injected PAF intraperitoneally into Swiss albino mice in the presence and absence of LPS. PAF alone (5 μg/mouse) caused death within 15–20 min, but this could be prevented by pretreating mice with PAF-receptor (PAF-R) antagonists or PAF-acetylhydrolase (PAF-AH). A low dose of LPS (5 mg/kg body wt) did not impair PAF-induced death, whereas higher doses (10 or 20 mg/kg body wt) delayed death, probably via LPS cross-tolerance. Cross-tolerance occurred only when PAF was injected simultaneously with LPS or within 30 min of LPS injection. Tolerance does not appear to be due to an abundant soluble mediator. Histologic examination of lungs and liver and measurement of circulating TNF-α and IL-10 levels suggested that the inflammatory response is not diminished during cross-tolerance. Interestingly, aspirin, a non-specific cyclooxygenase (COX) inhibitor, partially blocked PAF-induced sudden death, whereas NS-398, a specific COX-2 inhibitor, completely protected mice from the lethal effects of PAF. Both COX inhibitors (at 20 mg/kg body wt) independently amplified the cross-tolerance exerted by higher dose of LPS, suggesting that COX-derived eicosanoids may be involved in these events. Thus, PAF does not seem to have a protective role in endotoxemia, but its effects are delayed by LPS in a COX-sensitive way. These findings are likely to shed light on basic aspects of the endotoxin cross-tolerance occurring in many disease conditions and may offer new opportunities for clinical intervention. PMID:27064683

  6. Ultrasonic Vocalizations of Male Mice Differ among Species and Females Show Assortative Preferences for Male Calls

    PubMed Central

    Musolf, Kerstin; Meindl, Stefanie; Larsen, Angela L.; Kalcounis-Rueppell, Matina C.; Penn, Dustin J.

    2015-01-01

    Male house mice (Mus musculus) emit ultrasonic vocalizations (USVs) during courtship, which attract females, and we aimed to test whether females use these vocalizations for species or subspecies recognition of potential mates. We recorded courtship USVs of males from different Mus species, Mus musculus subspecies, and populations (F1 offspring of wild-caught Mus musculus musculus, Mus musculus domesticus (and F1 hybrid crosses), and Mus spicilegus), and we conducted playback experiments to measure female preferences for male USVs. Male vocalizations contained at least seven distinct syllable types, whose frequency of occurrence varied among species, subspecies, and populations. Detailed analyses of multiple common syllable types indicated that Mus musculus and Mus spicilegus could be discriminated based on spectral and temporal characteristics of their vocalizations, and populations of Mus musculus were also distinctive regardless of the classification model used. Females were able to discriminate USVs from different species, and showed assortative preferences for conspecific males. We found no evidence that females discriminate USVs of males from a different subspecies or separate populations of the same species, even though our spectral analyses identified acoustic features that differ between species, subspecies, and populations of the same species. Our results provide the first comparison of USVs between Mus species or between Mus musculus subspecies, and the first evidence that male USVs potentially facilitate species recognition. PMID:26309246

  7. Protective Effect of Nardostachys jatamansi Against Radiation-induced Damage at Biochemical and Chromosomal Levels in Swiss Albino Mice

    PubMed Central

    Madhu, L. N.; Kumari, N. Suchetha; Naveen, P.; Sanjeev, G.

    2012-01-01

    The effect of 100 mg of ethanol extract of Nardostachys jatamansi was studied on the mice exposed to 6 Gy electron beam radiation. Treatment of mice with 100 mg of Nardostachys jatamansi extract for 15 days before irradiation reduced the symptoms of radiation sickness when compared with the nondrug treated irradiated groups. The irradiation of animals resulted in an elevation in lipid peroxidation and reduction in glutathione, total antioxidants and antioxidant enzymes such as glutathione peroxidase and catalase activities. Irradiated group had shown micronucleus in the bone marrow cells. Treatment of mice with Nardostachys jatamansi extract before irradiation caused a significant depletion in lipid peroxidation followed by significant elevation in reduced glutathione, total antioxidants, glutathione peroxidase and catalase activity. It also showed a reduction in the micronucleus formation in the bone marrow cells. Our results indicate that the radioprotective activity of Nardostachys jatamansi extract may be due to free radical scavenging and increased antioxidant level in mice. PMID:23716877

  8. Efficacy of Spirulina platensis in improvement of the reproductive performance and easing teratogenicity in hyperglycemic albino mice

    PubMed Central

    Pankaj, Pranay Punj

    2015-01-01

    Objectives: The present study evaluates the therapeutic efficacy of cell suspension of Spirulina platensis (SP) on estrous cycle, fetal development and embryopathy in alloxan (AXN) induced hyperglycemic mice. Materials and Methods: Diabetes was induced by intra-peritoneal administration of AXN. Mice with blood glucose level above 200 mg/dl were divided into Group I (control), Group II (diabetic control), Group III (diabetic control mice fed with SP), and Group IV (control mice fed with SP). Litter counts, estrous cycles, percent survival of litter, and gestation length were recorded. Results: In hyperglycemic mice, a significant (P < 0.05) increase in duration of diestrus (14.48%), estrus (84.21%), and metestrus (164.15%) with concomitant decrease in proestrus phase by 26.13% was recorded when compared with control. Reduction in litter count and survival of litter was 68.67% and 88.38%, respectively, whereas gestation length increased to 14.51% day in diabetic mice, but recovery in these parameters was observed (P < 0.05) when subjected to SP treatment. SP resulted in increased fertility rate from 77.5% to 82.5% and dropped off resorption of the fetus to 33.73% while the survival rate of offspring of diabetic mice went up to 88.89% from 83.61%. Conclusions: These findings suggest that SP is effective in improving the reproductive performance and easing teratogenic effects in diabetic mice and hence warrants further detailed dose-dependent studies to understand its mechanism of action. PMID:26285837

  9. Corticosteroids Are Essential for Maintaining Cardiovascular Function in Male Mice.

    PubMed

    Cruz-Topete, Diana; Myers, Page H; Foley, Julie F; Willis, Monte S; Cidlowski, John A

    2016-07-01

    Activation of the hypothalamic-pituitary-adrenal axis results in the release of hormones from the adrenal glands, including glucocorticoids and mineralocorticoids. The physiological association between corticosteroids and cardiac disease is becoming increasingly recognized; however, the mechanisms underlying this association are not well understood. To determine the biological effects of corticosteroids on the heart, we investigated the impact of adrenalectomy in C57BL/6 male mice. Animals were adrenalectomized (ADX) at 1 month of age and maintained for 3-6 months after surgery to evaluate the effects of long-term adrenalectomy on cardiac function. Morphological evaluation suggested that ADX mice showed significantly enlarged hearts compared with age-matched intact controls. These changes in morphology correlated with deficits in left ventricular (LV) function and electrocardiogram (ECG) abnormalities in ADX mice. Correlating with these functional defects, gene expression analysis of ADX hearts revealed aberrant expression of a large cohort of genes associated with cardiac hypertrophy and arrhythmia. Combined corticosterone and aldosterone replacement treatment prevented the emergence of cardiac abnormalities in ADX mice, whereas corticosterone replacement prevented the effects of adrenalectomy on LV function but did not block the emergence of ECG alterations. Aldosterone replacement did not preserve the LV function but prevented ECG abnormalities. Together, the data indicate that adrenal glucocorticoids and mineralocorticoids either directly or indirectly have selective effects in the heart and their signaling pathways are essential in maintaining normal cardiac function. PMID:27219275

  10. Stimulatory effects of Cuminum cyminum and flavonoid glycoside on Cyclosporine-A and restraint stress induced immune-suppression in Swiss albino mice.

    PubMed

    Chauhan, Prashant Singh; Satti, Naresh Kumar; Suri, Krishan Avtar; Amina, Musarat; Bani, Sarang

    2010-04-15

    Many herbs and spices are known to modulate the immune system and have been shown to restore the immunity in immuno-compromised individuals. Spices generally used to increase the taste and flavor of food also has the history of usage as an ayurvedic medicine. Therefore to explore the health modulating effects of Cuminum cyminum and to identify the active compound, immunomodulatory properties were evaluated using flowcytometry and ELISA in normal and immune-suppressed animals. C. cyminum and compound 1 stimulated the T cells and Th1 cytokines expression in normal animals. Swiss albino mice subjected to Cyclosporine-A induced immune-suppression were dosed orally with C. cyminum (25, 50, 100 and 200 mg/kg) on consecutive days. The results showed that administration significantly increased T cells (CD4 and CD8) count and Th1 predominant immune response in a dose dependent manner thereby suggesting immunomodulatory activity through modulation of T lymphocytes expression. In restraint stress induced immune-suppressed animals, compound 1 countered the depleted T lymphocytes, decreased the elevated corticosterone levels and size of adrenal glands and increased the weight of thymus and spleen. Based on the data we may conclude that C. cyminum is a potent immunomodulator and may develop as a lead to recover the immunity of immuno-compromised individuals.

  11. Effect of carbon monoxide and nitrogen dioxide on ICR mice

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Cumming, H. J.

    1977-01-01

    Times to incapacitation and death and LC(50) values were determined for male ICR mice exposed to different concentration of carbon monoxide for 30 min and of nitrogen dioxide for 10 min in a 4.2 liter hemispherical chamber. The data indicate that ICR mice are more resistant to these two toxicants than Swiss albino mice. The carbon monoxide LC(50) for a 30-min exposure was about 8,000 ppm for ICR mice compared to 3,570 ppm for Swiss albino mice. The nitrogen dioxide LC(50) for a 10-min exposure was above 2,000 ppm for ICR mice compared to about 1,000 ppm for Swiss albino mice.

  12. Modulation of gamma radiation-inflicted damage in Swiss albino mice by an alcoholic fraction of Podophyllum hexandrum rhizome.

    PubMed

    Gupta, M L; Agrawala, P K; Kumar, Prem; Devi, M; Soni, N L; Tripathi, R P

    2008-09-01

    A partially characterized extract of Podophyllum hexandrum rhizomes was studied for its radioprotective potential in mice. A major portion of the podophyllotoxin was obtained from the extract by further fractionation. Acute toxicity and maximum tolerated dose (MTD) of a single intraperitoneal dose of the extract were studied in mice to evaluate the toxicity of the extract, if any. Radioprotective efficacy was determined in terms of survival against 10 Gy whole-body irradiation (WBI), protection against 1 Gy-induced chromosomal aberration (CA), and estimation of dose reduction factor (DRF) in irradiated and extract pretreated mice. The MTD was observed to be 60 mg/kg of body weight, whereas a dose of 90 mg/kg of body weight yielded 50% death in mice within 72 hours of intraperitoneal administration of the extract. A dose range of 15-20 mg/kg of body weight administered 2 hours before 10 Gy WBI of mice yielded 66% survival, while administration of 10-15 mg/kg of body weight of the extract 1 hour before WBI yielded more than 90% survival. A DRF of 1.625 was estimated for 10 and 15 mg/kg of body weight of the extract administered 1 hour before WBI. Further studies on modulation of 1 Gy-induced CA revealed significant radioprotective efficacy of the extract in mouse bone marrow cells. Partial removal of podophyllotoxin was useful in reducing toxicity of the extract without altering its radioprotective efficacy.

  13. In Vivo Antiplasmodial and Analgesic Effect of Crude Ethanol Extract of Piper guineense Leaf Extract in Albino Mice

    PubMed Central

    Kabiru, A. Y.; Ibikunle, G. F.; Innalegwu, D. A.; Bola, B. M.; Madaki, F. M.

    2016-01-01

    Antiplasmodial and analgesic effects of crude ethanol extract of Piper guineense was investigated in mice. The antiplasmodial and analgesic efficacy of the extract was judged on its ability to reduce parasitemia and writhing, respectively, in mice. The antiplasmodial screening involved treating infected mice with 200, 400, and 600 mg/kg body weight of extract while the positive control group was given standard artesunate drug. The analgesic test was carried out by administering 1000, 1500, and 2000 mg/kg body weight of extract to three groups of healthy mice, respectively, after induction of pain with 0.75% acetic acid. The positive control group was given aspirin drug. Parasitemia was reduced by 28.36%, 43.28%, and 62.69% in a dose-dependent pattern in the curative test which was significantly different (P < 0.05) from 96.03% of the standard drug. The reduction of writhing by mice given the extract was also dose-dependent (36.29, 45.43, and 59.07%). Aspirin drug was however more effective (86.36%). The extract was safe at 2000 mg/kg body weight. Phytochemical screening revealed the presence of flavonoids, tannins, phlobatannins, terpenoids, and coumarins. Result obtained in this study demonstrated the efficacy of ethanol extract of Piper guineense as an antiplasmodial and analgesic agent. PMID:27446637

  14. Adenosine analogs inhibit fighting in isolated male mice

    SciTech Connect

    Palmour, R.M.; Lipowski, C.J.; Simon, C.K.; Ervin, F.R.

    1989-01-01

    The potent adenosine analogs N-ethylcarboxamide adenosine (NECA) and phenylisopropyladenosine (PIA) inhibit fighting and associated agonistic behaviors in isolated male mice. These effects are reversed by methylxanthines; moderate doses of NECA which inhibit fighting have minimal effects on spontaneous locomotor activity. At very low doses, both NECA and PIA increase fighting in parallel with previously reported increases of motor activity. Brain levels of (/sup 3/H)-NECA and (/sup 3/H)-PIA achieved at behaviorally effective doses suggest an involvement of adenosine receptors. The biochemical mechanism of adenosine receptor action with respect to fighting is unknown, but may include neuromodulatory effects on the release of other, more classical neurotransmitters.

  15. Competitive ability in male house mice (Mus musculus): genetic influences.

    PubMed

    Cunningham, Christopher B; Ruff, James S; Chase, Kevin; Potts, Wayne K; Carrier, David R

    2013-03-01

    Conspecifics of many animal species physically compete to gain reproductive resources and thus fitness. Despite the importance of competitive ability across the animal kingdom, specific traits that influence or underpin competitive ability are poorly characterized. Here, we investigate whether there are genetic influences on competitive ability within male house mice. Additionally, we examined if litter demographics (litter size and litter sex ratio) influence competitive ability. We phenotyped two generations for a male's ability to possess a reproductive resource--a prime nesting site--using semi-natural enclosures with mixed sex groupings. We used the "Animal Model" coupled with an extensive pedigree to estimate several genetic parameters. Competitive ability was found to be highly heritable, but only displayed a moderate genetic correlation to body mass. Interestingly, litter sex ratio had a weak negative influence on competitive ability. Litter size had no significant influence on competitive ability. Our study also highlights how much remains unknown about the proximal causes of competitive ability.

  16. Chronic unpredictable stress (CUS) enhances the carcinogenic potential of 7,12-dimethylbenz(a)anthracene (DMBA) and accelerates the onset of tumor development in Swiss albino mice.

    PubMed

    Suhail, Nida; Bilal, Nayeem; Hasan, Shirin; Ahmad, Ausaf; Ashraf, Ghulam Md; Banu, Naheed

    2015-11-01

    Social stressors evolving from individual and population interactions produce stress reactions in many organisms (including humans), influencing homeostasis, altering the activity of the immunological system, and thus leading to various pathological states including cancer and their progression. The present study sought to validate the effectiveness of chronic unpredictable stress (CUS) in cancer promotion and to assess oxidative stress outcomes in terms of various in vivo biochemical parameters, oxidative stress markers, DNA damage, and the development of skin tumors in Swiss albino mice. Animals were randomized into different groups based on their exposure to CUS alone, 7,12-dimethylbenz(a)anthracene (DMBA) alone (topical), and DMBA-12-O-tetradecanoylphorbol-13-acetate (TPA) (topical) and exposure to CUS prior to DMBA or DMBA-TPA treatments and sacrificed after 16 weeks of treatment. Prior exposure to CUS significantly increased the pro-oxidant effect of carcinogen, depicted by compromised levels of antioxidants in the circulation and skin, accompanied by enhanced lipid peroxidation, plasma corticosterone, and marker enzymes as compared to DMBA-alone or DMBA-TPA treatments. DNA damage results corroborated the above biochemical outcomes. Also, the development of skin tumors (in terms of their incidence, tumor yield, and tumor burden) in mice in the presence and absence of stress further strongly supported our above biochemical measurements. CUS may work as a promoter of carcinogenesis by enhancing the pro-oxidant potential of carcinogens. Further studies may be aimed at the development of interventions for disease prevention by identifying the relations between psychological factors and DNA damage.

  17. Evaluation of Ratnaprash for its effect on strength, stamina and fatigue using swim endurance test and biochemical estimation in swiss albino mice

    PubMed Central

    Gupta, Arun; Kumar, Satyendra; Rajput, Rashmi; Srivastava, Ruchi; Rai, Rajiv K.; Sastry, J. L. N.

    2015-01-01

    Context: Traditional medicines have been considered as important resources for postponing fatigue, accelerating elimination of fatigue related metabolites and improving physical ability. Rasāyanās or rejuvenative therapies are mentioned as one of the eight clinical specialties in Ayurveda for attaining longevity, healthy life and regulation of bodily balance. Eventhough more detailed studies are needed to confirm the claims of benefits in the light of evidence based research, Ratnaprash, a herbo-mineral rasāyana formulation, is proposed here to be an antifatigue supplement that is good in promoting strength and stamina. Materials and Methods: In the present study, anti fatigue, strength and stamina enhancing properties of Ratnaprash were examined based on swim endurance capacity and the change in biochemical parameters in Swiss Albino mice. Treatment groups were orally administered Ratnaprash at various test doses (500, 1000, 2000 mg/Kg per day), while the control group received distilled water at similar dose volumes. Effect of therapy was evaluated after 28 days of treatment. Results: At the end of study period, the swimming times to exhaustion were longer in the treated groups than in the control group. Plasma lactate levels of treated groups were lower than those of the control group (P < 0.05) while tissue ATP levels were higher. These effects were dose dependent and the strongest effect was seen in groups treated at 1000 mg/Kg. Conclusion: Ratnaprash enhanced the forced swimming capacity of mice and exhibited elevated anti-fatigue activity, reduced blood lactate levels and increased tissue ATP levels in preclinical models in comparison to vehicle control, exhibiting possible role in increasing strength and stamina and contributing anti-fatigue activity. PMID:26600664

  18. Chronic unpredictable stress (CUS) enhances the carcinogenic potential of 7,12-dimethylbenz(a)anthracene (DMBA) and accelerates the onset of tumor development in Swiss albino mice.

    PubMed

    Suhail, Nida; Bilal, Nayeem; Hasan, Shirin; Ahmad, Ausaf; Ashraf, Ghulam Md; Banu, Naheed

    2015-11-01

    Social stressors evolving from individual and population interactions produce stress reactions in many organisms (including humans), influencing homeostasis, altering the activity of the immunological system, and thus leading to various pathological states including cancer and their progression. The present study sought to validate the effectiveness of chronic unpredictable stress (CUS) in cancer promotion and to assess oxidative stress outcomes in terms of various in vivo biochemical parameters, oxidative stress markers, DNA damage, and the development of skin tumors in Swiss albino mice. Animals were randomized into different groups based on their exposure to CUS alone, 7,12-dimethylbenz(a)anthracene (DMBA) alone (topical), and DMBA-12-O-tetradecanoylphorbol-13-acetate (TPA) (topical) and exposure to CUS prior to DMBA or DMBA-TPA treatments and sacrificed after 16 weeks of treatment. Prior exposure to CUS significantly increased the pro-oxidant effect of carcinogen, depicted by compromised levels of antioxidants in the circulation and skin, accompanied by enhanced lipid peroxidation, plasma corticosterone, and marker enzymes as compared to DMBA-alone or DMBA-TPA treatments. DNA damage results corroborated the above biochemical outcomes. Also, the development of skin tumors (in terms of their incidence, tumor yield, and tumor burden) in mice in the presence and absence of stress further strongly supported our above biochemical measurements. CUS may work as a promoter of carcinogenesis by enhancing the pro-oxidant potential of carcinogens. Further studies may be aimed at the development of interventions for disease prevention by identifying the relations between psychological factors and DNA damage. PMID:26272695

  19. The course of experimental staphylococcus infection in albino mice during action of certain factors of space flight

    NASA Technical Reports Server (NTRS)

    Prokhorov, V. Y.; Shilov, V. M.; Borman, E. A.

    1980-01-01

    A study was made of the effect of certain factors of space flight, acceleration and hypokinesia, on the course of experimental staphylococcus infection in mice. Combined action of hypokinesia and acceleration caused a marked depression of the phagocytic activity of leukocytes and formation of a considerable amount of alpha toxin.

  20. Statins enhance cognitive performance in object location test in albino Swiss mice: involvement of beta-adrenoceptors.

    PubMed

    Vandresen-Filho, Samuel; França, Lucas Moreira; Alcantara-Junior, José; Nogueira, Lucas Caixeta; de Brito, Thiago Marques; Lopes, Lousã; Junior, Fernando Mesquita; Vanzeler, Maria Luzinete; Bertoldo, Daniela Bohn; Dias, Paula Gomes; Colla, André R S; Hoeller, Alexandre; Duzzioni, Marcelo; Rodrigues, Ana Lúcia S; de Lima, Thereza C M; Tasca, Carla Inês; Viola, Giordano Gubert

    2015-05-01

    Statins are inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, thereby inhibiting cell synthesis of cholesterol and isoprenoids. Moreover, several studies have been evaluating pleiotropic effects of statins, mainly because they present neuroprotective effects in various pathological conditions. However, knowledge about behavioral effects of statins per se is relatively scarce. Considering these facts, we aimed to analyze behavioral responses of atorvastatin or simvastatin-treated mice in the open field test, elevated plus maze and object location test. Atorvastatin treatment for 7 consecutive days at 1 mg/kg or 10 mg/kg (v.o.) or simvastatin 10 mg/kg or 20 mg/kg enhanced cognitive performance in object location test when compared to control group (saline-treated mice). Simvastatin effects on mice performance in the object location test was abolished by post-training infusion of the beta-adrenoceptor antagonist propranolol. Atorvastatin and simvastatin did not change the behavioral response in open field and elevated plus-maze (EPM) tests in any of the used doses. These data demonstrate the positive effects of both statins in cognitive processes in mice, without any alteration in locomotor parameters in the open field test or anxiolytic-like behavior in EPM. In conclusion, we demonstrate that atorvastatin and simvastatin per se improve the cognitive performance in a rodent model of spatial memory and this effect is related to beta-adrenergic receptors modulation.

  1. Effects of garlic on Schistosoma mansoni harbored in albino mice: molecular characterization of the host and parasite.

    PubMed

    Riad, Nahed H A; Taha, Hoda A; Mahmoud, Yomna I

    2013-04-15

    Garlic has been used for its health benefits for thousands of years. Modern research confirmed many of the healing properties of garlic, including its antiparasitic activity. This study was designed to evaluate the antischistosomal action of garlic through detecting the changes in DNA profile of Schistosoma mansoni worms and the infected mouse. Forty mice were subcutaneously infected with ~200 Schistosoma mansoni cercariae/mouse. Infected mice were divided into four equal groups: non-treated, prophylactic, therapeutic, and continuously-treated. Non-infected control and garlic-treated groups were assigned for the sake of comparison. Garlic extract (50mg/kg bw/mouse) was given orally, day after day, at a fixed daytime. Seven weeks post-infection, adult schistosomes were recovered by perfusion and the livers of the mice were excised out and were processed for DNA extraction and Random Amplification of Polymorphic DNA-Polymerase Chain Reaction (RAPD-PCR). The results showed that garlic exerted no major changes in the genome of schistosomes. Nevertheless, that schistosomal infection induced genetic alterations in the DNA of mice, and garlic was able to ameliorate such alterations to a great extent.

  2. Exploring the Potential Role of Chemopreventive Agent, Hesperetin Conjugated Pegylated Gold Nanoparticles in Diethylnitrosamine-Induced Hepatocellular Carcinoma in Male Wistar Albino Rats.

    PubMed

    Gokuladhas, Krishnan; Jayakumar, Subramaniyan; Rajan, Balan; Elamaran, Ramasamy; Pramila, Chengalvarayan Subramani; Gopikrishnan, Mani; Tamilarasi, Sasivarman; Devaki, Thiruvengadam

    2016-04-01

    Liver cancer is the fifth most common cancer and is still one of the leading causes of death world wide, due to food additives, alcohol, fungal toxins, air, toxic industrial chemicals, and water pollutants. Chemopreventive drugs play a potential role in liver cancer treatment. Obviously in the production of anticancer drugs, the factors like poor solubility, bioavailability, biocompatibility, limited chemical stability, large amount of dose etc., plays a major role. Against this backdrop, the idea of designing the chemopreventive nature of bio flavanoid hesperetin (HP) drug conjugated with pegylated gold nanoparticles to increasing the solubility, improve bioavailability and enhance the targeting capabilities of the drug during diethylnitrosamine (DEN) induced liver cancer in male wistar albino rats. The dose fixation studies and the toxicity of pure HP and HP conjugated gold nanoparticles (Au-mPEG(5000)-S-HP) were analysed. After concluded the dose fixation and toxicity studies the experimental design were segregated in six groups for the anticancer analysis of DEN induced HCC for 16 weeks. After the experimental period the body weight, relative liver weight, number of nodules and size of nodules, the levels of tumor markers like CEA, AFP and the level of lipid peroxidation, lipid hydroperoxides and the activities of antioxidant enzymes were assessed. The administration of DEN to rats resulted in increased relative liver weight and serum marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma glutamyl transpeptidase. The levels of lipid peroxides elevated (in both serum and tissue) with subsequent decrease in the final body weight and tissue antioxidants like superoxide dismutase, catalase, reduced glutathione, glutathione peroxidise, and glutathione reductase. HP supplementation (20 mg/kg b.wt) significantly attenuated these alterations, thereby showing potent anticancer effect in liver cancer and the

  3. Exploring the Potential Role of Chemopreventive Agent, Hesperetin Conjugated Pegylated Gold Nanoparticles in Diethylnitrosamine-Induced Hepatocellular Carcinoma in Male Wistar Albino Rats.

    PubMed

    Gokuladhas, Krishnan; Jayakumar, Subramaniyan; Rajan, Balan; Elamaran, Ramasamy; Pramila, Chengalvarayan Subramani; Gopikrishnan, Mani; Tamilarasi, Sasivarman; Devaki, Thiruvengadam

    2016-04-01

    Liver cancer is the fifth most common cancer and is still one of the leading causes of death world wide, due to food additives, alcohol, fungal toxins, air, toxic industrial chemicals, and water pollutants. Chemopreventive drugs play a potential role in liver cancer treatment. Obviously in the production of anticancer drugs, the factors like poor solubility, bioavailability, biocompatibility, limited chemical stability, large amount of dose etc., plays a major role. Against this backdrop, the idea of designing the chemopreventive nature of bio flavanoid hesperetin (HP) drug conjugated with pegylated gold nanoparticles to increasing the solubility, improve bioavailability and enhance the targeting capabilities of the drug during diethylnitrosamine (DEN) induced liver cancer in male wistar albino rats. The dose fixation studies and the toxicity of pure HP and HP conjugated gold nanoparticles (Au-mPEG(5000)-S-HP) were analysed. After concluded the dose fixation and toxicity studies the experimental design were segregated in six groups for the anticancer analysis of DEN induced HCC for 16 weeks. After the experimental period the body weight, relative liver weight, number of nodules and size of nodules, the levels of tumor markers like CEA, AFP and the level of lipid peroxidation, lipid hydroperoxides and the activities of antioxidant enzymes were assessed. The administration of DEN to rats resulted in increased relative liver weight and serum marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma glutamyl transpeptidase. The levels of lipid peroxides elevated (in both serum and tissue) with subsequent decrease in the final body weight and tissue antioxidants like superoxide dismutase, catalase, reduced glutathione, glutathione peroxidise, and glutathione reductase. HP supplementation (20 mg/kg b.wt) significantly attenuated these alterations, thereby showing potent anticancer effect in liver cancer and the

  4. Steroid-independent male sexual behavior in B6D2F2 male mice.

    PubMed

    McInnis, Christine M; Venu, Samitha; Park, Jin Ho

    2016-09-01

    It is well established that male sexual behavior (MSB) is regulated by gonadal steroids; however, individual differences in MSB, independent of gonadal steroids, are prevalent across a wide range of species, and further investigation is necessary to advance our understanding of steroid-independent MSB. Studies utilizing B6D2F1 hybrid male mice in which a significant proportion retain MSB after long-term orchidectomy, identified as steroid-independent-maters (SI-maters), have begun to unravel the genetic underpinnings of steroid-independent MSB. A recent study demonstrated that steroid-independent MSB is a heritable behavioral phenotype that is mainly passed down from B6D2F1 hybrid SI-maters when crossed with C57BL6J female mice. To begin to uncover whether the strain of the dam plays a role in the inheritance of steroid-independent MSB, B6D2F1 hybrid females were crossed with B6D2F1 hybrid males. While the present study confirms the finding that steroid-independent MSB is a heritable behavioral phenotype and that SI-mater sires are more likely to pass down some components of MSB than SI-non-maters to their offspring, it also reveals that the B6D2F2 male offspring that were identified as SI-maters that displayed the full repertoire of steroid-independent MSB had the same probability of being sired from either a B6D2F1 SI-mater or SI-non-mater. These results, in conjunction with previous findings, indicate that the specific chromosomal loci pattern that codes for steroid-independent MSB in the B6D2F2 male offspring may result regardless of whether the father was a SI-mater or SI-non-mater, and that the maternal strain may be an important factor in the inheritance of steroid-independent MSB. PMID:27476435

  5. Evaluation of lemon fruit extract as an antioxidant agent against histopathological changes induced by cyclophosphamide in the testes of albino mice

    PubMed Central

    Quita, Salwa Mohammed

    2016-01-01

    Introduction The aim of this study was to determine the protective effects of lemon fruit extracts (LFE) against histopathological changes induced in the testes of male mice treated with cyclophosphamide (CP). Methods Thirty male mice were divided evenly into six groups: 1) group 1: the controls, 2) group 2: treated with LFE (10 ml/kg b wt.), 3) group 3: treated with CP (10 mg/kg b wt.), 4) group 4: treated with CP (20 mg/kg b wt.), 5) group 5: treated with LFE (10 ml/kg) + CP (10 mg/kg), 6) group 6: treated with LFE (10 ml/kg) + CP (20 mg/kg). Results Histological examination of the testes of mice treated with CP revealed histopathological changes, such as atrophy, degeneration, incomplete spermatogenic series in most seminiferous tubules, and spermatogenic necrosis with pyknotic nuclei. Advanced degree of improvement was seen in testes of mice treated with LFE co-administered with CP. Most of the seminiferous tubules restored their normal structure and spermatogenic layers appeared semi-normal with complete spermatogenic series. Conclusion Lemon fruit extract in conjunction with drug treatment protects the testicular tissue against CP-induced testicular injury in mice. PMID:26955455

  6. Intracellular survival of Staphylococcus aureus due to alteration of cellular activity in arsenic and lead intoxicated mature Swiss albino mice.

    PubMed

    Bishayi, Biswadev; Sengupta, Mahuya

    2003-02-14

    The role of heavy metals like arsenic (As) and lead (Pb) as environmental toxicants is established. However, the exact mechanism of their effect on immunocompetent cell activity is not well known. Staphylococcus aureus is a virulent pathogen that has the ability to cause a variety of potentially life-threatening infections. The objective of our study was to demonstrate in an experimental mouse model of bacteremic S. aureus infection, bacterial clearance from blood and spleen in arsenic, lead treated and control group of mice. Bacterial density was measured in blood and spleen after 0, 24, 48 and 72 h post-infection. Our findings show a significant increase in bacterial load in blood (P<0.025 for arsenic and P<0.01 for lead) and delayed bacterial clearance by spleen in both arsenic (P<0.05) and lead (P<0.025) treated groups as compared to control, thus highlighting an immuno-compromised state following heavy metal exposure. To further elucidate immunomodulatory effects of both arsenic and lead, cell function studies were performed on splenic macrophages (M(phi)) isolated from lead and arsenic treated as well as control group of mice. Our findings show a decrease in cell adhesion property (P<0.005) of splenic M(phi)s from 2.9925+/-0.053 in control to 1.395+/-0.106 in arsenic and 0.8835+/-0.0106 in lead treated mice at 60 min. Morphologic alteration of the splenic M(phi)s showed an increase (As: P<0.05, Pb: P<0.0005) in both arsenic (6.876+/-0.3287%) and lead (16.55+/-1.051%) treated mice to control (2.649+/-1.238%) which may be responsible for the formers' reduced functional status. The chemotactic index, a measure of chemotactic migration of the macrophages toward immune serum, was 16.43+/-1.007 in control cell and was reduced (P<0.0005) to 4.19+/-0.393 in arsenic and 2.92+/-0.649 in lead treated mice at 60 min. These altered cell functions could probably explain the intracellular survival of S. aureus but such a causal relationship awaits further detailed

  7. Chemopreventive Effect of Cardamom (Elettaria cardamomum L.) Against Benzo(α)Pyrene-Induced Forestomach Papillomagenesis in Swiss Albino Mice.

    PubMed

    Qiblawi, Samir; Dhanarasu, Sasikumar; Faris, Mo'ez Al-Islam

    2015-01-01

    Prevention of cancer through dietary intervention has recently gained significant recognition. Cardamom (Elettaria cardamomum), a dietary phytoproduct, is a popular spice that is regularly used as a flavoring agent in various cuisines, and is much valued for its medicinal properties. In the present study, the cancer chemopreventive potential of cardamom was investigated against benzo(α)pyrene [B(α)P]-induced forestomach papillomagenesis in mice. Results showed that treatment with cardamom [(B(α)P + cardamom] reduced tumor incidence and multiplicity significantly (P<0.001) by 41.67% and 74.55%, respectively, compared to that of the B(α)P control group. Biochemical assays revealed a significant enhancement in the hepatic activities of glutathione-S-transferases (P<0.01), superoxide dismutase (P<0.01), glutathione peroxidase (P<0.001), and catalase (P<0.001) in mice treated with cardamom compared with the control. Furthermore, the nonenzymatic antioxidant glutathione was significantly (P<0.001) increased in the cardamom-treated group, whereas the lipid peroxidation level along with lactate dehydrogenase activity exhibited a significant (P<0.01) reduction with cardamom treatment compared to the control. These results suggest that cardamom has the potential to become a pivotal chemopreventive agent against forestomach cancer. PMID:26081028

  8. The preventive effect of linalool on acute and chronic UVB-mediated skin carcinogenesis in Swiss albino mice.

    PubMed

    Gunaseelan, Srithar; Balupillai, Agilan; Govindasamy, Kanimozhi; Muthusamy, Ganesan; Ramasamy, Karthikeyan; Shanmugam, Mohana; Prasad, N Rajendra

    2016-07-01

    In this study, we evaluated the role of linalool in acute ultraviolet-B (UVB; 280-320 nm) radiation-induced inflammation and chronic UVB-mediated photocarcinogenesis in mouse skin. Acute UVB-irradiation (180 mJ cm(-2)) causes hyperplasia, edema formation, lipid peroxidation, antioxidant depletion, and overexpression of cyclooxygenase-2 (COX-2) and ornithine decarboxylase (ODC) in mouse skin. Topical or intraperitoneal (i.p.) treatment of linalool prevented acute UVB-induced hyperplasia, edema formation, lipid peroxidation, and antioxidant depletion in mouse skin. Further, linalool treatment prevented UVB-induced overexpression of COX-2 and ODC in mouse skin. In the chronic study, mice were subjected to UVB-exposure thrice weekly for 30 weeks. Chronic UVB-exposure induced tumor incidence and expression of proliferative markers such as NF-κB, TNF-α, IL-6, COX-2, VEGF, TGF-β1, Bcl-2 and mutated p53 in mouse skin. Treatment with linalool before each UVB-exposure significantly prevented the expression of these proliferative markers and subsequently decreased the tumor incidence in mice skin. Histopathological studies confirmed the development of dysplasia and squamous cell carcinoma (SCC) in the chronic UVB-exposed mouse skin; and this was prevented by both topical and i.p. linalool treatment. Therefore, linalool may be considered as a photochemopreventive agent against UVB radiation induced skin carcinogenesis.

  9. Chemopreventive Effect of Cardamom (Elettaria cardamomum L.) Against Benzo(α)Pyrene-Induced Forestomach Papillomagenesis in Swiss Albino Mice.

    PubMed

    Qiblawi, Samir; Dhanarasu, Sasikumar; Faris, Mo'ez Al-Islam

    2015-01-01

    Prevention of cancer through dietary intervention has recently gained significant recognition. Cardamom (Elettaria cardamomum), a dietary phytoproduct, is a popular spice that is regularly used as a flavoring agent in various cuisines, and is much valued for its medicinal properties. In the present study, the cancer chemopreventive potential of cardamom was investigated against benzo(α)pyrene [B(α)P]-induced forestomach papillomagenesis in mice. Results showed that treatment with cardamom [(B(α)P + cardamom] reduced tumor incidence and multiplicity significantly (P<0.001) by 41.67% and 74.55%, respectively, compared to that of the B(α)P control group. Biochemical assays revealed a significant enhancement in the hepatic activities of glutathione-S-transferases (P<0.01), superoxide dismutase (P<0.01), glutathione peroxidase (P<0.001), and catalase (P<0.001) in mice treated with cardamom compared with the control. Furthermore, the nonenzymatic antioxidant glutathione was significantly (P<0.001) increased in the cardamom-treated group, whereas the lipid peroxidation level along with lactate dehydrogenase activity exhibited a significant (P<0.01) reduction with cardamom treatment compared to the control. These results suggest that cardamom has the potential to become a pivotal chemopreventive agent against forestomach cancer.

  10. Protective effect of Clerodendrum colebrookianum leaves against iron-induced oxidative stress and hepatotoxicity in Swiss albino mice.

    PubMed

    Das, Abhishek; Chaudhuri, Dipankar; Ghate, Nikhil Baban; Panja, Sourav; Chatterjee, Anupam; Mandal, Nripendranath

    2015-05-01

    Liver toxicity due to iron overload leads to oxidative damage of proteins, lipids and nucleic acids which in turn manifests several human diseases. Here, we evaluated the improving effect of Clerodendrum colebrookianum leaf on iron overload induced liver injury along with in vitro iron chelation and the protection of Fenton reaction induced DNA damage was conducted. Iron overload was induced by intraperitoneal administration of iron-dextran into mice. Post oral administration of different doses of the extract (50, 100 and 200 mg/kg body weight) showed significant decrease in different biochemical markers such as liver iron, serum ferritin and serum enzyme levels, along with decreased lipid peroxidation, protein oxidation and collagen content. In addition, the extract effectively enhanced the antioxidant enzyme levels and also exhibited the potential activity of the reductive release of ferritin iron. The protective effect of C. colebrookianum extract on injured liver was furthermore supported by the histopathological studies that showed improvement histologically. In conclusion, the present results demonstrated the hepatoprotective efficiency of C. colebrookianum leaf in iron overloaded mice, and hence, a potential iron chelating drug for iron overload diseases. PMID:26040025

  11. Oxidative stress due to (R)-styrene oxide exposure and the role of antioxidants in non-Swiss albino (NSA) mice.

    PubMed

    Meszka-Jordan, Anna; Mahlapuu, Riina; Soomets, Ursel; Carlson, Gary P

    2009-01-01

    Styrene produces lung and liver damage that may be related to oxidative stress. The purpose of this study was to investigate the toxicity of (R)-styrene oxide (R-SO), the more active enantiomeric metabolite of styrene, and the protective properties of the antioxidants glutathione (GSH), N-acetylcysteine (NAC), and 4-methoxy-L-tyrosinyl-gamma-L-glutamyl-L-cysteinyl-glycine (UPF1) against R-SO-induced toxicity in non-Swiss Albino (NSA) mice. UPF1 is a synthetic GSH analog that was shown to have 60 times the ability to scavenge reactive oxygen species (ROS) in comparison to GSH. R-SO toxicity to the lung was measured by elevations in the activity of lactate dehydrogenase (LDH), protein concentration, and number of cells in bronchoalveolar lavage fluid (BALF). Toxicity to the liver was measured by increases in serum sorbitol dehydrogenase (SDH) activity. Antioxidants were not able to decrease the adverse effects of R-SO on lung. However, NAC (200 mg/kg) ip and GSH (600 mg/kg), administered orally prior to R-SO (300 mg/kg) ip, showed significant protection against liver toxicity as measured by SDH activity. Unexpectedly, a synthetic GSH analog, UPF1 (0.8 mg/kg), administered intravenously (iv) prior to R-SO, produced a synergistic effect with regard to liver and lung toxicity. Treatment with UPF1 (0.8 mg/kg) iv every other day for 1 wk for preconditioning prior to R-SO ip did not result in any protection against liver and lung toxicity, but rather enhanced the toxicity when administered prior R-SO. The results of the present study demonstrated protection against R-SO toxicity in liver but not lung by the administration of the antioxidants NAC and GSH.

  12. Sub-chronic toxicity of gold nanoparticles in male mice

    PubMed Central

    Ajdary, Marziyeh; Ghahnavieh, Marziyeh Ziaee; Naghsh, Nooshin

    2015-01-01

    Background: Gold nanoparticles have many industrial applications; moreover, they are photothermic agents for clinical treatment of cancer. This study was provided to investigate the effects associated with different doses of applied gold nanoparticles by injection and contact procedures on the alterations of the serum levels and certain factors in male mice. Materials and Methods: 72 male mice were randomly assigned into two protocols in terms of touching and injection. The injection protocol was included of five groups: Sham, control, 25, 50, and 100 ppm. They received gold nanoparticles at 25, 50, and 100 ppm concentrations administered in form of 0.3 ml/day for the period of 14 days and that of touching protocol were received 0.2 ml/day gold nanoparticles. Blood sample of which was taken to measure the serum level of creatine kinase phosphate, fasting blood, creatinine, albumin, blood urea nitrogen and eventually, the kidney was dissected for the intent of pathological analysis. Results: The serum level of creatine kinase phosphate and fasting blood sugar at middle dose was significantly different (P ≤ 0.05) in touching protocol. In both protocols, the serum level of creatinine in high and medium doses showed a significant difference (P < 0.05) associated with the treated group. In the touching method, in high and medium doses administered to the treated group, the alteration was significant (P ≤ 0.05). In the both protocols, the serum level of albumin in high and medium doses of the treated group showed significant difference (P < 0.05). Thus, the gold nanoparticles could result in undesirable effects upon kidney tissue. Conclusion: The result of this study indicated that the administration of gold nanoparticles by touching method was more effective on the serum levels of these factors than that of injection method. PMID:25878992

  13. FOXJ2 controls meiosis during spermatogenesis in male mice.

    PubMed

    Miao, Hui; Miao, Cong-Xiu; Li, Na; Han, Jing

    2016-08-01

    Spermatogenesis is a highly complex cell differentiation process necessary for production of haploid spermatozoa. Central to this unique process is spermatocyte meiosis. FOXJ2 (Forkhead box J2), a FOX transcription factor, is specifically expressed in meiotic spermatocytes in adult mouse testes, so we used a germ cell specific conditional knockout model (Foxj2(flox/flox) , Mvh-Cre) to explore its role in spermatogenesis. Loss of FOXJ2 in the male germ line led to meiotic arrest and complete infertility. Although, DNA double-strand breaks (DSBs) were initiated, Foxj2-deficient spermatocytes failed to form chromosomal synapses and perform DSB repair. Furthermore, Foxj2-deficient spermatocytes contained significantly less mRNA encoding DSB repair-associated factors (Rad18, Rad51, Brca1, Brca2, and Tex15) and meiotic arrest-related proteins (Fzr1, Hsp70-2, Spata22, Eif4g3, and Zpac); in contrast, no change was observed in the expression of spermatogonia markers (Gfra1, Zbtb16, and c-Kit) and germ cell markers (Dazl, Mvh, and Tra98). Taken together, FOXJ2 appears to promote meiotic progression in male mice by a mechanism that needs further investigation. Mol. Reprod. Dev. 83: 684-691, 2016 © 2016 Wiley Periodicals, Inc.

  14. Vanadium as a chemoprotectant: effect of vanadium(III)-L-cysteine complex against cyclophosphamide-induced hepatotoxicity and genotoxicity in Swiss albino mice.

    PubMed

    Basu, Abhishek; Bhattacharjee, Arin; Roy, Somnath Singha; Ghosh, Prosenjit; Chakraborty, Pramita; Das, Ila; Bhattacharya, Sudin

    2014-08-01

    Vanadium is an essential micronutrient for living systems and has antioxidant and genoprotective property. In the present study, the protective role of an organovanadium compound vanadium(III)-L-cysteine (VC-III) was evaluated against hepatotoxicity and genotoxicity induced by cyclophosphamide (CP) (25 mg/kg b.w., i.p.) in Swiss albino mice. Treatment with VC-III (1 mg/kg b.w., p.o.) mitigated CP-induced hepatic injury as indicated by reduction in activities of alanine transaminase, aspartate transaminase, alkaline phosphatase by 1.57-, 1.58- and 1.32-fold in concomitant treatment schedule and by 1.83-, 1.77- and 1.45-fold in pretreatment schedule, respectively, and confirmed by histopathological evidences. Parallel to these changes, VC-III ameliorated CP-induced oxidative stress in liver by 1.46-, 1.26-, 1.32- and 1.42-fold in concomitant treatment group and by 1.95-, 1.40-, 1.46- and 1.73-fold in pretreatment group at the level of H2O2, superoxide, nitric oxide and lipid peroxidation, respectively. VC-III also enhanced activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and glutathione (reduced) level in mice liver by 1.46-, 1.37-, 1.29-, 1.44- and 1.45-fold in concomitant treatment schedule and by 1.64-, 1.65-, 1.42-, 1.49- and 1.57-fold in pretreatment schedule, respectively. In addition, the organovanadium compound could efficiently attenuate CP-induced chromosomal aberrations, DNA fragmentation and apoptosis in bone marrow cells and DNA damage in lymphocytes by 1.49-, 1.43-, 1.48- and 1.59-fold in concomitant treatment group and by 1.76-, 1.92-, 1.99- and 2.15-fold in pretreatment group, respectively. Thus, the present study showed that VC-III could exert protection against CP-induced hepatotoxicity and genotoxicity.

  15. Efficacy of a combination of metrifonate and praziquantel in the treatment of Schistosoma mansoni infection in albino mice.

    PubMed

    Ebeid, F A

    1995-04-01

    This study aimed to test the therapeutic effect of two antischistosomal drugs metrifonate (CAS 52-68-6) and praziquantel (CAS 55268-74-1), either alone or in combination, on mice infected with schistosoma mansoni. Both drugs were given in half of their therapeutic doses 8 weeks post infection. Animals were sacrificed two weeks after the last dose. The efficacy of the drugs was evaluated using the number of ova/g tissue, the distribution and the number of Schistosoma worms. Praziquantel and metrifonate alone produced about 91% and 22% reduction in total worm burden. The reduction in ova count in intestine and liver was 96% and 85%, respectively, using praziquantel alone while it was only 6 and 12%, respectively, after metrifonate treatment. After treatment with both drugs given in combination the number of ova count was not changed as compared with praziquantel alone; also there was no change in the worm load as compared with praziquantel. It is concluded that a combination of a low dose of praziquantel with metrifonate failed to produce any significantly better effect. PMID:7779154

  16. Male mice deficient in microsomal epoxide hydrolase are not susceptible to benzene-induced toxicity.

    PubMed

    Bauer, Alison K; Faiola, Brenda; Abernethy, Diane J; Marchan, Rosemarie; Pluta, Linda J; Wong, Victoria A; Gonzalez, Frank J; Butterworth, Byron E; Borghoff, Susan J; Everitt, Jeffrey I; Recio, Leslie

    2003-04-01

    Enzymes involved in benzene metabolism are likely genetic determinants of benzene-induced toxicity. Polymorphisms in human microsomal epoxide hydrolase (mEH) are associated with an increased risk of developing leukemia, specifically those associated with benzene. This study was designed to investigate the importance of mEH in benzene-induced toxicity. Male and female mEH-deficient (mEH-/-) mice and background mice (129/Sv) were exposed to inhaled benzene (0, 10, 50, or 100 ppm) 5 days/week, 6 h/day, for a two-week duration. Total white blood cell counts and bone marrow cell counts were used to assess hematotoxicity and myelotoxicity. Micronucleated peripheral blood cells were counted to assess genotoxicity, and the p21 mRNA level in bone marrow cells was used as a determinant of the p53-regulated DNA damage response. Male mEH-/- mice did not have any significant hematotoxicity or myelotoxicity at the highest benzene exposure compared to the male 129/Sv mice. Significant hematotoxicity or myelotoxicity did not occur in the female mEH-/- or 129/Sv mice. Male mEH-/- mice were also unresponsive to benzene-induced genotoxicity compared to a significant induction in the male 129/Sv mice. The female mEH-/- and 129/Sv mice were virtually unresponsive to benzene-induced genotoxicity. While p21 mRNA expression was highly induced in male 129/Sv mice after exposure to 100-ppm benzene, no significant alteration was observed in male mEH-/- mice. Likewise, p21 mRNA expression in female mEH-/- mice was not significantly induced upon benzene exposure whereas a significant induction was observed in female 129/Sv mice. Thus mEH appears to be critical in benzene-induced toxicity in male, but not female, mice.

  17. Neuropharmacological effects of oleamide in male and female mice.

    PubMed

    Akanmu, Moses A; Adeosun, Samuel O; Ilesanmi, Olapade R

    2007-08-22

    Oleamide, a fatty acid amide accumulates selectively in the cerebrospinal fluid of sleep deprived cats and rats. Oleamide has been reported to have effects on a wide range of receptors and neurotransmitter systems especially the centrally acting ones for example, dopamine acetylcholine, serotonin, gamma aminobutyric acid (GABA), cannabinoid and vanilloid among others. This suggests a wide range of central nervous system effects of the compound. The effects of intraperitoneal administered oleamide on Novelty-induced behaviours, learning and memory and forced swimming-induced depression were studied. The relative effects of the compound on the male and female mice were also noted. Oleamide dose-dependently reduced (p<0.05) novelty induced rearing, grooming and locomotion. The effects on the all NIBs started within the first 10 min of the test and the peak of the effects was observed during the third 10 min period of the test. Effect of oleamide on short-term working memory was significantly (p<0.05) affected only with the dose of 5mg/kg while the other dose of 10mg/kg had no effect. In the forced swimming test, acute triple intraperitoneal administration of oleamide at 10mg/kg induced a significant reduction in the immobility duration in mice signifying an antidepressant effect. Sex differences in the effects of oleamide (10mg/kg, i.p.) were clearly evident in active behaviours in FST. These results confirm the multiplicity of central nervous system receptors and neurotransmitters that oleamide interacts with hence its numerous and diverse neuropharmacological effects. Most importantly, the present study suggests that oleamide has antidepressant-like property.

  18. Repeated administrations of carbon nanotubes in male mice cause reversible testis damage without affecting fertility

    NASA Astrophysics Data System (ADS)

    Bai, Yuhong; Zhang, Yi; Zhang, Jingping; Mu, Qingxin; Zhang, Weidong; Butch, Elizabeth R.; Snyder, Scott E.; Yan, Bing

    2010-09-01

    Soluble carbon nanotubes show promise as materials for in vivo delivery and imaging applications. Several reports have described the in vivo toxicity of carbon nanotubes, but their effects on male reproduction have not been examined. Here, we show that repeated intravenous injections of water-soluble multiwalled carbon nanotubes into male mice can cause reversible testis damage without affecting fertility. Nanotubes accumulated in the testes, generated oxidative stress and decreased the thickness of the seminiferous epithelium in the testis at day 15, but the damage was repaired at 60 and 90 days. The quantity, quality and integrity of the sperm and the levels of three major sex hormones were not significantly affected throughout the 90-day period. The fertility of treated male mice was unaffected; the pregnancy rate and delivery success of female mice that mated with the treated male mice did not differ from those that mated with untreated male mice.

  19. Inheritance of steroid-independent male sexual behavior in male offspring of B6D2F1 mice.

    PubMed

    McInnis, Christine M; Bonthuis, Paul J; Rissman, Emilie F; Park, Jin Ho

    2016-04-01

    The importance of gonadal steroids in modulating male sexual behavior is well established. Individual differences in male sexual behavior, independent of gonadal steroids, are prevalent across a wide range of species, including man. However, the genetic mechanisms underlying steroid-independent male sexual behavior are poorly understood. A high proportion of B6D2F1 hybrid male mice demonstrates steroid-independent male sexual behavior (identified as "maters"), providing a mouse model that opens up avenues of investigation into the mechanisms regulating male sexual behavior in the absence of gonadal hormones. Recent studies have revealed several proteins that play a significant factor in regulating steroid-independent male sexual behavior in B6D2F1 male mice, including amyloid precursor protein (APP), tau, and synaptophysin. The specific goals of our study were to determine whether steroid-independent male sexual behavior was a heritable trait by determining if it was dependent upon the behavioral phenotype of the B6D2F1 sire, and whether the differential expression of APP, tau, and synaptophysin in the medial preoptic area found in the B6D2F1 sires that did and did not mate after gonadectomy was similar to those found in their male offspring. After adult B6D2F1 male mice were bred with C57BL/6J female mice, they and their male offspring (BXB1) were orchidectomized and identified as either maters or "non-maters". A significant proportion of the BXB1 maters was sired only from B6D2F1 maters, indicating that the steroid-independent male sexual behavior behavioral phenotype of the B6D2F1 hybrid males, when crossed with C57BL/6J female mice, is inherited by their male offspring. Additionally, APP, tau, and synaptophysin were elevated in in the medial preoptic area in both the B6D2F1 and BXB1 maters relative to the B6D2F1 and BXB1 non-maters, respectively, suggesting a potential genetic mechanism for the inheritance of steroid-independent male sexual behavior.

  20. Mineral uptake by the femora of older female X-linked hypophosphatemic (HYP) mice but not older male HYP mice.

    PubMed

    Brault, B A; Meyer, M H; Meyer, R A; Iorio, R J

    1987-09-01

    X-linked hypophosphatemic (Hyp) mice are a model of human sex-linked vitamin D-resistant rickets. Young adult Hyp mice are characterized by osteomalacia and decreased bone mineral content. However, older heterozygous Hyp female mice increase in bone mineral content with age so that by one year of age the bone mass/mm femoral length equals or exceeds normal females. To test for the occurrence of this mineral accretion in Hyp male mice and in homozygous Hyp female mice, femora from all 3 Hyp genotypes as well as normal male and female mice were analyzed at various ages from one to 52 weeks of age. Compared to normal mice, all three Hyp genotypes were depressed in bone ash, femoral length, and ash/length ratio at 13 weeks of age. After that age the femora of both heterozygous and homozygous Hyp females showed a slow mineral accretion and, by 52 weeks of age, a normal ash/length ratio. However, the femora of Hyp males, as well as those of normal males, failed to increase in bone mineral content or ash/length ratio after 13 weeks of age. The differences between male and female Hyp mice could not be explained by differences in the plasma levels of calcium, phosphate, or alkaline phosphatase. Increased bone mineral content in older Hyp mice was seen in both heterozygous and homozygous females but not in hemizygous males. Thus, the basis for this increase is not incomplete dominance of the Hyp gene in females nor the Lyon hypothesis. The accretion of mineral in older female Hyp mice despite lifelong reduced plasma phosphate levels suggests that there are factors other than phosphate that also regulate mineral accretion in this bone disease.

  1. Of Mice and Men-Warning: Intact Versus Castrated Adult Male Mice as Xenograft Hosts Are Equivalent to Hypogonadal Versus Abiraterone Treated Aging Human Males, Respectively

    PubMed Central

    Sedelaar, J.P. Michiel; Dalrymple, Susan S.; Isaacs, John T.

    2014-01-01

    BACKGROUND Immune deficient male mice bearing human prostate cancer xenografts are used to evaluate therapeutic response to novel androgen ablation approaches and the results compared to surgical castration based upon assumption that testosterone microenvironment in intact and castrated adult male mice mimics eugonadal and castrated aging adult human males. METHODS To test these assumptions, serum total testosterone (TT) and free testosterone (FT) were determined longitudinally in groups (n > 20) of intact versus castrated adult male nude, NOG, and immune competent C57BL/6 mice. RESULTS In adult male mice, TT and FT varies by 30- to 100-fold within the same animal providing a microenvironment that is only equivalent to hypogonadal, not eugonadal, adult human males (TT is 1.7 ± 1.2 ng/ml [5.8 ± 4.1 nM] in nude and 2.5 ± 1.3 ng/ml [8.7 ± 4.4 nM] in NOG mice versus >4.2 ng/ml [14.7 nM] in eugonadal humans). This was confirmed based upon enhanced growth of androgen dependent human prostate cancer xenografts inoculated into mice supplemented with exogenous testosterone to elevate and chronically maintain serum TT at a level (5 ng/ml [18 nM]) equivalent to a 50-year-old eugonadal human male. In castrated mice, TT and FT range from 2 to 20 pg/ml (7–70 pM) and <0.8 pg/ml (<2.6 pM), respectively, which is equivalent to castrate resistant prostate cancer (CRPC) patients treated with abiraterone. This was confirmed based upon the inability of another CYP17A1 inhibitor, ketoconazole, to inhibit the growth of CRPC xenografts in castrated mice. CONCLUSIONS Adult male mice supplemented with testosterone mimic eugonadal human males, while unsupplemented animals mimic standard androgen ablation and castrated animals mimic abiraterone treated patients. These studies confirm what is claimed in Robert Burns’ poem “To a Mouse” that “The best laid schemes of mice and men/often go awry. PMID:23775398

  2. Immune responses in male mice with aggressive and submissive behavior patterns: strain differences.

    PubMed

    Devoino, L; Alperina, E; Kudryavtseva, N; Popova, N

    1993-03-01

    Immune responses in two strains of male mice with aggressive and submissive behavior patterns was studied. In aggressive CBA males immunized on the 10th day of agonistic confrontations with submissive partners, greater numbers of plaque-forming cells (PFC) and rosette-forming cells (RFC) were noted compared to control mice. Unlike the CBA strain, both PFC and RFC levels in aggressive C57BL males did not increase, but both PFC and RFC numbers decreased in submissive animals. PMID:8471801

  3. Gender-specific effects of CGP 55845, GABAB receptor antagonist, on neuromuscular coordination, learning and memory formation in albino mouse following neonatal hypoxia-ischemia insult.

    PubMed

    Gillani, Quratul Ane; Akbar, Atif; Ali, Muhammad; Iqbal, Furhan

    2015-06-01

    GABAB receptor antagonists are experimentally proved as spatial memory enhancers in mouse models but their role has not been described following hypoxic-ischemic insult. 10-day-old albino mice were subjected to Murine model of hypoxia and ischemia. Following brain damage, mice were fed on normal rodent diet till they were 13 weeks old. At this time point, mice were divided into two groups. Group 1 received saline and group 2 received intraperitoneally CGP 55845 (1 mg/ml solvent/Kg body weight) for 12 days. Behavioural observations were made during rota rod, open field and Morris water maze test along with brain infarct measurement in both CGP 55845 treated and untreated groups. It was observed that application of GABAB receptor antagonist improved the over all motor function in male and female albino mice but effects were more pronounced in males. In open field, CGP 55845-treated female mice showed poor performance. CGP 55845 had no significant effect on learning and memory formation during Morris water maze test and also on brain infract size in both genders following hypoxia ischemia encephalopathy. Effects of CGP 55845 can be further explored in a dose and duration dependent manner to improve the learning and memory in albino mice following neonatal brain damage.

  4. Differences in Susceptibility to Okadaic Acid, a Diarrhetic Shellfish Poisoning Toxin, between Male and Female Mice

    PubMed Central

    Suzuki, Hodaka

    2012-01-01

    The mouse bioassay (MBA) for diarrhetic shellfish poisoning (DSP) toxins has been widely used in many countries of the world. In the Japanese and EU methods, male mice are designated to be used for MBA. Female mice were described to be less susceptible than male mice. To the best of our knowledge, however, there have been no reports on the details of sex differences in susceptibility to DSP toxins. In this study, we investigated whether, and to what extent, female mice are less sensitive to DSP toxins. A lethal dose of okadaic acid (OA), one of the representative DSP toxins, was injected intraperitoneally into mice. The mice were observed until 24 hours after injection. Both male and female mice of ICR and ddY strains, which are designated in the Japanese official method, were compared. All the mice were four weeks old and weighed 18–20 g. The experiments were repeated twice. The lethality was 70%–100%. Survival analysis showed no sex differences in susceptibility to OA, but ICR female mice showed significant resistance compared with other groups in one out of two trials. These results indicate that sex differences were not clear but, nonetheless, male mice showed more stable results. PMID:23271638

  5. Differences in susceptibility to okadaic acid, a diarrhetic shellfish poisoning toxin, between male and female mice.

    PubMed

    Suzuki, Hodaka

    2012-12-27

    The mouse bioassay (MBA) for diarrhetic shellfish poisoning (DSP) toxins has been widely used in many countries of the world. In the Japanese and EU methods, male mice are designated to be used for MBA. Female mice were described to be less susceptible than male mice. To the best of our knowledge, however, there have been no reports on the details of sex differences in susceptibility to DSP toxins. In this study, we investigated whether, and to what extent, female mice are less sensitive to DSP toxins. A lethal dose of okadaic acid (OA), one of the representative DSP toxins, was injected intraperitoneally into mice. The mice were observed until 24 hours after injection. Both male and female mice of ICR and ddY strains, which are designated in the Japanese official method, were compared. All the mice were four weeks old and weighed 18-20 g. The experiments were repeated twice. The lethality was 70%-100%. Survival analysis showed no sex differences in susceptibility to OA, but ICR female mice showed significant resistance compared with other groups in one out of two trials. These results indicate that sex differences were not clear but, nonetheless, male mice showed more stable results.

  6. Aggression as Positive Reinforcement in Mice under Various Ratio- and Time-Based Reinforcement Schedules

    ERIC Educational Resources Information Center

    May, Michael E.; Kennedy, Craig H.

    2009-01-01

    There is evidence suggesting aggression may be a positive reinforcer in many species. However, only a few studies have examined the characteristics of aggression as a positive reinforcer in mice. Four types of reinforcement schedules were examined in the current experiment using male Swiss CFW albino mice in a resident-intruder model of aggression…

  7. Brain serotonin signaling does not determine sexual preference in male mice.

    PubMed

    Angoa-Pérez, Mariana; Herrera-Mundo, Nieves; Kane, Michael J; Sykes, Catherine E; Anneken, John H; Francescutti, Dina M; Kuhn, Donald M

    2015-01-01

    It was reported recently that male mice lacking brain serotonin (5-HT) lose their preference for females (Liu et al., 2011, Nature, 472, 95-100), suggesting a role for 5-HT signaling in sexual preference. Regulation of sex preference by 5-HT lies outside of the well established roles in this behavior established for the vomeronasal organ (VNO) and the main olfactory epithelium (MOE). Presently, mice with a null mutation in the gene for tryptophan hydroxylase 2 (TPH2), which are depleted of brain 5-HT, were tested for sexual preference. When presented with inanimate (urine scents from male or estrous female) or animate (male or female mouse in estrus) sexual stimuli, TPH2-/- males show a clear preference for female over male stimuli. When a TPH2-/- male is offered the simultaneous choice between an estrous female and a male mouse, no sexual preference is expressed. However, when confounding behaviors that are seen among 3 mice in the same cage are controlled, TPH2-/- mice, like their TPH2+/+ counterparts, express a clear preference for female mice. Female TPH2-/- mice are preferred by males over TPH2+/+ females but this does not lead to increased pregnancy success. In fact, if one or both partners in a mating pair are TPH2-/- in genotype, pregnancy success rates are significantly decreased. Finally, expression of the VNO-specific cation channel TRPC2 and of CNGA2 in the MOE of TPH2-/- mice is normal, consistent with behavioral findings that sexual preference of TPH2-/- males for females is intact. In conclusion, 5-HT signaling in brain does not determine sexual preference in male mice. The use of pharmacological agents that are non-selective for the 5-HT neuronal system and that have serious adverse effects may have contributed historically to the stance that 5-HT regulates sexual behavior, including sex partner preference.

  8. Topical application of Gallic acid suppresses the 7,12-DMBA/Croton oil induced two-step skin carcinogenesis by modulating anti-oxidants and MMP-2/MMP-9 in Swiss albino mice.

    PubMed

    Subramanian, Vimala; Venkatesan, Balaji; Tumala, Anusha; Vellaichamy, Elangovan

    2014-04-01

    Gallic acid (GA - 3,4,5-trihydroxybenzoic acid), a dietary anti-oxidant has been shown to inhibit cancer cell growth in in vitro. Herein, we investigated the in vivo chemo preventive activity of GA on 7,12-Dimethylbenz[a]anthracene (DMBA)/Croton oil induced two-step skin carcinogenesis in Swiss albino mice. Skin tumor incidence and tumor volume were recorded during the 16 weeks of experimental period. In addition, LDH-isozyme shift, skin collagen content, activities of matrix metalloproteinases (MMP-2/MMP-9) enzymes and enzymatic and non-enzymatic antioxidant were studied in the skin and serum of experimental mice. Tumor incidence was significantly increased in the DMBA/Croton oil induced mice (100%; p<0.001) when compared to GA co-treated mice (60%; p<0.01) and 5-FU treated mice (50%; p<0.01). Skin collagen content, MMPs activities, LDH-isoenzymes and MMP-2/-9 expressions were increased in DMBA/Croton oil induced skin while decreased levels of enzymatic (GST, SOD, CAT & GPx) and non-enzymatic anti-oxidant (GSH) were noticed. On the other hand, GA co-treatment exhibited a significant protection by reverting back the altered levels of LDH-isoenzymes, antioxidants, collagen and MMP-2/MMP-9 activities. The results of this study indicate that topical application of GA inhibits DMBA/Croton oil induced two-stage skin carcinogenic process by modulating the antioxidants and MMPs (-2 & -9) in the mouse skin.

  9. Contrasting effects of a dietary copper deficiency in male and female mice.

    PubMed

    Lynch, S M; Klevay, L M

    1994-02-01

    Female rats are protected from the lethal effects of a dietary copper (Cu) deficiency, but female mice fed a Cu-deficient diet develop atrial thromboses and die. To further investigate the effect of sex on Cu status in mice (n = 16), male and female adult Swiss-Webster mice were fed Cu-supplemented (8.4 mg Cu/kg) or Cu-deficient (0.3 mg Cu/kg) diets with deionized water for 43-49 days. Six female mice, but only one male mouse, fed the Cu-deficient diet died during the experiment. Both male and female mice fed the Cu-deficient diet exhibited typical features of deficiency. The severity of anemia and the values observed for several indicators of Cu status (plasma ceruloplasmin [EC 1.16.3.1.] and erythrocyte copper-zinc superoxide dismutase [EC 1.15.1.1.] activities, cardiac Cu) were similar in both male and female Cu-deficient mice. However, cardiac enlargement (0.97 vs 0.73 g/100 g body wt, P < 0.05), cardiac edema (79.9% vs 78.2% cardiac water, P < 0.05) and depletion of renal Cu (10.4 vs 12.5 micrograms/g dry weight, P < 0.05) were more severe in female compared with male, Cu-deficient mice. Furthermore, although hepatic Cu was significantly (P < 0.05) lower in female Cu-deficient compared with Cu-supplemented mice, it was not significantly decreased by deficiency in male mice. These data indicate that the female mice experienced a more extreme form of Cu deficiency than the males.

  10. Blood coagulation and metabolic profiles in middle-aged male and female ob/ob mice.

    PubMed

    Ohkura, Naoki; Oishi, Katsutaka; Atsumi, Gen-ichi

    2015-07-01

    Obese and diabetic states in humans are associated with an increased incidence of thrombotic diseases caused by various coagulation abnormalities. Genetically obese ob/ob mice produce metabolic abnormalities similar to those associated with type 2 diabetes. However, little is known about their coagulation features or sex differences. The present study aimed to determine the effects of obese and diabetic complications on blood coagulation and vascular diseases by exploring correlations between blood coagulation and metabolic profiles in middle-aged male and female ob/ob mice. Plasma levels of plasminogen activator inhibitor 1 (PAI-1) were significantly increased, whereas those that of platelet factor-4 (PF-4) was slightly, but significantly increased in male and female ob/ob mice compared with lean counterparts. Prothrombin time (PT) was significantly shortened in female ob/ob mice and activated partial thrombin time (APTT) significantly differed between male and female ob/ob mice. Plasma levels of antithrombin (AT) were significantly increased in male and female ob/ob mice. None of the other coagulation and fibrinolytic factors examined significantly differed between ob/ob mice and lean counterparts. On the contrary, factors such as body weight and cholesterol levels significantly differed between ob/ob and lean mice, whereas glucose, fructosamine and insulin levels significantly differed only in one sex of each strain. These results provided fundamental information about blood coagulation and metabolic features for exploring the function of altered blood coagulation states in ob/ob mice.

  11. The effect of mahogunin gene mutant on reproduction in male mice: a new sight for infertility?

    PubMed

    Cheng, D; Xiong, C; Li, J; Sui, C; Wang, S; Li, H; Jiang, X

    2014-03-01

    Mahogunin is an important mediator of chromogenesis and neurodegeneration. Mahoganoid is a mutation of the mahogunin gene, which causes a pleiotropic phenotype that includes suppression of obesity, spongiform neurodegeneration and improvement of insulin sensitivity. Our previous research found that mahoganoid widely expressed in the male rat reproductive system, and mahoganoid-deficient mice have reduced embryonic viability. But the reproductive change in mahogunin knockout (md(nc) ) male mice has not been reported previously. Here, we report that the mahogunin mRNA also widely exists in reproductive system of male mice, and its mRNA expression in the testis was in accordance with the first spermatogenesis wave cycle. Moreover, we find that md(nc) male mice were able to mate with females but no pups are delivered. Besides, the sperms' active progressive motility and hormone secretion (E2, FSH, LH, PRL) were obviously decreased while abnormal sperm rate showed no significant difference in md(nc) compared to wild-type (WT) male mice. This study indicates the mahogunin deficiency results in the infertility of male mice, disruption of hormones secretion and impaired active progressive motility, which may additionally illuminate the aetiology of male infertility in human.

  12. Social isolation prompts maternal behavior in sexually naïve male ddN mice.

    PubMed

    Orikasa, Chitose; Nagaoka, Kentaro; Katsumata, Harumi; Sato, Manami; Kondo, Yasuhiko; Minami, Shiro; Sakuma, Yasuo

    2015-11-01

    Maternal behavior in mice is considered to be sexually dimorphic; that is, females show maternal care for their offspring, whereas this behavior is rarely shown in males. Here, we examined how social isolation affects the interaction of adult male mice with pups. Three weeks of isolation during puberty (5-8 weeks old) induced retrieving and crouching when exposed to pups, while males with 1 week isolation (7-8 weeks old) also showed such maternal care, but were less responsive to pups. We also examined the effect of isolation during young adulthood (8-11 weeks old), and found an induction of maternal behavior comparable to that in younger male mice. This effect was blocked by exposure to chemosensory and auditory social signals derived from males in an attached compartment separated by doubled opaque barriers. These results demonstrate that social isolation in both puberty and postpuberty facilitates male maternal behavior in sexually naïve mice. The results also indicate that air-borne chemicals and/or sounds of male conspecifics, including ultrasonic vocalization and noise by their movement may be sufficient to interfere with the isolation effect on induction of maternal behavior in male mice.

  13. Postnatal Development of the Craniofacial Skeleton in Male C57BL/6J Mice

    PubMed Central

    2016-01-01

    C57BL/6J is one of the most commonly used inbred mouse strains in biomedical research, including studies of craniofacial development and teratogenic studies of craniofacial malformation. The current study quantitatively assessed the development of the skull in male C57BL/6J mice by using high-resolution 3D imaging of 55 landmarks from 48 male mice over 10 developmental time points from postnatal day 0 to 90. The growth of the skull plateaued at approximately postnatal day 60, and the shape of the skull did not change markedly thereafter. The amount of asymmetry in the craniofacial skeleton seemed to peak at birth, but considerable variation persisted in all age groups. For C57BL/6J male mice, postnatal day 60 is the earliest time point at which the skull achieves its adult shape and proportions. In addition, C57BL/6J male mice appear to have an inherent susceptibility to craniofacial malformation. PMID:27025802

  14. Differences in prolactin levels between three alternative male reproductive tactics in striped mice (Rhabdomys pumilio)

    PubMed Central

    Schradin, Carsten

    2008-01-01

    In male fishes, birds and mammals, increased prolactin secretion is thought to play a role in species showing paternal behaviours. This hypothesis was investigated in the striped mouse (Rhabdomys pumilio). This paper compares serum prolactin levels in 71 free-living male striped mice following three different reproductive tactics: (i) paternal group-living breeders, (ii) alloparental philopatric group-living males, and (iii) roaming non-paternal solitary males. Prolactin levels of breeding males were significantly higher than that of roamers. Alloparental philopatric males had low prolactin levels, which concur with studies of cooperatively breeding mammals, but contrasts with studies of cooperatively breeding birds. Both breeding males and females showed a decrease in prolactin levels after the breeding season, but not alloparental philopatric males. Prolactin levels were correlated with neither corticosterone levels nor age. These results are in agreement with the hypothesis that prolactin is one proximate mechanism of male reproductive tactics, possibly regulating differences in male parental care. PMID:18230588

  15. Effect of alpha lipoic acid co-administration on structural and immunohistochemical changes in subcutaneous tissue of anterior abdominal wall of adult male albino rat in response to polypropylene mesh implantation

    PubMed Central

    Mazroa, Shireen A; Asker, Samar A; Asker, Waleed; Abd Ellatif, Mohamed

    2015-01-01

    Polypropylene mesh is commonly used in the treatment of abdominal hernia. Different approaches were addressed to improve their tissue integration and consequently reduce long-term complications. This study aimed to investigate the effect of alpha-lipoic acid (ALA) co-administration on structural and immunohistochemical (IHC) changes in the subcutaneous tissues of the anterior abdominal wall of the adult rat in response to polypropylene mesh implantation. Forty adult male albino rats were divided into: group I (control), group II (receiving ALA), group III (polypropylene mesh implantation) and group IV (mesh implantation + ALA co-administration). After 4 weeks, subcutaneous tissue samples were prepared for light microscopy and IHC study of CD34 as a marker for angiogenesis. In groups I and II rats, positive CD34 expression was demonstrated by IHC reaction, localized to endothelial cells lining small blood vessels. Group III showed an excess inflammatory reaction, deposition of both regular and irregularly arranged collagen fibres around mesh pores and few elastic fibres. CD34-positive was detected not only in cells lining small blood vessels but also in other cells scattered in the connective tissue indicating angiogenesis. In group IV, ALA co-administration resulted in less inflammatory reaction, regular collagen deposition, enhanced elastic fibres synthesis and a significant increase in CD34-positive cells and small blood vessels reflecting improved angiogenesis. ALA co-administration with polypropylene mesh implantation controlled the inflammatory reaction, helped regular collagen deposition, enhanced elastic fibres synthesis and improved angiogenesis in the subcutaneous tissue of anterior abdominal wall of adult albino rats, suggesting a possible role of ALA in optimizing mesh integration in subcutaneous tissue. PMID:25891652

  16. Effect of alpha lipoic acid co-administration on structural and immunohistochemical changes in subcutaneous tissue of anterior abdominal wall of adult male albino rat in response to polypropylene mesh implantation.

    PubMed

    Mazroa, Shireen A; Asker, Samar A; Asker, Waleed; Abd Ellatif, Mohamed

    2015-06-01

    Polypropylene mesh is commonly used in the treatment of abdominal hernia. Different approaches were addressed to improve their tissue integration and consequently reduce long-term complications. This study aimed to investigate the effect of alpha-lipoic acid (ALA) co-administration on structural and immunohistochemical (IHC) changes in the subcutaneous tissues of the anterior abdominal wall of the adult rat in response to polypropylene mesh implantation. Forty adult male albino rats were divided into: group I (control), group II (receiving ALA), group III (polypropylene mesh implantation) and group IV (mesh implantation + ALA co-administration). After 4 weeks, subcutaneous tissue samples were prepared for light microscopy and IHC study of CD34 as a marker for angiogenesis. In groups I and II rats, positive CD34 expression was demonstrated by IHC reaction, localized to endothelial cells lining small blood vessels. Group III showed an excess inflammatory reaction, deposition of both regular and irregularly arranged collagen fibres around mesh pores and few elastic fibres. CD34-positive was detected not only in cells lining small blood vessels but also in other cells scattered in the connective tissue indicating angiogenesis. In group IV, ALA co-administration resulted in less inflammatory reaction, regular collagen deposition, enhanced elastic fibres synthesis and a significant increase in CD34-positive cells and small blood vessels reflecting improved angiogenesis. ALA co-administration with polypropylene mesh implantation controlled the inflammatory reaction, helped regular collagen deposition, enhanced elastic fibres synthesis and improved angiogenesis in the subcutaneous tissue of anterior abdominal wall of adult albino rats, suggesting a possible role of ALA in optimizing mesh integration in subcutaneous tissue.

  17. Sexual partner preference requires a functional aromatase (cyp19) gene in male mice.

    PubMed

    Bakker, J; Honda, S; Harada, N; Balthazart, J

    2002-09-01

    Sexual motivation, sexual partner preference, and sexual performance represent three different aspects of sexual behavior that are critical in determining the reproductive success of a species. Although the display of sexual behavior is under strict hormonal control in both sexes, the relative roles of androgen and estrogen receptors in activating the various components of male sexual behavior are still largely unknown. A recently developed mouse model that is deficient in estradiol due to targeted disruption of exons 1 and 2 of the Cyp19 gene (aromatase knockout (ArKO) mice) was used here to analyze the role of estradiol in the control of all three aspects of male sexual behavior. When tested in a Y-maze providing volatile olfactory cues, male ArKO mice did not show a preference for the odors from an estrous female over those from an intact male, whereas wild-type (WT) and heterozygous (HET) males clearly preferred to sniff estrous odors. When provided with visual and olfactory cues, male ArKO mice also failed to show a preference for an estrous female when given a choice between an estrous female and an empty arm. However, sexual partner preferences of male ArKO mice were not sex-reversed: they did not prefer to investigate an intact male over an estrous female or empty arm. Thus, male ArKO mice seemed to have general deficits in discriminating between conspecifics by using olfactory and visual cues. Male coital behavior was also severely impaired in male ArKO mice: they displayed significantly fewer mounts, intromissions, and ejaculations than WT and HET males. Latencies to first mount or intromission were also significantly longer in ArKO males compared to WT and HET males, in addition to them showing less interest in investigating olfactory and visual cues in a Y-maze, suggesting that they were sexually less motivated. However, three out of seven male ArKO mice were capable of siring litters provided they were housed with a female for a prolonged period of

  18. Morphological Alterations in Gastrocnemius and Soleus Muscles in Male and Female Mice in a Fibromyalgia Model

    PubMed Central

    Oezel, Lisa; Schwarzbach, Hans; Ocker, Matthias; Thieme, Kati; Di Fazio, Pietro; Kinscherf, Ralf

    2016-01-01

    Background Fibromyalgia (FM) is a chronic musculoskeletal pain disorder, characterized by chronic widespread pain and bodily tenderness and is often accompanied by affective disturbances, however often with unknown etiology. According to recent reports, physical and psychological stress trigger FM. To develop new treatments for FM, experimental animal models for FM are needed to be development and characterized. Using a mouse model for FM including intermittent cold stress (ICS), we hypothesized that ICS leads to morphological alterations in skeletal muscles in mice. Methods Male and female ICS mice were kept under alternating temperature (4°C/room temperature [22°C]); mice constantly kept at room temperature served as control. After scarification, gastrocnemius and soleus muscles were removed and snap-frozen in liquid nitrogen–cooled isopentane or fixed for electron microscopy. Results In gastrocnemius/soleus muscles of male ICS mice, we found a 21.6% and 33.2% decrease of fiber cross sectional area (FCSA), which in soleus muscle concerns the loss of type IIa and IIx FCSA. This phenomenon was not seen in muscles of female ICS mice. However, this loss in male ICS mice was associated with an increase in gastrocnemius of the density of MIF+ (8.6%)-, MuRF+ (14.7%)-, Fbxo32+ (17.8%)-cells, a 12.1% loss of capillary contacts/muscle fiber as well as a 30.7% increase of damaged mitochondria in comparison with male control mice. Moreover, significant positive correlations exist among densities (n/mm2) of MIF+, MuRF+, Fbxo32+-cells in gastrocnemius/ soleus muscles of male ICS mice; these cell densities inversely correlate with FCSA especially in gastrocnemius muscle of male ICS mice. Conclusion The ICS-induced decrease of FCSA mainly concerns gastrocnemius muscle of male mice due to an increase of inflammatory and atrogenic cells. In soleus muscle of male ICS and soleus/gastrocnemius muscles of female ICS mice morphological alterations seem to occur not at all or

  19. Generation of viable male and female mice from two fathers.

    PubMed

    Deng, Jian Min; Satoh, Kei; Wang, Hongran; Chang, Hao; Zhang, Zhaoping; Stewart, M David; Cooney, Austin J; Behringer, Richard R

    2011-03-01

    In sexual species, fertilization of oocytes produces individuals with alleles derived from both parents. Here we use pluripotent stem cells derived from somatic cells to combine the haploid genomes from two males to produce viable sons and daughters. Male (XY) mouse induced pluripotent stem cells (Father #1) were used to isolate subclones that had spontaneously lost the Y chromosome to become genetically female (XO). These male-derived XO stem cells were used to generate female chimeras that were bred with genetically distinct males (Father #2), yielding progeny possessing genetic information that was equally derived from both fathers. Thus, functional oocytes can be generated from male somatic cells after reprogramming and spontaneous sex reversal. These findings have novel implications for mammalian reproduction and assisted reproductive technology.

  20. Castration Induces Parkinson Disease Pathologies in Young Male Mice via Inducible Nitric-oxide Synthase*

    PubMed Central

    Khasnavis, Saurabh; Ghosh, Anamitra; Roy, Avik; Pahan, Kalipada

    2013-01-01

    Although Parkinson disease (PD) is a progressive neurodegenerative disorder, available animal models do not exhibit irreversible neurodegeneration, and this is a major obstacle in finding out an effective drug against this disease. Here we delineate a new irreversible model to study PD pathogenesis. The model is based on simple castration of young male mice. Levels of inducible nitric-oxide synthase (iNOS), glial markers (glial fibrillary acidic protein and CD11b), and α-synuclein were higher in nigra of castrated male mice than normal male mice. On the other hand, after castration, the level of glial-derived neurotrophic factor (GDNF) markedly decreased in the nigra of male mice. Accordingly, castration also induced the loss of tyrosine hydroxylase-positive neurons in the nigra and decrease in tyrosine hydroxylase-positive fibers and neurotransmitters in the striatum. Reversal of nigrostriatal pathologies in castrated male mice by subcutaneous implantation of 5α-dihydrotestosterone pellets validates an important role of male sex hormone in castration-induced nigrostriatal pathology. Interestingly, castration was unable to cause glial activation, decrease nigral GDNF, augment the death of nigral dopaminergic neurons, induce the loss of striatal fibers, and impair neurotransmitters in iNOS−/− male mice. Furthermore, we demonstrate that iNOS-derived NO is responsible for decreased expression of GDNF in activated astrocytes. Together, our results suggest that castration induces nigrostriatal pathologies via iNOS-mediated decrease in GDNF. These results are important because castrated young male mice may be used as a simple, toxin-free, and nontransgenic animal model to study PD-related nigrostriatal pathologies, paving the way for easy drug screening against PD. PMID:23744073

  1. Castration induces Parkinson disease pathologies in young male mice via inducible nitric-oxide synthase.

    PubMed

    Khasnavis, Saurabh; Ghosh, Anamitra; Roy, Avik; Pahan, Kalipada

    2013-07-19

    Although Parkinson disease (PD) is a progressive neurodegenerative disorder, available animal models do not exhibit irreversible neurodegeneration, and this is a major obstacle in finding out an effective drug against this disease. Here we delineate a new irreversible model to study PD pathogenesis. The model is based on simple castration of young male mice. Levels of inducible nitric-oxide synthase (iNOS), glial markers (glial fibrillary acidic protein and CD11b), and α-synuclein were higher in nigra of castrated male mice than normal male mice. On the other hand, after castration, the level of glial-derived neurotrophic factor (GDNF) markedly decreased in the nigra of male mice. Accordingly, castration also induced the loss of tyrosine hydroxylase-positive neurons in the nigra and decrease in tyrosine hydroxylase-positive fibers and neurotransmitters in the striatum. Reversal of nigrostriatal pathologies in castrated male mice by subcutaneous implantation of 5α-dihydrotestosterone pellets validates an important role of male sex hormone in castration-induced nigrostriatal pathology. Interestingly, castration was unable to cause glial activation, decrease nigral GDNF, augment the death of nigral dopaminergic neurons, induce the loss of striatal fibers, and impair neurotransmitters in iNOS(-/-) male mice. Furthermore, we demonstrate that iNOS-derived NO is responsible for decreased expression of GDNF in activated astrocytes. Together, our results suggest that castration induces nigrostriatal pathologies via iNOS-mediated decrease in GDNF. These results are important because castrated young male mice may be used as a simple, toxin-free, and nontransgenic animal model to study PD-related nigrostriatal pathologies, paving the way for easy drug screening against PD.

  2. Sexual experience affects reproductive behavior and preoptic androgen receptors in male mice

    PubMed Central

    Swaney, William T.; Dubose, Brittany N.; Curley, James P.; Champagne, Frances A.

    2012-01-01

    Reproductive behavior in male rodents is made up of anticipatory and consummatory elements which are regulated in the brain by sensory systems, reward circuits and hormone signaling. Gonadal steroids play a key role in the regulation of male sexual behavior via steroid receptors in the hypothalamus and preoptic area. Typical patterns of male reproductive behavior have been characterized, however these are not fixed but are modulated by adult experience. We assessed the effects of repeated sexual experience on male reproductive behavior of C57BL/6 mice; including measures of olfactory investigation of females, mounting, intromission and ejaculation. The effects of sexual experience on the number of cells expressing either androgen receptor (AR) or estrogen receptor alpha (ERα) in the primary brain nuclei regulating male sexual behavior was also measured. Sexually experienced male mice engaged in less sniffing of females before initiating sexual behavior and exhibited shorter latencies to mount and intromit, increased frequency of intromission, and increased duration of intromission relative to mounting. No changes in numbers of ERα-positive cells were observed, however sexually experienced males had increased numbers of AR-positive cells in the medial preoptic area (MPOA); the primary regulatory nucleus for male sexual behavior. These results indicate that sexual experience results in a qualitative change in male reproductive behavior in mice that is associated with increased testosterone sensitivity in the MPOA and that this nucleus may play a key integrative role in mediating the effects of sexual experience on male behavior. PMID:22266118

  3. Individuality and Transgenerational Inheritance of Social Dominance and Sex Pheromones in Isogenic Male Mice.

    PubMed

    Fang, Qi; Zhang, Yao-Hua; Shi, Yao-Long; Zhang, Jin-Hua; Zhang, Jian-Xu

    2016-06-01

    Phenotypic variation and its epigenetic regulations within the inbred isogenic mice have long intrigued biologists. Here, we used inbred C57BL/6 mice to examine the individual differences and the inheritance of social dominance and male pheromones, expecting to create a model for studying the underlying epigenetic mechanisms for the evolution of these traits. We used a repeated male-male contest paradigm to form stable dominance-submission relationships between paired males and make superior or inferior quality manifest. Females showed olfactory preferences for the urine of dominant males to that of subordinate opponents. Gas chromatography-mass spectrometer analysis revealed that dominance-related or superior quality related pheromones were actually exaggerated male pheromone components (e.g., E-β-farnesene, hexadecanol, and 1-hexadecanol acetate) of preputial gland origin. Although the socially naïve sons of both dominant and subordinate males elicited the same female attraction when reaching adulthood, the former could dominated over the latter during undergoing the male-male competition and then gained more attraction of females. Our results demonstrated that social dominance or superior quality and the related pheromones were heritable and could be expressed through the interaction between aggression-related epigenotypes and male-male contests. It suggested that the evolution of sexually selected traits could be epigenetically determined and promoted through female mate choice. The epigenetic mechanisms driving the individual differences in behavior and male pheromones deserve further studies.

  4. Individuality and Transgenerational Inheritance of Social Dominance and Sex Pheromones in Isogenic Male Mice.

    PubMed

    Fang, Qi; Zhang, Yao-Hua; Shi, Yao-Long; Zhang, Jin-Hua; Zhang, Jian-Xu

    2016-06-01

    Phenotypic variation and its epigenetic regulations within the inbred isogenic mice have long intrigued biologists. Here, we used inbred C57BL/6 mice to examine the individual differences and the inheritance of social dominance and male pheromones, expecting to create a model for studying the underlying epigenetic mechanisms for the evolution of these traits. We used a repeated male-male contest paradigm to form stable dominance-submission relationships between paired males and make superior or inferior quality manifest. Females showed olfactory preferences for the urine of dominant males to that of subordinate opponents. Gas chromatography-mass spectrometer analysis revealed that dominance-related or superior quality related pheromones were actually exaggerated male pheromone components (e.g., E-β-farnesene, hexadecanol, and 1-hexadecanol acetate) of preputial gland origin. Although the socially naïve sons of both dominant and subordinate males elicited the same female attraction when reaching adulthood, the former could dominated over the latter during undergoing the male-male competition and then gained more attraction of females. Our results demonstrated that social dominance or superior quality and the related pheromones were heritable and could be expressed through the interaction between aggression-related epigenotypes and male-male contests. It suggested that the evolution of sexually selected traits could be epigenetically determined and promoted through female mate choice. The epigenetic mechanisms driving the individual differences in behavior and male pheromones deserve further studies. PMID:27283352

  5. Exogenous Testosterone, Aging, and Changes in Behavioral Response of Gonadally Intact Male Mice

    PubMed Central

    Onaolapo, Olakunle J.; Onaolapo, Adejoke Y.; Omololu, Tope A.; Oludimu, Adedunke T.; Segun-Busari, Toluwalase; Omoleke, Taofeeq

    2016-01-01

    This study tested the hypothesis that aging significantly affects the influence of exogenous testosterone on neurobehavior in gonadally intact male mice. Groups of prepubertal and aged male mice received daily vehicle or testosterone propionate (TP; 2.5 or 5.0 mg/kg intraperitoneal [i.p.]) for 21 days. Behaviors were assessed on days 1 and 21. Weight gain was significant in prepubertal mice. Locomotion and rearing increased in prepubertal mice after first dose and decreased after last dose of TP. Rearing was suppressed in aged mice throughout. Suppression of grooming occurred in both age groups at day 21. Significant increase in working memory in both age groups was seen in the radial-arm maze (at specific doses) and in prepubertal mice in the Y-maze. Elevated plus maze test showed mixed anxiolytic/anxiogenic effects. Aged mice had higher serum testosterone. In conclusion, age is an important determinant for the influence of exogenous testosterone on behavior in gonadally intact male mice. PMID:27158222

  6. The role of p38 in mitochondrial respiration in male and female mice.

    PubMed

    Ju, Xiaohua; Wen, Yi; Metzger, Daniel; Jung, Marianna

    2013-06-01

    p38 is a mitogen-activated protein kinase and mediates cell growth, cell differentiation, and synaptic plasticity. The aim of this study is to determine the extent to which p38 plays a role in maintaining mitochondrial respiration in male and female mice under a normal condition. To achieve this aim, we have generated transgenic mice that lack p38 in cerebellar Purkinje neurons by crossing Pcp2 (Purkinje cell protein 2)-Cre mice with p38(loxP/loxP) mice. Mitochondria from cerebellum were then isolated from the transgenic and wild-type mice to measure mitochondrial respiration using XF24 respirometer. The mRNA and protein expression of cytochrome c oxidase (COX) in cerebellum were also measured using RT-PCR and immunoblot methods. Separately, HT22 cells were used to determine the involvement of 17β-estradiol (E2) and COX in mitochondrial respiration. The genetic knockout of p38 in Purkinje neurons suppressed the mitochondrial respiration only in male mice and increased COX expression only in female mice. The inhibition of COX by sodium azide (SA) sharply suppressed mitochondrial respiration of HT22 cells in a manner that was protected by E2. These data suggest that p38 is required for the mitochondrial respiration of male mice. When p38 is below a normal level, females may maintain mitochondrial respiration through COX up-regulation.

  7. Castration of male mice prevents the progression of established angiotensin II-induced abdominal aortic aneurysms

    PubMed Central

    Zhang, Xuan; Thatcher, Sean; Wu, Congqing; Daugherty, Alan; Cassis, Lisa A.

    2014-01-01

    Objective Male sex is a non-modifiable risk factor for abdominal aortic aneurysm (AAA) development. Similar to humans, male mice are more susceptible to angiotensin II (AngII)-induced AAAs than females. Previous studies demonstrated that castration of males markedly reduced the formation of AngII-induced AAAs. Progression of AAA size is associated with increased risk of aneurysm rupture. In this study, we hypothesized that castration of male mice would reduce the progression of established AngII-induced AAAs. Methods Male apolipoprotein E (ApoE)-/- mice were infused with AngII for 1 month to induce AAA formation. Aortic diameters were measured by ultrasound and mice were stratified into 2 groups that were either sham-operated or castrated. AngII infusions were continued for a further 2 months. Ultrasound was used to quantify lumen diameters, and excised aortas were processed for quantification of AAA size, volume, and tissue characteristics. Results Sham-operated mice exhibited progressive dilation of suprarenal aortic lumen diameters during continued AngII infusion. Castration significantly decreased aortic lumen diameters (study endpoint: 1.88 ± 0.05 mm vs 1.63 ± 0.04 mm; P<.05; sham-operated [n = 15] vs castration [n = 17], respectively). However, maximal external AAA diameters were not significantly different between sham-operated and castrated mice. The vascular volume/lumen volume ratio of excised AAAs imaged by ultrasound was significantly increased by castration (sham-operated, 4.8 ± 0.9; castration, 9.5 ± 2.0 %; n = 11/group; P<.05). Moreover, compared to thin walled AAAs of sham-operated mice, aneurysm sections from castrated mice exhibited increased smooth muscle -actin and collagen. Conclusions Removal of endogenous male hormones by castration selectively reduces aortic lumen expansion while not altering the external AAA dimensions. PMID:24439319

  8. Two different pathways for the maintenance of trabecular bone in adult male mice.

    PubMed

    Lindberg, Marie K; Movérare, Sofia; Skrtic, Stanko; Alatalo, Sari; Halleen, Jussi; Mohan, Subburaman; Gustafsson, J A; Ohlsson, Claes

    2002-04-01

    Androgens may regulate the male skeleton either directly via activation of the androgen receptor (AR) or indirectly via aromatization of androgens into estrogen and, thereafter, via activation of estrogen receptors (ERs). There are two known estrogen receptors, ER-alpha and ER-beta. The aim of this study was to investigate the relative roles of ER-alpha, ER-beta, and AR in the maintenance of trabecular bone in male mice. Seven-month-old male mice, lacking ER-alpha (ERKO), ER-beta (BERKO), or both receptors (DERKO), were orchidectomized (orx) and treated for 3 weeks with 0.7 microg/mouse per day of 17beta-estradiol or vehicle. No reduction in trabecular bone mineral density (BMD) was seen in ERKO, BERKO, or DERKO mice before orx, showing that neither ER-a nor ER-beta is required for the maintenance of a normal trabecular BMD in male mice. After orx, there was a pronounced decrease in trabecular BMD, similar for all groups, resulting in equal levels of trabecular BMD in all genotypes. This reduction was reversed completely in wild-type (WT) and BERKO mice treated with estrogen, and no significant effect of estrogen was found in ERKO or DERKO mice. In summary, the trabecular bone is preserved both by a testicular factor, presumably testosterone acting via AR and by an estrogen-induced activation of ER-alpha. These results indicate that AR and ER-alpha are redundant in the maintenance of the trabecular bone in male mice. In contrast, ER-beta is of no importance for the regulation of trabecular bone in male mice.

  9. Spectrographic analysis of the ultrasonic vocalisations of adult male and female BALB/c mice

    NASA Astrophysics Data System (ADS)

    Gourbal, Benjamin E. F.; Barthelemy, Mathieu; Petit, Gilles; Gabrion, Claude

    In this study, a spectrographic analysis was designed to improve the description of the shape, the modulations, the rate, length and frequencies of BALB/c mouse calls in different behavioural situations. Male and female calls emitted during investigation of cages with clean bedding, soiled with male or female bedding, and during same-sex encounters, were recorded and described. BALB/c male mice uttered different types of vocalisations both when investigating counterpart odour cues and when interacting with same-sex counterparts. BALB/c female mice vocalised solely during same-sex counterpart encounters and it appeared that calls were uttered mainly by the resident females. Male and female mice present a complex array of calls, which seem to be linked to particular behavioural situations. Further studies using this technology may help to improve our understanding of the role of vocal communication in natural rodent populations.

  10. Acute behavioral effects of nicotine in male and female HINT1 knockout mice.

    PubMed

    Jackson, K J; Wang, J B; Barbier, E; Chen, X; Damaj, M I

    2012-11-01

    Human genetic association and brain expression studies, and mouse behavioral and molecular studies implicate a role for the histidine triad nucleotide-binding protein 1 (HINT1) in schizophrenia, bipolar disorder, depression and anxiety. The high comorbidity between smoking and psychiatric disorders, schizophrenia in particular, is well established. Associations with schizophrenia and HINT1 are also sex specific, with effects more predominant in males; however, it is unknown if sex differences associated with the gene extend to other phenotypes. Thus, in this study, using a battery of behavioral tests, we elucidated the role of HINT1 in acute nicotine-mediated behaviors using male and female HINT1 wild-type (+/+) and knockout (-/-) mice. The results show that male HINT1 -/- mice were less sensitive to acute nicotine-induced antinociception in the tail-flick, but not hot-plate test. At low nicotine doses, male and female HINT1 -/- mice were less sensitive to nicotine-induced hypomotility, although the effect was more pronounced in females. Baseline differences in locomotor activity observed in male HINT1 +/+ and -/- mice were absent in females. Nicotine did not produce an anxiolytic effect in male HINT1 -/- mice, but rather an anxiogenic response. Diazepam also failed to induce an anxiolytic response in these mice, suggesting a general anxiety phenotype not specific to nicotine. Differences in anxiety-like behavior were not observed in female mice. These results further support a role for HINT1 in nicotine-mediated behaviors and suggest that alterations in the gene may have differential effects on phenotype in males and females. PMID:22827509

  11. Behavioral transition from attack to parenting in male mice: a crucial role of the vomeronasal system.

    PubMed

    Tachikawa, Kashiko S; Yoshihara, Yoshihiro; Kuroda, Kumi O

    2013-03-20

    Sexually naive male mice show robust aggressive behavior toward pups. However, the proportion of male mice exhibiting pup-directed aggression declines after cohabitation with a pregnant female for 2 weeks after mating. Subsequently, on becoming fathers, they show parental behavior toward pups, similar to maternal behavior by mothers. To elucidate the neural mechanisms underlying this behavioral transition, we examined brain regions differentially activated in sexually naive males and fathers after exposure to pups, using c-Fos expression as a neuronal activation marker. We found that, after pup exposure, subsets of neurons along the vomeronasal neural pathway-including the vomeronasal sensory neurons, the accessory olfactory bulb, the posterior medial amygdala, the medioposterior division of the bed nucleus of stria terminalis, and the anterior hypothalamic area-were more strongly activated in sexually naive males than in fathers. Notably, c-Fos induction was not observed in the vomeronasal sensory neurons of fathers after pup exposure. Surgical ablation of the vomeronasal organ in sexually naive males resulted in the abrogation of pup-directed aggression and simultaneous induction of parental behavior. These results suggest that chemical cues evoking pup-directed aggression are received by the vomeronasal sensory neurons and activate the vomeronasal neural pathway in sexually naive male mice but not in fathers. Thus, the downregulation of pup pheromone-induced activation of the vomeronasal system might be important for the behavioral transition from attack to parenting in male mice.

  12. Male mice song syntax depends on social contexts and influences female preferences

    PubMed Central

    Chabout, Jonathan; Sarkar, Abhra; Dunson, David B.; Jarvis, Erich D.

    2015-01-01

    In 2005, Holy and Guo advanced the idea that male mice produce ultrasonic vocalizations (USV) with some features similar to courtship songs of songbirds. Since then, studies showed that male mice emit USV songs in different contexts (sexual and other) and possess a multisyllabic repertoire. Debate still exists for and against plasticity in their vocalizations. But the use of a multisyllabic repertoire can increase potential flexibility and information, in how elements are organized and recombined, namely syntax. In many bird species, modulating song syntax has ethological relevance for sexual behavior and mate preferences. In this study we exposed adult male mice to different social contexts and developed a new approach of analyzing their USVs based on songbird syntax analysis. We found that male mice modify their syntax, including specific sequences, length of sequence, repertoire composition, and spectral features, according to stimulus and social context. Males emit longer and simpler syllables and sequences when singing to females, but more complex syllables and sequences in response to fresh female urine. Playback experiments show that the females prefer the complex songs over the simpler ones. We propose the complex songs are to lure females in, whereas the directed simpler sequences are used for direct courtship. These results suggest that although mice have a much more limited ability of song modification, they could still be used as animal models for understanding some vocal communication features that songbirds are used for. PMID:25883559

  13. Male mice song syntax depends on social contexts and influences female preferences.

    PubMed

    Chabout, Jonathan; Sarkar, Abhra; Dunson, David B; Jarvis, Erich D

    2015-01-01

    In 2005, Holy and Guo advanced the idea that male mice produce ultrasonic vocalizations (USV) with some features similar to courtship songs of songbirds. Since then, studies showed that male mice emit USV songs in different contexts (sexual and other) and possess a multisyllabic repertoire. Debate still exists for and against plasticity in their vocalizations. But the use of a multisyllabic repertoire can increase potential flexibility and information, in how elements are organized and recombined, namely syntax. In many bird species, modulating song syntax has ethological relevance for sexual behavior and mate preferences. In this study we exposed adult male mice to different social contexts and developed a new approach of analyzing their USVs based on songbird syntax analysis. We found that male mice modify their syntax, including specific sequences, length of sequence, repertoire composition, and spectral features, according to stimulus and social context. Males emit longer and simpler syllables and sequences when singing to females, but more complex syllables and sequences in response to fresh female urine. Playback experiments show that the females prefer the complex songs over the simpler ones. We propose the complex songs are to lure females in, whereas the directed simpler sequences are used for direct courtship. These results suggest that although mice have a much more limited ability of song modification, they could still be used as animal models for understanding some vocal communication features that songbirds are used for.

  14. Severe Brown Fat Lipoatrophy Aggravates Atherosclerotic Process in Male Mice.

    PubMed

    Gómez-Hernández, Almudena; Beneit, Nuria; Escribano, Óscar; Díaz-Castroverde, Sabela; García-Gómez, Gema; Fernández, Silvia; Benito, Manuel

    2016-09-01

    Obesity is one of the major risk factors for the development of cardiovascular diseases and is characterized by abnormal accumulation of adipose tissue, including perivascular adipose tissue (PVAT). However, brown adipose tissue (BAT) activation reduces visceral adiposity. To demonstrate that severe brown fat lipoatrophy might accelerate atherosclerotic process, we generated a new mouse model without insulin receptor (IR) in BAT and without apolipoprotein (Apo)E (BAT-specific IR knockout [BATIRKO];ApoE(-/-) mice) and assessed vascular and metabolic alterations associated to obesity. In addition, we analyzed the contribution of the adipose organ to vascular inflammation. Brown fat lipoatrophy induces visceral adiposity, mainly in gonadal depot (gonadal white adipose tissue [gWAT]), severe glucose intolerance, high postprandial glucose levels, and a severe defect in acute insulin secretion. BATIRKO;ApoE(-/-) mice showed greater hypertriglyceridemia than the obtained in ApoE(-/-) and hypercholesterolemia similar to ApoE(-/-) mice. BATIRKO;ApoE(-/-) mice, in addition to primary insulin resistance in BAT, also showed a significant decrease in insulin signaling in liver, gWAT, heart, aorta artery, and thoracic PVAT. More importantly, our results suggest that severe brown fat lipoatrophy aggravates the atherosclerotic process, characterized by a significant increase of lipid depots, atherosclerotic coverage, lesion size and complexity, increased macrophage infiltration, and proinflammatory markers expression. Finally, an increase of TNF-α and leptin as well as a decrease of adiponectin by BAT, gWAT, and thoracic PVAT might also be responsible of vascular damage. Our results suggest that severe brown lipoatrophy aggravates atherosclerotic process. Thus, BAT activation might protect against obesity and its associated metabolic alterations. PMID:27414981

  15. Urinary Retention, Incontinence, and Dysregulation of Muscarinic Receptors in Male Mice Lacking Mras

    PubMed Central

    Ehrhardt, Annette; Wang, Bin; Yung, Andrew C.; Wang, Yanni; Kozlowski, Piotr; van Breemen, Cornelis; Schrader, John W.

    2015-01-01

    Here we show that male, but not female mice lacking expression of the GTPase M-Ras developed urinary retention with distention of the bladder that exacerbated with age but occurred in the absence of obvious anatomical outlet obstruction. There were changes in detrusor morphology in Mras-/- males: Smooth muscle tissue, which exhibited a compact organization in WT mice, appeared disorganized and became increasingly ‘layered’ with age in Mras-/- males, but was not fibrotic. Bladder tissue near the apex of bladders of Mras-/- males exhibited hypercontractility in response to the cholinergic agonist carbachol in in vitro, while responses in Mras-/- females were normal. In addition, spontaneous phasic contractions of detrusors from Mras-/- males were increased, and Mras-/- males exhibited urinary incontinence. We found that expression of the muscarinic M2 and M3 receptors that mediate the cholinergic contractile stimuli of the detrusor muscle was dysregulated in both Mras-/- males and females, although only males exhibited a urinary phenotype. Elevated expression of M2R in young males lacking M-Ras and failure to upregulate M3R with age resulted in significantly lower ratios of M3R/M2R expression that correlated with the bladder abnormalities. Our data suggests that M-Ras and M3R are functionally linked and that M-Ras is an important regulator of male bladder control in mice. Our observations also support the notion that bladder control is sexually dimorphic and is regulated through mechanisms that are largely independent of acetylcholine signaling in female mice. PMID:26516777

  16. Age and isolation influence steroids release and chemical signaling in male mice.

    PubMed

    Mucignat-Caretta, Carla; Cavaggioni, Andrea; Redaelli, Marco; Da Dalt, Laura; Zagotto, Giuseppe; Gabai, Gianfranco

    2014-05-01

    Social interactions in mice involve olfactory signals, which convey information about the emitter. In turn, the mouse social and physiological status may modify the release of chemical cues. In this study, the influences of age and social isolation on the endocrine response and the release of chemical signals were investigated in male CD1 mice, allocated into four groups: Young Isolated (from weaning till 60days; N=6), Adult Isolated (till 180days; N=6), Young Grouped (6 mice/cage; till 60days; N=18), Adult Grouped (6 mice/cage; till 180days; N=18). Mice were transferred in a clean cage to observe the micturition pattern and then sacrificed. Body and organs weights, serum testosterone, dehydroepiandrosterone, corticosterone and the ratio Major Urinary Protein/creatinine were measured. Urinary volatile molecules potentially involved in pheromonal communication were identified. Androgen secretion was greater in isolated mice (P<0.05), suggesting a greater reactivity of the Hypothalamic-Pituitary-Gonadal axis. Grouped mice presented a higher degree of adrenal activity, and young mice showed a higher serum corticosterone (P<0.05) suggesting a greater stimulation of the Hypothalamic-Pituitary-Adrenal axis. The micturition pattern typical of dominant male, consisting in voiding numerous droplets, was observed in Young Isolated mice only, which showed a higher protein/creatinine ratio (P<0.05). Urinary 2-s-butyl-thiazoline was higher in both Young and Adult Isolated mice (P<0.005). Young Isolated mice showed the most prominent difference in both micturition pattern and potentially active substance emission, while long term isolation resulted in a less extreme phenotype; therefore social isolation had a higher impact on young mice hormone and pheromone release.

  17. Reproductive effects of lipid soluble components of Syzygium aromaticum flower bud in male mice

    PubMed Central

    Mishra, Raghav Kumar; Singh, Shio Kumar

    2013-01-01

    Background: The flower buds of Syzygium aromaticum (clove) have been used in indigenous medicines for the treatment of male sexual disorders in Indian subcontinent. Objective: To evaluate the effect of Syzygium aromaticum flower bud on male reproduction, using Parkes (P) strain mice as animal model. Materials and Methods: Mice were orally administered lipid soluble components of Syzygium aromaticum flower bud in doses of 15, 30, and 60 mg/kg body weight for 35 days, and several male reproductive endpoints were evaluated. Results: Treatment with lower dose (15 mg) of Syzygium increased the motility of sperm and stimulated the secretory activities of epididymis and seminal vesicle, while higher doses (30 and 60 mg) had adverse effects on sperm dynamics of cauda epididymidis and on the secretory activities of epididymis and seminal vesicle. Libido was not affected in treated males; however, a significant decrease in litter in females sired by males treated with higher doses of Syzygium was recorded. Conclusion: Treatment with Syzygium aromaticum flower bud causes dose-dependent biphasic effect on male reproductive indices in P mice; lower dose of Syzygium appears stimulatory, while the higher doses have adverse effect on male reproduction. The results suggest that the lower dose of Syzygium may have androgenic effect, but further studies are needed to support this contention. PMID:23930041

  18. Disruption of the fifth melanocortin receptor alters the urinary excretion of aggression-modifying pheromones in male house mice.

    PubMed

    Caldwell, Heather K; Lepri, John J

    2002-01-01

    The preputial glands of house mice express the gene for the fifth melanocortin receptor (MC5-R) and are a primary source of urinary pheromones involved in inter-male aggression. A 'resident-intruder' behavioral model was used to compare the responses of resident males to urine from mice with an engineered disruption of the fifth melanocortin receptor (MC5-RKO) with residents' responses to urine from wild-type mice (WT). Each type of urine was presented in combination with a castrated intruder male to provide the appropriate biological context. Resident males responded with a longer latency to bite when the urine was from gonadally intact WT males compared with urine from MC5-RKO mice. These results are consistent with the hypothesis that activation of the fifth melanocortin receptor in the preputial glands of male house mice causes excretion of urinary pheromones that delay aggressive responses by other males.

  19. Curcumin improves liver damage in male mice exposed to nicotine.

    PubMed

    Salahshoor, Mohammadreza; Mohamadian, Sabah; Kakabaraei, Seyran; Roshankhah, Shiva; Jalili, Cyrus

    2016-04-01

    The color of turmeric ( jiāng huáng) is because of a substance called curcumin. It has different pharmacological effects, such as antioxidant and anti-inflammatory properties. Nicotine is a major pharmacologically active substance in cigarette smoke. It is mainly metabolized in the liver and causes devastating effects. This study was designed to evaluate the protective role of curcumin against nicotine on the liver in mice. Forty-eight mice were equally divided into eight groups; control (normal saline), nicotine (2.5 mg/kg), curcumin (10, 30, and 60 mg/kg) and curcumin plus nicotine-treated groups. Curcumin, nicotine, and curcumin plus nicotine (once a day) were intraperitoneally injected for 4 weeks. The liver weight and histology, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and serum nitric oxide levels have been studied. The results indicated that nicotine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein, liver enzymes level, and blood serum nitric oxide level compared with the saline group (p < 0.05). However, curcumin and curcumin plus nicotine administration substantially increased liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes, and nitric oxide levels in all groups compared with the nicotine group (p < 0.05). Curcumin demonstrated its protective effect against nicotine-induced liver toxicity. PMID:27114942

  20. Curcumin improves liver damage in male mice exposed to nicotine

    PubMed Central

    Salahshoor, Mohammadreza; Mohamadian, Sabah; Kakabaraei, Seyran; Roshankhah, Shiva; Jalili, Cyrus

    2015-01-01

    The color of turmeric (薑黃 jiāng huáng) is because of a substance called curcumin. It has different pharmacological effects, such as antioxidant and anti-inflammatory properties. Nicotine is a major pharmacologically active substance in cigarette smoke. It is mainly metabolized in the liver and causes devastating effects. This study was designed to evaluate the protective role of curcumin against nicotine on the liver in mice. Forty-eight mice were equally divided into eight groups; control (normal saline), nicotine (2.5 mg/kg), curcumin (10, 30, and 60 mg/kg) and curcumin plus nicotine-treated groups. Curcumin, nicotine, and curcumin plus nicotine (once a day) were intraperitoneally injected for 4 weeks. The liver weight and histology, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and serum nitric oxide levels have been studied. The results indicated that nicotine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein, liver enzymes level, and blood serum nitric oxide level compared with the saline group (p < 0.05). However, curcumin and curcumin plus nicotine administration substantially increased liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes, and nitric oxide levels in all groups compared with the nicotine group (p < 0.05). Curcumin demonstrated its protective effect against nicotine-induced liver toxicity. PMID:27114942

  1. Why do male house mice have such small testes?

    PubMed

    Frynta, Daniel; Slábová, Markéta; Vohralík, Vladimír

    2009-01-01

    We studied testes size in free-living and laboratory-born commensal and non-commensal populations of various Mus species (M. musculus musculus, M. m. domesticus, M. spicilegus, M. spretus, M. macedonicus, and laboratory mice). We found no apparent differences between wild-caught and laboratory-born individuals, or among commensal, non-commensal, and laboratory populations of M. musculus. There were, however, considerable differences among the species studied. The highest values of relative testes size were found in the aboriginal species M. spicilegus (4.4% and 2.9% for wild and laboratory populations, respectively), followed by those of M. macedonicus (from 1.7% to 0.9% for various samples) and M. spretus (1.5%). All thirteen samples representing various populations of Mus musculus exhibited smaller testes (0.7-1.0%), and finally the three lowest mean values came from laboratory mice (0.5-0.7%). It is very surprising that aboriginal species, in particular M. spicilegus, which is widely considered to be monogamous, have relatively larger testes than the polygynous/promiscuous M. musculus. This result is in apparent contradiction to the current views on evolutionary forces affecting testes size, and suggests that there could be another uncontrolled factor obscuring the relationship between testes size and multiple paternity. This raises a question concerning the proper interpretation of social organisation in the genus Mus. PMID:19267608

  2. Attraction to male pheromones and sexual behaviour show different regulatory mechanisms in female mice.

    PubMed

    Moncho-Bogani, Jose; Lanuza, Enrique; Lorente, Maria José; Martinez-Garcia, Fernando

    2004-05-01

    In rodents, female sexual behaviour is under hormonal control. The attraction females show for male-derived nonvolatile chemicals (pheromones) can be regarded as the first step of this behaviour, but it is unknown whether this attraction is also modulated by sexual steroids. To test this possibility, ovariectomized adult female mice with no experience of chemical signals from adult males were randomly assigned to four groups that received oil (control), progesterone, estradiol (E) or estradiol+progesterone (E+P) injections, respectively. Females were then tested for their attraction to male-soiled bedding and, subsequently, for their proceptive behaviour when confronted to adult males. Females showed attraction to male-soiled bedding irrespective of the hormonal treatment, whereas only those females treated with E or E+P showed proceptive behaviour. Therefore, in contrast to proceptive and copulatory behaviour, the female attraction to male pheromones is independent of sexual steroids, thus indicating that those parts of the vomeronasal system involved in this attraction do not respond to steroids. In summary, sexual behaviour in female mice can be seen as a two-step process. First, females are attracted by male pheromones, a process which is independent of their hormonal status. After encountering the males, females show proceptive behaviour only in estrous, when fertilization is more likely. The attraction exerted by male sexual pheromones promotes female autostimulation that might ensure anticipatory endocrine changes leading to ovulation by the time of sexual intercourse.

  3. Attenuation of Cocaine-Induced Locomotor Activity in Male and Female Mice by Active Immunization

    PubMed Central

    Kosten, Therese A.; Shen, Xiaoyun Y.; Kinsey, Berma M.; Kosten, Thomas R.; Orson, Frank M.

    2014-01-01

    Background and objectives Immunotherapy for drug addiction is being investigated in several laboratories but most studies are conducted in animals of one sex. Yet, women show heightened immune responses and are more likely to develop autoimmune diseases than men. The purpose of this study was to compare the effects of an active anti-cocaine vaccine, succinyl-norcocaine conjugated to keyhole limpet hemocyanin, for its ability to elicit antibodies and alter cocaine-induced ambulatory activity in male versus female mice. Methods Male and female BALB/c mice were vaccinated (n=44) or served as non-vaccinated controls (n=34). Three weeks after initial vaccination, a booster was given. Ambulatory activity induced by cocaine (20 mg/kg) was assessed at 7-wk and plasma obtained at 8-wk to assess antibody levels. Results High antibody titers were produced in mice of both sexes. The vaccine reduced ambulatory activity cocaine-induced but this effect was greater in female compared to male mice. Discussion and conclusions The efficacy of this anti-cocaine vaccine is demonstrated in mice of both sexes but its functional consequences are greater in females than males. Scientific significance Results point to the importance of testing animals of both sexes in studies of immunotherapies for addiction. PMID:25251469

  4. Male pheromones initiate prolactin-induced neurogenesis and advance maternal behavior in female mice.

    PubMed

    Larsen, Caroline M; Kokay, Ilona C; Grattan, David R

    2008-04-01

    Prolactin is required for rapid onset of maternal behavior after parturition, inducing adaptive changes in the maternal brain including enhanced neurogenesis in the subventricular zone during pregnancy. The resultant increase in olfactory interneurons may be required for altered processing of olfactory cues during the establishment of maternal behavior. Pheromones act through olfactory pathways to exert powerful effects on behavior in rodents and also affect prolactin secretion. Hence, this study aimed to investigate the effect of male pheromones on neurogenesis and maternal behavior in female mice. Virgin female mice were housed individually or in split-cages where they had pheromonal but not physical contact with a male. Maternal behavior was assessed in a foster pup retrieval paradigm. Some mice were injected with bromodeoxyuridine, and the labeled cells visualized using immunohistochemistry. The data show that exposure to male pheromones, for a duration equivalent to a murine pregnancy, advanced maternal behavior in both virgin and postpartum female mice. The pheromone action was dependent on prolactin and ovarian steroids, and was associated with increased cell proliferation in the subventricular zone and subsequent increases in new neurons in the olfactory bulb. Moreover, the effect of pheromones on both cell proliferation and maternal behavior could be induced solely through administration of exogenous prolactin to mimic the pheromone-induced changes in prolactin secretion. The data suggest that male pheromones induce a prolactin-mediated increase in neurogenesis in female mice, resulting in advanced maternal behavior.

  5. Social experience modulates ocular dominance plasticity differentially in adult male and female mice.

    PubMed

    Balog, Jenny; Matthies, Ulrike; Naumann, Lisa; Voget, Mareike; Winter, Christine; Lehmann, Konrad

    2014-12-01

    Environmental factors have long been known to regulate brain plasticity. We investigated the potential influence of social experience on ocular dominance plasticity. Fully adult female or male mice were monocularly deprived for four days and kept a) either alone or in pairs of the same sex and b) either in a small cage or a large, featureless arena. While mice kept alone did not show ocular dominance plasticity, no matter whether in a cage or in an arena, paired female mice in both environmental conditions displayed a shift of ocular dominance towards the open eye. Paired male mice, in contrast, showed no plasticity in the cage, but a very strong ocular dominance shift in the arena. This effect was not due to increased locomotion, since the covered distance was similar in single and paired male mice in the arena, and furnishing cages with a running wheel did not enable ocular dominance plasticity in cage-housed mice. Confirming recent results in rats, the plasticity-enhancing effect of the social environment was shown to be mediated by serotonin. Our results demonstrate that social experience has a strong effect on cortical plasticity that is sex-dependent. This has potential consequences both for animal research and for human education and rehabilitation.

  6. Behavioral analysis of male and female Fmr1 knockout mice on C57BL/6 background.

    PubMed

    Ding, Qi; Sethna, Ferzin; Wang, Hongbing

    2014-09-01

    Fragile X syndrome (FXS) is a monogenic disease caused by mutations in the FMR1 gene. The Fmr1 knockout (KO) mice show many aspects of FXS-related phenotypes, and have been used as a major pre-clinical model for FXS. Although FXS occurs in both male and female patients, most studies on the mouse model use male animals. Few studies test whether gender affects the face validity of the mouse model. Here, we examined multiple behavioral phenotypes with male hemizygous and female homozygous Fmr1 KO mice on C57BL/6 background. For each behavioral paradigm, we examined multiple cohorts from different litters. We found that both male and female Fmr1 KO mice displayed significant audiogenic seizures, hyperactivity in the open field test, deficits in passive avoidance and contextual fear memory, and significant enhancement of PPI at low stimulus intensity. Male and female Fmr1 KO mice also showed more transitional movement between the lit and dark chambers in the light-dark tests. The lack of gender effects suggests that the Fmr1 KO mouse is a reasonable tool to test the efficacy of potential FXS therapies.

  7. Reproductive toxicity in male mice exposed to Nanjing City tap water.

    PubMed

    Zhao, Dayong; Chen, Yajun; Zhou, Kemei; Cheng, Shupei; Ma, Ting; Jiang, Cuiling; Yan, Wenming; Zhu, Liqin; Gu, Xijun; Zhu, Xiaohua; Wu, Bing; Zhang, Yan; Zhang, Xuxiang

    2011-07-01

    End points of reproductive toxicity were investigated in male mice (Mus musculus, ICR) fed Nanjing City tap water for 90 days. There was no significant alteration in body weights between treatment and control mice. In treated mice, flow cytometry analysis of testicular tissue indicated that the relative percentage of the elongated spermatid (HC) decreased significantly (P < 0.05). Also slight increases in the relative percentage of round spermatids (1C) and primary spermatocytes (4C) were noted. The ratios of 4C:2C (diploid germ cells) and 1C:2C increased, and testicular histopathology indicated an expansion of interstitial space and a decreased number and size of Leydig cells in treated mice. The current study suggests that Nanjing City tap water is toxic to the reproductive system of mice and additional study to evaluate its effects on other species, including human beings, would be warranted. PMID:21431922

  8. Expression of GAT1 in male reproductive system and its effects on reproduction in mice.

    PubMed

    Zhang, JinFu; Gui, YaPing; Yuan, Tao; Bian, CuiDong; Guo, LiHe

    2009-12-01

    The present study was carried out to identify GABA (gamma-aminobutyric acid) transport protein I (GAT1) in male reproductive organs and to study the effect of GAT1 overexpression on the male reproductive system in GAT1 transgenic mice (TG). Expression and location of GAT1 in testes, epididymis, and sperm of wild-type (WT) mice were identified by immunohistochemistry and western-blot. Histological changes of testes, epididymis, and sperm of transgenic mice overexpressing GAT1 were detected by immunofluorenscent staining and haematoxylin and eosin (HE) staining. GAT1 expression was detected in the testes, epididymis, and sperm of non-transgenic mice. Vacuolization and deformity of spermatogenic cells were observed in the transgenic mice, but the epididymis was unremarkable. Immunofluorenscent staining showed that the number of diastrophic and decapitated sperm increased significantly in transgenic mice to 46.9% from 7.3% in nontransgenic mice. These results suggest that abnormal expression of GAT1 could result in spermiogenesis function injury, sperm paramorphia and dysgenesis.

  9. Overexpression of PRL7D1 in Leydig Cells Causes Male Reproductive Dysfunction in Mice.

    PubMed

    Liu, Yaping; Su, Xingyu; Hao, Jie; Chen, Maoxin; Liu, Weijia; Liao, Xiaogang; Li, Gang

    2016-01-01

    Prolactin family 7, subfamily d, member 1 (PRL7D1) is found in mouse placenta. Our recent work showed that PRL7D1 is also present in mouse testis Leydig cells, and the expression of PRL7D1 in the testis exhibits an age-related increase. In the present study, we generated transgenic mice with Leydig cell-specific PRL7D1 overexpression to explore its function during male reproduction. Prl7d1 male mice exhibited subfertility as reflected by reduced sperm counts and litter sizes. The testes from Prl7d1 transgenic mice appeared histologically normal, but the frequency of apoptotic germ cells was increased. Prl7d1 transgenic mice also had lower testosterone concentrations than wild-type mice. Mechanistic studies revealed that Prl7d1 transgenic mice have defects in the testicular expression of steroidogenic acute regulatory protein (STAR) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B). Further studies revealed that PRL7D1 overexpression affected the expression of transferrin (TF) in Sertoli cells. These results suggest that PRL7D1 overexpression could lead to increased germ cell apoptosis and exert an inhibitory effect on testosterone production in Leydig cells by reducing the expression of certain steroidogenic-related genes. In addition, PRL7D1 appears to have important roles in the function of Sertoli cells, which, in turn, affects male fertility. We conclude that the expression level of PRL7D1 is associated with the reproductive function of male mice. PMID:26771609

  10. Overexpression of PRL7D1 in Leydig Cells Causes Male Reproductive Dysfunction in Mice.

    PubMed

    Liu, Yaping; Su, Xingyu; Hao, Jie; Chen, Maoxin; Liu, Weijia; Liao, Xiaogang; Li, Gang

    2016-01-13

    Prolactin family 7, subfamily d, member 1 (PRL7D1) is found in mouse placenta. Our recent work showed that PRL7D1 is also present in mouse testis Leydig cells, and the expression of PRL7D1 in the testis exhibits an age-related increase. In the present study, we generated transgenic mice with Leydig cell-specific PRL7D1 overexpression to explore its function during male reproduction. Prl7d1 male mice exhibited subfertility as reflected by reduced sperm counts and litter sizes. The testes from Prl7d1 transgenic mice appeared histologically normal, but the frequency of apoptotic germ cells was increased. Prl7d1 transgenic mice also had lower testosterone concentrations than wild-type mice. Mechanistic studies revealed that Prl7d1 transgenic mice have defects in the testicular expression of steroidogenic acute regulatory protein (STAR) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B). Further studies revealed that PRL7D1 overexpression affected the expression of transferrin (TF) in Sertoli cells. These results suggest that PRL7D1 overexpression could lead to increased germ cell apoptosis and exert an inhibitory effect on testosterone production in Leydig cells by reducing the expression of certain steroidogenic-related genes. In addition, PRL7D1 appears to have important roles in the function of Sertoli cells, which, in turn, affects male fertility. We conclude that the expression level of PRL7D1 is associated with the reproductive function of male mice.

  11. Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice.

    PubMed

    Lecoq, Anne-Lise; Zizzari, Philippe; Hage, Mirella; Decourtye, Lyvianne; Adam, Clovis; Viengchareun, Say; Veldhuis, Johannes D; Geoffroy, Valérie; Lombès, Marc; Tolle, Virginie; Guillou, Anne; Karhu, Auli; Kappeler, Laurent; Chanson, Philippe; Kamenický, Peter

    2016-10-01

    Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas, particularly of the somatotroph lineage. Mice with global heterozygous inactivation of Aip (Aip(+/-)) also develop pituitary adenomas but differ from AIP-mutated patients by the high penetrance of pituitary disease. The endocrine phenotype of these mice is unknown. The aim of this study was to determine the endocrine phenotype of Aip(+/-) mice by assessing the somatic growth, ultradian pattern of GH secretion and IGF1 concentrations of longitudinally followed male mice at 3 and 12 months of age. As the early stages of pituitary tumorigenesis are controversial, we also studied the pituitary histology and somatotroph cell proliferation in these mice. Aip(+/-) mice did not develop gigantism but exhibited a leaner phenotype than wild-type mice. Analysis of GH pulsatility by deconvolution in 12-month-old Aip(+/-) mice showed a mild increase in total GH secretion, a conserved GH pulsatility pattern, but a normal IGF1 concentration. No pituitary adenomas were detected up to 12 months of age. An increased ex vivo response to GHRH of pituitary explants from 3-month-old Aip(+/-) mice, together with areas of enlarged acini identified on reticulin staining in the pituitary of some Aip(+/-) mice, was suggestive of somatotroph hyperplasia. Global heterozygous Aip deficiency in mice is accompanied by subtle increase in GH secretion, which does not result in gigantism. The absence of pituitary adenomas in 12-month-old Aip(+/-) mice in our experimental conditions demonstrates the important phenotypic variability of this congenic mouse model.

  12. Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice.

    PubMed

    Lecoq, Anne-Lise; Zizzari, Philippe; Hage, Mirella; Decourtye, Lyvianne; Adam, Clovis; Viengchareun, Say; Veldhuis, Johannes D; Geoffroy, Valérie; Lombès, Marc; Tolle, Virginie; Guillou, Anne; Karhu, Auli; Kappeler, Laurent; Chanson, Philippe; Kamenický, Peter

    2016-10-01

    Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas, particularly of the somatotroph lineage. Mice with global heterozygous inactivation of Aip (Aip(+/-)) also develop pituitary adenomas but differ from AIP-mutated patients by the high penetrance of pituitary disease. The endocrine phenotype of these mice is unknown. The aim of this study was to determine the endocrine phenotype of Aip(+/-) mice by assessing the somatic growth, ultradian pattern of GH secretion and IGF1 concentrations of longitudinally followed male mice at 3 and 12 months of age. As the early stages of pituitary tumorigenesis are controversial, we also studied the pituitary histology and somatotroph cell proliferation in these mice. Aip(+/-) mice did not develop gigantism but exhibited a leaner phenotype than wild-type mice. Analysis of GH pulsatility by deconvolution in 12-month-old Aip(+/-) mice showed a mild increase in total GH secretion, a conserved GH pulsatility pattern, but a normal IGF1 concentration. No pituitary adenomas were detected up to 12 months of age. An increased ex vivo response to GHRH of pituitary explants from 3-month-old Aip(+/-) mice, together with areas of enlarged acini identified on reticulin staining in the pituitary of some Aip(+/-) mice, was suggestive of somatotroph hyperplasia. Global heterozygous Aip deficiency in mice is accompanied by subtle increase in GH secretion, which does not result in gigantism. The absence of pituitary adenomas in 12-month-old Aip(+/-) mice in our experimental conditions demonstrates the important phenotypic variability of this congenic mouse model. PMID:27621108

  13. Chronic stress does not further exacerbate the abnormal psychoneuroendocrine phenotype of Cbg-deficient male mice.

    PubMed

    de Medeiros, Gabriela F; Minni, Amandine M; Helbling, Jean-Christophe; Moisan, Marie-Pierre

    2016-08-01

    Chronic stress leads to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis which can constitute a base for pathophysiological consequences. Using mice totally deficient in Corticosteroid binding globulin (CBG), we have previously demonstrated the important role of CBG in eliciting an adequate response to an acute stressor. Here, we have studied its role in chronic stress situations. We have submitted Cbg ko and wild-type (WT) male mice to two different chronic stress paradigms - the unpredictable chronic mild stress and the social defeat. Then, their impact on neuroendocrine function - through corticosterone and CBG measurement - and behavioral responses - via anxiety and despair-like behavioral tests - was evaluated. Both chronic stress paradigms increased the display of despair-like behavior in WT mice, while that from Cbg ko mice - which was already high - was not aggravated. We have also found that control and defeated (stressed) Cbg ko mice show no difference in the social interaction test, while defeated WT mice reduce their interaction time when compared to unstressed WT mice. Interestingly, the same pattern was observed for corticosterone levels, where both chronic stress paradigms lowered the corticosterone levels of WT mice, while those from Cbg ko mice remained low and unaltered. Plasma CBG binding capacity remained unaltered in WT mice regardless of the stress paradigm. Through the use of the Cbg ko mice, which only differs genetically from WT mice by the absence of CBG, we demonstrated that CBG is crucial in modulating the effects of stress on plasma corticosterone levels and consequently on behavior. In conclusion, individuals with CBG deficiency, whether genetically or environmentally-induced, are vulnerable to acute stress but do not have their abnormal psychoneuroendocrine phenotype further affected by chronic stress.

  14. Response of male mice to odours of female mice in different stages of oestrous cycle: self-grooming behaviour and the effect of castration.

    PubMed

    Achiraman, Shanmugam; SankarGanesh, Devaraj; Kannan, Soundarapandian; Kamalakkannan, Soundararajan; Nirmala, Natarajan; Archunan, Govindaraju

    2014-01-01

    The behavioural assays were carried out in a Y-maze wherein intact, castrated and testosterone-treated male mice were exposed to oestrus and non-oestrus urine samples. The intact male mice investigated more frequently and spent more time in the Y-maze arm with oestrus urine than in that with non-oestrus urine. In contrast, the castrated mice were not attracted to oestrus urine, whereas testosterone-treated mice showed preference for oestrus urine. The rate of self-grooming was higher in intact males in case of exposure to oestrus urine while the rate was lower with respect to non-oestrus urine. However, castrated mice exhibited less self-grooming behaviour which was partially restored by testosterone treatment. The results suggest that self-grooming behaviour is an indicator of detection and discrimination of oestrus by males, and supports the androgen role in male chemosensory ability to discriminate between oestrus and non-oestrus female odours.

  15. Toxic effects of sub-chronic exposure of male albino rats to emamectin benzoate and possible ameliorative role of Foeniculum vulgare essential oil.

    PubMed

    El-Sheikh, El-Sayed A; Galal, Azza A A

    2015-05-01

    Emamectin benzoate (EB) is an avermectin insecticide used extensively in pest control on vegetable and field crops. Few studies have been done for evaluating adverse effects of EB. In the current study, we evaluated the toxic effects of EB on male rats and the possible ameliorative role of fennel essential oil (FEO). Thirty two male rats were randomly divided into 4 equal groups. All groups were treated orally with distilled water (control group), 0.5mlFEOkg(-1) BW (FEO group), 2.5mgEBkg(-1) BW (EB group), and 0.5mlFEOkg(-1) BW+2.5mgEBkg(-1) BW (FEO+EB group) for 28 days. The obtained results showed that EB treatment resulted in a significant decrease in body weight, body weight gain, RBC count, Hb concentration, % PCV, MCV and MCHC. Moreover, EB significantly decreased total leukocyte, lymphocyte, monocyte and platelet count but significantly increased granulocyte count. EB markedly decreased total protein, albumin, globulin, IgG and IgM concentrations with a significant increase in TNF-α secretion. EB had a negative impact on the liver as it significantly increased ALT, ALP, and MDA, while decreasing SOD activity. Regarding to the histopathological examination, EB treatment induced coagulative necrosis and blood vessels congestion of the liver in treated rats. Furthermore, it resulted in depletion and necrosis of the white pulp of the spleen in treated rats. The co-administration of FEO with EB, however, improved the majority of parameters studied, suggesting that FEO is an important substance in decreasing toxic effects of EB.

  16. Toxic effects of sub-chronic exposure of male albino rats to emamectin benzoate and possible ameliorative role of Foeniculum vulgare essential oil.

    PubMed

    El-Sheikh, El-Sayed A; Galal, Azza A A

    2015-05-01

    Emamectin benzoate (EB) is an avermectin insecticide used extensively in pest control on vegetable and field crops. Few studies have been done for evaluating adverse effects of EB. In the current study, we evaluated the toxic effects of EB on male rats and the possible ameliorative role of fennel essential oil (FEO). Thirty two male rats were randomly divided into 4 equal groups. All groups were treated orally with distilled water (control group), 0.5mlFEOkg(-1) BW (FEO group), 2.5mgEBkg(-1) BW (EB group), and 0.5mlFEOkg(-1) BW+2.5mgEBkg(-1) BW (FEO+EB group) for 28 days. The obtained results showed that EB treatment resulted in a significant decrease in body weight, body weight gain, RBC count, Hb concentration, % PCV, MCV and MCHC. Moreover, EB significantly decreased total leukocyte, lymphocyte, monocyte and platelet count but significantly increased granulocyte count. EB markedly decreased total protein, albumin, globulin, IgG and IgM concentrations with a significant increase in TNF-α secretion. EB had a negative impact on the liver as it significantly increased ALT, ALP, and MDA, while decreasing SOD activity. Regarding to the histopathological examination, EB treatment induced coagulative necrosis and blood vessels congestion of the liver in treated rats. Furthermore, it resulted in depletion and necrosis of the white pulp of the spleen in treated rats. The co-administration of FEO with EB, however, improved the majority of parameters studied, suggesting that FEO is an important substance in decreasing toxic effects of EB. PMID:25935540

  17. Castration induced browning in subcutaneous white adipose tissue in male mice.

    PubMed

    Hashimoto, Osamu; Noda, Tatsuya; Morita, Atsushi; Morita, Masahiro; Ohtsuki, Hirofumi; Sugiyama, Makoto; Funaba, Masayuki

    2016-09-30

    We demonstrated that castration enhanced the expression of uncoupling protein 1 (Ucp1), a thermogenic protein, in brown adipose tissue (BAT) and subcutaneous (sc) white adipose tissue (WAT) in male mice. Castration of male mice increased body temperature and reduced body weight gain compared with those of sham-operated mice. BAT Ucp1 mRNA expression in castrated male mice was significantly higher than that in sham-operated mice. Histologically, cells with multilocular fat droplets were observed in the castrated inguinal scWAT. Immunohistochemical staining revealed that these cells positively reacted with the anti-Ucp1 antibody. The Ucp1-positive area near the inguinal lymph node in the castrated WAT was extensive compared with that of the sham-operated WAT. Castration-induced Ucp1 up-regulation in scWAT was suppressed by high-fat diet feeding. These findings suggest that thermogenesis by BAT activation and scWAT browning contribute to castration-induced inhibition of body weight gain. However, considering that the effect of castration was blunted by high-fat diet consumption, thermogenesis stimulation in response to castration is inhibited by chronic over-nutrition. PMID:27608598

  18. The SocioBox: A Novel Paradigm to Assess Complex Social Recognition in Male Mice

    PubMed Central

    Krueger-Burg, Dilja; Winkler, Daniela; Mitkovski, Mišo; Daher, Fernanda; Ronnenberg, Anja; Schlüter, Oliver M.; Dere, Ekrem; Ehrenreich, Hannelore

    2016-01-01

    Impairments in social skills are central to mental disease, and developing tools for their assessment in mouse models is essential. Here we present the SocioBox, a new behavioral paradigm to measure social recognition. Using this paradigm, we show that male wildtype mice of different strains can readily identify an unfamiliar mouse among 5 newly acquainted animals. In contrast, female mice exhibit lower locomotor activity during social exploration in the SocioBox compared to males and do not seem to discriminate between acquainted and unfamiliar mice, likely reflecting inherent differences in gender-specific territorial tasks. In addition to a simple quantification of social interaction time of mice grounded on predefined spatial zones (zone-based method), we developed a set of unbiased, data-driven analysis tools based on heat map representations and characterized by greater sensitivity. First proof-of-principle that the SocioBox allows diagnosis of social recognition deficits is provided using male PSD-95 heterozygous knockout mice, a mouse model related to psychiatric pathophysiology. PMID:27563287

  19. The SocioBox: A Novel Paradigm to Assess Complex Social Recognition in Male Mice.

    PubMed

    Krueger-Burg, Dilja; Winkler, Daniela; Mitkovski, Mišo; Daher, Fernanda; Ronnenberg, Anja; Schlüter, Oliver M; Dere, Ekrem; Ehrenreich, Hannelore

    2016-01-01

    Impairments in social skills are central to mental disease, and developing tools for their assessment in mouse models is essential. Here we present the SocioBox, a new behavioral paradigm to measure social recognition. Using this paradigm, we show that male wildtype mice of different strains can readily identify an unfamiliar mouse among 5 newly acquainted animals. In contrast, female mice exhibit lower locomotor activity during social exploration in the SocioBox compared to males and do not seem to discriminate between acquainted and unfamiliar mice, likely reflecting inherent differences in gender-specific territorial tasks. In addition to a simple quantification of social interaction time of mice grounded on predefined spatial zones (zone-based method), we developed a set of unbiased, data-driven analysis tools based on heat map representations and characterized by greater sensitivity. First proof-of-principle that the SocioBox allows diagnosis of social recognition deficits is provided using male PSD-95 heterozygous knockout mice, a mouse model related to psychiatric pathophysiology. PMID:27563287

  20. Expression and localization of cysteine sulfinate decarboxylase in major salivary glands of male mice.

    PubMed

    Liu, Shengnan; Liu, Ying; Ma, Qiwang; Cui, Sheng; Liu, Jiali

    2015-04-01

    Taurine (2-aminoethanesulfonic acid) is the most abundant free amino acid in mammalian cells. It plays a significant role in cell development, nutrition, and survival, such as in the regulation of ion transport and osmoregulation. Cysteine sulfinate decarboxylase (CSD) is the rate-limiting biosynthetic enzyme of taurine. Recently, the synthesis of taurine has been observed in the central nervous system, kidney, liver, and muscle. However, the synthesis of taurine in the salivary glands has still not been described in detail. We have detected CSD expression in the major salivary glands of adult male mice by real-time polymerase chain reaction (RT-PCR), Western blot, and immunofluorescence. In addition, we determined the content of taurine by high-performance liquid chromatography (HPLC). The results show that taurine is present in high concentrations in the major salivary glands of male mice. CSD messenger RNA (mRNA) and protein are expressed in the major salivary glands of male mice. The relative levels of CSD mRNA increase from the submandibular gland (SMG) to the sublingual gland (SLG) and parotid gland (PG), but the levels of the CSD protein are the opposite. The immunofluorescence results indicate that CSD is mainly located in the excretory ducts (EDs) and interlobular duct (IL) of SMG and ED in SLG, respectively. These results suggest that the major salivary glands of male mice produce taurine through the CSD pathway, and the synthesis of taurine might be related to sodium reabsorption in the salivary glands. PMID:25645459

  1. [Effect of sodium valproate on aggressive behavior of male mice with various aggression experience].

    PubMed

    Smagin, D A; Bondar', N P; Kudriavtseva, N N

    2010-01-01

    Sector of Social Behavior Neurogenetics, Institute of Cytology and Genetics, Siberian Branch, Effects of sodium valproate on the aggressive behavior of male mice with 2- and 20-day positive fighting experience have been studied. It is established that valproate administered in a singe dose of 100 mg/kg has no effect on the behavior of male mice with a 2-day experience of aggression. The treatment of mice with 300 mg/kg of valproate significantly decreased the level of aggressive motivation and the percentage of animals demonstrating attacks and threats. In male mice with a 20-day experience of aggression, valproate decreased the time of hostile behavior in a dose-dependent manner. Valproate in a single dose of 300 mg/kg significantly decreased the level of aggressive motivation, but also produced a toxic effect, whereby 73% of aggressive males demonstrated long-term immobility and 45% exhibited movement abnormalities (falls) upon the treatment. It is suggested that changes in the brain neurochemical activity, which are caused by a prolonged experience of aggression, modify the effects of sodium valproate.

  2. THE EFFECTS OF HYPERTHERMIA ON SPERMATOGENESIS, APOPTOSIS, GENE EXPRESSION AND FERTILITY IN ADULT MALE MICE

    EPA Science Inventory

    The effects of hyperthermia on spermatogenesis, apoptosis, gene expression and fertility in adult male mice
    John C. Rockett1, Faye L. Mapp1, J. Brian Garges1, J. Christopher Luft1, Chisato Mori2 and David J. Dix1.
    1Reproductive Toxicology Division, National Health and Envir...

  3. Soy protein isolate protects against ethanol mediated tumor progression in diethylnitrosamine treated male mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, DEN-treated male mice were assigned to 3 groups: a 35% high fat ethanol liquid diet (EtOH) with casein as the protein source, the same EtOH liquid diet with soy protein isolate as the sole protein source (EtOH/soy) and a chow group. EtOH feeding continued for 16 wks. As expected, E...

  4. Adipocyte deficiency of angiotensinogen prevents obesity-induced hypertension in male mice.

    PubMed

    Yiannikouris, Frederique; Gupte, Manisha; Putnam, Kelly; Thatcher, Sean; Charnigo, Richard; Rateri, Debra L; Daugherty, Alan; Cassis, Lisa A

    2012-12-01

    Previous studies demonstrated that diet-induced obesity increased plasma angiotensin II concentrations and elevated systolic blood pressures in male mice. Adipocytes express angiotensinogen and secrete angiotensin peptides. We hypothesize that adipocyte-derived angiotensin II mediates obesity-induced increases in systolic blood pressure in male high fat-fed C57BL/6 mice. Systolic blood pressure was measured by radiotelemetry during week 16 of low-fat or high-fat feeding in Agt(fl/fl) and adipocyte angiotensinogen-deficient mice (Agt(aP2)). Adipocyte angiotensinogen deficiency had no effect on diet-induced obesity. Basal 24-hour systolic blood pressure was not different in low fat-fed Agt(fl/fl) compared with Agt(aP2) mice (124 ± 3 versus 128 ± 3 mm Hg, respectively). In Agt(fl/fl) mice, high-fat feeding significantly increased systolic blood pressure (24 hours; 134 ± 2 mm Hg; P<0.05). In contrast, high fat-fed Agt(aP2) mice did not exhibit an increase in systolic blood pressure (126 ± 2 mm Hg). Plasma angiotensin II concentrations were increased by high-fat feeding in Agt(fl/fl) mice (low fat, 32 ± 14; high fat, 219 ± 58 pg/mL; P<0.05). In contrast, high fat-fed Agt(aP2) mice did not exhibit elevated plasma angiotensin II concentrations (high fat, 18 ± 7 pg/mL). Similarly, adipose tissue concentrations of angiotensin II were significantly decreased in low fat- and high fat-fed Agt(aP2) mice compared with controls. In conclusion, adipocyte angiotensinogen deficiency prevented high fat-induced elevations in plasma angiotensin II concentrations and systolic blood pressure. These results suggest that adipose tissue serves as a major source of angiotensin II in the development of obesity hypertension.

  5. Spatiotemporal features of early neuronogenesis differ in wild-type and albino mouse retina

    NASA Technical Reports Server (NTRS)

    Rachel, Rivka A.; Dolen, Gul; Hayes, Nancy L.; Lu, Alice; Erskine, Lynda; Nowakowski, Richard S.; Mason, Carol A.

    2002-01-01

    In albino mammals, lack of pigment in the retinal pigment epithelium is associated with retinal defects, including poor visual acuity from a photoreceptor deficit in the central retina and poor depth perception from a decrease in ipsilaterally projecting retinal fibers. Possible contributors to these abnormalities are reported delays in neuronogenesis (Ilia and Jeffery, 1996) and retinal maturation (Webster and Rowe, 1991). To further determine possible perturbations in neuronogenesis and/or differentiation, we used cell-specific markers and refined birth dating methods to examine these events during retinal ganglion cell (RGC) genesis in albino and pigmented mice from embryonic day 11 (E11) to E18. Our data indicate that relative to pigmented mice, more ganglion cells are born in the early stages of neuronogenesis in the albino retina, although the initiation of RGC genesis in the albino is unchanged. The cellular organization of the albino retina is perturbed as early as E12. In addition, cell cycle kinetics and output along the nasotemporal axis differ in retinas of albino and pigmented mice, both absolutely, with the temporal aspect of the retina expanded in albino, and relative to the position of the optic nerve head. Finally, blocking melanin synthesis in pigmented eyecups in culture leads to an increase in RGC differentiation, consistent with a role for melanin formation in regulating RGC neuronogenesis. These results point to spatiotemporal defects in neuronal production in the albino retina, which could perturb expression of genes that specify cell fate, number, and/or projection phenotype.

  6. The protective effect of aged garlic extract on nonsteroidal anti-inflammatory drug-induced gastric inflammations in male albino rats.

    PubMed

    Badr, Gehan Moustafa; Al-Mulhim, Jawaher Abdulaziz

    2014-01-01

    Natural products have long gained wide acceptance among the public and scientific community in the gastrointestinal ulcerative field. The present study explore the potential effects of aged garlic extract (AGE) on indomethacin-(IN-) induced gastric inflammation in male rats. Animals were divided into six groups (n = 8) control group, IN-induced gastric inflammation group via oral single dose (30 mg/kg to fasted rats) two AGE orally administered groups (100 and 200 mg/kg for 30 consecutive days) two AGE orally administered groups to rats pretreated with IN at the same aforementioned doses. The results declared the more potent effect of the higher AGE dose (200 mg/kg) as compared to that of the 100 mg/kg dose in the gastroprotective effects reflected by significant gastric mucosal healing of damage and reduction in the total microbial induced due to indomethacin administration. In addition to the significant effect to normalize the significant increase in malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor- α (TNF- α ) values, and the significant decrease in the total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) values induced by indomethacin. The results support AGE antioxidant, anti-inflammatory, and antimicrobial potency reflected by the healing of the gastric tissue damage induced by indomethacin.

  7. The Protective Effect of Aged Garlic Extract on Nonsteroidal Anti-Inflammatory Drug-Induced Gastric Inflammations in Male Albino Rats

    PubMed Central

    Badr, Gehan Moustafa; AL-Mulhim, Jawaher Abdulaziz

    2014-01-01

    Natural products have long gained wide acceptance among the public and scientific community in the gastrointestinal ulcerative field. The present study explore the potential effects of aged garlic extract (AGE) on indomethacin-(IN-) induced gastric inflammation in male rats. Animals were divided into six groups (n = 8) control group, IN-induced gastric inflammation group via oral single dose (30 mg/kg to fasted rats) two AGE orally administered groups (100 and 200 mg/kg for 30 consecutive days) two AGE orally administered groups to rats pretreated with IN at the same aforementioned doses. The results declared the more potent effect of the higher AGE dose (200 mg/kg) as compared to that of the 100 mg/kg dose in the gastroprotective effects reflected by significant gastric mucosal healing of damage and reduction in the total microbial induced due to indomethacin administration. In addition to the significant effect to normalize the significant increase in malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α) values, and the significant decrease in the total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) values induced by indomethacin. The results support AGE antioxidant, anti-inflammatory, and antimicrobial potency reflected by the healing of the gastric tissue damage induced by indomethacin. PMID:24876878

  8. The protective effect of aged garlic extract on nonsteroidal anti-inflammatory drug-induced gastric inflammations in male albino rats.

    PubMed

    Badr, Gehan Moustafa; Al-Mulhim, Jawaher Abdulaziz

    2014-01-01

    Natural products have long gained wide acceptance among the public and scientific community in the gastrointestinal ulcerative field. The present study explore the potential effects of aged garlic extract (AGE) on indomethacin-(IN-) induced gastric inflammation in male rats. Animals were divided into six groups (n = 8) control group, IN-induced gastric inflammation group via oral single dose (30 mg/kg to fasted rats) two AGE orally administered groups (100 and 200 mg/kg for 30 consecutive days) two AGE orally administered groups to rats pretreated with IN at the same aforementioned doses. The results declared the more potent effect of the higher AGE dose (200 mg/kg) as compared to that of the 100 mg/kg dose in the gastroprotective effects reflected by significant gastric mucosal healing of damage and reduction in the total microbial induced due to indomethacin administration. In addition to the significant effect to normalize the significant increase in malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor- α (TNF- α ) values, and the significant decrease in the total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) values induced by indomethacin. The results support AGE antioxidant, anti-inflammatory, and antimicrobial potency reflected by the healing of the gastric tissue damage induced by indomethacin. PMID:24876878

  9. Corrective role of Eugenia jambolana on testicular impairment in streptozotocin-induced diabetic male albino rat: an approach through genomic and proteomic study.

    PubMed

    Ghosh, A; Jana, K; Ali, K M; De, D; Chatterjee, K; Ghosh, D

    2014-04-01

    The present study was conducted to explore the effect of ethyl acetate fraction of hydro-methanolic (40 : 60) extract of seed of Eugenia jambolana on testicular impairment in diabetic rats. In this respect, biomarkers of oxidative stress, genomics and proteomics in testicular tissue were assessed. Side by side, glycated haemoglobin, serum testosterone, activities of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in serum, epididymal sperm count including reproductive organosomatic indices were evaluated. Results indicate that a significant recovery (P < 0.05) in the levels of these parameters in fraction-treated diabetic group in comparison with diabetic control. A significant recovery was noted (P < 0.05) in the expression of Bax and Bcl-2 gene towards the control after the treatment of said fraction. Histological study also focused a significant recovery (P < 0.05) in the number of different generation of germ cells at stage VII of spermatogenesis in fraction-treated diabetic group. The said fraction treatment to diabetic rat can recover the activities of serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase significantly towards the control (P < 0.05). Finally, it may be concluded that ethyl acetate fraction of seed of E. jambolana has a promiseable remedial effect on diabetes-induced testicular dysfunctions in male rat without inducing any metabolic toxicity.

  10. Sex hormone influence on hepatitis in young male A/JCr mice infected with Helicobacter hepaticus.

    PubMed

    Theve, Elizabeth J; Feng, Yan; Taghizadeh, Koli; Cormier, Kathleen S; Bell, David R; Fox, James G; Rogers, Arlin B

    2008-09-01

    Hepatitis B virus (HBV), the leading cause of human hepatocellular carcinoma, is especially virulent in males infected at an early age. Likewise, the murine liver carcinogen Helicobacter hepaticus is most pathogenic in male mice infected before puberty. We used this model to investigate the influence of male sex hormone signaling on infectious hepatitis. Male A/JCr mice were infected with H. hepaticus or vehicle at 4 weeks and randomized into surgical and pharmacologic treatment groups. Interruption of androgen pathways was confirmed by hormone measurements, histopathology, and liver gene and Cyp4a protein expression. Castrated males and those receiving the competitive androgen receptor antagonist flutamide had significantly less severe hepatitis as determined by histologic activity index than intact controls at 4 months. Importantly, the powerful androgen receptor agonist dihydrotestosterone did not promote hepatitis. No effect on hepatitis was evident in males treated with the 5alpha-reductase inhibitor dutasteride, the peroxisome proliferator-activated receptor-alpha agonist bezafibrate, or the nonsteroidal anti-inflammatory drug flufenamic acid. Consistent with previous observations of hepatitis-associated liver-gender disruption, transcriptional alterations involved both feminine (cytochrome P450 4a14) and masculine (cytochrome P450 4a12 and trefoil factor 3) genes, as well gender-neutral (H19 fetal liver mRNA, lipocalin 2, and ubiquitin D) genes. Hepatitis was associated with increased unsaturated C(18) long-chain fatty acids (oleic acid and linoleic acid) relative to saturated stearic acid. Our results indicate that certain forms of androgen interruption can inhibit H. hepaticus-induced hepatitis in young male mice, whereas androgen receptor agonism does not worsen disease. This raises the possibility of targeted hormonal therapy in young male patients with childhood-acquired HBV.

  11. Efficacy of Tramadol as a Sole Analgesic for Postoperative Pain in Male and Female Mice.

    PubMed

    Wolfe, A Marissa; Kennedy, Lucy H; Na, Jane J; Nemzek-Hamlin, Jean A

    2015-07-01

    Tramadol is a centrally acting weak μ opioid agonist that has few of the adverse side effects common to other opioids. Little work has been done to establish an effective analgesic dose of tramadol specific for surgical laparotomy and visceral manipulation in mice. We used general appearance parameters to score positive indicators of pain including posture, coat condition, activity, breathing, and interactions with other mice, activity events (that is, the number of times each mouse stretched up in a 3-min period) used as an indicator of decreased pain, von Frey fibers, and plasma levels of corticosterone to determine whether tramadol at 20, 40, or 80 mg/kg prevented postoperative pain in male and female C57BL/6 mice. A ventral midline laparotomy with typhlectomy was used as a model of postoperative pain. In male mice, none of the markers differed between groups that received tramadol (regardless of dose) and the saline-treated controls. However, general appearance scores and plasma corticosterone levels were lower in female mice that received 80 mg/kg tramadol compared with saline. In summary, for severe postoperative pain after laparotomy and aseptic typhlectomy, tramadol was ineffective in male C57BL/6 mice at all doses tested. Although 80 mg/kg ameliorated postoperative pain in female C57BL/6 mice, this dose is very close to the threshold reported to cause toxic side effects, such as tremors and seizures. Therefore, we do not recommend the use of tramadol as a sole analgesic in this mouse model of postoperative pain.

  12. Efficacy of Tramadol as a Sole Analgesic for Postoperative Pain in Male and Female Mice.

    PubMed

    Wolfe, A Marissa; Kennedy, Lucy H; Na, Jane J; Nemzek-Hamlin, Jean A

    2015-07-01

    Tramadol is a centrally acting weak μ opioid agonist that has few of the adverse side effects common to other opioids. Little work has been done to establish an effective analgesic dose of tramadol specific for surgical laparotomy and visceral manipulation in mice. We used general appearance parameters to score positive indicators of pain including posture, coat condition, activity, breathing, and interactions with other mice, activity events (that is, the number of times each mouse stretched up in a 3-min period) used as an indicator of decreased pain, von Frey fibers, and plasma levels of corticosterone to determine whether tramadol at 20, 40, or 80 mg/kg prevented postoperative pain in male and female C57BL/6 mice. A ventral midline laparotomy with typhlectomy was used as a model of postoperative pain. In male mice, none of the markers differed between groups that received tramadol (regardless of dose) and the saline-treated controls. However, general appearance scores and plasma corticosterone levels were lower in female mice that received 80 mg/kg tramadol compared with saline. In summary, for severe postoperative pain after laparotomy and aseptic typhlectomy, tramadol was ineffective in male C57BL/6 mice at all doses tested. Although 80 mg/kg ameliorated postoperative pain in female C57BL/6 mice, this dose is very close to the threshold reported to cause toxic side effects, such as tremors and seizures. Therefore, we do not recommend the use of tramadol as a sole analgesic in this mouse model of postoperative pain. PMID:26224442

  13. Efficacy of Tramadol as a Sole Analgesic for Postoperative Pain in Male and Female Mice

    PubMed Central

    Wolfe, A Marissa; Kennedy, Lucy H; Na, Jane J; Nemzek-Hamlin, Jean A

    2015-01-01

    Tramadol is a centrally acting weak μ opioid agonist that has few of the adverse side effects common to other opioids. Little work has been done to establish an effective analgesic dose of tramadol specific for surgical laparotomy and visceral manipulation in mice. We used general appearance parameters to score positive indicators of pain including posture, coat condition, activity, breathing, and interactions with other mice, activity events (that is, the number of times each mouse stretched up in a 3-min period) used as an indicator of decreased pain, von Frey fibers, and plasma levels of corticosterone to determine whether tramadol at 20, 40, or 80 mg/kg prevented postoperative pain in male and female C57BL/6 mice. A ventral midline laparotomy with typhlectomy was used as a model of postoperative pain. In male mice, none of the markers differed between groups that received tramadol (regardless of dose) and the saline-treated controls. However, general appearance scores and plasma corticosterone levels were lower in female mice that received 80 mg/kg tramadol compared with saline. In summary, for severe postoperative pain after laparotomy and aseptic typhlectomy, tramadol was ineffective in male C57BL/6 mice at all doses tested. Although 80 mg/kg ameliorated postoperative pain in female C57BL/6 mice, this dose is very close to the threshold reported to cause toxic side effects, such as tremors and seizures. Therefore, we do not recommend the use of tramadol as a sole analgesic in this mouse model of postoperative pain. PMID:26224442

  14. Reproductive toxicity of chronic lead exposure in male and female mice.

    PubMed

    Pinon-Lataillade, G; Thoreux-Manlay, A; Coffigny, H; Masse, R; Soufir, J C

    1995-11-01

    The reproductive toxicity of lead was investigated in NMRI mice exposed to 0.5% lead acetate in drinking water from day 1 of intra-uterine life until 60 days after birth. Compared with control mice, the weights of lead-exposed fetuses and subsequently of the lead-exposed weaned pups, male and female, diminished by 11 and 13% respectively. The lead-exposed male and female offspring of lead-exposed dams were mated with unexposed females and males, to examine the effect of lead exposure on reproductive function. Male fertility was not affected but reduced female fertility was observed: litters were smaller and a smaller number of implantation sites was found in lead-exposed females. In lead-exposed males, the weights of the body, testes and epididymes diminished by about 13%, and seminal vesicle and ventral prostate weights, by about 29%. Testicular histology and the number and morphology of epididymal spermatozoa were normal. The levels of plasma FSH, LH and testosterone, and of testicular testosterone, were not modified. These results suggest that the hypothalamic-pituitary-testicular axis is not adversely affected by the above lead exposure, and that therefore the decreased seminal vesicle and ventral prostate weights might not be the consequence of reduced testosterone levels. The hypothesis that lead has a direct effect on these organs as well as a secondary effect resulting from possibly reduced food consumption by lead-exposed mice cannot be excluded. Consequently, in male NMRI mice, exposure to lead might affect reproductive function by acting directly and/or indirectly on accessory sex organs.

  15. Microclones derived from the mouse chromosome 7 D-E bands map within the proximal region of the c14CoS deletion in albino mutant mice

    SciTech Connect

    Toenjes, R.R.W.; Weith, A.; Rinchik, E.M.; Winking, H.; Carnwath, J.W.; Kaliner, B.; Paul, D. )

    1991-07-01

    A group of radiation-induced perinatal-lethal deletions that include the albino (c) locus on mouse chromosome 7 causes failure of expression of various hepatocyte-specific genes when homozygous. The transcription of such genes could be controlled in trans by a regulatory gene(s) located within the proximal region of the C14CoS deletion. To identify this potential regulatory gene, a microclone library was established from microdissected D and E bands of chromosome 7. Three nonoverlapping microclones (E305, E336B, and E453B) hybridizing with wildtype but not with C14CoS/C14CoS DNA were isolated. E336B represents a single-copy DNA fragment, whereas E305 and E453B hybridized with 3 and 10 EcoRI DNA restriction fragments, respectively. All fragments map exclusively within the deletion. The microclones hybridized to DNA of viable C6H/C14CoS deletion heterozygotes but not to DNA of homozygotes for the lethal mutation c10R75M, which belongs to the same complementation group as c14CoS. DNA of viable homozygous mutant C62DSD, which carries a deletion breakpoint proximal to that of c6H, hybridized only with E453B. This microclone identified 6 EcoRI restriction fragments in C62DSD/C62DSD DNA. The results demonstrate that of the isolated microclones, E453B identifies a locus (D7RT453B) that maps closest to the hsdr-1 (hepatocyte-specific developmental regulation) locus, which maps between the proximal breakpoints of deletions c10R75M and c62DSD.

  16. Hydrolyzed casein reduces diet-induced obesity in male C57BL/6J mice.

    PubMed

    Lillefosse, Haldis H; Tastesen, Hanne Sørup; Du, Zhen-Yu; Ditlev, Ditte B; Thorsen, Frits A; Madsen, Lise; Kristiansen, Karsten; Liaset, Bjørn

    2013-09-01

    The digestion rate of dietary protein is a regulating factor for postprandial metabolism both in humans and animal models. However, few data exist about the habitual consumption of proteins with different digestion rates with regard to the development of body mass and diet-induced obesity. Here, we used a factorial ANOVA design to investigate the effects of protein form (intact vs. hydrolyzed casein) and protein level (16 vs. 32 energy percent protein) on body mass gain and adiposity in obesity-prone male C57BL/6J mice fed Western diets with 35 energy percent fat. Mice fed the hydrolyzed casein diets had higher spontaneous locomotor activity than mice fed intact casein. During the light phase, mice fed hydrolyzed casein tended (P = 0.08) to have a lower respiratory exchange ratio, indicating lower utilization of carbohydrates as energy substrate relative to those fed intact casein. In further support of less carbohydrate oxidation, plasma concentrations of glucose and those of the glucose metabolite lactate were lower in fed mice that consumed the hydrolyzed compared with the intact casein diet. Concomitantly, the plasma insulin concentration was strongly reduced in fed mice given hydrolyzed casein relative to those given intact casein. The mice fed hydrolyzed casein had greater ex vivo inguinal white adipose tissue non-CO2 β-oxidation capacity along with induced expression of genes involved in mitochondrial fatty acid oxidation and mitochondrial uncoupling. The physiological changes induced by hydrolyzed casein ingestion translated into decreased body and adipose tissue masses. We conclude that chronic consumption of extensively hydrolyzed casein reduces body mass gain and diet-induced obesity in male C57BL/6J mice.

  17. Variation in airway responsiveness of male C57BL/6 mice from 5 vendors.

    PubMed

    Chang, Herng-Yu Sucie; Mitzner, Wayne; Watson, Julie

    2012-07-01

    Mice are now the most commonly used animal model for the study of asthma. The mouse asthma model has many characteristics of the human pathology, including allergic sensitization and airway hyperresponsiveness. Inbred strains are commonly used to avoid variations due to genetic background, but variations due to rearing environment are not as well recognized. After a change in mouse vendors and a switch from C57BL/6J mice to C57BL/6N mice, we noted significant differences in airway responsiveness between the substrains. To further investigate the effect of vendor, we tested C57BL/6N mice from 3 other vendors and found significant differences between several of the substrains. To test whether this difference was due to genetic drift or rearing environment, we purchased new groups of mice from all 5 vendors, bred them in separate vendor-specific groups under uniform environmental conditions, and tested male first generation (F1) offspring at 8 to 10 wk of age. These F1 mice showed no significant differences in airway responsiveness, indicating that the rearing environment rather than genetic differences was responsible for the initial variation in pulmonary phenotype. The environmental factors that caused the phenotypic variation are unknown. However, differences between vendor in feed components, bedding type, or microbiome could have contributed. Whatever the basis, investigators using mouse models of asthma should be cautious in comparing data from mice obtained from different vendors.

  18. Reproductive abnormalities in adult male mice following preimplantation exposures to estradiol or pesticide methoxychlor.

    PubMed

    Amstislavsky, Sergei Ya; Amstislavskaya, Tamara G; Amstislavsky, Vjacheslav S; Tibeikina, Marina A; Osipov, Kiril V; Eroschenko, Victor P

    2006-02-01

    Adult females of ICR strain of mice were bred, separated into different experimental groups, and treated as follows. On Days 2-4 of pregnancy, the mice received daily subcutaneous injections of either 0.05 ml sesame oil (vehicle) or same volume of 5.0mg of purified methoxychlor (MXC) suspended in the vehicle. Another group received a single subcutaneous injection of 1.0 microg of estradiol-17beta (E) on Day 2 of pregnancy only. Male offspring were tested at 3 and 6 months of age. At 3 months, E or MXC did not alter the weights of seminal vesicles, preputial glands, or testes, although after exposure for 30 min to a female in estrus behind a partition, testosterone levels were significantly reduced in treated males in comparison to control males exposed to the same partition test. At 6 months, the preputial glands and testes weight remained unchanged, while the seminal vesicles were significantly heavier in E- and MXC-treated males. Same partition tests again revealed that in E and MXC groups, testosterone levels remained significantly lower in comparison to control males. MXC or E exposures during preimplantation appear to induce long-term effects on the sexual development in 3 and 6 month-old-males by compromising their sexual arousal and altering seminal vesicles weights in the older group.

  19. Steroid Tumor Environment in Male and Female Mice Model of Canine and Human Inflammatory Breast Cancer

    PubMed Central

    Caceres, Sara; Peña, Laura; Silvan, Gema; Illera, Maria J.; Woodward, Wendy A.; Reuben, James M.; Illera, Juan C.

    2016-01-01

    Canine inflammatory mammary cancer (IMC) shares clinical and histopathological characteristics with human inflammatory breast cancer (IBC) and has been proposed as a good model for studying the human disease. The aim of this study was to evaluate the capacity of female and male mice to reproduce IMC and IBC tumors and identify the hormonal tumor environment. To perform the study sixty 6–8-week-old male and female mice were inoculated subcutaneously with a suspension of 106IPC-366 and SUM149 cells. Tumors and serum were collected and used for hormonal analysis. Results revealed that IPC-366 reproduced tumors in 90% of males inoculated after 2 weeks compared with 100% of females that reproduced tumor at the same time. SUM149 reproduced tumors in 40% of males instead of 80% of females that reproduced tumors after 4 weeks. Both cell lines produce distant metastasis in lungs being higher than the metastatic rates in females. EIA analysis revealed that male tumors had higher T and SO4E1 concentrations compared to female tumors. Serum steroid levels were lower than those found in tumors. In conclusion, IBC and IMC male mouse model is useful as a tool for IBC research and those circulating estrogens and intratumoral hormonal levels are crucial in the development and progression of tumors. PMID:27195300

  20. Papain-induced experimental pulmonary emphysema in male and female mice.

    PubMed

    Machado, Mariana Nascimento; Figueirôa, Silviane Fernandes da Silva; Mazzoli-Rocha, Flavia; Valença, Samuel dos Santos; Zin, Walter Araújo

    2014-08-15

    In papain-induced models of emphysema, despite the existing extensive description of the cellular and molecular aspects therein involved, sexual hormones may play a complex and still not fully understood role. Hence, we aimed at exploring the putative gender-related differences in lung mechanics, histology and oxidative stress in papain-exposed mice. Thirty adult BALB/c mice received intratracheally either saline (50 μL) or papain (10 U/50 μL saline) once a week for 2 weeks. In males papain increased lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance, while females showed higher static elastance and resistive pressure only. Both genders presented similar higher parenchymal cellularity and mean alveolar diameter, and less collagen-elastic fiber content and body weight gain than their respective controls. Increased functional residual capacity was more prominent in males. Female papain-treated mice were more susceptible to oxidative stress. Thus, male and female papain-exposed mice respond differently, which should be carefully considered to avoid confounding results.

  1. Perinatal exposure to diethylstilbestrol improves olfactory discrimination learning in male and female Swiss-Webster mice.

    PubMed

    Mihalick, Sheila M

    2003-07-01

    During late prenatal and early postnatal brain development, estrogen induces structural sex differences that correspond to behavioral differences in certain domains such as learning and memory. The typically superior performance of males is attributed to the action of elevated concentrations of estrogen, derived inside neurons from the aromatization of testosterone. In contrast, female performance appears dependent on minimal estrogenic activity. Rat models of the relationship between hormones and cognitive behavior predominate the field, but the advent of genetically modified mice as research tools necessitates development of analogous mouse models. This study examined how early postnatal exposure to the synthetic estrogen diethylstilbestrol (DES) affected the ability of male and female Swiss-Webster mice to learn a two-choice olfactory discrimination and three repeated reversals. Mice treated with subcutaneous injections of DES from postnatal days 1-10 learned reversals more readily than oil-treated controls, a difference that became evident after repeated testing. DES-exposed males and females learned reversals at a comparable rate, suggesting that early postnatal estrogen exposure does not influence this mode of learning through a sexually differentiated mechanism in mice. An analysis of response patterns during qualitatively different phases of reversal learning revealed that DES-induced improvements probably were not due to greater inhibitory control. Instead, DES appeared to enhance associative ability. Early postnatal estrogen exposure may have the potential to preserve certain cognitive skills in adulthood.

  2. Citrus limon extract: possible inhibitory mechanisms affecting testicular functions and fertility in male mice.

    PubMed

    Singh, Nidhi; Singh, Shio Kumar

    2016-01-01

    The effect of oral administration of 50% ethanolic leaf extract of Citrus limon (500 and 1,000 mg/kg body weight/day) for 35 days on fertility and various male reproductive endpoints was evaluated in Parkes strain of mice. Testicular indices such as histology, 3β- and 17β-HSD enzymes activity, immunoblot expression of StAR and P450scc, and germ cell apoptosis by TUNEL and CASP- 3 expression were assessed. Motility, viability, and number of spermatozoa in the cauda epididymidis, level of serum testosterone, fertility indices, and toxicological parameters were also evaluated. Histologically, testes in extract-treated mice showed nonuniform degenerative changes in the seminiferous tubules. Treatment had adverse effects on steroidogenic markers in the testis and induced germ cell apoptosis. Significant reductions were noted in epididymal sperm parameters and serum level of testosterone in Citrus-treated mice compared to controls. Fertility of the extract-treated males was also suppressed, but libido remained unaffected. By 56 days of treatment withdrawal, alterations induced in the above parameters returned to control levels suggesting that Citrus treatment causes reversible suppression of spermatogenesis and fertility in Parkes mice. Suppression of spermatogenesis may result from germ cell apoptosis because of decreased production of testosterone. The present work indicated that Citrus leaves can affect male reproduction. PMID:26787324

  3. Generation of progeny from embryonic stem cells by microinsemination of male germ cells from chimeric mice.

    PubMed

    Mizutani, Eiji; Ohta, Hiroshi; Kishigami, Satoshi; Van Thuan, Nguyen; Hikichi, Takafusa; Wakayama, Sayaka; Sato, Eimei; Wakayama, Teruhiko

    2005-09-01

    Mice chimeric for embryonic stem (ES) cells have not always successfully produced ES-derived offspring. Here we show that the male gametes from ES cells could be selected in male chimeric mice testes by labeling donor ES cells or host blastocytes with GFP. Male GFP-expressing ES-derived germ cells occurred as colonies in the chimeric testes, where the seminiferous tubules were separated into green and non-green regions. When mature spermatozoa from green tubules were used for microinsemination, GFP-expressing offspring were efficiently obtained. Using a reverse study, we also obtained ES-derived progeny from GFP-negative ES cells in GFP-labeled host chimeras. Furthermore, we showed this approach could be accelerated by using round spermatids from the testes of 20-day-old chimeric mice. Thus, this technique allowed us to generate the ES cell-derived progeny even from the low contributed chimeric mice, which cannot produce ES-origin offspring by natural mating.

  4. Crocin Improves Damage Induced by Nicotine on A Number of Reproductive Parameters in Male Mice

    PubMed Central

    Salahshoor, Mohammad Reza; Khazaei, Mozafar; Jalili, Cyrus; Keivan, Mona

    2016-01-01

    Background Crocin, a carotenoid isolated from Crocus sativus L. (saffron), is a pharmacologically active component of saffron. Nicotine consumption can decrease fertility in males through induction of oxidative stress and DNA damage. The aim of this study is to determine the effects of crocin on reproductive parameter damages in male mice exposed to nicotine. Materials and Methods In this experimental study, we divided 48 mice into 8 groups (n=6 per group): control (normal saline), nicotine (2.5 mg/kg), crocin (12.5, 25 and 50 mg/kg) and crocin (12.5, 25 and 50 mg/kg)+nicotine (2.5 mg/kg). Mice received once daily intraperitoneal injections of crocin, nicotine and crocin+nicotine for 4 weeks. Sperm parameters (count, motility, and viability), testis weight, seminiferous tube diameters, testosterone, and serum nitric oxide levels were analyzed and compared. Results Nicotine administration significantly decreased testosterone level; sperm count, viability, and motility; testis weight and seminiferous tubule diameters compared to the control group (P<0.05). However, increasing the dose of crocin in the crocin and crocin+nicotine groups significantly boosted sperm motility and viability; seminiferous tubule diameters; testis weight; and testosterone levels in all groups compared to the nicotine group (P<0.05). Conclusion Crocin improves nicotine-induced adverse effects on reproductive parameters in male mice. PMID:27123203

  5. Citrus limon extract: possible inhibitory mechanisms affecting testicular functions and fertility in male mice.

    PubMed

    Singh, Nidhi; Singh, Shio Kumar

    2016-01-01

    The effect of oral administration of 50% ethanolic leaf extract of Citrus limon (500 and 1,000 mg/kg body weight/day) for 35 days on fertility and various male reproductive endpoints was evaluated in Parkes strain of mice. Testicular indices such as histology, 3β- and 17β-HSD enzymes activity, immunoblot expression of StAR and P450scc, and germ cell apoptosis by TUNEL and CASP- 3 expression were assessed. Motility, viability, and number of spermatozoa in the cauda epididymidis, level of serum testosterone, fertility indices, and toxicological parameters were also evaluated. Histologically, testes in extract-treated mice showed nonuniform degenerative changes in the seminiferous tubules. Treatment had adverse effects on steroidogenic markers in the testis and induced germ cell apoptosis. Significant reductions were noted in epididymal sperm parameters and serum level of testosterone in Citrus-treated mice compared to controls. Fertility of the extract-treated males was also suppressed, but libido remained unaffected. By 56 days of treatment withdrawal, alterations induced in the above parameters returned to control levels suggesting that Citrus treatment causes reversible suppression of spermatogenesis and fertility in Parkes mice. Suppression of spermatogenesis may result from germ cell apoptosis because of decreased production of testosterone. The present work indicated that Citrus leaves can affect male reproduction.

  6. Enzalutamide Reduces the Bone Mass in the Axial But Not the Appendicular Skeleton in Male Mice.

    PubMed

    Wu, Jianyao; Movérare-Skrtic, Sofia; Börjesson, Anna E; Lagerquist, Marie K; Sjögren, Klara; Windahl, Sara H; Koskela, Antti; Grahnemo, Louise; Islander, Ulrika; Wilhelmson, Anna S; Tivesten, Åsa; Tuukkanen, Juha; Ohlsson, Claes

    2016-02-01

    Testosterone is a crucial regulator of the skeleton, but the role of the androgen receptor (AR) for the maintenance of the adult male skeleton is unclear. In the present study, the role of the AR for bone metabolism and skeletal growth after sexual maturation was evaluated by means of the drug enzalutamide, which is a new AR antagonist used in the treatment of prostate cancer patients. Nine-week-old male mice were treated with 10, 30, or 100 mg/kg·d of enzalutamide for 21 days or were surgically castrated and were compared with vehicle-treated gonadal intact mice. Although orchidectomy reduced the cortical bone thickness and trabecular bone volume fraction in the appendicular skeleton, these parameters were unaffected by enzalutamide. In contrast, both enzalutamide and orchidectomy reduced the bone mass in the axial skeleton as demonstrated by a reduced lumbar spine areal bone mineral density (P < .001) and trabecular bone volume fraction in L5 vertebrae (P < .001) compared with vehicle-treated gonadal intact mice. A compression test of the L5 vertebrae revealed that the mechanical strength in the axial skeleton was significantly reduced by enzalutamide (maximal load at failure -15.3% ± 3.5%; P < .01). The effects of enzalutamide in the axial skeleton were associated with a high bone turnover. In conclusion, enzalutamide reduces the bone mass in the axial but not the appendicular skeleton in male mice after sexual maturation. We propose that the effect of testosterone on the axial skeleton in male mice is mainly mediated via the AR.

  7. The forkhead transcription factor, FOXP3: a critical role in male fertility in mice.

    PubMed

    Jasurda, Jake S; Jung, Deborah O; Froeter, Erin D; Schwartz, David B; Hopkins, Torin D; Farris, Corrie L; McGee, Stacey; Narayan, Prema; Ellsworth, Buffy S

    2014-01-01

    Fertility is dependent on the hypothalamic-pituitary-gonadal axis. Each component of this axis is essential for normal reproductive function. Mice with a mutation in the forkhead transcription factor gene, Foxp3, exhibit autoimmunity and infertility. We have previously shown that Foxp3 mutant mice have significantly reduced expression of pituitary gonadotropins. To address the role of Foxp3 in gonadal function, we examined the gonadal phenotype of these mice. Foxp3 mutant mice have significantly reduced seminal vesicle and testis weights compared with Foxp3(+/Y) littermates. Spermatogenesis in Foxp3 mutant males is arrested prior to spermatid elongation. Activation of luteinizing hormone signaling in Foxp3 mutant mice by treatment with human chorionic gonadotropin significantly increases seminal vesicle and testis weights as well as testicular testosterone content and seminiferous tubule diameter. Interestingly, human chorionic gonadotropin treatments rescue spermatogenesis in Foxp3 mutant males, suggesting that their gonadal phenotype is due primarily to a loss of pituitary gonadotropin stimulation rather than an intrinsic gonadal defect.

  8. Hypokalemia decreases testosterone production in male mice by altering luteinizing hormone secretion.

    PubMed

    Sánchez-Capelo, A; Castells, M T; Cremades, A; Peñafiel, R

    1996-09-01

    Potassium deficiency produced by feeding mice a low potassium diet caused a marked decrease in plasma and testicular testosterone concentrations and a concomitant fall in the weight of seminal vesicles and in renal ornithine decarboxylase activity. All of these parameters were rapidly restored when potassium supply was normalized. Immunocytochemical analysis of gonadotropes and plasma LH values suggested that the pulsatile liberation of LH by the pituitary was impaired in the potassium-deficient male mice. Because the synthesis of testosterone in the potassium-deficient mice was stimulated by exogenous LH, hCG, or GnRH, one can conclude that alteration of the transcellular potassium gradient could affect the regulation of the hypothalamo-hypophyseal-testicular axis by affecting the pulsatile release of GnRH. Our results showing that the stimulation of LH secretion after castration was similar in control and potassium-deficient male mice suggest that a testicular factor(s) different from testosterone could be implicated in the abnormal regulation of LH secretion in potassium-deficient mice. We conclude that plasma potassium concentration is an important factor in the regulation of gonadotropin secretion and testicular functions. PMID:8756540

  9. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    PubMed

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia.

  10. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    PubMed

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. PMID:26965573

  11. Vasoactive Intestinal Peptide Excites GnRH Neurons in Male and Female Mice.

    PubMed

    Piet, Richard; Dunckley, Henry; Lee, Kiho; Herbison, Allan E

    2016-09-01

    A variety of external and internal factors modulate the activity of GnRH neurons to control fertility in mammals. A direct, vasoactive intestinal peptide (VIP)-mediated input to GnRH neurons originating from the suprachiasmatic nucleus is thought to relay circadian information within this network. In the present study, we examined the effects of VIP on GnRH neuron activity in male and female mice at different stages of the estrous cycle. We carried out cell-attached recordings in slices from GnRH-green fluorescent protein mice and calcium imaging in slices from a mouse line expressing the genetically encoded calcium indicator GCaMP3 selectively in GnRH neurons. We show that 50%-80% of GnRH neurons increase their firing rate in response to bath-applied VIP (1nM-1000nM) in both male and female mice and that this is accompanied by a robust increase in intracellular calcium concentrations. This effect is mediated directly at the GnRH neuron likely through activation of high-affinity VIP receptors. Because suprachiasmatic nucleus-derived timing cues trigger the preovulatory surge only on the afternoon of proestrus in female mice, we examined the effects of VIP during the estrous cycle at different times of day. VIP responsiveness in GnRH neurons did not vary significantly in diestrous and proestrous mice before or around the time of the expected preovulatory surge. These results indicate that the majority of GnRH neurons in male and female mice express functional VIP receptors and that the effects of VIP on GnRH neurons do not alter across the estrous cycle. PMID:27501185

  12. Study on The Reproductive Organs and Fertility of The Male Mice following Administration of Metronidazole

    PubMed Central

    Kumari, Mrinalini; Singh, Poonam

    2013-01-01

    Background: Metronidazole (MTZ) is commonly used as an antibacterial and antiprotozoal drug. Various doses of MTZ have been reported to inhibit spermatogenic activity and sperm indices. Materials and Methods: In this experimental study, dose-dependent effects of MTZ on the structural and functional integrity of the testis and accessory reproductive organs have been investigated. Adult male mice of Swiss strain were administered orally with MTZ at the doses of 250 mg/kgBW/day and 500 mg/kgBW/day for 28 consecutive days to study the changes in the testis, epididymis, seminal vesicle, sperm indices and fertility. Reversal effects of the drug were also studied on the same mice, 42 days after cessation of the treatment. Results: Therapeutic dose of MTZ (250 mg/kgBW/day) neither altered the weights of the testis, epididymis and seminal vesicle nor their histoarchitecture and sperm indices. The drug at the high dose (500 mg/kg BW/day) caused significant reductions in the weights of the testis and epididymis. Histoarchitecture of the testis and epididymis at the high dose revealed marked regressive changes while that of seminal vesicle remained unaffected. Significant reductions were noticed in the motility, viability and count of epididymal spermatozoa while the concentrations of epididymal sialic acid and seminal vesicular fructose remained unaltered after the treatment. No significant changes were noticed in the mating ability as well as in the level of serum testosterone in the treated mice. Fertility of the male mice treated with high dose of MTZ declined markedly leading to an increase in pre- and postimplantation loss while a significant decrease was noticed in the number of live blastocysts in females impregnated with such males. MTZinduced changes in the male reproductive organs and fertility were reinstated 42 days after cessation of the treatment. Conclusion: High dose of MTZ induced reversible deleterious effects on the male reproduction and fertility. PMID

  13. Beta-Catenin Haplo Insufficient Male Mice Do Not Lose Bone in Response to Hindlimb Unloading.

    PubMed

    Maurel, Delphine B; Duan, Peipei; Farr, Joshua; Cheng, An-Lin; Johnson, Mark L; Bonewald, Lynda F

    2016-01-01

    As the β-catenin pathway has been shown to be involved in mechanotransduction, we sought to determine if haploinsufficiency would affect skeletal response to unloading. It has previously been shown that deletion of both alleles of β-catenin in bone cells results in a fragile skeleton highly susceptible to fracture, but deletion of one allele using Dmp1-Cre (Ctnnb1+/loxP; Dmp1-Cre, cKO HET) has little effect on the 2 mo old skeleton. We found that under normal housing conditions, trabecular bone volume was significantly less in 5 mo old male cKO HET mice compared to controls (Ctrl/HET:Tb. BV/TV = 13.96±2.71/8.92±0.95%, Tb.N. = 4.88±0.51/3.95±0.44/mm, Tb. Sp. = 0.20±0.02/0.26±0.03mm, a 36%, 19% and 30% change respectively) but not in females suggesting an age and gender related effect. Before performing suspension experiments and to control for the environmental effects, animals with the same tail attachment and housing conditions, but not suspended (NS), were compared to normally housed (NH) animals. Attachment and housing resulted in weight loss in both genders and phenotypes. Cortical bone loss was observed in the cKO HET males (NH/NS, Ct BV/TV: 90.45±0.72/89.12±0.56%) and both diaphyseal (0.19±0.01/0.17±0.01mm) and metaphyseal (0.10±0.01/0.08±0.01mm) thickness, but not in female cKO HET mice suggesting that male cKO HET mice are susceptible to attachment and housing conditions. These results with transgenic mice emphasizes the importance of proper controls when attributing skeletal responses to unloading. With suspension, cKO HET male mice did not lose bone unlike female cKO HET mice that had greater trabecular bone loss than controls (Ctrl 9%:cKO HET 21% decrease Tb. N; Ctrl 12%:cKO HET 27% increase Tb. Sp.). Suspended and non-suspended mice lost weight compared to normally housed animals. Taken together, the data suggest a protective effect of β-catenin against the effects of stress in males and partial protection against unloading in females

  14. Beta-Catenin Haplo Insufficient Male Mice Do Not Lose Bone in Response to Hindlimb Unloading

    PubMed Central

    Farr, Joshua; Cheng, An-Lin; Johnson, Mark L.; Bonewald, Lynda F.

    2016-01-01

    As the β-catenin pathway has been shown to be involved in mechanotransduction, we sought to determine if haploinsufficiency would affect skeletal response to unloading. It has previously been shown that deletion of both alleles of β-catenin in bone cells results in a fragile skeleton highly susceptible to fracture, but deletion of one allele using Dmp1-Cre (Ctnnb1+/loxP; Dmp1-Cre, cKO HET) has little effect on the 2 mo old skeleton. We found that under normal housing conditions, trabecular bone volume was significantly less in 5 mo old male cKO HET mice compared to controls (Ctrl/HET:Tb. BV/TV = 13.96±2.71/8.92±0.95%, Tb.N. = 4.88±0.51/3.95±0.44/mm, Tb. Sp. = 0.20±0.02/0.26±0.03mm, a 36%, 19% and 30% change respectively) but not in females suggesting an age and gender related effect. Before performing suspension experiments and to control for the environmental effects, animals with the same tail attachment and housing conditions, but not suspended (NS), were compared to normally housed (NH) animals. Attachment and housing resulted in weight loss in both genders and phenotypes. Cortical bone loss was observed in the cKO HET males (NH/NS, Ct BV/TV: 90.45±0.72/89.12±0.56%) and both diaphyseal (0.19±0.01/0.17±0.01mm) and metaphyseal (0.10±0.01/0.08±0.01mm) thickness, but not in female cKO HET mice suggesting that male cKO HET mice are susceptible to attachment and housing conditions. These results with transgenic mice emphasizes the importance of proper controls when attributing skeletal responses to unloading. With suspension, cKO HET male mice did not lose bone unlike female cKO HET mice that had greater trabecular bone loss than controls (Ctrl 9%:cKO HET 21% decrease Tb. N; Ctrl 12%:cKO HET 27% increase Tb. Sp.). Suspended and non-suspended mice lost weight compared to normally housed animals. Taken together, the data suggest a protective effect of β-catenin against the effects of stress in males and partial protection against unloading in females

  15. The contribution of the Y chromosome to hybrid male sterility in house mice.

    PubMed

    Campbell, Polly; Good, Jeffrey M; Dean, Matthew D; Tucker, Priscilla K; Nachman, Michael W

    2012-08-01

    Hybrid sterility in the heterogametic sex is a common feature of speciation in animals. In house mice, the contribution of the Mus musculus musculus X chromosome to hybrid male sterility is large. It is not known, however, whether F1 male sterility is caused by X-Y or X-autosome incompatibilities or a combination of both. We investigated the contribution of the M. musculus domesticus Y chromosome to hybrid male sterility in a cross between wild-derived strains in which males with a M. m. musculus X chromosome and M. m. domesticus Y chromosome are partially sterile, while males from the reciprocal cross are reproductively normal. We used eight X introgression lines to combine different X chromosome genotypes with different Y chromosomes on an F1 autosomal background, and we measured a suite of male reproductive traits. Reproductive deficits were observed in most F1 males, regardless of Y chromosome genotype. Nonetheless, we found evidence for a negative interaction between the M. m. domesticus Y and an interval on the M. m. musculus X that resulted in abnormal sperm morphology. Therefore, although F1 male sterility appears to be caused mainly by X-autosome incompatibilities, X-Y incompatibilities contribute to some aspects of sterility.

  16. Effect of Fenbendazole on Three Behavioral Tests in Male C57BL/6N Mice

    PubMed Central

    Gadad, Bharathi S; Daher, João P L; Hutchinson, Eric K; Brayton, Cory F; Dawson, Ted M; Pletnikov, Mikhail V; Watson, Julie

    2010-01-01

    Pinworms are highly contagious parasites of laboratory rodents that often are treated with fenbendazole. To our knowledge, the effect of fenbendazole at therapeutic dosages on behavioral tests in mice has not been evaluated. Here we studied 6-wk-old male C57BL/6N mice. We compared the behavior of control mice (fed regular diet) with 3 groups of mice treated with dietary fenbendazole. Treatment groups were 4 wk of fenbendazole, 2 wk of fenbendazole followed by 2 wk of regular diet, and 2 wk of regular diet followed by 2 wk of fenbendazole. At the end of dietary treatment all groups were tested by open field for central, peripheral and vertical activity; elevated plus maze for anxiety; and rotarod for motor ability and then evaluated by clinical pathology and selected histopathology. Treated and control groups showed no differences in open field or elevated plus maze testing, histopathology, or clinical pathology. However mice treated for 4 wk with fenbendazole or 2 wk of fenbendazole followed by 2 wk regular diet stayed on the rotarod for shorter periods than did controls, and mice treated with 2 wk of regular diet followed by 2 wk fenbendazole showed a trend toward shorter rotarod times. In light of this study, we suggest that open field and elevated plus maze testing is unlikely to be affected by 4 wk fenbendazole treatment in male C57BL/6 mice; however, behavioral tests of motor ability such as rotarod tests may be affected during and for at least 2 wk after fenbendazole treatment. PMID:21205447

  17. Effect of fenbendazole on three behavioral tests in male C57BL/6N mice.

    PubMed

    Gadad, Bharathi S; Daher, João P L; Hutchinson, Eric K; Brayton, Cory F; Dawson, Ted M; Pletnikov, Mikhail V; Watson, Julie

    2010-11-01

    Pinworms are highly contagious parasites of laboratory rodents that often are treated with fenbendazole. To our knowledge, the effect of fenbendazole at therapeutic dosages on behavioral tests in mice has not been evaluated. Here we studied 6-wk-old male C57BL/6N mice. We compared the behavior of control mice (fed regular diet) with 3 groups of mice treated with dietary fenbendazole. Treatment groups were 4 wk of fenbendazole, 2 wk of fenbendazole followed by 2 wk of regular diet, and 2 wk of regular diet followed by 2 wk of fenbendazole. At the end of dietary treatment all groups were tested by open field for central, peripheral and vertical activity; elevated plus maze for anxiety; and rotarod for motor ability and then evaluated by clinical pathology and selected histopathology. Treated and control groups showed no differences in open field or elevated plus maze testing, histopathology, or clinical pathology. However mice treated for 4 wk with fenbendazole or 2 wk of fenbendazole followed by 2 wk regular diet stayed on the rotarod for shorter periods than did controls, and mice treated with 2 wk of regular diet followed by 2 wk fenbendazole showed a trend toward shorter rotarod times. In light of this study, we suggest that open field and elevated plus maze testing is unlikely to be affected by 4 wk fenbendazole treatment in male C57BL/6 mice; however, behavioral tests of motor ability such as rotarod tests may be affected during and for at least 2 wk after fenbendazole treatment.

  18. Chronic social stress does not affect behavioural habituation in male CD1 mice.

    PubMed

    Boleij, Hetty; Willems, Jeroen; Leijten, Marieke; van't Klooster, José; Lesscher, Heidi; Kirchhoff, Susanne; Lavrijsen, Marla; Arndt, Saskia S; Ohl, Frauke

    2014-10-15

    Various protocols to induce chronic stress in rodents are being used to determine the effects and underlying mechanisms of prolonged stress experience. Recently, a novel chronic social stress (CSS) protocol has been developed for mice where social instability in adolescence and early adulthood is induced. This protocol has been shown to cause an increase in HPA-axis activity and acute avoidance behaviour in the elevated plus maze. The aim of the present study was to investigate the effect of this CSS protocol on habituation to an initially novel environment in CD1 mice, since it has been shown that initially high avoidance behaviour in mice can still be followed by rapid habituation, pointing towards an adaptive response. One group of male mice, the CSS group, was exposed to the CSS protocol for 7 weeks and we compared their behavioural and physiological responses with male mice that were housed in a stable social group, the SH group. The results reveal a decrease in body weight gain and fur condition, changes in adrenal weight and decreased GR mRNA expression in the CA1 and the dentate gyrus of the hippocampus in chronically stressed CD1 animals. Irrespective of such evidence for a significantly stressful effect of the protocol, CD 1 mice, after termination of the stress procedure, revealed habituation profiles that matched those of control animals. We conclude that the physiological and central-nervous effects caused by a CSS procedure as used in this experiment fall within the coping capacities of CD1 mice at the behavioural level. PMID:25036428

  19. Developmental exposure to Ethinylestradiol affects transgenerationally sexual behavior and neuroendocrine networks in male mice.

    PubMed

    Derouiche, Lyes; Keller, Matthieu; Duittoz, Anne Hélène; Pillon, Delphine

    2015-12-07

    Reproductive behavior and physiology in adulthood are controlled by hypothalamic sexually dimorphic neuronal networks which are organized under hormonal control during development. These organizing effects may be disturbed by endocrine disrupting chemicals (EDCs). To determine whether developmental exposure to Ethinylestradiol (EE2) may alter reproductive parameters in adult male mice and their progeny, Swiss mice (F1 generation) were exposed from prenatal to peripubertal periods to EE2 (0.1-1 μg/kg/d). Sexual behavior and reproductive physiology were evaluated on F1 males and their F2, F3 and F4 progeny. EE2-exposed F1 males and their F2 to F4 progeny exhibited EE2 dose-dependent increased sexual behavior, with reduced latencies of first mount and intromission, and higher frequencies of intromissions with a receptive female. The EE2 1 μg/kg/d exposed animals and their progeny had more calbindin immunoreactive cells in the medial preoptic area, known to be involved in the control of male sexual behavior in rodents. Despite neuroanatomical modifications in the Gonadotropin-Releasing Hormone neuron population of F1 males exposed to both doses of EE2, no major deleterious effects on reproductive physiology were detected. Therefore EE2 exposure during development may induce a hypermasculinization of the brain, illustrating how widespread exposure of animals and humans to EDCs can impact health and behaviors.

  20. Altered somatotroph feedback regulation improves metabolic efficiency and limits adipose deposition in male mice.

    PubMed

    Romero, Christopher J; Wolfe, Andrew; Law, Yi Ying; Costelloe, ChenChen Z; Miller, Ryan; Wondisford, Fredric; Radovick, Sally

    2016-04-01

    Several transgenic mouse models with disruption in the growth hormone (GH) axis support the role of GH in augmenting metabolic homeostasis. Specifically, interest has focused on GH's lipolytic properties and ability to affect adipose deposition. Furthermore, both GH and insulin growth factor 1 (IGF-1) may also play a direct or indirect role in adipose development. The somatotroph insulin-like growth factor-1 receptor knockout (SIGFRKO) mouse with only a modest increase in serum GH and IGF-1 demonstrates less adipose tissue than controls. In order to characterize the metabolic phenotype of SIGFRKO mice, histologic analysis of fat depots confirmed a smaller average diameter of adipocytes in the SIGFRKO mice compared to controls. These changes were accompanied by an increase in lipolytic gene expression in fat depots. Indirect calorimetry performed on 6-8week old male mice and again at 25weeks of age demonstrated that SIGFRKO mice, at both ages, had a higher VO2 and increased energy expenditure when compared with controls. The calculated respiratory exchange ratio (RER) was lower in the younger SIGFRKO mice compared to controls. No differences in food consumption or in either ambulatory or total activity were seen between SIGFRKO and control mice in either age group. These studies highlight the role of GH in adipose deposition and its influence on the expression of lipolytic genes resulting in an altered metabolic state, thus providing a mechanism for the decrease in weight gain seen in the SIGFRKO mouse model.

  1. Ssb2/Nabp1 is dispensable for thymic maturation, male fertility, and DNA repair in mice.

    PubMed

    Boucher, Didier; Vu, Therese; Bain, Amanda L; Tagliaro-Jahns, Marina; Shi, Wei; Lane, Steven W; Khanna, Kum Kum

    2015-08-01

    SSB1 and SSB2 are newly identified single-stranded (ss) DNA binding proteins that play a crucial role in genome maintenance in humans. We recently generated a knockout mouse model of Ssb1 and revealed its essential role for neonatal survival. Notably, we found compensatory up-regulation of Ssb2 protein levels in multiple tissues of conditional Ssb1(-/-) mice, suggesting functional compensation between these 2 proteins. We report here the first description of Ssb2(-/-) knockout mice. Surprisingly, unlike Ssb1 knockout mice, Ssb2(-/-) mice are viable and fertile and do not exhibit marked phenotypic changes when compared with their Ssb2(+/+) and Ssb2(+/-) littermates. Notably, we did not detect any pathologic changes in the thymus, spleen, or testes, tissues with the most abundant expression of Ssb2. Moreover, Ssb2(-/-) mouse embryonic fibroblasts (MEFs) did not show any sensitivity to DNA-damaging agents, or defects in DNA repair capacity. However, we observed modest up-regulation of Ssb1 levels in Ssb2(-/-) MEFs as well as in Ssb2(-/-) thymus and spleen, suggesting that Ssb1 is likely able to compensate for the loss of Ssb2 in mice. Altogether, our results show that Ssb2 is dispensable for embryogenesis and adult tissue homeostasis, including thymopoiesis, splenic development, male fertility, and DNA repair in mice.

  2. Administration of Saccharin to Neonatal Mice Influences Body Composition of Adult Males and Reduces Body Weight of Females

    PubMed Central

    Parlee, Sebastian D.; Simon, Becky R.; Scheller, Erica L.; Alejandro, Emilyn U.; Learman, Brian S.; Krishnan, Venkatesh; Bernal-Mizrachi, Ernesto

    2014-01-01

    Nutritional or pharmacological perturbations during perinatal growth can cause persistent effects on the function of white adipose tissue, altering susceptibility to obesity later in life. Previous studies have established that saccharin, a nonnutritive sweetener, inhibits lipolysis in mature adipocytes and stimulates adipogenesis. Thus, the current study tested whether neonatal exposure to saccharin via maternal lactation increased susceptibility of mice to diet-induced obesity. Saccharin decreased body weight of female mice beginning postnatal week 3. Decreased liver weights on week 14 corroborated this diminished body weight. Initially, saccharin also reduced male mouse body weight. By week 5, weights transiently rebounded above controls, and by week 14, male body weights did not differ. Body composition analysis revealed that saccharin increased lean and decreased fat mass of male mice, the latter due to decreased adipocyte size and epididymal, perirenal, and sc adipose weights. A mild improvement in glucose tolerance without a change in insulin sensitivity or secretion aligned with this leaner phenotype. Interestingly, microcomputed tomography analysis indicated that saccharin also increased cortical and trabecular bone mass of male mice and modified cortical bone alone in female mice. A modest increase in circulating testosterone may contribute to the leaner phenotype in male mice. Accordingly, the current study established a developmental period in which saccharin at high concentrations reduces adiposity and increases lean and bone mass in male mice while decreasing generalized growth in female mice. PMID:24456165

  3. Administration of saccharin to neonatal mice influences body composition of adult males and reduces body weight of females.

    PubMed

    Parlee, Sebastian D; Simon, Becky R; Scheller, Erica L; Alejandro, Emilyn U; Learman, Brian S; Krishnan, Venkatesh; Bernal-Mizrachi, Ernesto; MacDougald, Ormond A

    2014-04-01

    Nutritional or pharmacological perturbations during perinatal growth can cause persistent effects on the function of white adipose tissue, altering susceptibility to obesity later in life. Previous studies have established that saccharin, a nonnutritive sweetener, inhibits lipolysis in mature adipocytes and stimulates adipogenesis. Thus, the current study tested whether neonatal exposure to saccharin via maternal lactation increased susceptibility of mice to diet-induced obesity. Saccharin decreased body weight of female mice beginning postnatal week 3. Decreased liver weights on week 14 corroborated this diminished body weight. Initially, saccharin also reduced male mouse body weight. By week 5, weights transiently rebounded above controls, and by week 14, male body weights did not differ. Body composition analysis revealed that saccharin increased lean and decreased fat mass of male mice, the latter due to decreased adipocyte size and epididymal, perirenal, and sc adipose weights. A mild improvement in glucose tolerance without a change in insulin sensitivity or secretion aligned with this leaner phenotype. Interestingly, microcomputed tomography analysis indicated that saccharin also increased cortical and trabecular bone mass of male mice and modified cortical bone alone in female mice. A modest increase in circulating testosterone may contribute to the leaner phenotype in male mice. Accordingly, the current study established a developmental period in which saccharin at high concentrations reduces adiposity and increases lean and bone mass in male mice while decreasing generalized growth in female mice.

  4. Effects of velvet antler polypeptide on sexual behavior and testosterone synthesis in aging male mice

    PubMed Central

    Zang, Zhi-Jun; Tang, Hong-Feng; Tuo, Ying; Xing, Wei-Jie; Ji, Su-Yun; Gao, Yong; Deng, Chun-Hua

    2016-01-01

    Twenty-four-month-old male C57BL/6 mice with low serum testosterone levels were used as a late-onset hypogonadism (LOH) animal model for examining the effects of velvet antler polypeptide (VAP) on sexual function and testosterone synthesis. These mice received VAP for 5 consecutive weeks by daily gavage at doses of 100, 200, or 300 mg kg−1 body weight per day (n = 10 mice per dose). Control animals (n = 10) received the same weight-based volume of vehicle. Sexual behavior and testosterone levels in serum and interstitial tissue of testis were measured after the last administration of VAP. Furthermore, to investigate the mechanisms of how VAP affects sexual behavior and testosterone synthesis in vivo, the expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) in Leydig cells was also measured by immunofluorescence staining and quantitative real-time PCR. As a result, VAP produced a significant improvement in the sexual function of these aging male mice. Serum testosterone level and intratesticular testosterone (ITT) concentration also increased in the VAP-treated groups. The expression of StAR, P450scc, and 3β-HSD was also found to be enhanced in the VAP-treated groups compared with the control group. Our results suggested that VAP was effective in improving sexual function in aging male mice. The effect of velvet antler on sexual function was due to the increased expression of several rate-limiting enzymes of testosterone synthesis (StAR, P450scc, and 3β-HSD) and the following promotion of testosterone synthesis in vivo. PMID:26608944

  5. Impaired 17,20-Lyase Activity in Male Mice Lacking Cytochrome b5 in Leydig Cells

    PubMed Central

    Sondhi, Varun; Owen, Bryn M.; Liu, Jiayan; Chomic, Robert; Kliewer, Steven A.; Hughes, Beverly A.; Arlt, Wiebke; Mangelsdorf, David J.

    2016-01-01

    Androgen and estrogen biosynthesis in mammals requires the 17,20-lyase activity of cytochrome P450 17A1 (steroid 17-hydroxylase/17,20-lyase). Maximal 17,20-lyase activity in vitro requires the presence of cytochrome b5 (b5), and rare cases of b5 deficiency in human beings causes isolated 17,20-lyase deficiency. To study the consequences of conditional b5 removal from testicular Leydig cells in an animal model, we generated Cyb5flox/flox:Sf1-Cre (LeyKO) mice. The LeyKO male mice had normal body weights, testis and sex organ weights, and fertility compared with littermates. Basal serum and urine steroid profiles of LeyKO males were not significantly different than littermates. In contrast, marked 17-hydroxyprogesterone accumulation (100-fold basal) and reduced testosterone synthesis (27% of littermates) were observed after human chorionic gonadotropin stimulation in LeyKO animals. Testis homogenates from LeyKO mice showed reduced 17,20-lyase activity and a 3-fold increased 17-hydroxylase to 17,20-lyase activity ratio, which were restored to normal upon addition of recombinant b5. We conclude that Leydig cell b5 is required for maximal androgen synthesis and to prevent 17-hydroxyprogesterone accumulation in the mouse testis; however, the b5-independent 17,20-lyase activity of mouse steroid 17-hydroxylase/17,20-lyase is sufficient for normal male genital development and fertility. LeyKO male mice are a good model for the biochemistry but not the physiology of isolated 17,20-lyase deficiency in human beings. PMID:26974035

  6. Potential O-acyl-substituted (-)-Epicatechin gallate prodrugs as inhibitors of DMBA/TPA-induced squamous cell carcinoma of skin in Swiss albino mice.

    PubMed

    Vyas, Sandeep; Manon, Benu; Vir Singh, Tej; Dev Sharma, Pritam; Sharma, Manu

    2011-04-01

    (-)-Epicatechin-3-gallate (1) is one of the principal catechins of green tea and exhibits cancer-preventive activities in various animal models. However, this compound is unstable in neutral or alkaline medium and, therefore, has a poor bioavailability. To improve its stability, O-acyl derivatives of 1 were prepared by isolating the partially purified tea catechin fraction from green tea extract and treating it with a variety of acylating agents. The resulting derivatives, compounds 2-6, were screened for their antitumor potential against 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced squamous cell carcinogenesis of skin in mice. The results showed that the antitumor activity decreased with the increase in size of the chain length of the acyl groups, i.e., from compound 2, derivative with an Ac group, to compound 6, possessing a valeryl group. Moreover, the C(4) derivative with a branched acyl chain, 5, had a lower activity than the linear C(4) derivative 4. This reduction in the inhibitory activity may be due to the steric hindrance by the two Me groups. Moreover, significant increases in the protein levels analyzed by ELISA of c-Jun, p65, and p53 were observed in the skin of DMBA/TPA treated mice, whereas mice treated with 2 and DMBA/TPA had a similar expression of these transcription factors than the control mice. The prodrug potential of the O-acyl derivatives 2-6 showed that they were adequately stable to be absorbed intact from the intestine, more stable at gastric pH, and suitable for oral administration. PMID:21480506

  7. NGF induces appearance of adult-like response to spatial novelty in 18-day male mice.

    PubMed

    Calamandrei, Gemma; Valanzano, Angela; Ricceri, Laura

    2002-10-17

    We investigated the effects of Nerve Growth Factor (NGF) administration on the maturation of reactivity to spatial and non-spatial novelty in developing mice. CD-1 mice of both sexes received intracerebral administration of NGF on postnatal day (pnd) 15, and their response to object displacement (spatial novelty) and object substitution (object novelty) were assessed in a spatial open-field with four objects on pnd 18 or 28. On pnd 18, NGF induced only in males precocious appearance of spatial novelty discrimination, while increasing choline acetyltransferase activity in neocortex and hippocampus of both sexes. The behavioral and neurochemical effects disappeared by pnd 28. NGF triggers adult-like responding to spatial novelty in developing mice and such effect is gender-specific.

  8. Protective Effect of Parsley Juice (Petroselinum crispum, Apiaceae) against Cadmium Deleterious Changes in the Developed Albino Mice Newborns (Mus musculus) Brain.

    PubMed

    Allam, Ahmed A; Maodaa, Salah N; Abo-Eleneen, Rasha; Ajarem, Jamaan

    2016-01-01

    Parsley was used as a probe of the current experiment to prevent the behavioral, morphological and biochemical changes in the newborn brain following the administration of cadmium (Cd) to the pregnant mice. The nonanesthetized pregnant mice were given daily parsley juice (Petroselinum crispum) at doses of 20 mg/kg and 10 mg/kg. Pregnant mothers were given Cd at a dose of 30 mg/kg divided into 3 equal times. The newborns have been divided into 6 groups: Group A, mothers did not take treatment; Groups B and C, mothers were treated with low and high dose of parsley, respectively; Group D, mothers were treated only with Cd (perinatal intoxication); Groups E and F, mothers were treated with Cd doses and protected by low and high doses of parsley, respectively. Light microscopy showed that Cd-induced neuronal degeneration by chromatolysis and pyknosis in the brain regions. The low dose of parsley 10 g/kg/day exhibited significant effects in neutralizing and reducing the deleterious changes due to Cd exposure during pregnancy on the behavioral activities, neurotransmitters, oxidative stress, and brain neurons morphology of the mice newborns.

  9. Protective Effect of Parsley Juice (Petroselinum crispum, Apiaceae) against Cadmium Deleterious Changes in the Developed Albino Mice Newborns (Mus musculus) Brain

    PubMed Central

    Allam, Ahmed A.; Maodaa, Salah N.; Abo-Eleneen, Rasha; Ajarem, Jamaan

    2016-01-01

    Parsley was used as a probe of the current experiment to prevent the behavioral, morphological and biochemical changes in the newborn brain following the administration of cadmium (Cd) to the pregnant mice. The nonanesthetized pregnant mice were given daily parsley juice (Petroselinum crispum) at doses of 20 mg/kg and 10 mg/kg. Pregnant mothers were given Cd at a dose of 30 mg/kg divided into 3 equal times. The newborns have been divided into 6 groups: Group A, mothers did not take treatment; Groups B and C, mothers were treated with low and high dose of parsley, respectively; Group D, mothers were treated only with Cd (perinatal intoxication); Groups E and F, mothers were treated with Cd doses and protected by low and high doses of parsley, respectively. Light microscopy showed that Cd-induced neuronal degeneration by chromatolysis and pyknosis in the brain regions. The low dose of parsley 10 g/kg/day exhibited significant effects in neutralizing and reducing the deleterious changes due to Cd exposure during pregnancy on the behavioral activities, neurotransmitters, oxidative stress, and brain neurons morphology of the mice newborns. PMID:26966507

  10. Soy Content of Basal Diets Determines the Effects of Supplemental Selenium in Male Mice123

    PubMed Central

    Quiner, Trevor E.; Nakken, Heather L.; Mason, Brock A.; Lephart, Edwin D.; Hancock, Chad R.; Christensen, Merrill J.

    2011-01-01

    The effects of supplemental Se in rodent models may depend upon composition of the basal diet to which it is added. Wild-type male littermates of Transgenic Adenocarcinoma of Mouse Prostate mice were fed until 18 wk of age 1 of 2 Se-adequate stock diets high in soy (HS) or low in phytoestrogens (LP) or the same diets supplemented with 3.0 mg Se/kg diet as seleno-methylselenocysteine. Body and abdominal fat pad weights were lower (P < 0.01) in mice fed the HS diet. Supplemental Se reduced fat pad weights in mice receiving the LP diet but increased body and fat pad weights in mice consuming the HS formulation (P-interaction < 0.005). Serum free triiodothyronine concentrations were unaffected by supplemental Se in mice fed the LP diet but were decreased by Se supplementation of mice given the HS feed (P-interaction < 0.02). Free thyroxine concentrations were higher in mice consuming the HS diet regardless of Se intake (P < 0.001). Hepatic mRNA for iodothyronine deiodinase I was lower (P < 0.001) in mice fed the HS diet. Supplementation of Se increased this mRNA (P < 0.001) in both diet groups. Results from this study show a significant interaction between the composition of basal diets and the effects of supplemental Se with respect to body composition. These findings have important implications for future studies in rodent models of the effects of supplemental Se on heart disease, cancer, diabetes, and other conditions related to body weight and composition. PMID:22031663

  11. Elevated Systolic Blood Pressure in Male GH Transgenic Mice Is Age Dependent

    PubMed Central

    Jara, Adam; Benner, Chance M.; Sim, Don; Liu, Xingbo; List, Edward O.; Householder, Lara A.; Berryman, Darlene E.

    2014-01-01

    Acromegaly is associated with an increased incidence of cardiovascular disease. Transgenic mice expressing bovine GH (bGH) gene have previously been used to examine the effects of chronic GH stimulation on cardiovascular function. Results concerning systolic blood pressure (SBP) in bGH mice are conflicting. We hypothesized that these discrepancies may be the result of the various ages of the mice used in previous studies. In the current study, SBP was assessed monthly in male bGH mice from 3–12 months of age. Factors known to alter blood pressure were assessed during this time and included: levels of brain natriuretic peptide (BNP) and glucose homeostasis markers, and renal levels of angiotensin-converting enzyme 2 and endothelial nitric oxide synthase. Beginning at 6 months of age bGH had increased SBP compared with wild-type controls, which remained elevated through 12 months of age. Despite having increased blood pressure and cardiac BNP mRNA, bGH mice had decreased circulating levels of BNP. Additionally, bGH mice had an age-dependent decline in insulin levels. For example, they were hyperinsulinemic at 3 months, but by 11 months of age were hypoinsulinemic relative to wild-type controls. This decrease in insulin was accompanied by improved glucose tolerance at 11 months. Finally, both angiotensin-converting enzyme 2 and endothelial nitric oxide synthase expression were severely depressed in kidneys of 11-month-old bGH mice. These results indicate that elevated SBP in bGH mice is dependent on age, independent of insulin resistance, and related to alterations in both the natriuretic peptide and renin-angiotensin systems. PMID:24424040

  12. The catalytic function of hormone-sensitive lipase is essential for fertility in male mice.

    PubMed

    Wang, Shu Pei; Wu, Jiang Wei; Bourdages, Hugo; Lefebvre, Jean François; Casavant, Stéphanie; Leavitt, Blair R; Labuda, Damian; Trasler, Jacquetta; Smith, Charles E; Hermo, Louis; Mitchell, Grant A

    2014-08-01

    In male mice, deficiency of hormone sensitive lipase (HSL, Lipe gene, E.C.3.1.1.3) causes deficient spermatogenesis, azoospermia, and infertility. Postmeiotic germ cells express a specific HSL isoform that includes a 313 amino acid N-terminus encoded by a testis-specific exon (exon T1). The remainder of testicular HSL is identical to adipocyte HSL. The amino acid sequence of the testis-specific exon is poorly conserved, showing only a 46% amino acid identity with orthologous human and rat sequences, compared with 87% over the remainder of the HSL coding sequence, providing no evidence in favor of a vital functional role for the testis-specific N-terminus of HSL. However, exon T1 is important for Lipe transcription; in mouse testicular mRNA, we identified 3 major Lipe transcription start sites, finding numerous testicular transcription factor binding motifs upstream of the transcription start site. We directly explored two possible mechanisms for the infertility of HSL-deficient mice, using mice that expressed mutant HSL transgenes only in postmeiotic germ cells on a HSL-deficient background. One transgene expressed human HSL lacking enzyme activity but containing the testis-specific N-terminus (HSL-/-muttg mice). The other transgene expressed catalytically inactive HSL with the testis-specific N-terminal peptide (HSL-/-atg mice). HSL-/-muttg mice were infertile, with abnormal histology of the seminiferous epithelium and absence of spermatozoa in the epididymal lumen. In contrast, HSL-/-atg mice had normal fertility and normal testicular morphology. In conclusion, whereas the catalytic function of HSL is necessary for spermatogenesis in mice, the presence of the N-terminal testis-specific fragment is not essential.

  13. Elevated systolic blood pressure in male GH transgenic mice is age dependent.

    PubMed

    Jara, Adam; Benner, Chance M; Sim, Don; Liu, Xingbo; List, Edward O; Householder, Lara A; Berryman, Darlene E; Kopchick, John J

    2014-03-01

    Acromegaly is associated with an increased incidence of cardiovascular disease. Transgenic mice expressing bovine GH (bGH) gene have previously been used to examine the effects of chronic GH stimulation on cardiovascular function. Results concerning systolic blood pressure (SBP) in bGH mice are conflicting. We hypothesized that these discrepancies may be the result of the various ages of the mice used in previous studies. In the current study, SBP was assessed monthly in male bGH mice from 3-12 months of age. Factors known to alter blood pressure were assessed during this time and included: levels of brain natriuretic peptide (BNP) and glucose homeostasis markers, and renal levels of angiotensin-converting enzyme 2 and endothelial nitric oxide synthase. Beginning at 6 months of age bGH had increased SBP compared with wild-type controls, which remained elevated through 12 months of age. Despite having increased blood pressure and cardiac BNP mRNA, bGH mice had decreased circulating levels of BNP. Additionally, bGH mice had an age-dependent decline in insulin levels. For example, they were hyperinsulinemic at 3 months, but by 11 months of age were hypoinsulinemic relative to wild-type controls. This decrease in insulin was accompanied by improved glucose tolerance at 11 months. Finally, both angiotensin-converting enzyme 2 and endothelial nitric oxide synthase expression were severely depressed in kidneys of 11-month-old bGH mice. These results indicate that elevated SBP in bGH mice is dependent on age, independent of insulin resistance, and related to alterations in both the natriuretic peptide and renin-angiotensin systems. PMID:24424040

  14. Aqueous fruit extract of Mimusops elengi causes reversible suppression of spermatogenesis and fertility in male mice.

    PubMed

    Singh, N; Singh, S K

    2016-09-01

    Antifertility efficacy of oral administration of aqueous fruit extract of Mimusops elengi (200, 400 and 600 mg kg(-1) body weight/day for 35 days) was evaluated in Parkes strain male mice. Various reproductive end points such as histopathology, sperm parameters, testosterone level, haematology, serum biochemistry and fertility indices were assessed; activities of 3β- and 17β-hydroxysteroid dehydrogenases, and immunoblot expressions of StAR and P450scc in the testis were also assessed. Histologically, testes in Mimusops-treated mice showed nonuniform and diverse degenerative changes in the seminiferous tubules; both affected and normal tubules were observed in the same sections of testis. The treatment had adverse effects on testicular hydroxysteroid dehydrogenases and StAR and P450scc, serum level of testosterone and on motility, viability and number of spermatozoa in cauda epididymis. However, serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine, and haematological parameters were not affected by the treatment. Also, libido was not affected in treated males, but their fertility was markedly suppressed. By 56 days of treatment withdrawal, the alterations caused in the above parameters recovered to control levels, suggesting that Mimusops treatment causes reversible suppression of spermatogenesis and fertility in Parkes mice. Further, there were no detectable signs of toxicity in treated males. PMID:27489141

  15. Focal lesions within the ventral striato-pallidum abolish attraction for male chemosignals in female mice.

    PubMed

    Agustín-Pavón, Carmen; Martínez-García, Fernando; Lanuza, Enrique

    2014-02-01

    In rodents, socio-sexual behaviour is largely mediated by chemosensory cues, some of which are rewarding stimuli. Female mice display an innate attraction towards male chemosignals, dependent on the vomeronasal system. This behaviour likely reflects the hedonic value of sexual chemosignals. The anteromedial aspect of the olfactory tubercle, along with its associated islands of Calleja, receives vomeronasal inputs and sexually-dimorphic vasopressinergic innervation. Thus, we hypothesised that this portion of the ventral striato-pallidum, known to be involved in reward processing, might be important for sexual odorant-guided behaviours. In this study, we demonstrate that lesions of this region, but not of regions in the posterolateral striato-pallidum, abolish the attraction of female mice for male chemosignals, without affecting significantly their preference for a different natural reward (a sucrose solution). These results show that, at least in female mice, the integrity of the anterior aspect of the medioventral striato-pallidum, comprising a portion of the olfactory tubercle and associated islands of Calleja, is necessary for the attraction for male chemosignals. We suggest that this region contributes to the processing of the hedonic properties of biologically significant odorants.

  16. Chronic exposure to ethanol in male mice may be associated with hearing loss in offspring.

    PubMed

    Liang, Fei; Diao, Lei; Jiang, Nan; Zhang, Jin; Wang, Hui-Jun; Zhou, Wen-Hao; Huang, Guo-Ying; Ma, Duan

    2015-01-01

    Although paternal ethanol (EtOH) abuse has been shown to affect the growth and behavior of offspring, the exact molecular and mechanistic basis remains largely unclear. Methylation alterations in imprinted genes may be related to well-documented teratogenic effects of ethanol. Here we show that chronic paternal ethanol exposure increases the susceptibility to abnormal behavior in offspring through male game epigenetic alteration. In our study, different doses of ethanol (0, 1.1, 3.3 g kg-1 ) were administered intra-gastrically to male mice and decreased sperm motility was found in the highest ethanol-exposed group compared with the controls. Data also showed a dose-dependent increase in deaf mice of the paternally ethanol-exposed groups. The methylation of H19, Peg3, Ndn and Snrpn was assessed in paternal spermatozoa and in the cerebral cortices of deaf mice. EtOH affected methylation of Peg3 (CpG 3, 7 and 9) in paternal spermatozoa and in the cerebral cortices of deaf mice, but the level of mRNA expression did not change, suggesting that other gene regulation may be involved in these processes. Overall, chronic paternal ethanol exposure could alter the methylation of imprinted genes in sire spermatozoa that could also be passed on to offspring, giving rise to developmental disorders. Our results provide possible epigenetic evidence for a paternal ethanol exposure contribution to Fetal Alcohol Syndrome (FAS).

  17. Chronic exposure to ethanol in male mice may be associated with hearing loss in offspring.

    PubMed

    Liang, Fei; Diao, Lei; Jiang, Nan; Zhang, Jin; Wang, Hui-Jun; Zhou, Wen-Hao; Huang, Guo-Ying; Ma, Duan

    2015-01-01

    Although paternal ethanol (EtOH) abuse has been shown to affect the growth and behavior of offspring, the exact molecular and mechanistic basis remains largely unclear. Methylation alterations in imprinted genes may be related to well-documented teratogenic effects of ethanol. Here we show that chronic paternal ethanol exposure increases the susceptibility to abnormal behavior in offspring through male game epigenetic alteration. In our study, different doses of ethanol (0, 1.1, 3.3 g kg-1 ) were administered intra-gastrically to male mice and decreased sperm motility was found in the highest ethanol-exposed group compared with the controls. Data also showed a dose-dependent increase in deaf mice of the paternally ethanol-exposed groups. The methylation of H19, Peg3, Ndn and Snrpn was assessed in paternal spermatozoa and in the cerebral cortices of deaf mice. EtOH affected methylation of Peg3 (CpG 3, 7 and 9) in paternal spermatozoa and in the cerebral cortices of deaf mice, but the level of mRNA expression did not change, suggesting that other gene regulation may be involved in these processes. Overall, chronic paternal ethanol exposure could alter the methylation of imprinted genes in sire spermatozoa that could also be passed on to offspring, giving rise to developmental disorders. Our results provide possible epigenetic evidence for a paternal ethanol exposure contribution to Fetal Alcohol Syndrome (FAS). PMID:26262775

  18. Lutein alleviates arsenic-induced reproductive toxicity in male mice via Nrf2 signaling.

    PubMed

    Li, S G; Xu, S Z; Niu, Q; Ding, Y S; Pang, L J; Ma, R L; Jing, M X; Wang, K; Ma, X M; Feng, G L; Liu, J M; Zhang, X F; Xiang, H L; Li, F

    2016-05-01

    This study aims to investigate the mechanisms involved in the action of lutein (LU) alleviating arsenic-induced reproductive toxicity using mice model. Forty male Kunming mice were received following treatments by gavage: normal saline solution (control), arsenic trioxide (ATO; 5 mg/kg/day), LU (40 mg/kg/day), and ATO + LU (5 mg/kg/day + 40 mg/kg/day). At the end, the mice were killed by cervical dislocation and weighed. Pathological examination was done on the testis. The biomedical parameters including superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. The messenger RNA (mRNA) and protein expression of Nrf2, heme oxygenase 1 (HO-1), glutathione S-transferase (GST), nicotinamide adenine dinucleotide phosphate dehydrogenase, quinone 1 (NQO1) in testis were detected by real-time polymerase chain reaction and Western blot. We found that there was a decrease in sperm count; testis somatic index; the activities of SOD, GSH, total antioxidative capacity (p < 0.01, respectively) in ATO-treated mice, while there was an increase in the levels of sperm abnormalities, MDA, and 8-OHdG than control (p < 0.01, respectively). The groups treated with ATO + LU showed recovery of the measured parameters between those of ATO or saline-treated group. The antagonized interaction between ATO and LU was statistically significant (p < 0.01). Mice treated with ATO + LU also showed greater mRNA expression of Nrf2, HO-1, NQO1, and GST than ATO or saline-treated groups. These findings suggest that LU alleviates reproductive toxicity induced by arsenic in male mice via Nrf2 signaling, which implicates a possible mechanism of LU in preventing the reproductive injury, and elucidates that consuming the rich plant sources of LU will alleviate the reproductive toxicity induced by chemicals.

  19. Early deprivation induces competitive subordinance in C57BL/6 male mice.

    PubMed

    Benner, Seico; Endo, Toshihiro; Endo, Nozomi; Kakeyama, Masaki; Tohyama, Chiharu

    2014-10-01

    Rodent models have been widely used to investigate the impact of early life stress on adult health and behavior. However, the social dimension has rarely been incorporated into the analysis due to methodological limitations. This study characterized the effects of neonatal social isolation (early deprivation, ED) on adult C57BL/6 mouse behavior in a social context using our recently developed behavioral test protocols for group-housed mice. During the first two postnatal weeks, half of the pups per dam were separated from their dam and littermates for 3h per day (ED group). Post weaning, ED and control pups were electronically tagged and co-housed. At 12weeks, the mixed cohorts were transferred to IntelliCages, equipped with computer-controlled operant chambers. Access to the chambers was used as an index to analyze novel object response, behavioral flexibility, and competitive dominance with minimal experimenter intervention. In general, ED had greater effects on males; ED males exhibited reduced body weight, increased novelty response, and were subordinate to control littermates when competing for reward access. Male ED mice also demonstrated mildly impaired reversal learning. Analyzing gene expression changes in brain regions controlling emotion, stress, spatial memory, and executive function revealed reduced BDNF and c-Fos in hippocampal CA1, enhanced c-Fos in the basolateral amygdala, reduced Map2 while enhanced HSD11β2 in prefrontal cortex of ED males. In male mice, it was suggested that neonatal social isolation results in sustained changes in social behavior with altered function of limbic and frontal cortices.

  20. Removal of growth hormone receptor (GHR) in muscle of male mice replicates some of the health benefits seen in global GHR−/− mice

    PubMed Central

    List, Edward O.; Berryman, Darlene E.; Ikeno, Yuji; Hubbard, Gene B.; Funk, Kevin; Comisford, Ross; Young, Jonathan A.; Stout, Michael B.; Tchkonia, Tamar; Masternak, Michal M.; Bartke, Andrzej; Kirkland, James L.; Miller, Richard A.; Kopchick, John J.

    2015-01-01

    Global disruption of the GH receptor in mice (GHR−/−) produces a large and reproducible extension in lifespan. Since lack of GH action in muscle resulting in improved glucose homeostasis is potentially a mechanism by which GHR−/− mice are long-lived, and since no information on muscle-specific GHR disruption in females is available, we generated and characterized a line of muscle-specific GHR disrupted (MuGHRKO) mice. As expected, male MuGHRKO mice had improved fasting blood glucose, insulin, c-peptide, and glucose tolerance. In contrast, female MuGHRKO mice exhibited normal glucose, insulin, and glucose tolerance. Body weight was mildly but significantly altered in opposite directions in males (decreased) and females (increased) compared to controls. Grip strength and treadmill endurance were unchanged with advanced age in both sexes, suggesting that the direct action of GH on muscle has minimal effect on age-related musculoskeletal frailty. Longevity was unchanged in both sexes at Ohio University and significantly increased for males at University of Michigan. These data suggest that removal of GHR in muscle of male MuGHRKO mice replicates some of the health benefits seen in global GHR−/− mice including improvements to glucose homeostasis and smaller body weight in males, which may explain the trends observed in lifespan. PMID:26233957

  1. Removal of growth hormone receptor (GHR) in muscle of male mice replicates some of the health benefits seen in global GHR-/- mice.

    PubMed

    List, Edward O; Berryman, Darlene E; Ikeno, Yuji; Hubbard, Gene B; Funk, Kevin; Comisford, Ross; Young, Jonathan A; Stout, Michael B; Tchkonia, Tamar; Masternak, Michal M; Bartke, Andrzej; Kirkland, James L; Miller, Richard A; Kopchick, John J

    2015-07-01

    Global disruption of the GH receptor in mice (GHR-/-) produces a large and reproducible extension in lifespan. Since lack of GH action in muscle resulting in improved glucose homeostasis is potentially a mechanism by which GHR-/- mice are long-lived, and since no information on muscle-specific GHR disruption in females is available, we generated and characterized a line of muscle-specific GHR disrupted (MuGHRKO) mice. As expected, male MuGHRKO mice had improved fasting blood glucose, insulin, c-peptide, and glucose tolerance. In contrast, female MuGHRKO mice exhibited normal glucose, insulin, and glucose tolerance. Body weight was mildly but significantly altered in opposite directions in males (decreased) and females (increased) compared to controls. Grip strength and treadmill endurance were unchanged with advanced age in both sexes, suggesting that the direct action of GH on muscle has minimal effect on age-related musculoskeletal frailty. Longevity was unchanged in both sexes at Ohio University and significantly increased for males at University of Michigan. These data suggest that removal of GHR in muscle of male MuGHRKO mice replicates some of the health benefits seen in global GHR-/- mice including improvements to glucose homeostasis and smaller body weight in males, which may explain the trends observed in lifespan. PMID:26233957

  2. Removal of growth hormone receptor (GHR) in muscle of male mice replicates some of the health benefits seen in global GHR-/- mice.

    PubMed

    List, Edward O; Berryman, Darlene E; Ikeno, Yuji; Hubbard, Gene B; Funk, Kevin; Comisford, Ross; Young, Jonathan A; Stout, Michael B; Tchkonia, Tamar; Masternak, Michal M; Bartke, Andrzej; Kirkland, James L; Miller, Richard A; Kopchick, John J

    2015-07-01

    Global disruption of the GH receptor in mice (GHR-/-) produces a large and reproducible extension in lifespan. Since lack of GH action in muscle resulting in improved glucose homeostasis is potentially a mechanism by which GHR-/- mice are long-lived, and since no information on muscle-specific GHR disruption in females is available, we generated and characterized a line of muscle-specific GHR disrupted (MuGHRKO) mice. As expected, male MuGHRKO mice had improved fasting blood glucose, insulin, c-peptide, and glucose tolerance. In contrast, female MuGHRKO mice exhibited normal glucose, insulin, and glucose tolerance. Body weight was mildly but significantly altered in opposite directions in males (decreased) and females (increased) compared to controls. Grip strength and treadmill endurance were unchanged with advanced age in both sexes, suggesting that the direct action of GH on muscle has minimal effect on age-related musculoskeletal frailty. Longevity was unchanged in both sexes at Ohio University and significantly increased for males at University of Michigan. These data suggest that removal of GHR in muscle of male MuGHRKO mice replicates some of the health benefits seen in global GHR-/- mice including improvements to glucose homeostasis and smaller body weight in males, which may explain the trends observed in lifespan.

  3. Asymmetry and polymorphism of hybrid male sterility during the early stages of speciation in house mice.

    PubMed

    Good, Jeffrey M; Handel, Mary Ann; Nachman, Michael W

    2008-01-01

    House mice offer a powerful system for dissecting the genetic basis of phenotypes that isolate species in the early stages of speciation. We used a series of reciprocal crosses between wild-derived strains of Mus musculus and M. domesticus to examine F(1) hybrid male sterility, one of the primary phenotypes thought to isolate these species. We report four main results. First, we found significantly smaller testes and fewer sperm in hybrid male progeny of most crosses. Second, in some crosses hybrid male sterility was asymmetric and depended on the species origin of the X chromosome. These observations confirm and extend previous findings, underscoring the central role that the M. musculus X chromosome plays in reproductive isolation. Third, comparisons among reciprocal crosses revealed polymorphism at one or more hybrid incompatibilities within M. musculus. Fourth, the spermatogenic phenotype of this polymorphic interaction appears distinct from previously described hybrid incompatibilities between these species. These data build on previous studies of speciation in house mice and show that the genetic basis of hybrid male sterility is fairly complex, even at this early stage of divergence.

  4. Phase-Specific Vocalizations of Male Mice at the Initial Encounter during the Courtship Sequence.

    PubMed

    Matsumoto, Yui K; Okanoya, Kazuo

    2016-01-01

    Mice produce ultrasonic vocalizations featuring a variety of syllables. Vocalizations are observed during social interactions. In particular, males produce numerous syllables during courtship. Previous studies have shown that vocalizations change according to sexual behavior, suggesting that males vary their vocalizations depending on the phase of the courtship sequence. To examine this process, we recorded large sets of mouse vocalizations during male-female interactions and acoustically categorized these sounds into 12 vocal types. We found that males emitted predominantly short syllables during the first minute of interaction, more long syllables in the later phases, and mainly harmonic sounds during mounting. These context- and time-dependent changes in vocalization indicate that vocal communication during courtship in mice consists of at least three stages and imply that each vocalization type has a specific role in a phase of the courtship sequence. Our findings suggest that recording for a sufficiently long time and taking the phase of courtship into consideration could provide more insights into the role of vocalization in mouse courtship behavior in future study. PMID:26841117

  5. Differential effects of relaxin deficiency on vascular aging in arteries of male mice.

    PubMed

    Jelinic, Maria; Tare, Marianne; Conrad, Kirk P; Parry, Laura J

    2015-08-01

    Exogenous treatment with the naturally occurring peptide relaxin increases arterial compliance and reduces vascular stiffness. In contrast, relaxin deficiency reduces the passive compliance of small renal arteries through geometric and compositional vascular remodeling. The role of endogenous relaxin on passive mechanical wall properties in other vascular beds is unknown. Importantly, no studies have investigated the effects of aging in arteries of relaxin-deficient mice. Therefore, we tested the hypothesis that mesenteric and femoral arteries stiffen with aging, and this is exacerbated with relaxin deficiency. Male wild-type (Rln (+/+)) and relaxin knockout (Rln (-/-)) mice were aged to 3, 6, 12, 18, and 23 months. Passive mechanical wall properties were assessed by pressure myography. In both genotypes, there was a significant increase in circumferential stiffening in mesenteric arteries with aging, whereas in the femoral artery, aging reduced volume compliance. This was associated with a reduced ability of the artery to lengthen with aging. The predominant phenotype observed in Rln (-/-) mice was reduced volume compliance in young mice in both mesenteric and femoral arteries. In summary, aging induces circumferential stiffening in mesenteric arteries and axial stiffening in femoral arteries. Passive mechanical wall properties of Rln (-/-) mouse arteries predominantly differ at younger ages compared with Rln (+/+) mice, suggesting that a lack of endogenous relaxin only has a minor effect on vascular aging.

  6. Melanin-concentrating hormone is necessary for olanzapine-inhibited locomotor activity in male mice.

    PubMed

    Chee, Melissa J S; Douris, Nicholas; Forrow, Avery B; Monnard, Arnaud; Lu, Shuangyu; Flaherty, Stephen E; Adams, Andrew C; Maratos-Flier, Eleftheria

    2015-10-01

    Olanzapine (OLZ), an atypical antipsychotic, can be effective in treating patients with restricting type anorexia nervosa who exercise excessively. Clinical improvements include weight gain and reduced pathological hyperactivity. However the neuronal populations and mechanisms underlying OLZ actions are not known. We studied the effects of OLZ on hyperactivity using male mice lacking the hypothalamic neuropeptide melanin-concentrating hormone (MCHKO) that are lean and hyperactive. We compared the in vivo effects of systemic or intra-accumbens nucleus (Acb) OLZ administration on locomotor activity in WT and MCHKO littermates. Acute systemic OLZ treatment in WT mice significantly reduced locomotor activity, an effect that is substantially attenuated in MCHKO mice. Furthermore, OLZ infusion directly into the Acb of WT mice reduced locomotor activity, but not in MCHKO mice. To identify contributing neuronal mechanisms, we assessed the effect of OLZ treatment on Acb synaptic transmission ex vivo and in vitro. Intraperitoneal OLZ treatment reduced Acb GABAergic activity in WT but not MCHKO neurons. This effect was also seen in vitro by applying OLZ to acute brain slices. OLZ reduced the frequency and amplitude of GABAergic activity that was more robust in WT than MCHKO Acb. These findings indicate that OLZ reduced Acb GABAergic transmission and that MCH is necessary for the hypolocomotor effects of OLZ.

  7. Ephrin-A5 regulates inter-male aggression in mice.

    PubMed

    Sheleg, Michal; Yochum, Carrie L; Richardson, Jason R; Wagner, George C; Zhou, Renping

    2015-06-01

    The Eph family of receptor tyrosine kinases play key roles in both the patterning of the developing nervous system and neural plasticity in the mature brain. To determine functions of ephrin-A5, a GPI-linked ligand to the Eph receptors, in animal behavior regulations, we examined effects of its inactivation on male mouse aggression. When tested in the resident-intruder paradigm for offensive aggression, ephrin-A5-mutant animals (ephrin-A5(-/-)) exhibited severe reduction in conspecific aggression compared to wild-type controls. On the contrary, defensive aggression in the form of target biting was higher in ephrin-A5(-/-) mice, indicating that the mutant mice are capable of attacking behavior. In addition, given the critical role of olfaction in aggressive behavior, we examined the ability of the ephrin-A5(-/-) mice to smell and found no differences between the mutant and control animals. Testosterone levels in the mutant mice were also found to be within the normal range. Taken together, our data reveal a new role of ephrin-A5 in the regulation of aggressive behavior in mice.

  8. A Cmv2 QTL on chromosome X affects MCMV resistance in New Zealand male mice.

    PubMed

    Rodriguez, Marisela R; Lundgren, Alyssa; Sabastian, Pearl; Li, Qian; Churchill, Gary; Brown, Michael G

    2009-07-01

    NK cell-mediated resistance to viruses is subject to genetic control in humans and mice. Here we used classical and quantitative genetic strategies to examine NK-mediated murine cytomegalovirus (MCMV) control in genealogically related New Zealand white (NZW) and black (NZB) mice. NZW mice display NK cell-dependent MCMV resistance while NZB NK cells fail to limit viral replication after infection. Unlike Ly49H(+) NK resistance in C57BL/6 mice, NZW NK-mediated MCMV control was Ly49H-independent. Instead, MCMV resistance in NZW (Cmv2) involves multiple genetic factors. To establish the genetic basis of Cmv2 resistance, we further characterized a major chromosome X-linked resistance locus (DXMit216) responsible for innate MCMV control in NZW x NZB crosses. We found that the DXMit216 locus affects early MCMV control in New Zealand F(2) crosses and demonstrate that the NZB-derived DXMit216 allele enhances viral resistance in F(2) males. The evolutionary conservation of the DXMit216 region in mice and humans suggests that a Cmv2-related mechanism may affect human antiviral responses.

  9. Chronic psychosocial stress increases the risk for inflammation-related colon carcinogenesis in male mice.

    PubMed

    Peters, Sebastian; Grunwald, Nicole; Rümmele, Petra; Endlicher, Esther; Lechner, Anja; Neumann, Inga D; Obermeier, Florian; Reber, Stefan O

    2012-07-01

    Patients with inflammatory bowel diseases (IBDs) have a higher risk of developing colorectal cancer (CRC) than the general population. Furthermore, chronic psychosocial stress increases the likelihood of developing IBD and multiple types of malignant neoplasms, including CRC. Here, for the first time, we investigate the effects of chronic psychosocial stress in male mice on an artificially induced CRC, by employing the chronic subordinate colony (CSC) housing paradigm in combination with the reliable azoxymethane (AOM)/dextran sodium sulfate (DSS) CRC model. Colonoscopy revealed that CSC mice showed accelerated macroscopic suspect lesions. In addition, more CSC mice developed low-grade dysplasia (LGD) and/or high-grade dysplasia (HGD) in the colonic tissue compared to the single-housed control mice (SHC). CSC mice showed an increased number of Ki67+ and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling epithelial cells in colonic tissue. Colonic liver receptor homolog-1 (LRH-1), cyclooxygenase II (COXII), tumor necrosis factor, forkhead box P3 (FoxP3) mRNA as well as colonic ß-catenin, COXII, and LRH-1 protein expression were also increased in CSC compared with SHC mice. Although the number of CD4+ Th cells was increased, a tendency toward a decreased colonic interferon-γ (IFN-γ) mRNA expression was observed. Furthermore, despite an increased percentage of CD3+ cells and CD3+/FoxP3+ double-positive cells within mesenteric lymph node cells of CSC mice, IFN-γ secretion from these cells was unaffected. Altogether, our results suggest that chronic psychosocial stress increases the risk for AOM/DSS-induced and, thus, inflammation-related CRC. Finally, assessment of additional time points may test whether the shift from tumor-protective Th1 cell to regulatory T-cell immunity represents a consequence of increased carcinogenesis or a causal factor involved in its development.

  10. Social stress in male mice impairs long-term antiviral immunity selectively in wounded subjects.

    PubMed

    de Groot, Johanna; Boersma, Wim J A; Scholten, Jan Willem; Koolhaas, Jaap M

    2002-03-01

    An important property of the antiviral immune response is its time-dependent character. Beginning with a few antigen-specific cells upon infection, it evolves to a stage where there is an abundance of antigen-specific cells and antibodies that are needed to clear the pathogen, and ends with circulating antibodies and a population of virus-specific memory cells to protect the animal from reinfection. Short-term effects of stress on the immune system have been investigated extensively, showing that stress acutely changes many aspects of immunity. However, relatively little is known about the consequences of stress for the quality and quantity of long-term immunological memory. In the present study, we have investigated the effect of social stress, applied in mice at Days 1, 2 and 3 after inoculation with a herpes virus, on long-term antibody and memory cytokine responses to the virus. Male mice were subjected to three 5-min confrontations with an aggressive conspecific. Approximately half of the mice was wounded by bites of the aggressor during this stress procedure, and these mice were analyzed separately from nonwounded mice. It appeared that wounded mice showed suppressed protective antibody responses and impaired memory for virus-specific IL-4 and IL-10 production, whereas mice that were not wounded showed intact long-term immune responses and memory. It is concluded that the combination of wounds and the social stress of repeated confrontations is associated with impaired protective immunity as a consequence of suppressed antibody levels and impairment of some aspects of antiviral immunological memory. PMID:11897253

  11. Immune alterations in male and female mice after 2-deoxy-D-glucose administration

    NASA Technical Reports Server (NTRS)

    Dreau, D.; Morton, D. S.; Foster, M.; Swiggett, J. P.; Sonnenfeld, G.

    1997-01-01

    Administration of 2-deoxy-D-glucose (2-DG) induces acute cellular glucoprivation. In the current study, we examined differences in immune parameters after 2-DG administration in both sexes. Male and female BDF1 mice were injected three times, 48 h apart, either with a saline solution (control group) or with 2-DG in saline (500 mg/kg). Two hours after the last injection, blood and spleens were collected. Plasma levels of interleukin-1beta, and interferon-gamma levels were measured. Additionally, the levels of the specific leukocyte antigens CD3, CD4, CD8, T cell receptor (TCR) alpha/beta, I-Ad, and H-2Ld/H-2Db were evaluated by flow cytometry on both blood and spleen cells. The blastogenic response of leukocytes from both tissues to mitogens was assessed. Levels of glucose, corticosterone, testosterone, progesterone, 17beta-estradiol, follicle-stimulating hormone, and luteinizing hormone were also determined. Increases in the percentage of cells bearing TCR alpha/beta and I-Ad in the blood and H-2Ld/H-2Db in the spleen were observed in the 2-DG-treated group for both sexes. In contrast, higher corticosterone and IL-1beta plasma concentrations, as well as higher percentages of splenocytes bearing TCR alpha/beta and I-Ad, and lower mitogen-induced proliferation of mature T splenocytes (79%) were observed in female but not in male mice injected with 2-DG compared with those injected with saline (p < 0.05). Taken together, these results suggest that female mice are more sensitive than male mice to immune alterations induced by 2-DG administration.

  12. Deficits in reproduction and pro-gonadotropin-releasing hormone processing in male Cpefat mice.

    PubMed

    Srinivasan, Sudha; Bunch, Donna O; Feng, Yun; Rodriguiz, Ramona M; Li, Min; Ravenell, Roneka L; Luo, Guo X; Arimura, Akira; Fricker, Lloyd D; Eddy, Edward M; Wetsel, William C

    2004-04-01

    Cpe(fat/fat) mice are obese, diabetic, and infertile. These animals have a point mutation in carboxypeptidase E (CPE), an exopeptidase that removes C-terminal basic amino acids from peptide intermediates. The mutation renders the enzyme unstable, and it is rapidly degraded. Although the infertility of Cpe(fat/fat) mice has not been systematically investigated, it is thought to be due to a deficit in GnRH processing. We have evaluated this hypothesis and found hypothalamic GnRH levels to be reduced by 65-78% and concentrations of pro-GnRH and C-terminal-extended intermediates to be high. Basal serum gonadotropin contents are similar among wild-type, heterozygous, and homozygous mice. Testis morphology and function are abnormal in older obese Cpe(fat/fat) mice. Matings between homozygous mutants yield a 5% pregnancy rate. By comparison, when 50-d-old Cpe(fat/fat) males are paired with heterozygous females, rates increase to 43%, and they rapidly decrease to negligible levels by 120 d. As fertility declines without accompanying changes in the hypothalamic-pituitary-gonadal axis and before obesity is evident, reproduction is more complex than originally thought. This suspicion is confirmed in 90-d-old Cpe(fat/fat) males, who readily interact with females, but rarely mount and fail to show intromission or ejaculation behaviors. Together, these findings show that CPE is a key enzyme for pro-GnRH processing in vivo; however, the reproductive deficits in Cpe(fat/fat) males appear to be due primarily to abnormal sexual behavior.

  13. Animal models of physiologic markers of male reproduction: genetically defined infertile mice

    SciTech Connect

    Chubb, C.

    1987-10-01

    The present report focuses on novel animal models of male infertility: genetically defined mice bearing single-gene mutations that induce infertility. The primary goal of the investigations was to identify the reproductive defects in these mutant mice. The phenotypic effects of the gene mutations were deciphered by comparing the mutant mice to their normal siblings. Initially testicular steroidogenesis and spermatogenesis were investigated. The physiologic markers for testicular steroidogenesis were steroid secretion by testes perifused in vitro, seminal vesicle weight, and Leydig cell histology. Spermatogenesis was evaluated by the enumeration of homogenization-resistant sperm/spermatids in testes and by morphometric analyses of germ cells in the seminiferous epithelium. If testicular function appeared normal, the authors investigated the sexual behavior of the mice. The parameters of male sexual behavior that were quantified included mount patency, mount frequency, intromission latency, thrusts per intromission, ejaculation latency, and ejaculation duration. Females of pairs breeding under normal circumstances were monitored for the presence of vaginal plugs and pregnancies. The patency of the ejaculatory process was determined by quantifying sperm in the female reproductive tract after sexual behavior tests. Sperm function was studied by quantitatively determining sperm motility during videomicroscopic observation. Also, the ability of epididymal sperm to function within the uterine environment was analyzed by determining sperm capacity to initiate pregnancy after artificial insemination. Together, the experimental results permitted the grouping of the gene mutations into three general categories. They propose that the same biological markers used in the reported studies can be implemented in the assessment of the impact that environmental toxins may have on male reproduction.

  14. Photoperiodic regulation of hippocampal neurogenesis in adult male white-footed mice (Peromyscus leucopus).

    PubMed

    Walton, James C; Aubrecht, Taryn G; Weil, Zachary M; Leuner, Benedetta; Nelson, Randy J

    2014-08-01

    Photoperiodic organisms monitor environmental day length to engage in seasonally appropriate adaptions in physiology and behavior. Among these adaptations are changes in brain volume and neurogenesis, which have been well described in multiple species of birds, yet few studies have described such changes in the brains of adult mammals. White-footed mice (Peromyscus leucopus) are an excellent species in which to investigate the effects of day length on adult hippocampal neurogenesis, as males, in addition to having reduced hippocampal volume in short days (SD) with concomitant impairments in hippocampus-mediated behaviors, have photoperiod-dependent changes in olfactory bulb neurogenesis. We performed the current experiment to assess the effects of photoperiod on hippocampal neurogenesis longitudinally, using the thymidine analog bromodeoxyuridine at multiple time points across 10 weeks of SD exposure. Compared with counterparts held in long day (LD) lengths, across the first 8 weeks of SD exposure hippocampal neurogenesis was reduced. However, at 10 weeks in SD lengths neurogenic levels in the hippocampus were elevated above those levels in mice held in LD lengths. The current findings are consistent with the natural photoperiodic cycle of hippocampal function in male white-footed mice, and may help to inform research on photoperiodic plasticity in neurogenesis and provide insight into how the complex interplay among the environment, genes and adaptive responses to changing day lengths affects brain structure, function and behavior at multiple levels. PMID:24893623

  15. Photoperiodic regulation of hippocampal neurogenesis in adult male white-footed mice (Peromyscus leucopus).

    PubMed

    Walton, James C; Aubrecht, Taryn G; Weil, Zachary M; Leuner, Benedetta; Nelson, Randy J

    2014-08-01

    Photoperiodic organisms monitor environmental day length to engage in seasonally appropriate adaptions in physiology and behavior. Among these adaptations are changes in brain volume and neurogenesis, which have been well described in multiple species of birds, yet few studies have described such changes in the brains of adult mammals. White-footed mice (Peromyscus leucopus) are an excellent species in which to investigate the effects of day length on adult hippocampal neurogenesis, as males, in addition to having reduced hippocampal volume in short days (SD) with concomitant impairments in hippocampus-mediated behaviors, have photoperiod-dependent changes in olfactory bulb neurogenesis. We performed the current experiment to assess the effects of photoperiod on hippocampal neurogenesis longitudinally, using the thymidine analog bromodeoxyuridine at multiple time points across 10 weeks of SD exposure. Compared with counterparts held in long day (LD) lengths, across the first 8 weeks of SD exposure hippocampal neurogenesis was reduced. However, at 10 weeks in SD lengths neurogenic levels in the hippocampus were elevated above those levels in mice held in LD lengths. The current findings are consistent with the natural photoperiodic cycle of hippocampal function in male white-footed mice, and may help to inform research on photoperiodic plasticity in neurogenesis and provide insight into how the complex interplay among the environment, genes and adaptive responses to changing day lengths affects brain structure, function and behavior at multiple levels.

  16. Regulation of phase II enzymes by genistein and daidzein in male and female Swiss Webster mice.

    PubMed

    Froyen, Erik B; Reeves, Jaime L Rudolf; Mitchell, Alyson E; Steinberg, Francene M

    2009-12-01

    The consumption of soy and soy isoflavones has been associated with a decreased risk of certain cancers. A factor contributing to this dietary chemoprevention is the activity of phase I and II biotransformation enzymes. This study evaluated the hypothesis that dietary soy isoflavones will increase hepatic and extrahepatic quinone reductase (QR), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) phase II enzyme activities, under short-term feeding and basal (non-pharmacologic-induced) conditions. Male and female Swiss Webster mice were fed for 1, 3, 5, or 7 days of one of four treatments: control (casein AIN-93G) or control supplemented with flavone (positive control), genistein, or daidzein aglycones at 1,500 mg/kg of diet. QR activity was increased by daidzein in the liver, by both isoflavones in the kidney and small intestine, and by genistein in the heart. Genistein and daidzein slightly decreased UGT activities in some tissues. Liver GST activity was decreased by genistein in females. In contrast, genistein and daidzein increased kidney GST activity. In general, the greatest effects of isoflavones on phase II enzymes were observed in liver and kidney tissues, occurring at day 3, and peaking at day 5. Sex effects in the liver and kidney included females exhibiting higher QR activities and males exhibiting higher UGT and GST activities. In conclusion, individual soy isoflavones modulate phase II enzymes in mice under short-term feeding and basal conditions. This study provides insights into the actions of isolated isoflavones in mice.

  17. Prolyl Endopeptidase (PREP) is Associated With Male Reproductive Functions and Gamete Physiology in Mice.

    PubMed

    Dotolo, Raffaele; Kim, Jung Dae; Pariante, Paolo; Minucci, Sergio; Diano, Sabrina

    2016-03-01

    Prolyl endopeptidase (PREP) is a serine protease which has been implicated in many biological processes, such as the maturation and degradation of peptide hormones and neuropeptides, learning and memory, cell proliferation and differentiation, and glucose metabolism. A small number of reports have also suggested PREP participation in both male and female reproduction-associated processes. In the present work, we examined PREP distribution in male germ cells and studied the effects of its knockdown (Prep(gt/gt)) on testis and sperm in adult mice. The protein is expressed and localized in elongating spermatids and luminal spermatozoa of wild type (wt) mice, as well as Sertoli, Leydig, and peritubular cells. PREP is also expressed in the head and midpiece of epididymal spermatozoa, whereas the remaining tail region shows a weaker signal. Furthermore, testis weight, histology of seminiferous tubules, and epididymal sperm parameters were assessed in wt and Prep(gt/gt) mice: wild type testes have larger average tubule and lumen diameter; in addition, lumenal composition of seminiferous tubules is dissimilar between wt and Prep(gt/gt), as the percentage of spermiated tubules is much higher in wt. Finally, total sperm count, sperm motility, and normal morphology are also higher in wt than in Prep(gt/gt). These results show for the first time that the expression of PREP could be necessary for a correct reproductive function, and suggest that the enzyme may play a role in mouse spermatogenesis and sperm physiology.

  18. Partial Müllerian Duct Retention in Smad4 Conditional Mutant Male Mice.

    PubMed

    Petit, Fabrice G; Deng, Chuxia; Jamin, Soazik P

    2016-01-01

    Müllerian duct regression is a complex process which involves the AMH signalling pathway. We have previously demonstrated that besides AMH and its specific type II receptor (AMHRII), BMPR-IA and Smad5 are two essential factors implicated in this mechanism. Mothers against decapentaplegic homolog 4 (Smad4) is a transcription factor and the common Smad (co-Smad) involved in transforming growth factor beta (TGF-β) signalling pathway superfamily. Since Smad4 null mutants die early during gastrulation, we have inactivated Smad4 in the Müllerian duct mesenchyme. Specific inactivation of Smad4 in the urogenital ridge leads to the partial persistence of the Müllerian duct in adult male mice. Careful examination of the urogenital tract reveals that the Müllerian duct retention is randomly distributed either on one side or both sides. Histological analysis shows a uterus-like structure, which is confirmed by the expression of estrogen receptor α. As previously described in a β-catenin conditional mutant mouse model, β-catenin contributes to Müllerian duct regression. In our mutant male embryos, it appears that β-catenin expression is locally reduced along the urogenital ridge as compared to control mice. Moreover, the expression pattern is similar to those observed in control female mice. This study shows that reduced Smad4 expression disrupts the Wnt/β-catenin signalling leading to the partial persistence of Müllerian duct.

  19. Partial Müllerian Duct Retention in Smad4 Conditional Mutant Male Mice

    PubMed Central

    Petit, Fabrice G.; Deng, Chuxia; Jamin, Soazik P.

    2016-01-01

    Müllerian duct regression is a complex process which involves the AMH signalling pathway. We have previously demonstrated that besides AMH and its specific type II receptor (AMHRII), BMPR-IA and Smad5 are two essential factors implicated in this mechanism. Mothers against decapentaplegic homolog 4 (Smad4) is a transcription factor and the common Smad (co-Smad) involved in transforming growth factor beta (TGF-β) signalling pathway superfamily. Since Smad4 null mutants die early during gastrulation, we have inactivated Smad4 in the Müllerian duct mesenchyme. Specific inactivation of Smad4 in the urogenital ridge leads to the partial persistence of the Müllerian duct in adult male mice. Careful examination of the urogenital tract reveals that the Müllerian duct retention is randomly distributed either on one side or both sides. Histological analysis shows a uterus-like structure, which is confirmed by the expression of estrogen receptor α. As previously described in a β-catenin conditional mutant mouse model, β-catenin contributes to Müllerian duct regression. In our mutant male embryos, it appears that β-catenin expression is locally reduced along the urogenital ridge as compared to control mice. Moreover, the expression pattern is similar to those observed in control female mice. This study shows that reduced Smad4 expression disrupts the Wnt/β-catenin signalling leading to the partial persistence of Müllerian duct. PMID:27194944

  20. Influence of chronic exposure to uranium on male reproduction in mice

    SciTech Connect

    Llobet, J.M.; Sirvent, J.J.; Ortega, A.; Domingo, J.L. )

    1991-05-01

    Relatively few data are available concerning the reproductive and developmental toxicity of uranium. The present study was designed to evaluate the reproductive effects of this metal in male Swiss mice. The animals were treated with uranyl acetate dihydrate at doses of 0, 10, 20, 40, and 80 mg/kg/day given in the drinking water for 64 days. To evaluate the fertility of the uranium-treated males, mice were mated with untreated females for 4 days. There was a significant but non-dose-related decrease in the pregnancy rate of these animals. Body weights were significantly depressed only in the 80 mg/kg/day group. Testicular function/spermatogenesis was not affected by uranium at any dose, as evidenced by normal testes and epididymis weights and normal spermatogenesis, whereas interstitial alterations and vacuolization of Leydig cells were seen at 80 mg/kg/day. The results of this investigation indicate that uranium does not cause any adverse effect on testicular function in mice at the concentrations usually ingested in the diet and drinking water, with a safety factor of more than 1000. However, although spermatogenesis was not affected by uranium administration, uranium produces a significant decrease in the pregnancy rate at 10, 20, 40, or 80 mg/kg/day.

  1. Male Fertility Is Reduced by Chronic Intermittent Hypoxia Mimicking Sleep Apnea in Mice

    PubMed Central

    Torres, Marta; Laguna-Barraza, Ricardo; Dalmases, Mireia; Calle, Alexandra; Pericuesta, Eva; Montserrat, Josep M.; Navajas, Daniel; Gutierrez-Adan, Alfonso; Farré, Ramon

    2014-01-01

    Study Objectives: Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia and oxidative stress. However, it is unknown whether intermittent hypoxia mimicking OSA modifies male fertility. We tested the hypothesis that male fertility is reduced by chronic intermittent hypoxia mimicking OSA in a mouse model. Design: Case-control comparison in a murine model. Setting: University research laboratory. Participants: Eighteen F1 (C57BL/6xCBA) male mice. Interventions: Mice were subjected to a pattern of periodic hypoxia (20 sec at 5% O2 followed by 40 sec of room air) 6 h/day for 60 days or normoxia. After this period, mice performed a mating trial to determine effective fertility by assessing the number of pregnant females and fetuses. Measurements and Results: After euthanasia, oxidative stress in testes was assessed by measuring the expression of glutathione peroxidase 1 (Gpx1) and superoxide dismutase-1 (Sod1) by reverse-transcription polymerase chain reaction. Sperm motility was determined by Integrated Semen Analysis System (ISAS). Intermittent hypoxia significantly increased testicular oxidative stress, showing a reduction in the expression of Gpx1 and Sod1 by 38.9% and 34.4%, respectively, as compared with normoxia (P < 0.05). Progressive sperm motility was significantly reduced from 27.0 ± 6.4% in normoxia to 12.8 ± 1.8% in the intermittent hypoxia group (P = 0.04). The proportion of pregnant females and number of fetuses per mating was significantly lower in the intermittent hypoxia group (0.33 ± 0.10 and 2.45 ± 0.73, respectively) than in normoxic controls (0.72 ± 0.16 and 5.80 ± 1.24, respectively). Conclusions: These results suggest that the intermittent hypoxia associated with obstructive sleep apnea (OSA) could induce fertility reduction in male patients with this sleep breathing disorder. Citation: Torres M, Laguna-Barraza R, Dalmases M, Calle A, Pericuesta E, Montserrat JM, Navajas D, Gutierrez-Adan A, Farré R. Male fertility is

  2. The albino mutation of tyrosinase alters ocular angiogenic responsiveness.

    PubMed

    Rogers, Michael S; Adini, Irit; McBride, Aaron F; Birsner, Amy E; D'Amato, Robert J

    2013-07-01

    We have observed substantial differences in angiogenic responsiveness in mice and have mapped the genetic loci responsible for these differences. We have found that the albino mutation is one of the loci responsible for such differences. Using B6.A consomic strains, we determined that chromosome 7 bears a locus that inhibits VEGF-induced corneal neovascularization. F2 crosses between B6.A consomic mice and C57BL/6J parents along with AXB and BXA recombinant inbred strains demonstrated highest linkage near the tyrosinase gene. This region was named AngVq4. Congenic animals confirmed this locus, but could not demonstrate that the classical tyrosinase albino (c) mutation was causative because of the existence of additional linked loci in the congenic region. However, in 1970, a second tyrosinase albino mutation (c-2J) arose in the C57BL/6J background at Jackson Labs. Testing this strain (C57BL/6J) demonstrated that the albino mutation is sufficient to completely explain the alteration in angiogenic response that we observed in congenic animals. Thus, we conclude that the classical tyrosinase mutation is responsible for AngVq4. In contrast to the cornea, where pigmented animals exhibit increased angiogenic responsiveness, iris neovascularization was inhibited in pigmented animals. These results may partially explain increased aggressiveness in amelanotic melanoma, as well as ethnic differences in diabetic retinopathy and macular degeneration. PMID:23423728

  3. Behavioral effects of combined environmental enrichment and chronic nicotine administration in male NMRI mice.

    PubMed

    Mesa-Gresa, Patricia; Pérez-Martinez, Asunción; Redolat, Rosa

    2013-04-10

    Environmental enrichment (EE) is an experimental paradigm which provides sensory, social, physical and cognitive stimulation for rodents. Experimental evidence indicates that this type of housing induces different neurobiological and behavioral changes. However, few studies have evaluated the consequences of combined exposure to an enriched environment and nicotine administration during a critical period of development such as adolescence. Taking into account previous studies, it can be hypothesized that a chronic treatment with nicotine would modulate the effects of rearing animals in enriched environments. In the current study, our main aim was to evaluate the effects of EE and chronic nicotine administration on physiological parameters (weight, fluid intake and cotinine levels), motor activity, exploratory behavior, anxiety and learning in male NMRI mice. Half of the mice (n=32) were exposed to an enriched environment (EE) and the other half (n=32) were housed in standard environments (SE) with or without oral nicotine administration (100 μg/ml). After 3 weeks, mice were evaluated in a behavioral battery that included an elevated plus-maze, a hole board, an actimeter and an inhibitory avoidance task. Blood cotinine levels were measured in an additional group of 32 mice in order to confirm nicotine intake. Results indicated that mice reared in an enriched environment gained less body weight and displayed higher fluid intake than those maintained in a standard environment. EE reduced motor activity, exploratory behavior and anxiety, whereas it enhanced inhibitory avoidance learning. In relation to the effects of chronic nicotine treatment, the data reflected a lower increase in body weight and a reduced fluid intake in nicotine-treated mice. In the elevated plus-maze, nicotine induced a reduction of total arm entries and rearings. Cotinine levels were higher in mice that received oral nicotine than in the control group. We conclude that the EE paradigm applied in

  4. Excessive Growth Hormone Expression in Male GH Transgenic Mice Adversely Alters Bone Architecture and Mechanical Strength

    PubMed Central

    Lim, S. V.; Marenzana, M.; Hopkinson, M.; List, E. O.; Kopchick, J. J.; Pereira, M.; Javaheri, B.; Roux, J. P.; Chavassieux, P.; Korbonits, M.

    2015-01-01

    Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites. PMID:25646711

  5. Acrylonitrile is a multisite carcinogen in male and female B6C3F1 mice.

    PubMed

    Ghanayem, Burhan I; Nyska, Abraham; Haseman, Joseph K; Bucher, John R

    2002-07-01

    Acrylonitrile is a heavily produced unsaturated nitrile, which is used in the production of synthetic fibers, plastics, resins, and rubber. Acrylonitrile is a multisite carcinogen in rats after exposure via gavage, drinking water, or inhalation. No carcinogenicity studies of acrylonitrile in a second animal species were available. The current studies were designed to assess the carcinogenicity of acrylonitrile in B6C3F1 mice of both sexes. Acrylonitrile was administered by gavage at 0, 2.5, 10, or 20 mg/kg/day, 5 days per week, for 2 years. Urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine were measured as markers of exposure to acrylonitrile. In general, there were dose-related increases in urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine concentrations in all dosed groups of mice and at all time points. Survival was significantly (p < 0.001) reduced in the top dose (20 mg/kg) group of male and female mice relative to controls. The incidence of forestomach papillomas and carcinomas was increased in mice of both sexes in association with an increase in forestomach epithelial hyperplasia. The incidence of Harderian gland adenomas and carcinomas was also markedly increased in the acrylonitrile-dosed groups. In female mice, the incidence of benign or malignant granulosa cell tumors (combined) in the ovary in the 10 mg/kg dose group was greater than that in the vehicle control group, but because of a lack of dose response, this was considered an equivocal finding. In addition, the incidences of atrophy and cysts in the ovary of the 10 and 20 mg/kg dose groups were significantly increased. The incidences of alveolar/bronchiolar adenoma or carcinoma (combined) were significantly increased in female mice treated with acrylonitrile at 10 mg/kg/day for 2 years. This was also considered an equivocal result. In conclusion, these studies demonstrated that acrylonitrile causes multiple carcinogenic effects after gavage administration to male and female B6

  6. Phase-Specific Vocalizations of Male Mice at the Initial Encounter during the Courtship Sequence

    PubMed Central

    Matsumoto, Yui K.; Okanoya, Kazuo

    2016-01-01

    Mice produce ultrasonic vocalizations featuring a variety of syllables. Vocalizations are observed during social interactions. In particular, males produce numerous syllables during courtship. Previous studies have shown that vocalizations change according to sexual behavior, suggesting that males vary their vocalizations depending on the phase of the courtship sequence. To examine this process, we recorded large sets of mouse vocalizations during male–female interactions and acoustically categorized these sounds into 12 vocal types. We found that males emitted predominantly short syllables during the first minute of interaction, more long syllables in the later phases, and mainly harmonic sounds during mounting. These context- and time-dependent changes in vocalization indicate that vocal communication during courtship in mice consists of at least three stages and imply that each vocalization type has a specific role in a phase of the courtship sequence. Our findings suggest that recording for a sufficiently long time and taking the phase of courtship into consideration could provide more insights into the role of vocalization in mouse courtship behavior in future study. PMID:26841117

  7. Morphine withdrawal syndrome: involvement of the dopaminergic system in prepubertal male and female mice.

    PubMed

    Diaz, Silvina L; Kemmling, Alma K; Rubio, Modesto C; Balerio, Graciela N

    2005-12-01

    Morphine (MOR) withdrawal signs are more marked in males than in females. Considering that the influence of the dopaminergic system on these differences is unclear, we analyzed dopamine (DA) and dihydroxyphenylacetic-acid (DOPAC) brain levels during naloxone (NAL)-precipitated withdrawal as well as the involvement of D(1) and D(2) receptors in the expression of MOR withdrawal in either sex. Prepubertal Swiss-Webster mice received MOR (2 mg/kg, i.p.) twice daily for 9 days. On the tenth day, dependent animals received NAL (6 mg/kg, i.p.) after MOR and were sacrificed 30 min later. DA and DOPAC concentrations were determined in different brain areas using HPLC with electrochemical detection. Other pool of mice received either a D(1) (SCH 23390; 0.2 mg/kg, i.p.) or D(2) (raclopride; 0.3 mg/kg, i.p.) receptor antagonist before NAL and withdrawal signs were evaluated. DA and DOPAC levels only decreased in striatum and cortex of withdrawn males. Conversely, both DA receptor antagonists decreased the expression of MOR withdrawal signs in either sex. The neurochemical sex differences described here could partially explain the behavioral sex differences observed during MOR withdrawal. Additionally, SCH-23390 and raclopride effects suggest an important role of both DA receptors in the expression of MOR withdrawal in males and females.

  8. Quaternary ammonium disinfectants cause subfertility in mice by targeting both male and female reproductive processes.

    PubMed

    Melin, Vanessa E; Melin, Travis E; Dessify, Brian J; Nguyen, Christina T; Shea, Caroline S; Hrubec, Terry C

    2016-01-01

    Alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) are common ingredients in household bathroom and kitchen cleaning sprays. ADBAC+DDAC cause reproductive toxicity in mice. The aim of the present study was to investigate gender-specific reproductive effects from ADBAC+DDAC. Female reproduction was assessed through ovulation, oocyte implantation, and estrus cycling. Male reproductive function was assessed by sperm concentration, motility, and viability. Numbers of corpora lutea were not different after 2 weeks, but decreased after 8 weeks of ADBAC+DDAC exposure. Dams exposed for 5 weeks to ADBAC+DDAC spent significantly less time in estrus. ADBAC+DDAC exposed males exhibited declines in both sperm concentration and motility, but not sperm viability. Subfertility in mice from ADBAC+DDAC exposure is, therefore, mediated through reproductive disturbances in both females and males. While the effect of ADBAC+DDAC exposure on human health is unclear, widespread exposure necessitates further consideration of their potential reproductive toxicity. PMID:26582257

  9. Developmental exposure to methylmercury alters learning and induces depression-like behavior in male mice.

    PubMed

    Onishchenko, Natalia; Tamm, Christoffer; Vahter, Marie; Hökfelt, Tomas; Johnson, Jeffrey A; Johnson, Delinda A; Ceccatelli, Sandra

    2007-06-01

    To investigate the long-term effects of developmental exposure to methylmercury (MeHg), pregnant mice were exposed to at 0.5 mg MeHg/kg/day via drinking water from gestational day 7 until day 7 after delivery. The behavior of offspring was monitored at 5-15 and 26-36 weeks of age using an automated system (IntelliCage) designed for continuous long-term recording of the home cage behavior in social groups and complex analysis of basic activities and learning. In addition, spontaneous locomotion, motor coordination on the accelerating rotarod, spatial learning in Morris water maze, and depression-like behavior in forced swimming test were also studied. The analysis of behavior performed in the IntelliCage without social deprivation occurred to be more sensitive in detecting alterations in activity and learning paradigms. We found normal motor function but decreased exploratory activity in MeHg-exposed male mice, especially at young age. Learning disturbances observed in MeHg-exposed male animals suggest reference memory impairment. Interestingly, the forced swimming test revealed a predisposition to depressive-like behavior in the MeHg-exposed male offspring. This study provides novel evidence that the developmental exposure to MeHg can affect not only cognitive functions but also motivation-driven behaviors.

  10. Atrial natriuretic peptide (ANP) inhibits DMBA/croton oil induced skin tumor growth by modulating NF-κB, MMPs, and infiltrating mast cells in swiss albino mice.

    PubMed

    Subramanian, Vimala; Vellaichamy, Elangovan

    2014-10-01

    Cardiac hormone atrial natriuretic peptide (ANP) and its receptor, natriuretic peptide receptor-A (NPR-A) are implicated as a vital regulator of cancer cell growth and tumor progression. However, the underlying mechanism by which ANP opposes the cancer growth in in-vivo remains unknown. Herein, we investigated the anti-cancer activity of ANP on 7, 12-dimethyl benzanthracence (DMBA)/Croton oil- induced two-step skin carcinogenic mouse model. Skin tumor incidence and tumor volume were recorded during the experimental period of 16 weeks. ANP (1 μg/kg body weight/alternate days for 4 weeks) was injected subcutaneously from the 13th week of DMBA/Croton oil induction. ANP treatment markedly inhibited the skin tumor growth (P<0.001). A significant reduction in the level of NF-κB activation (P<0.001), infiltrating mast cell count (P<0.01) and MMP-2/-9 (P<0.001, respectively) were noticed in the ANP treated mice skin tissue. Further, ANP treatment revert back the altered levels of serum LDH-4, C-reactive protein (CRP), and enzymatic antioxidants (SOD and CAT activities) to near normal level. Taken together, the results of this study suggest that ANP opposes the skin carcinogenesis by suppressing the inflammatory response and MMPs.

  11. Antischistosomal effects of praziquantel, its alkaline hydrolysis and sun decomposed products on experimentally S. mansoni infected albino mice. (A) Efficacy assessment based on clinicopathological findings.

    PubMed

    Suleiman, M I; Akarim, E I; Ibrahim, K E E; Saad, A M; Mohammed, A E; Ahmed, B M; Sulaiman, S M

    2004-04-01

    The antischistosomal activity of praziquantel (PZQ), its alkaline hydrolysis product (HP) and its sun-decomposed (SD) products was investigated in S. mansoni experimentally infected mice. The evaluation was made depending on the degree of clinico-pathological changes. The results obtained revealed that, PZQ, HP and the SD have induced partial suppression of worm fecundity as judged by the significant reduction in eggs per gram of faeces in comparison with the infected untreated control. The effect on tissue egg deposition in the treated groups was comparable to the infection of untrea ted control. Worm recovery showed large reduction in the number of worms for SD (47.6%) and HP (28.6%) compared to PZQ (16.6%) treated groups. So, the former two compounds have the superior antischistosomal activities. Glutamate pyruvate transominase (GPT) and glutamate oxaloacetate transaminase (GOT) concentrations were measured. The GOT values for all treated groups were significantly higher than those for the healthy control group (p=0.01). The SD group enzyme concentration was even higher than the infected untreated control. The GPT values of all groups were greater than the uninfected control and the difference was significant for the infected untreated, PZQ and the SD treated groups (p=0.05). PMID:15143740

  12. Bortezomib treatment causes long-term testicular dysfunction in young male mice

    PubMed Central

    2014-01-01

    Background With increased long-term survivors of childhood cancer patients, therapy-associated infertility has become one of the most common late side-effects and significantly affects their life-quality. Therefore, evaluation of anti-cancer agents on male reproduction and infertility prevention are urgently demanding. The proteasome inhibitor bortezomib has been launched in clinical trials for childhood cancers, however, its potential side effects on reproduction have so far been neither investigated experimentally nor reported in treated children. Thus the present study is designed to explore the impact of bortezomib on male reproductive function and to gain insights into how bortezomib exerts its adverse effects on man gonad, thereby providing pediatric oncologists relevant information. Methods 35 day-old male mice were treated with one 11-day cycle of bortezomib and then sacrificed 2 days, 45 days, or 6 months later. A mating study was performed in the group followed for 6 months, and their pups were analyzed on postnatal day 50. Serum follicle-stimulating hormone (FSH) and testicular testosterone levels were measured. Testicular morphology was evaluated by light- and electron microscopy, and the underlying mechanisms and pathways of testis damage were investigated. Results Testicular damage was visible already 2 days after stopping bortezomib and increased in severity by day 45. Then 80% of seminiferous tubules exhibited hypospermatogenesis with arrest at the levels of spermatogonia, spermatocytes and round spermatids. Germ cells were specifically targeted by bortezomib as evidenced by increased apoptosis mediated through activation of p53 and caspases. Even six months after the bortezomib treatment, testis weight, sperm concentration and seminiferous tubule length remained at a decreased level, indicating that spermatogenesis and tubular outgrowth could not fully recover. Combined with persistently increased serum levels of FSH in these mice, our

  13. Dearth and Delayed Maturation of Testicular Germ Cells in Fanconi Anemia E Mutant Male Mice

    PubMed Central

    Fu, Chun; Begum, Khurshida; Jordan, Philip W.; He, Yan; Overbeek, Paul A.

    2016-01-01

    After using a self-inactivating lentivirus for non-targeted insertional mutagenesis in mice, we identified a transgenic family with a recessive mutation that resulted in reduced fertility in homozygous transgenic mice. The lentiviral integration site was amplified by inverse PCR. Sequencing revealed that integration had occurred in intron 8 of the mouse Fance gene, which encodes the Fanconi anemia E (Fance) protein. Fanconi anemia (FA) proteins play pivotal roles in cellular responses to DNA damage and Fance acts as a molecular bridge between the FA core complex and Fancd2. To investigate the reduced fertility in the mutant males, we analyzed postnatal development of testicular germ cells. At one week after birth, most tubules in the mutant testes contained few or no germ cells. Over the next 2–3 weeks, germ cells accumulated in a limited number of tubules, so that some tubules contained germ cells around the full periphery of the tubule. Once sufficient numbers of germ cells had accumulated, they began to undergo the later stages of spermatogenesis. Immunoassays revealed that the Fancd2 protein accumulated around the periphery of the nucleus in normal developing spermatocytes, but we did not detect a similar localization of Fancd2 in the Fance mutant testes. Our assays indicate that although Fance mutant males are germ cell deficient at birth, the extant germ cells can proliferate and, if they reach a threshold density, can differentiate into mature sperm. Analogous to previous studies of FA genes in mice, our results show that the Fance protein plays an important, but not absolutely essential, role in the initial developmental expansion of the male germ line. PMID:27486799

  14. Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice

    SciTech Connect

    Fu, Zidong Donna; Klaassen, Curtis D.

    2013-12-15

    Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a “dose–response” model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and small intestinal contents. In addition, CR “dose-dependently” increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum. - Highlights: • Dose response effects of short-term CR on BA homeostasis in male mice. • CR increased the BA pool size and many individual BAs. • CR altered BA composition (increased proportion of 12α-hydroxylated BAs). • Increased mRNAs of BA enzymes in liver (Cyp7a1 and BAL) and ileal BA binding protein.

  15. The role of ghrelin signalling for sexual behaviour in male mice.

    PubMed

    Egecioglu, Emil; Prieto-Garcia, Luna; Studer, Erik; Westberg, Lars; Jerlhag, Elisabet

    2016-03-01

    Ghrelin, a gut-brain signal, is well known to regulate energy homeostasis, food intake and appetite foremost via hypothalamic ghrelin receptors (GHS-R1A). In addition, ghrelin activates the reward systems in the brain, namely the mesolimbic dopamine system, and regulates thereby the rewarding properties of addictive drugs as well as of palatable foods. Given that the mesolimbic dopamine system mandates the reinforcing properties of addictive drugs and natural rewards, such as sexual behaviour, we hypothesize that ghrelin plays an important role for male sexual behaviour, a subject for the present studies. Herein we show that ghrelin treatment increases, whereas pharmacological suppression (using the GHSR-1A antagonist JMV2959) or genetic deletion of the GHS-R1A in male mice decreases the sexual motivation for as well as sexual behaviour with female mice in oestrus. Pre-treatment with L-dopa (a dopamine precursor) prior to treatment with JMV2959 significantly increased the preference for female mouse compared with vehicle treatment. On the contrary, treatment with 5-hydroxythyptohan (a precursor for serotonin) prior to treatment with JMV2959 decreased the sexual motivation compared to vehicle. In separate experiments, we show that ghrelin and GHS-R1A antagonism do not affect the time spent over female bedding as measured in the androgen-dependent bedding test. Collectively, these data show that the hunger hormone ghrelin and its receptor are required for normal sexual behaviour in male mice and that the effects of the ghrelin signalling system on sexual behaviour involve dopamine neurotransmission.

  16. Alteration in plasma testosterone levels in male mice lacking soluble epoxide hydrolase.

    PubMed

    Luria, Ayala; Morisseau, Christophe; Tsai, Hsing-Ju; Yang, Jun; Inceoglu, Bora; De Taeye, Bart; Watkins, Steven M; Wiest, Michelle M; German, J Bruce; Hammock, Bruce D

    2009-08-01

    Soluble epoxide hydrolase (Ephx2, sEH) is a bifunctional enzyme with COOH-terminal hydrolase and NH(2)-terminal phosphatase activities. sEH converts epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), and the phosphatase activity is suggested to be involved in cholesterol metabolism. EETs participate in a wide range of biological functions, including regulation of vascular tone, renal tubular transport, cardiac contractility, and inflammation. Inhibition of sEH is a potential approach for enhancing the biological activity of EETs. Therefore, disruption of sEH activity is becoming an attractive therapeutic target for both cardiovascular and inflammatory diseases. To define the physiological role of sEH, we characterized a knockout mouse colony lacking expression of the Ephx2 gene. Lack of sEH enzyme is characterized by elevation of EET to DHET ratios in both the linoleate and arachidonate series in plasma and tissues of both female and male mice. In male mice, this lack of expression was also associated with decreased plasma testosterone levels, sperm count, and testicular size. However, this genotype was still able to sire litters. Plasma cholesterol levels also declined in this genotype. Behavior tests such as anxiety-like behavior and hedonic response were also examined in Ephx2-null and WT mice, as all can be related to hormonal changes. Null mice showed a level of anxiety with a decreased hedonic response. In conclusion, this study provides a broad biochemical, physiological, and behavioral characterization of the Ephx2-null mouse colony and suggests a mechanism by which sEH and its substrates may regulate circulating levels of testosterone through cholesterol biosynthesis and metabolism. PMID:19458064

  17. Dose-Dependent Adverse Effects of Salinomycin on Male Reproductive Organs and Fertility in Mice

    PubMed Central

    Ojo, Olajumoke Omolara; Bhadauria, Smrati; Rath, Srikanta Kumar

    2013-01-01

    Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage proteins (CYP11A1) were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of steroidogenesis

  18. Alteration in plasma testosterone levels in male mice lacking soluble epoxide hydrolase

    PubMed Central

    Luria, Ayala; Morisseau, Christophe; Tsai, Hsing-Ju; Yang, Jun; Inceoglu, Bora; De Taeye, Bart; Watkins, Steven M.; Wiest, Michelle M.; German, J. Bruce; Hammock, Bruce D.

    2009-01-01

    Soluble epoxide hydrolase (Ephx2, sEH) is a bifunctional enzyme with COOH-terminal hydrolase and NH2-terminal phosphatase activities. sEH converts epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), and the phosphatase activity is suggested to be involved in cholesterol metabolism. EETs participate in a wide range of biological functions, including regulation of vascular tone, renal tubular transport, cardiac contractility, and inflammation. Inhibition of sEH is a potential approach for enhancing the biological activity of EETs. Therefore, disruption of sEH activity is becoming an attractive therapeutic target for both cardiovascular and inflammatory diseases. To define the physiological role of sEH, we characterized a knockout mouse colony lacking expression of the Ephx2 gene. Lack of sEH enzyme is characterized by elevation of EET to DHET ratios in both the linoleate and arachidonate series in plasma and tissues of both female and male mice. In male mice, this lack of expression was also associated with decreased plasma testosterone levels, sperm count, and testicular size. However, this genotype was still able to sire litters. Plasma cholesterol levels also declined in this genotype. Behavior tests such as anxiety-like behavior and hedonic response were also examined in Ephx2-null and WT mice, as all can be related to hormonal changes. Null mice showed a level of anxiety with a decreased hedonic response. In conclusion, this study provides a broad biochemical, physiological, and behavioral characterization of the Ephx2-null mouse colony and suggests a mechanism by which sEH and its substrates may regulate circulating levels of testosterone through cholesterol biosynthesis and metabolism. PMID:19458064

  19. Rare earths exposure and male infertility: the injury mechanism study of rare earths on male mice and human sperm.

    PubMed

    Chen, Jun; Xiao, Heng-Jun; Qi, Tao; Chen, Di-Ling; Long, He-Ming; Liu, Song-Hao

    2015-02-01

    The weight; testis/body coefficient; levels of LDH, SDH, SODH, G-6PD, and testosterone; cell cycle; and cell apoptosis of the male mice were influenced after being treated with 200 mg/[kg/day] of rare earths suspension for 3 weeks. The "Raman fingerprints" of the human sperm DNA exposed to 0.040 mg/ml CeCl3 were very different from those of the untreated; the Raman bands at 789 cm(-1) (backbone phosphodiester), PO4 backbone at 1,094 cm(-1), methylene deformation mode at 1,221 cm(-1), methylene deformation mode at 1,485 cm(-1), and amide II at 1,612 cm(-1), of which intensities and shifts were changed, might be the diagnostic biomarkers or potential therapeutic targets. The injury mechanism might be that the rare earths influence the oxidative stress and blood testosterone barrier, tangle the big biomolecule concurrently, which might cause the testicular cells and vascular system disorder and/or dysfunction, and at the same time change the physical and chemical properties of the sperm directly.

  20. Silibinin (Milk Thistle) potentiates ethanol-dependent hepatocellular carcinoma progression in male mice.

    PubMed

    Brandon-Warner, Elizabeth; Eheim, Ashley L; Foureau, David M; Walling, Tracy L; Schrum, Laura W; McKillop, Iain H

    2012-12-29

    Hepatocellular carcinoma (HCC) is a global health burden with limited treatment options and poor prognosis. Silibinin, an antioxidant derived from the Milk Thistle plant (Silybum marianum), is reported to exert hepatoprotective and antitumorigenic effects in vitro and in vivo by suppressing oxidative stress and proliferation. Using a DEN-initiated mouse model of HCC, this study examined the effects of dietary silibinin supplementation alone, or in combination with chronic ethanol consumption on HCC progression. Our data demonstrate silibinin exerted marginal hepatoprotective effects in early stages of hepatocarcinogenesis but, when co-administered with ethanol, exacerbated the promotional effects of ethanol in HCC bearing mice, but only in males.

  1. Regulatory divergence of X-linked genes and hybrid male sterility in mice.

    PubMed

    Oka, Ayako; Shiroishi, Toshihiko

    2014-01-01

    Postzygotic reproductive isolation is the reduction of fertility or viability in hybrids between genetically diverged populations. One example of reproductive isolation, hybrid male sterility, may be caused by genetic incompatibility between diverged genetic factors in two distinct populations. Genetic factors involved in hybrid male sterility are disproportionately located on the X chromosome. Recent studies showing the evolutionary divergence in gene regulatory networks or epigenetic effects suggest that the genetic incompatibilities occur at much broader levels than had previously been thought (e.g., incompatibility of protein-protein interactions). The latest studies suggest that evolutionary divergence of transcriptional regulation causes genetic incompatibilities in hybrid animals, and that such incompatibilities preferentially involve X-linked genes. In this review, we focus on recent progress in understanding hybrid sterility in mice, including our studies, and we discuss the evolutionary significance of regulatory divergence for speciation.

  2. Floor Space Needs for Laboratory Mice: C56BL/6 Males in Solid-bottom Cages with Bedding.

    PubMed

    Fullwood, Steven; Hicks, Tiffanie A.; Brown, Jack C.; Norman, Reid L.; McGlone, John J.

    1998-12-01

    Measures of performance, mortality, adrenal weights, plasma glucocorticoid concentration, and selected immune measures were collected in an attempt to define space needs of laboratory mice. Six replications of 3 C57BL/6 male mice per cage were examined while housed on bedding at 5, 10, 15, or 20 in(2) (32.2, 64.5, 96.8, or 129 cm(2)) per mouse. Body weights were not influenced by treatment; however, mice in smaller spaces (5 in(2) per mouse) consumed or wasted more feed and water than mice given greater space allowances. Mice given the least amount of space (5 in(2) per mouse) had greater lymphocyte proliferation in response to the T-cell mitogen PHA than mice given more space. Mice provided 10 in(2) per mouse had greater natural killer cytotoxicity than mice given greater or less space. Mouse mortality was greater as more space was provided. In contrast, adrenal weights and plasma glucocorticoid concentrations were progressively greater with lower space allowances. The National Research Council 1996 recommendation of 15 in(2) per mouse, for this strain and sex of mice, would result in greater mortality and reduced activity of some immune measures. Socially housed male C57BL/6 mice will benefit from less space than recommended by the National Research Council in 1996.

  3. Basal Bone Phenotype and Increased Anabolic Responses to Intermittent Parathyroid Hormone in Healthy Male COX-2 Knockout Mice

    PubMed Central

    Xu, Manshan; Choudhary, Shilpa; Voznesensky, Olga; Gao, Qi; Adams, Douglas; Diaz-Doran, Vilmaris; Wu, Qian; Goltzman, David; Raisz, Lawrence G.; Pilbeam, Carol C.

    2011-01-01

    Cyclooxygenase-2 (COX-2) knockout (KO) mice in inbred strains can have renal dysfunction with secondary hyperparathyroidism (HPTH), making direct effects of COX-2 KO on bone difficult to assess. COX-2 KO mice in an outbred CD-1 background did not have renal dysfunction but still had two-fold elevated PTH compared to wild type (WT) mice. Compared to WT mice, KO mice had increased serum markers of bone turnover, decreased femoral bone mineral density (BMD) and cortical bone thickness, but no differences in trabecular bone volume by μCT or dynamic histomorphometry. Because PTH is a potent inducer of COX-2 and prostaglandin (PG) production, we examined effects of COX-2 KO on bone responses after three weeks of intermittent PTH. Intermittent PTH increased femoral BMD and cortical bone area more in KO mice than in WT mice and increased trabecular bone volume in the distal femur in both WT and KO mice. Although not statistically significant, PTH-stimulated increases in trabecular bone tended to be greater in KO mice than in WT mice. PTH increased serum markers of bone formation and resorption more in KO than in WT mice but increased the ratio of osteoblastic surface to osteoclastic surface only in KO mice. PTH also increased femoral mineral apposition rates and bone formation rates in KO mice more than in WT mice. Acute mRNA responses to PTH of genes that might mediate some anabolic and catabolic effects of PTH tended to be greater in KO than WT mice. We conclude that (1) the basal bone phenotype in male COX-2 KO mice might reflect HPTH, COX-2 deficiency or both, and (2) increased responses to intermittent PTH in COX-2 KO mice, despite the presence of chronic HPTH, suggest that absence of COX-2 increased sensitivity to PTH. It is possible that manipulation of endogenous PGs could have important clinical implications for anabolic therapy with PTH. PMID:20471507

  4. CYP7B1 Enzyme Deletion Impairs Reproductive Behaviors in Male Mice

    PubMed Central

    Oyola, Mario G.; Zuloaga, Damian G.; Carbone, David; Malysz, Anna M.; Acevedo-Rodriguez, Alexandra; Handa, Robert J.

    2015-01-01

    In addition to androgenic properties mediated via androgen receptors, dihydrotestosterone (DHT) also regulates estrogenic functions via an alternate pathway. These estrogenic functions of DHT are mediated by its metabolite 5α-androstane-3β, 17β-diol (3β-diol) binding to estrogen receptor β (ERβ). CYP7B1 enzyme converts 3β-diol to inactive 6α- or 7α-triols and plays an important role as a regulator of estrogenic functions mediated by 3β-diol. Using a mutant mouse carrying a null mutation for the CYP7B1 gene (CYP7B1KO), we examined the contribution of CYP7B1 on physiology and behavior. Male, gonadectomized (GDX) CYP7B1KO and their wild type (WT) littermates were assessed for their behavioral phenotype, anxiety-related behavioral measures, and hypothalamic pituitary adrenal axis reactivity. No significant effects of genotype were evident in anxiety-like behaviors in open field (OFA), light-dark (L/D) exploration, and elevated plus maze (EPM). T significantly reduced open arm time on the EPM while not affecting L/D exploratory and OFA behaviors in CYP7B1KO and WT littermates. T also attenuated the corticosterone response to EPM in both genotypes. In GDX animals, T was able to reinstate male-specific reproductive behaviors (latencies and number of mounts, intromission, and ejaculations) in the WT but not in the CYP7B1KO mice. The male reproductive behavior defect in CYP7B1KO seems to be due to their inability to distinguish olfactory cues from a behavioral estrus female. CYP7B1KO mice also showed a reduction in androgen receptor mRNA expression in the olfactory bulb. Our findings suggest a novel role for the CYP7B1 enzyme in the regulation of male reproductive behaviors. PMID:25849728

  5. The lonely mouse - single housing affects serotonergic signaling integrity measured by 8-OH-DPAT-induced hypothermia in male mice.

    PubMed

    Kalliokoski, Otto; Teilmann, A Charlotte; Jacobsen, Kirsten R; Abelson, Klas S P; Hau, Jann

    2014-01-01

    Male BALB/c mice single-housed for a period of three weeks were found to respond with a more marked hypothermia to a challenge with a selective serotonergic agonist (8-OH-DPAT) than their group-housed counterparts. This effect of single housing was verified by screening a genetically heterogeneous population of male mice on a C57BL/6 background from a breeding colony. Enhanced activity of the implicated receptor (5-HT1A) leading to an amplified hypothermic effect is strongly associated with depressive states. We therefore suggest that the 8-OH-DPAT challenge can be used to demonstrate a negative emotional state brought on by e.g. long-term single housing in male laboratory mice. The study emphasizes the importance of social housing, and demonstrates that male mice deprived of social contact respond with altered serotonergic signaling activity. Male mice not only choose social contact when given the option, as has previously been shown, but will also, when it is deprived, be negatively affected by its absence. We propose that the 8-OH-DPAT challenge constitutes a simple, but powerful, tool capable of manifesting the effect of social deprivation in laboratory mice. It potentially allows not only for an unbiased, biochemical evaluation of psychological stressors, but may also allow for determining whether the effect of these can be counteracted.

  6. Androgens Attenuate Vitamin D Production Induced by UVB Irradiation of the Skin of Male Mice by an Enzymatic Mechanism.

    PubMed

    Xue, Yingben; Ying, Lee; Horst, Ronald L; Watson, Gordon; Goltzman, David

    2015-12-01

    Cutaneous exposure to UVB irradiation is an important source of vitamin D. Here, we examined sex-specific differences in cutaneous vitamin D production in mice. Both male and female mice on a vitamin D-deficient diet manifested vitamin D deficiency, with mineral abnormalities, secondary hyperparathyroidism, and osteomalacia. UVB irradiation significantly increased vitamin D levels in the skin of female mice and normalized serum 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 levels, as well as mineral and skeletal abnormalities. However, in male mice, the vitamin D response to UVB was attenuated and mineral and skeletal abnormalities were not normalized. The vitamin D precursor, 7-dehydrocholesterol (7DHC), was significantly lower in the skin of male than female mice. This reduction was due to local androgen action in the skin as demonstrated by castration studies and skin-specific androgen receptor deletion in male mice, both of which reversed the male phenotype. Local androgen regulation in the skin of the CYP11A1 gene, which encodes a crucial enzyme that metabolizes cholesterol, 7DHC, and vitamin D, appeared to contribute to the gender differences in UVB-induced vitamin D production and to its reversal of vitamin D deficiency. Sex-specific, enzymatically regulated differences in cutaneous production of vitamin D may therefore be of importance to ensure vitamin D sufficiency.

  7. Central oxytocin regulates social familiarity and scent marking behavior that involves amicable odor signals between male mice.

    PubMed

    Arakawa, Hiroyuki; Blanchard, D Caroline; Blanchard, Robert J

    2015-07-01

    The effect of oxytocin on social behavior and odor communication was investigated in male C57BL/6J mice. In three-male colonies, in visible burrow systems, icv oxytocin (OT) infusion before colony formation substantially increased huddling together over the initial 8 h of grouping, accompanied by decreased expression of a number of social approaches associated with conspecific aggression and defense. OT antagonist infusion had little impact on expression of social approaches but decreased time engaging in social components including huddle over the initial 8 h. These results demonstrate a linkage of social familiarity to OT availability in the brain. In a scent marking paradigm central infusion of OT reduced territorial marking towards male conspecifics, and this in turn reduced the scent marking of untreated stimulus males to OT-infused subjects. Infusion of an OT antagonist into stimulus mice who were confronted with OT-infused subjects prevented the reduction/suppression of scent marking that was normally seen following exposure of social odors released from OT-injected mice. Odor of pair-housed mice also induced a suppression of territorial scent marking in odor recipients, but OT antagonist administration into pair-housed mice blocked this suppressive effect of odor cue. These results indicate that central OT modulates release as well as detection of amicable signals facilitating/maintaining familiar relationships and suppressing territorial behavior between male mice. Overall, these findings suggest that OT plays a significant role in regulating social familiarity via changing qualities of conspecific odor cues.

  8. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice.

    PubMed

    Strong, Randy; Miller, Richard A; Astle, Clinton M; Floyd, Robert A; Flurkey, Kevin; Hensley, Kenneth L; Javors, Martin A; Leeuwenburgh, Christiaan; Nelson, James F; Ongini, Ennio; Nadon, Nancy L; Warner, Huber R; Harrison, David E

    2008-10-01

    The National Institute on Aging's Interventions Testing Program was established to evaluate agents that are purported to increase lifespan and delay the appearance of age-related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4-OH-alpha-phenyl-N-tert-butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex,with 80% power, using data from two of the three sites. Pooling data from all three sites, a log-rank test showed that both NDGA (p=0.0006) and aspirin (p=0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan;neither NDGA (p=0.12) nor aspirin (p=0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on life span in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses,might prove to postpone death and various age-related outcomes reproducibly in mice. PMID:18631321

  9. Cholestasis induced by model organic anions protects from acetaminophen hepatotoxicity in male CD-1 mice.

    PubMed

    Silva, Vanessa M; Hennig, Gayle E; Manautou, José E

    2006-01-25

    Administration of the non-metabolizable organic anion indocyanine green (ICG) prior to a toxic dose of acetaminophen (4-acetamidophenol; APAP) reduces liver injury 24h after dosing. ICG also produces a dose-dependent decrease in bile flow in mice and rats. Studies in bile duct-cannulated rats suggest that cholestasis can play a role in this protection. This study was conducted to determine if the ability of model organic anions to produce cholestasis is relevant to the protection against APAP hepatotoxicity afforded by ICG. In these studies, overnight fasted male CD-1 mice were dosed (i.v.) with the cholestatic dyes bromcresol green (BCG, 30 micromol/kg) and rose bengal (RB, 60 micromol/kg) immediately prior APAP administration (500 mg/kg, i.p.). Other groups of mice received the non-cholestatic dyes dibromosulphthalein (DBSP, 150 micromol/kg) and amaranth (AM, 300 micromol/kg) prior to APAP. Controls were given vehicle only. Hepatocellular necrosis was evident at 24 h in control mice receiving APAP. Pretreatment with the cholestatic dyes BCG and RB decreased the severity of hepatocellular necrosis induced by APAP. However, administration of the non-cholestatic dyes DBSP and AM did not alter APAP-induced liver damage. Glutathione replenishment was not altered by pretreatment with any of these dyes. Furthermore, ICG protected mice against carbon tetrachloride (CCl4) hepatotoxicity. Since CCl4 undergoes minimal biliary excretion and does not compete for biliary transport function, this finding supports the notion that cholestasis itself rather than competition for canalicular transporters is central to the hepatoprotection by ICG and other cholephilic dyes.

  10. Psoralen and Isopsoralen Ameliorate Sex Hormone Deficiency-Induced Osteoporosis in Female and Male Mice

    PubMed Central

    Yuan, Xiaomei; Bi, Yanan; Yan, Zeman; Pu, Weiling; Li, Yuhong; Zhou, Kun

    2016-01-01

    Osteoporosis is a systemic skeletal disease, which is characterized by a systemic destruction of bone mass and microarchitecture. With life standard improved, the treatment of osteoporosis attracted more attention. The aim of this study is to verify the osteoprotective effect of psoralen and isopsoralen in females and males. Female and male mice were divided into 7 groups in this study: control group (sham-operation), model group (by ovariectomy or orchidectomy), positive control group (females given estradiol valerate; males given alendronate sodium), psoralen groups (10 mg/kg and 20 mg/kg), and isopsoralen groups (10 mg/kg and 20 mg/kg). After administration of psoralen and isopsoralen for 8 weeks, osteoporosis was ameliorated with increasing bone strength and improving trabecular bone microstructure as indicated by CT scan and pathology. Serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRACP), osteocalcin (OC), and C-terminal cross-linking telopeptides of type I collagen (CTX-1) were examined. Decreased TRACP and increased ALP/TRACP suggested restoring from bone destruction. These results suggest that psoralen and isopsoralen may be used as good natural compounds for the treatment of osteoporosis in males, as well as females. PMID:27239473

  11. Social isolation increases cell proliferation in male and cell survival in female California mice (Peromyscus californicus).

    PubMed

    Ruscio, Michael G; Bradley King, S; Haun, Harold L

    2015-11-01

    Social environment has direct effects on an animal's behavior, physiology and neurobiology. In particular, adult neurogenesis is notably affected by a variety of social manipulations, including social isolation. We hypothesized that social isolation should have particularly acute effects on neurogenesis in a highly social (monogamous and bi-parental) species such as Peromyscus californicus, the California mouse. Adult male and female P. californicus mice were housed in isolation or in same-sex pairs for 4 or 24 days. At the end of each period, either cell proliferation or cell survival was quantified with BrdU label and neuronal markers (either TuJ1 or NeuN). After 4 days, isolated males had greater cellular proliferation in the dentate gyrus of the hippocampus (DG) than pair housed males. After 24 days, isolate females demonstrated greater cell survival in the DG than paired females. Males demonstrated a similar, but non-significant pattern. No differences in cellular proliferation or cell survival were found in the subventricular zone (SVZ), or medial amygdala (MeA). These results add to the evidence which demonstrates that neurogenic responses to environmental conditions are not identical across species. These data may be critical in understanding the functional significance of neurogenesis as it relates to the interactions between social systems, social environment and the display of social behaviors.

  12. Promotion of hepatic preneoplastic lesions in male B6C3F1 mice by unleaded gasoline.

    PubMed Central

    Standeven, A M; Wolf, D C; Goldsworthy, T L

    1995-01-01

    In previous studies, unleaded gasoline (UG) vapor was found to be a liver tumor promoter and hepatocarcinogen in female mice, but UG was not a hepatocarcinogen in male mice. However, UG vapor had similar transient mitogenic effects in nonlesioned liver of both male and female mice under the conditions of the cancer bioassay. We used an initiation-promotion protocol to determine whether UG vapor acts as a liver tumor promoter in male mice and to examine proliferative effects that may be critical to tumor development. Twelve-day-old male B6C3F1 mice were injected with N-nitrosodiethylamine (DEN; 5 mg/kg, intraperitoneally) or vehicle. Starting at 5-7 weeks of age, mice were exposed by inhalation 6 hr/day, 5 days/week for 16 weeks to 0 or 2046 ppm of PS-6 blend UG. UG treatment caused a significant 2.3-fold increase in the number of macroscopic hepatic masses in DEN-initiated mice, whereas no macroscopic masses were observed in non-initiated mice. Altered hepatic foci (AHF), which were predominantly basophilic in phenotype, were found almost exclusively in DEN-initiated mice. UG treatment significantly increased both the mean volume (threefold) and the volume fraction (twofold) of the AHF without increasing the number of AHF per unit area. UG also induced hepatic pentoxyresorufin-O-dealkylase (PROD) activity, a marker of CYP2B, by more than 12-fold over control with or without DEN cotreatment. To study hepatocyte proliferative effects of UG, we treated mice with 5-bromo-2'-deoxyuridine (BrdU) via osmotic pump for 3 days before necropsy and measured hepatocyte BrdU labeling index (LI) in AHF and nonlesioned liver.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. PMID:7588481

  13. Male Fertility Defect Associated with Disrupted BRCA1-PALB2 Interaction in Mice*

    PubMed Central

    Simhadri, Srilatha; Peterson, Shaun; Patel, Dharm S.; Huo, Yanying; Cai, Hong; Bowman-Colin, Christian; Miller, Shoreh; Ludwig, Thomas; Ganesan, Shridar; Bhaumik, Mantu; Bunting, Samuel F.; Jasin, Maria; Xia, Bing

    2014-01-01

    PALB2 links BRCA1 and BRCA2 in homologous recombinational repair of DNA double strand breaks (DSBs). Mono-allelic mutations in PALB2 increase the risk of breast, pancreatic, and other cancers, and biallelic mutations cause Fanconi anemia (FA). Like Brca1 and Brca2, systemic knock-out of Palb2 in mice results in embryonic lethality. In this study, we generated a hypomorphic Palb2 allele expressing a mutant PALB2 protein unable to bind BRCA1. Consistent with an FA-like phenotype, cells from the mutant mice showed hypersensitivity and chromosomal breakage when treated with mitomycin C, a DNA interstrand crosslinker. Moreover, mutant males showed reduced fertility due to impaired meiosis and increased apoptosis in germ cells. Interestingly, mutant meiocytes showed a significant defect in sex chromosome synapsis, which likely contributed to the germ cell loss and fertility defect. Our results underscore the in vivo importance of the PALB2-BRCA1 complex formation in DSB repair and male meiosis. PMID:25016020

  14. Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice.

    PubMed

    Fu, Zidong Donna; Klaassen, Curtis D

    2013-12-15

    Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a "dose-response" model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and small intestinal contents. In addition, CR "dose-dependently" increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum.

  15. Glutamate input in the dorsal raphe nucleus as a determinant of escalated aggression in male mice.

    PubMed

    Takahashi, Aki; Lee, Ray X; Iwasato, Takuji; Itohara, Shigeyoshi; Arima, Hiroshi; Bettler, Bernhard; Miczek, Klaus A; Koide, Tsuyoshi

    2015-04-22

    Although the dorsal raphe nucleus (DRN) has long been linked to neural control of aggression, little is known about the regulatory influences of the DRN when an animal engages in either adaptive species-typical aggressive behavior or escalated aggression. Therefore it is important to explore which neurotransmitter inputs into the DRN determine the escalation of aggression in male mice. Previously, we observed that microinjection of the GABAB receptor agonist baclofen into the DRN escalates aggressive behavior in male mice. Here, we used a serotonin (5-HT) neuron-specific GABAB receptor knock-out mouse to demonstrate that baclofen acts on nonserotonergic neurons to escalate aggression. Intra-DRN baclofen administration increased glutamate release, but did not alter GABA release, within the DRN. Microinjection of l-glutamate into the DRN escalated dose-dependently attack bites toward an intruder. In vivo microdialysis showed that glutamate release increased in the DRN during an aggressive encounter, and the level of glutamate was further increased when the animal was engaged in escalated aggressive behavior after social instigation. Finally, 5-HT release was increased within the DRN and also in the medial prefrontal cortex when animals were provoked by social instigation, and during escalated aggression after social instigation, but this increase in 5-HT release was not observed when animals were engaged in species-typical aggression. In summary, glutamate input into the DRN is enhanced during escalated aggression, which causes a phasic increase of 5-HT release from the DRN 5-HT neurons.

  16. Inhibitory effects of H2-receptor antagonists on cytochrome P450 in male ICR mice.

    PubMed

    Kim, D H; Kim, E J; Han, S S; Roh, J K; Jeong, T C; Park, J H

    1995-08-01

    1. The present study was undertaken to examine the effects of H2-receptor antagonists including newly developed mifentidine derivatives, IY-80843 and IY-80845, on cytochrome P450(P450) in vitro and in vivo. 2. Initially, 3-methylcholanthrene-, phenobarbital-, ethanol- and dexamethasone-induced liver microsomes were prepared from male ICR mice to study in vitro effects of above chemicals on ethoxyresorufin O-deethylase(EROD), pentoxyresorufin O-dealkylase(PROD), p-nitrophenol hydroxylase and erythromycin N-demethylase(ERDM) activities, respectively. It was found that histamine, cimetidine and famotidine were not inhibitory to four enzyme activities. Meanwhile, mifentidine slightly inhibited EROD and PROD activities and its derivatives IY-80843 and IY-80845 strongly inhibited PROD, EROD and ERDM activities. 3. Prolongation of hexobarbital-induced sleeping time was determined in male ICR mice to confirm in vitro inhibitory effects of mifentidine and its derivatives in vivo. It was observed that cimetidine, mifentidine, IY-80843 and IY-80845 caused dose-dependent increases in the sleeping time, indicating the inhibition of P450 responsible for hexobarbital metabolism. 4. It was concluded that mifentidine and its derivatives are P450 inhibitors and that our newly synthesized IY-80843 is most inhibitory. 5. The present results indicate that mifentidine and its derivatives not only antagonise the H2-receptor but also inhibit P450 enzymes. PMID:7576828

  17. Effects of social stress on tumor development in dominant male mice with diverse behavioral activity profiles.

    PubMed

    Cacho Fernández, Raúl; Garmendia Rezola, Larraitz; Vegas Moreno, Oscar; Azpíroz Sánchez, Arantxa

    2008-11-01

    We examined the influence of individual psychological profile and social behavior on tumor development in dominant male mice. Male OF1 mice were subjected to an open field test (OFT) to observe their motor activity and latency. Subsequently, the animals were divided into three groups: Stress-Non-Inoculated (SNI), Stress-Inoculated (SI) and Control-Inoculated (CI). The SI and CI groups were inoculated with tumor cells and the SNI group with vehicle. SNI and SI were exposed to social stress with an anosmic intruder six (T1) and twenty one (T2) days after inoculation and their behavior was analyzed. After T2, subjects were put down and the pulmonary metastatic foci counted. SI developed greater pulmonary metastasis than CI, indicating an effect of stress despite the animal's dominant status. Active animals developed less pulmonary metastasis than their passive counterparts. No differences were found in social behavior at T1. Differences were found, however, in some behavioral categories at T2 between SI and SNI, and between active and passive animals. These differences indicate an effect of tumor development on social behavior that is more evident in passive subjects.

  18. Fecundity of F/sub 1/ male mice exposed to lead acetate in-utero

    SciTech Connect

    Figgs, L.W.

    1983-01-01

    Four studies were performed to examine the reproductive capacity of male mice exposed to lead in-utero. These studies concerned the fecundity/fertility, sperm and semen analysis, scanning electron microscopic (SEM) analysis of the testis, and the analysis of seminiferous tubule cell populations for chromosomal aberrations. The fecundity study revealed that male mice exposed to lead acetate in-utero showed a significant reduction in the following parameters for the F/sub 2/ litters they produced. There was a significant reduction in the number of pups produced per litter, the number of females per litter, the number of pups weaned per litter, and the percent survival of those pups. Sperm and semen analysis revealed a decrease in sperm numbers and motility. It was concluded that lead acertate exposure in-utero resulted in a decrease in reproductive capacity which was evidenced by the reduction in certain fecundity parameters pups weaned per litter, etc. It was concluded that lead acetate causes a mutation or functional change in the stem cell population of the embryonic gonad that resulted in a slowed transition from spermatocyte to spermatid during spermatogenesis in the adult. This slowed transition may have been translated into decreased sperm production, a decrease in x-bearing sperm, and genetic changes that caused decreased numbers of pups and decreased survivorship of the pups in those litters. This was not demonstrated by microscopic analysis of the sperm and testis but was suggested by an analysis of a sample population of cells from the seminiferous tubules.

  19. Gene dosage of Otx2 is important for fertility in male mice.

    PubMed

    Larder, Rachel; Kimura, Ikuo; Meadows, Jason; Clark, Daniel D; Mayo, Susan; Mellon, Pamela L

    2013-09-01

    Together, the hypothalamus, pituitary and gonads direct the development and regulation of reproductive function in mammals. Gonadotropin-releasing hormone (GnRH) expression is limited to ∼800 neurons that originate in the olfactory placode then migrate to the hypothalamus. Coordination of the hypothalamic-pituitary-gonadal (HPG) axis is dependent upon correct neuronal migration of GnRH neurons into the hypothalamus followed by proper synthesis and pulsatile secretion of GnRH. Defects in any one of these processes causes infertility. Otx2, the vertebrate homologue of Drosophila orthodenticle, is a transcription factor that has been shown to be critical for normal brain and eye development and is expressed in both the developing GnRH neurons and the pituitary, suggesting that this gene may play a critical role in development of the HPG axis. As Otx2-null mice are embryonic lethal, we have analyzed the reproductive capacity of heterozygous Otx2 mice to determine the contribution of Otx2 gene dosage to normal HPG axis function. Our data reveal that correct dosage of Otx2 is critical for normal fertility as loss of one allele of Otx2 leads to a discernible reproductive phenotype in male mice due to disruption of the migration of GnRH neurons during development.

  20. Sodium fluoride and sulfur dioxide affected male reproduction by disturbing blood-testis barrier in mice.

    PubMed

    Zhang, Jianhai; Li, Zhihui; Qie, Mingli; Zheng, Ruibo; Shetty, Jagathpala; Wang, Jundong

    2016-08-01

    Fluoride and sulfur dioxide (SO2), two well-known environmental toxicants, have been implicated to have adverse effects on male reproductive health in humans and animals. The objective of this study to investigate if the BTB is one of the pathways that lead to reproductive toxicity of sodium fluoride and sulfur dioxide alone or in combination, in view of the key role of blood testis barrier (BTB) in testis. The results showed that a marked decrease in sperm quality, and altered morphology and ultrastructure of BTB in testis of mice exposure to fluoride (100 mg NaF/L in drinking water) or/and sulfur dioxide (28 mg SO2/m(3), 3 h/day). Meanwhile, the mRNA expression levels of some vital BTB-associated proteins, including occluding, claudin-11, ZO-1, Ncadherin, α-catenin, and connexin-43 were all strikingly reduced after NaF exposure, although only the reduction of DSG-2 was statistically significant in all treatment groups. Moreover, the proteins expressions also decreased significantly in claudin-11, N-cadherin, α-catenin, connexin-43 and desmoglein-2 in mice treated with fluoride and/or SO2. These changes in BTB structure and constitutive proteins may therefore be connected with the low sperm quality in these mice. The role of fluoride should deserves more attention in this process. PMID:27237588

  1. Sodium fluoride and sulfur dioxide affected male reproduction by disturbing blood-testis barrier in mice.

    PubMed

    Zhang, Jianhai; Li, Zhihui; Qie, Mingli; Zheng, Ruibo; Shetty, Jagathpala; Wang, Jundong

    2016-08-01

    Fluoride and sulfur dioxide (SO2), two well-known environmental toxicants, have been implicated to have adverse effects on male reproductive health in humans and animals. The objective of this study to investigate if the BTB is one of the pathways that lead to reproductive toxicity of sodium fluoride and sulfur dioxide alone or in combination, in view of the key role of blood testis barrier (BTB) in testis. The results showed that a marked decrease in sperm quality, and altered morphology and ultrastructure of BTB in testis of mice exposure to fluoride (100 mg NaF/L in drinking water) or/and sulfur dioxide (28 mg SO2/m(3), 3 h/day). Meanwhile, the mRNA expression levels of some vital BTB-associated proteins, including occluding, claudin-11, ZO-1, Ncadherin, α-catenin, and connexin-43 were all strikingly reduced after NaF exposure, although only the reduction of DSG-2 was statistically significant in all treatment groups. Moreover, the proteins expressions also decreased significantly in claudin-11, N-cadherin, α-catenin, connexin-43 and desmoglein-2 in mice treated with fluoride and/or SO2. These changes in BTB structure and constitutive proteins may therefore be connected with the low sperm quality in these mice. The role of fluoride should deserves more attention in this process.

  2. Protective Effect of Royal Jelly on In Vitro Fertilization (IVF) in Male Mice Treated with Oxymetholone

    PubMed Central

    Zahmatkesh, Ensieh; Najafi, Gholamreza; Nejati, Vahid

    2015-01-01

    Objective This study aimed to investigate the effects of royal jelly (RJ) on catalase, total antioxidant capacity and embryo development in adult mice treated with oxymetholone (OXM). Materials and Methods In this exprimental study, 32 male and 96 female adult Naval Medical Research Institute (NMRI) mice (7-9 weeks of age) with a ratio of 1:3 for fertili- zation purposes were randomly divided into 4 groups as follows: i. Control group (n=8) receiving 0.1 ml/mice saline daily by gavage for 30 day, ii. RJ group (n=8) treated with RJ at a dose of 100 mg/kg daily by gavage for 30 days, iii. OXM group (n=8) receiving OXM at the dose of 5 mg/kg daily by gavage for 30 days and iv. RJ+OXM group (n=8) receiving RJ at the dose of 100 mg/kg daily by gavage concomitant with 100 mg/kg OXM adminis- tration for 30 days. Results Analysis revealed a significant reduction in catalase, total antioxidant, as well as embryo development in OXM group (P<0.05). However, RJ group showed a salient recovery in the all of the above mentioned parameters and embryo toxicity. Conclusion The results of this study indicated a partially protective effect of RJ against OXM-induced embryo toxicity. PMID:26464831

  3. Androgens inhibit the osteogenic response to mechanical loading in adult male mice.

    PubMed

    Sinnesael, Mieke; Laurent, Michaël R; Jardi, Ferran; Dubois, Vanessa; Deboel, Ludo; Delisser, Peter; Behets, Geert J; D'Haese, Patrick C; Carmeliet, Geert; Claessens, Frank; Vanderschueren, Dirk

    2015-04-01

    Androgens are well known to enhance exercise-induced muscle hypertrophy; however, whether androgens also influence bone's adaptive response to mechanical loading remains unclear. We studied the adaptive osteogenic response to unilateral in vivo mechanical loading of tibia in adult male mice in both a long- and a short-term experimental set-up. Mice were divided into four groups: sham operated, orchidectomized (ORX), T (ORX+T), or nonaromatizable dihydrotestosterone (ORX+DHT) replacement. Significant interactions between androgen status and osteogenic response to mechanical loading were observed. Cortical thickness increased by T (0.14 vs 0.11 mm sham, P<.05) and DHT (0.17 vs 0.11 mm sham, P<.05). However, T partially (+36%) and DHT completely (+10%) failed to exhibit the loading-related increase observed in sham (+107%) and ORX (+131%, all P<.05) mice. ORX decreased periosteal bone formation, which was restored to sham levels by T and DHT. However, both androgens completely suppressed the loading-related increase in periosteal bone formation. Short-term loading decreased the number of sclerostin-positive osteocytes in sham, whereas in control fibulas, ORX decreased and T increased the number of sclerostin-positive osteocytes. Loading no longer down-regulated sclerostin in the ORX or T groups. In conclusion, both T and DHT suppress the osteogenic response to mechanical loading.

  4. Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice

    PubMed Central

    Sheikhbahaei, Fatemeh; Khazaei, Mozafar; Rabzia, Arezou; Mansouri, Kamran; Ghanbari, Ali

    2016-01-01

    Background Toxic effects of anti-cancer and other drugs on the normal tissues could be reduced by the herbal plants and their fractions. This study investigated the protective effect of thymoquinone (TQ) as a fraction of Nigella sativa on methotrexate (MTX)- induced germ cell apoptosis in male mice. Materials and Methods In this experimental study, thirty male Balb/c mice were divided randomly into 5 groups (n=6). A single dose of MTX (20 mg/kg) and different concentrations of TQ were administrated for 4 consecutive days. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed on paraffin embedded tissue sections to analysis the occurrence of apoptosis in the testis. Reverse transcription polymerase chain reaction (RT-PCR) of apoptosis-related genes was performed with RNA extracted from testes of the mice. Statistical analysis was done using one-way ANOVA. Results In the MTX group, there was a significant increase in morphologic sign of germ cell degeneration of tubules (48 ± 0.6%), apoptotic index (AI; 2.3 ± 0.6%), as well as mRNA expression of p53 (P=0.008), caspase 8 (P=0.002), caspase 3 (P=0.005), caspase 9 (P=0.000), bax (P=0.004) and the ratio of bax/bcl-2 (P=0.000), whereas there was an decrease in the expression of bcl-2 (P=0.003), as compared to control group. In MTX+TQ groups, the data showed that different concentrations of TQ could improve the harmful effects caused by the MTX. The best protective effects were achieved in MTX+TQ (10 mg/kg). Conclusion TQ protects testicular germ cell against MTX-induced apoptosis by affecting related genes regulation. PMID:26985343

  5. Androgen Deficiency Exacerbates High-Fat Diet-Induced Metabolic Alterations in Male Mice.

    PubMed

    Dubois, Vanessa; Laurent, Michaël R; Jardi, Ferran; Antonio, Leen; Lemaire, Katleen; Goyvaerts, Lotte; Deldicque, Louise; Carmeliet, Geert; Decallonne, Brigitte; Vanderschueren, Dirk; Claessens, Frank

    2016-02-01

    Androgen deficiency is associated with obesity, metabolic syndrome, and type 2 diabetes mellitus in men, but the mechanisms behind these associations remain unclear. In this study, we investigated the combined effects of androgen deficiency and high-fat diet (HFD) on body composition and glucose homeostasis in C57BL/6J male mice. Two models of androgen deficiency were used: orchidectomy (ORX) and androgen receptor knockout mice. Both models displayed higher adiposity and serum leptin levels upon HFD, whereas no differences were seen on a regular diet. Fat accumulation in HFD ORX animals was accompanied by increased sedentary behavior and occurred in spite of reduced food intake. HFD ORX mice showed white adipocyte hypertrophy, correlated with decreased mitochondrial content but not function as well as increased lipogenesis and decreased lipolysis suggested by the up-regulation of fatty acid synthase and the down-regulation of hormone-sensitive lipase. Both ORX and androgen receptor knockout exacerbated HFD-induced glucose intolerance by impairing insulin action in liver and skeletal muscle, as evidenced by the increased triglyceride and decreased glycogen content in these tissues. In addition, serum IL-1β levels were elevated, and pancreatic insulin secretion was impaired after ORX. Testosterone but not dihydrotestosterone supplementation restored the castration effects on body composition and glucose homeostasis. We conclude that sex steroid deficiency in combination with HFD exacerbates adiposity, insulin resistance, and β-cell failure in 2 preclinical male mouse models. Our findings stress the importance of a healthy diet in a clinical context of androgen deficiency and may have implications for the prevention of metabolic alterations in hypogonadal men.

  6. Normal phenotype in conditional androgen receptor (AR) exon 3-floxed neomycin-negative male mice.

    PubMed

    Rana, Kesha; Clarke, Michele V; Zajac, Jeffrey D; Davey, Rachel A; MacLean, Helen E

    2014-01-01

    Androgens (testosterone and dihydrotestosterone) acting via the androgen receptor (AR) are required for male sexual differentiation, and also regulate the development of many other tissues including muscle, fat and bone. We previously generated an AR(lox) mouse line with exon 3 of the AR gene targeted by loxP sites. The deletion of exon 3 is in-frame, so only the DNA binding-dependent actions of the AR are deleted, but non-DNA binding-dependent actions are retained. This line also contained an antibiotic resistance selection cassette, neomycin (neo) in intron 3, which was also flanked by loxP sites. Hemizygous AR(lox) male mice demonstrated a phenotype of hyperandrogenization, with increased mass of androgen-dependent tissues. We hypothesized that this hyperandrogenization was likely to be due to the presence of the neo cassette. In this study, we have generated an AR(lox) neo-negative mouse line, using the EIIa-cre deleter mouse line to remove the neo cassette. Hemizygous AR(lox) neo-negative male mice have a normal phenotype, with normal body mass and normal mass of androgen-dependent tissues including the testis, seminal vesicles, kidney, spleen, heart and retroperitoneal fat. This neo-negative exon 3-targeted mouse line is the only floxed AR mouse line available to study the DNA binding-dependent actions of the AR in a tissue-specific manner, and is suitable for investigation in all tissues. This study demonstrates the importance of removing the selection cassette, which can potentially alter the phenotype of floxed mouse lines even in the absence of detectable effects on target gene expression.

  7. Correlated responses in male reproductive traits in mice selected for litter size and body weight.

    PubMed

    Eisen, E J; Johnson, B H

    1981-01-01

    Correlated responses in male reproductive traits were determined at 4, 6 and 8 weeks of age in lines of mice selected for large litter size (L+), large 6-week body weight (W+), large litter size and small body weight (L+W-) and small litter size and large body weight (L-W+), and in an unselected control (K). Concentration of serum testosterone and weights of testes, seminal vesicles, epididymides and adrenal glands increased with age. Line differences in testosterone concentration were not detected. L+ and W+ males exhibited positive correlated responses in testes, epididymides and seminal vesicle weights. Testis weight adjusted for body weight was significantly larger for L+ than controls and approached significance for W+. Realized genetic correlation be-testis weight and litter size was 0.60 +/- 0.04, and the realized partial genetic correlation holding body weight constant was 0.42. Therefore, pleiotropic loci, acting via the hypothalamic-pituitary axis, affect testis weight and litter size independently of body weight. Additionally, genes influencing overall growth have a pleiotropic effect on testis weight and litter size in mice; the realized genetic correlations of body weight with testis weight and with litter size were 0.60 +/- 0.03 and 0.52 +/- 0.10. Testis weight increased in both L+W- and L-W+ males. The positive correlated response in L+W- may have resulted from changes in frequency of genes controlling reproductive processes; whereas, in L-W+ it could have been the result of changes in the frequency of genes associated with body weight.

  8. Male mice housed in groups engage in frequent fighting and show a lower response to additional bone loading than females or individually housed males that do not fight.

    PubMed

    Meakin, Lee B; Sugiyama, Toshihiro; Galea, Gabriel L; Browne, William J; Lanyon, Lance E; Price, Joanna S

    2013-05-01

    Experiments to investigate bone's physiological adaptation to mechanical loading frequently employ models that apply dynamic loads to bones in vivo and assess the changes in mass and architecture that result. It is axiomatic that bones will only show an adaptive response if the applied artificial loading environment differs in a significant way from that to which the bones have been habituated by normal functional loading. It is generally assumed that this normal loading is similar between experimental groups. In the study reported here we found that this was not always the case. Male and female 17-week-old C57BL/6 mice were housed in groups of six, and a single episode (40 cycles) of non-invasive axial loading, engendering 2,200 με on the medial surface of the proximal tibiae in sample mice, was applied to right tibiae on alternate days for two weeks. This engendered an adaptive increase in bone mass in females, but not males. Observation revealed the main difference in behaviour between males and females was that males were involved in fights 1.3 times per hour, whereas the females never fought. We therefore housed all mice individually. In females, there was a similar significant osteogenic response to loading in cortical and trabecular bone of both grouped and individual mice. In contrast, in males, adaptive increases in the loaded compared with non-loaded control bones was only apparent in animals housed individually. Our interpretation of these findings is that the frequent vigorous fighting that occurs between young adult males housed in groups could be sufficient to engender peak strains and strain rates that equal or exceed the stimulus derived from artificial loading. This indicates the importance of ensuring that physical activity is consistent between groups. Reducing the background level of the naturally engendered strain environment allows adaptive responses to artificial loading to be demonstrated at lower loads.

  9. Effects of methylphenidate on the behavior of male 5xFAD mice.

    PubMed

    Schneider, F; Baldauf, K; Wetzel, W; Reymann, K G

    2015-01-01

    Alzheimer's disease is a neurodegenerative disorder characterized by a loss of memory and spatial orientation. It is also reported that the dopamine system is affected. Dopamine plays a prominent role in motor functions, motivation, emotion, arousal and reward, and it is important for learning and memory. One model that represents characteristic hallmarks of Alzheimer's disease is the 5xFAD mouse model, in which parenchymal plaque load starts at 2months of age. Transgenic 5xFAD mice show the first behavioral deficits at 6months, which are evident at 9months of age. In this study, we investigated the pharmacological influence of methylphenidate (MPH) on behavioral deficits of 5xFAD mice. Using a battery of behavioral tests, we observed no influence of MPH on anxiety in the elevated plus maze, whereas the locomotion and explorative activity in the open field was increased in transgenic and non-transgenic 5xFAD mice after the application of MPH. Further MPH inhibits habituation in the open field in healthy 5xFAD littermates after the application of 10mg/kg MPH. On the other hand, 10mg/kg MPH improved spatial memory in 6-month-old transgenic 5xFAD males, i.e., at a time point when deficits start to occur. However, in 9-month-old transgenic mice, MPH did not improve persisting learning and memory deficits. We concluded that MPH might improve the non-cognitive, apathy-like behavior (indicated by a reduced exploration), but it has no influence on sustained Alzheimer typical learning and memory deficits.

  10. Effects of methylphenidate on the behavior of male 5xFAD mice.

    PubMed

    Schneider, F; Baldauf, K; Wetzel, W; Reymann, K G

    2015-01-01

    Alzheimer's disease is a neurodegenerative disorder characterized by a loss of memory and spatial orientation. It is also reported that the dopamine system is affected. Dopamine plays a prominent role in motor functions, motivation, emotion, arousal and reward, and it is important for learning and memory. One model that represents characteristic hallmarks of Alzheimer's disease is the 5xFAD mouse model, in which parenchymal plaque load starts at 2months of age. Transgenic 5xFAD mice show the first behavioral deficits at 6months, which are evident at 9months of age. In this study, we investigated the pharmacological influence of methylphenidate (MPH) on behavioral deficits of 5xFAD mice. Using a battery of behavioral tests, we observed no influence of MPH on anxiety in the elevated plus maze, whereas the locomotion and explorative activity in the open field was increased in transgenic and non-transgenic 5xFAD mice after the application of MPH. Further MPH inhibits habituation in the open field in healthy 5xFAD littermates after the application of 10mg/kg MPH. On the other hand, 10mg/kg MPH improved spatial memory in 6-month-old transgenic 5xFAD males, i.e., at a time point when deficits start to occur. However, in 9-month-old transgenic mice, MPH did not improve persisting learning and memory deficits. We concluded that MPH might improve the non-cognitive, apathy-like behavior (indicated by a reduced exploration), but it has no influence on sustained Alzheimer typical learning and memory deficits. PMID:25449360

  11. Induction of Suppressor Cells and Increased Tumor Growth following Chronic Psychosocial Stress in Male Mice

    PubMed Central

    Schmidt, Dominic; Peterlik, Daniel; Reber, Stefan O.; Lechner, Anja; Männel, Daniela N.

    2016-01-01

    To study the impact of psychosocial stress on the immune system, male mice were subjected to chronic subordinate colony housing (CSC), a preclinically validated mouse model for chronic psychosocial stress. CSC substantially affected the cell composition of the bone marrow, blood, and spleen by inducing myelopoiesis and enhancing the frequency of regulatory T cells in the CD4 population. Expansion of the myeloid cell compartment was due to cells identified as immature inflammatory myeloid cells having the phenotype of myeloid-derived suppressor cells of either the granulocytic or the monocytic type. Catecholaminergic as well as TNF signaling were implicated in these CSC-induced cellular shifts. Although the frequency of regulatory cells was enhanced following CSC, the high capacity for inflammatory cytokine secretion of total splenocytes indicated an inflammatory immune status in CSC mice. Furthermore, CSC enhanced the suppressive activity of bone marrow-derived myeloid-derived suppressor cells towards proliferating T cells. In line with the occurrence of suppressor cell types such as regulatory T cells and myeloid-derived suppressor cells, transplanted syngeneic fibrosarcoma cells grew better in CSC mice than in controls, a process accompanied by pronounced angiogenesis and clustering of immature myeloid cells in the tumor tissue. In addition, tumor implantation after CSC reinforced the CSC-induced increase in myeloid-derived suppressor cells and regulatory T cell frequencies while the CSC-induced cellular changes eased off in mice without tumor. Together, our data suggest a role for suppressor cells such as regulatory T cells and myeloid-derived suppressor cells in the enhanced tumor growth after chronic psychosocial stress. PMID:27391954

  12. The effects of imperatorin on anxiety and memory-related behavior in male Swiss mice.

    PubMed

    Budzynska, Barbara; Kruk-Slomka, Marta; Skalicka-Wozniak, Krystyna; Biala, Grazyna; Glowniak, Kazimierz

    2012-08-01

    The purpose of the reported experiments was to examine the effects of imperatorin [9-(3-methylbut-2-enyloxy)-7H-furo[3,2-g]chromen-7-one], a bioactive furanocoumarin isolated from the fruits of Angelica archangelica (Angelica officinalis) on anxiety and memory-related behaviors of mice. Male Swiss mice were tested for anxiety and cognition, in the elevated plus maze test (EPM), using two different procedures. In the present experiments, imperatorin was administered acutely (at the doses of 5, 10, 20, 30, and 50 mg/kg); injections were made 15, 30, and 60 min before test (anxiety); 30 min before the first trial (memory acquisition); or immediately after the first trial (memory consolidation), as well as subchronically, twice a day for 6 days. On the seventh day, the mice were injected once with imperatorin (10 and 20 mg/kg, i.p.) 30 min before the test (anxiety) and 30 min before the first trial (memory acquisition), or immediately after the first trial (memory consolidation). We observed that imperatorin when administered acutely and repeatedly, at the doses of 10 and 20 mg/kg, exerted an anxiolytic effect on mice tested 30 min after the injection measured in the EPM test. By contrast, no such effect was observed after the acute administration of imperatorin at the doses of 5, 30 and 50 mg/kg. Moreover, other observations carried out 15 and 60 min after a single injection of the drug did not reveal any effect of imperatorin on anxiety behavior in the EPM test. Furthermore, acute and repeated administration of imperatorin (10 and 20 mg/kg) improved different stages of memory processes (both acquisition and consolidation) in a modified EPM test (mEPM). The results of our research suggest imperatorin to be an interesting therapeutical option in disorders with high anxiety levels and memory impairment. PMID:22686497

  13. Membrane-Localized Estrogen Receptor 1 Is Required for Normal Male Reproductive Development and Function in Mice.

    PubMed

    Nanjappa, Manjunatha K; Hess, Rex A; Medrano, Theresa I; Locker, Seth H; Levin, Ellis R; Cooke, Paul S

    2016-07-01

    Estrogen receptor 1 (ESR1) mediates major reproductive functions of 17β-estradiol (E2). Male Esr1 knockout (Esr1KO) mice are infertile due to efferent ductule and epididymal abnormalities. The majority of ESR1 is nuclear/cytoplasmic; however, a small fraction is palmitoylated at cysteine 451 in mice and localized to cell membranes, in which it mediates rapid E2 actions. This study used an Esr1 knock-in mouse containing an altered palmitoylation site (C451A) in ESR1 that prevented cell membrane localization, although nuclear ESR1 was expressed. These nuclear-only estrogen receptor 1 (NOER) mice were used to determine the roles of membrane ESR1 in males. Epididymal sperm motility was reduced 85% in 8-month-old NOER mice compared with wild-type controls. The NOER mice had decreased epididymal sperm viability and greater than 95% of sperm had abnormalities, including coiled midpieces and tails, absent heads, and folded tails; this was comparable to 4-month Esr1KO males. At 8 months, daily sperm production in NOER males was reduced 62% compared with controls. The NOER mice had histological changes in the rete testes, efferent ductules, and seminiferous tubules that were comparable with those previously observed in Esr1KO males. Serum T was increased in NOER males, but FSH, LH, and E2 were unchanged. Critically, NOER males were initially subfertile, becoming infertile with advancing age. These findings identify a previously unknown role for membrane ESR1 in the development of normal sperm and providing an adequate environment for spermatogenesis. PMID:27145009

  14. Reduced Melanocortin Production Causes Sexual Dysfunction in Male Mice With POMC Neuronal Insulin and Leptin Insensitivity

    PubMed Central

    Faulkner, Latrice D.; Dowling, Abigail R.; Stuart, Ronald C.; Nillni, Eduardo A.

    2015-01-01

    Proopiomelanocortin (POMC)-derived peptides like α-melanocyte-stimulating hormone (MSH) substantially improve hepatic insulin sensitivity and regulate energy expenditure. Melanocortinergic agents are also powerful inducers of sexual arousal that are being investigated for a possible therapeutic role in erectile dysfunction. It is currently unclear whether reduced melanocortin (MC) activity may contribute to the sexual dysfunction accompanying obesity and type 2 diabetes. Male rodents with leptin and insulin resistance targeted to POMC neurons (leptin receptor [LepR]/insulin receptor [IR]POMC mice) exhibit obesity, hyperinsulinemia, hyperglycemia, and systemic insulin resistance. In this study, we demonstrate that LepR/IRPOMC males are also subfertile due to dramatic alterations in sexual behavior. Remarkably, these reproductive changes are accompanied by decreased α-MSH production not present when a single receptor type is deleted. Unexpectedly, behavioral sensitivity to α-MSH and MC receptor expression are also reduced in LepR/IRPOMC males, a potential adaptation of the MC system to altered α-MSH production. Together, these results suggest that concurrent insulin and leptin resistance in POMC neurons in individuals with obesity or type 2 diabetes can reduce endogenous α-MSH levels and impair sexual function. PMID:25590244

  15. Steady-State Methadone Effect on Generalized Arousal in Male and Female Mice

    PubMed Central

    Devidze, N.; Ho, A.; Zhang, Q.; Pfaff, D.W.; Kreek, M.J.

    2009-01-01

    Methadone is widely used in treatment of short-acting opiate addiction. The on-off effects of opioids have been documented to have profound differences from steady-state opioids. We hypothesize that opioids play important roles in either generalized arousal (GA) or aversive state of arousal during opioid withdrawal. Both male and female C57BL6 mice received steady-state methadone (SSM) through osmotic pumps at 10 or 20 mg/kg/day and GA was measured in voluntary motor activity, sensory responsivity, and contextual fear conditioning. SSM did not have any effect on those GA behaviors in either sex. Females had higher activity and less fear conditioning than males. The effects of SSM on stress responsive orexin gene expression in the lateral hypothalamus (LH) and medial hypothalamus (MH, including perifornical and dorsomedial areas) were measured after the behavioral tests. Females showed significantly lower basal LH (but not MH) orexin mRNA levels than males. A panel of GA stressors increased LH orexin mRNA levels in females only; these increases were blunted by SSM at 20 mg/kg. In summary, SSM had no effect on GA behaviors. In females, SSM blunted the GA stress-induced LH orexin gene expression. PMID:19045944

  16. Cued and spatial learning in the water maze: equivalent learning in male and female mice.

    PubMed

    Baldan Ramsey, Lissandra C; Pittenger, Christopher

    2010-10-11

    Mammals navigate a complex environment using a variety of strategies, which can operate in parallel and even compete with one another. We have recently described a variant water maze task in which two of these strategies, hippocampus-dependent spatial learning and striatum-dependent cued learning, can be dissociated. Male rodents perform better at some spatial learning tasks, while female rodents more readily learn certain striatum-dependent behavioral strategies. We therefore predicted that sex would differentially influence spatial and cued learning in the water maze. We trained adult male and female C57Bl/6 mice for 7 days in the two-cue variant of the water maze, with probe trials on days 5 and 7. In two independent experiments, males and females performed similarly, with both groups showing good spatial learning after 5 and 7 days of training, and both groups showing trend-level cued learning after 5 days and robust learning after 7. Therefore, contrary to our hypothesis, sex does not significantly affect cued or spatial learning in this task.

  17. Effects of Saikokaryukotsuboreito on Spermatogenesis and Fertility in Aging Male Mice

    PubMed Central

    Zang, Zhi-Jun; Ji, Su-Yun; Zhang, Ya-Nan; Gao, Yong; Zhang, Bin

    2016-01-01

    Background: Aspermia caused by exogenous testosterone limit its usage in late-onset hypogonadism (LOH) patients desiring fertility. Saikokaryukotsuboreito (SKRBT) is reported to improve serum testosterone and relieve LOH-related symptoms. However, it is unclear whether SKRBT affects fertility. We aimed to examine the effects of SKRBT on spermatogenesis and fertility in aging male mice. Methods: Thirty aging male mice were randomly assigned to three groups. Mice were orally administered with phosphate-buffer solution or SKRBT (300 mg/kg, daily) or received testosterone by subcutaneous injections (10 mg/kg, every 3 days). Thirty days later, each male mouse was mated with two female mice. All animals were sacrificed at the end of 90 days. Intratesticular testosterone (ITT) levels, quality of sperm, expression of synaptonemal complex protein 3 (SYCP3), and fertility were assayed. Results: In the SKRBT-treated group, ITT, quality of sperm, and expression of SYCP3 were all improved compared with the control group (ITT: 85.50 ± 12.31 ng/g vs. 74.10 ± 11.45 ng/g, P = 0.027; sperm number: [14.94 ± 4.63] × 106 cells/ml vs. [8.79 ± 4.38] × 106 cells/ml, P = 0.002; sperm motility: 43.16 ± 9.93% vs. 33.51 ± 6.98%, P = 0.015; the number of SYCP3-positive cells/tubule: 77.50 ± 11.01 ng/ml vs. 49.30 ± 8.73 ng/ml, P < 0.001; the expression of SYCP3 protein: 1.23 ± 0.09 vs. 0.84 ± 0.10, P < 0.001), but fertility was not significantly changed (P > 0.05, respectively). In the testosterone-treated group, ITT, quality of sperm, and expression of SYCP3 were markedly lower than the control group (ITT: 59.00 ± 8.67, P = 0.005; sperm number: [4.34 ± 2.45] × 106 cells/ml, P = 0.018; sperm motility: 19.53 ± 7.69%, P = 0.001; the number of SYCP3-positive cells/tubule: 30.00 ± 11.28, P < 0.001; the percentage of SYCP3-positive tubules/section 71.98 ± 8.88%, P = 0.001; the expression of SYCP3 protein: 0.71 ± 0.09, P < 0.001), and fertility was also suppressed (P < 0

  18. Weekly administration of rapamycin improves survival and biomarkers in obese male mice on high-fat diet.

    PubMed

    Leontieva, Olga V; Paszkiewicz, Geraldine M; Blagosklonny, Mikhail V

    2014-08-01

    Recent discoveries have revealed the key role of mTOR (target of rapamycin) in aging. Furthermore, rapamycin extends lifespan in mice, especially in female mice. Here, we treated obese male mice on high-fat diet with rapamycin given intermittently: either weekly (once a week) or alternating bi-weekly (three injections every other week). While only marginally reducing obesity, intermittent administration of rapamycin significantly extended lifespan. Significance was achieved for weekly treated group and for the three rapamycin-received groups combined. In weekly treatment group, 100% mice were alive by the age of 2 years, whereas 60% of mice died in untreated group by this age. The effect of weekly treatment on survival was highly significant and cannot be fully explained by partial reduction in obesity. Alternating bi-weekly treatments seem to be less effective than weekly treatment, although effects of additional factors (see ) may not be excluded. After one year of treatment, all survived mice were sacrificed 8 days after the last administration of rapamycin to avoid its direct interference with parameters examined. Fasting levels of cardiac and hepatic p-S6, a marker of mTORC1 activity, were lower in weekly treatment group compared with control mice. In contrast, levels of p-Akt (S473), glucose, triglycerides and insulin were unchanged, whereas leptin and IGF-1 tended to be lower. Thus, weekly treatment with rapamycin may slow down aging in obese male mice on high-fat diet. PMID:24655348

  19. Osteoprotegerin-deficient male mice as a model for severe alveolar bone loss: comparison with RANKL-overexpressing transgenic male mice.

    PubMed

    Koide, Masanori; Kobayashi, Yasuhiro; Ninomiya, Tadashi; Nakamura, Midori; Yasuda, Hisataka; Arai, Yoshinori; Okahashi, Nobuo; Yoshinari, Nobuo; Takahashi, Naoyuki; Udagawa, Nobuyuki

    2013-02-01

    Periodontitis, an inflammatory disease of periodontal tissues, is characterized by excessive alveolar bone resorption. An increase in the receptor activator of nuclear factor-κB ligand (RANKL) to osteoprotegerin (OPG) ratio is thought to reflect the severity of periodontitis. Here, we examined alveolar bone loss in OPG-deficient (OPG(-/-)) mice and RANKL-overexpressing transgenic (RANKL-Tg) mice. Alveolar bone loss in OPG(-/-) mice at 12 weeks was significantly higher than that in RANKL-Tg mice. OPG(-/-) but not RANKL-Tg mice exhibited severe bone resorption especially in cortical areas of the alveolar bone. An increased number of osteoclasts was observed in the cortical areas in OPG(-/-) but not in RANKL-Tg mice. Immunohistochemical analyses showed many OPG-positive signals in osteocytes but not osteoblasts. OPG-positive osteocytes in the cortical area of alveolar bones and long bones were abundant in both wild-type and RANKL-Tg mice. This suggests the resorption in cortical bone areas to be prevented by OPG produced locally. To test the usefulness of OPG(-/-) mice as an animal model for screening drugs to prevent alveolar bone loss, we administered an antimouse RANKL antibody or risedronate, a bisphosphonate, to OPG(-/-) mice. They suppressed alveolar bone resorption effectively. OPG(-/-) mice are useful for screening therapeutic agents against alveolar bone loss.

  20. Lead-induced modifications of immune responses in aging male and female mice

    SciTech Connect

    Genova, T.F.

    1982-01-01

    This study was designed to analyze the effects of lead intoxication on the immunological responses of aging male and female Balb/c mice. Both males and females on the lead diet exhibited a loss of weight after one week of treatment. The animals began to gain weight again after eight or fifteen weeks for males and females respectively. Although both groups continued to gain weight at a rate consistent with control animals, they never reached the same weights as their same-sex control counterparts. Immunofluorescent staining indicated the presence of greater renal pathology in lead-fed animals as compared to controls. Lead-fed males demonstrated the greatest pathology of any group. Both T and B cell mitogenic responses declined during the early phases of the experiment. This was followed, at age 25-27 weeks, by an increase in activity to levels greater than those of control animals. The depression and subsequent increase in mitogenic responses was mirrored in the ability of T cells to regulate B cell plaque formation when stimulated with sheep red blood cells. T cell function returned to control levels in coincidence with the increase in T and B cell mitogenicity. The return of T cell functionality to control levels coincides with the increased mitogenesis noted in T and B cell populations and the onset of weight gains by lead-fed animals. This coincidence suggests the occurrence of a physiological or immunological change which is compensating for the continued lead intoxication. One such change may be a lead induced reduction in the number or function of a T cell subset, eg. T suppressors.

  1. Adult male mice emit context-specific ultrasonic vocalizations that are modulated by prior isolation or group rearing environment.

    PubMed

    Chabout, Jonathan; Serreau, Pierre; Ey, Elodie; Bellier, Ludovic; Aubin, Thierry; Bourgeron, Thomas; Granon, Sylvie

    2012-01-01

    Social interactions in mice are frequently analysed in genetically modified strains in order to get insight of disorders affecting social interactions such as autism spectrum disorders. Different types of social interactions have been described, mostly between females and pups, and between adult males and females. However, we recently showed that social interactions between adult males could also encompass cognitive and motivational features. During social interactions, rodents emit ultrasonic vocalizations (USVs), but it remains unknown if call types are differently used depending of the context and if they are correlated with motivational state. Here, we recorded the calls of adult C57BL/6J male mice in various behavioral conditions, such as social interaction, novelty exploration and restraint stress. We introduced a modulator for the motivational state by comparing males maintained in isolation and males maintained in groups before the experiments. Male mice uttered USVs in all social and non-social situations, and even in a stressful restraint context. They nevertheless emitted the most important number of calls with the largest diversity of call types in social interactions, particularly when showing a high motivation for social contact. For mice maintained in social isolation, the number of calls recorded was positively correlated with the duration of social contacts, and most calls were uttered during contacts between the two mice. This correlation was not observed in mice maintained in groups. These results open the way for a deeper understanding and characterization of acoustic signals associated with social interactions. They can also help evaluating the role of motivational states in the emission of acoustic signals.

  2. Epidermal growth factor receptor plays a role in the regulation of liver and plasma lipid levels in adult male mice.

    PubMed

    Scheving, Lawrence A; Zhang, Xiuqi; Garcia, Oscar A; Wang, Rebecca F; Stevenson, Mary C; Threadgill, David W; Russell, William E

    2014-03-01

    Dsk5 mice have a gain of function in the epidermal growth factor receptor (EGFR), caused by a point mutation in the kinase domain. We analyzed the effect of this mutation on liver size, histology, and composition. We found that the livers of 12-wk-old male Dsk5 heterozygotes (+/Dsk5) were 62% heavier compared with those of wild-type controls (+/+). The livers of the +/Dsk5 mice compared with +/+ mice had larger hepatocytes with prominent, polyploid nuclei and showed modestly increased cell proliferation indices in both hepatocytes and nonparenchymal cells. An analysis of total protein, DNA, and RNA (expressed relative to liver weight) revealed no differences between the mutant and wild-type mice. However, the livers of the +/Dsk5 mice had more cholesterol but less phospholipid and fatty acid. Circulating cholesterol levels were twice as high in adult male +/Dsk5 mice but not in postweaned young male or female mice. The elevated total plasma cholesterol resulted mainly from an increase in low-density lipoprotein (LDL). The +/Dsk5 adult mouse liver expressed markedly reduced protein levels of LDL receptor, no change in proprotein convertase subtilisin/kexin type 9, and a markedly increased fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Increased expression of transcription factors associated with enhanced cholesterol synthesis was also observed. Together, these findings suggest that the EGFR may play a regulatory role in hepatocyte proliferation and lipid metabolism in adult male mice, explaining why elevated levels of EGF or EGF-like peptides have been positively correlated to increased cholesterol levels in human studies.

  3. Epidermal growth factor receptor plays a role in the regulation of liver and plasma lipid levels in adult male mice.

    PubMed

    Scheving, Lawrence A; Zhang, Xiuqi; Garcia, Oscar A; Wang, Rebecca F; Stevenson, Mary C; Threadgill, David W; Russell, William E

    2014-03-01

    Dsk5 mice have a gain of function in the epidermal growth factor receptor (EGFR), caused by a point mutation in the kinase domain. We analyzed the effect of this mutation on liver size, histology, and composition. We found that the livers of 12-wk-old male Dsk5 heterozygotes (+/Dsk5) were 62% heavier compared with those of wild-type controls (+/+). The livers of the +/Dsk5 mice compared with +/+ mice had larger hepatocytes with prominent, polyploid nuclei and showed modestly increased cell proliferation indices in both hepatocytes and nonparenchymal cells. An analysis of total protein, DNA, and RNA (expressed relative to liver weight) revealed no differences between the mutant and wild-type mice. However, the livers of the +/Dsk5 mice had more cholesterol but less phospholipid and fatty acid. Circulating cholesterol levels were twice as high in adult male +/Dsk5 mice but not in postweaned young male or female mice. The elevated total plasma cholesterol resulted mainly from an increase in low-density lipoprotein (LDL). The +/Dsk5 adult mouse liver expressed markedly reduced protein levels of LDL receptor, no change in proprotein convertase subtilisin/kexin type 9, and a markedly increased fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Increased expression of transcription factors associated with enhanced cholesterol synthesis was also observed. Together, these findings suggest that the EGFR may play a regulatory role in hepatocyte proliferation and lipid metabolism in adult male mice, explaining why elevated levels of EGF or EGF-like peptides have been positively correlated to increased cholesterol levels in human studies. PMID:24407590

  4. Epidermal growth factor receptor plays a role in the regulation of liver and plasma lipid levels in adult male mice

    PubMed Central

    Zhang, Xiuqi; Garcia, Oscar A.; Wang, Rebecca F.; Stevenson, Mary C.; Threadgill, David W.; Russell, William E.

    2014-01-01

    Dsk5 mice have a gain of function in the epidermal growth factor receptor (EGFR), caused by a point mutation in the kinase domain. We analyzed the effect of this mutation on liver size, histology, and composition. We found that the livers of 12-wk-old male Dsk5 heterozygotes (+/Dsk5) were 62% heavier compared with those of wild-type controls (+/+). The livers of the +/Dsk5 mice compared with +/+ mice had larger hepatocytes with prominent, polyploid nuclei and showed modestly increased cell proliferation indices in both hepatocytes and nonparenchymal cells. An analysis of total protein, DNA, and RNA (expressed relative to liver weight) revealed no differences between the mutant and wild-type mice. However, the livers of the +/Dsk5 mice had more cholesterol but less phospholipid and fatty acid. Circulating cholesterol levels were twice as high in adult male +/Dsk5 mice but not in postweaned young male or female mice. The elevated total plasma cholesterol resulted mainly from an increase in low-density lipoprotein (LDL). The +/Dsk5 adult mouse liver expressed markedly reduced protein levels of LDL receptor, no change in proprotein convertase subtilisin/kexin type 9, and a markedly increased fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Increased expression of transcription factors associated with enhanced cholesterol synthesis was also observed. Together, these findings suggest that the EGFR may play a regulatory role in hepatocyte proliferation and lipid metabolism in adult male mice, explaining why elevated levels of EGF or EGF-like peptides have been positively correlated to increased cholesterol levels in human studies. PMID:24407590

  5. Immunomodulatory effects of maternal atrazine exposure on male Balb/c mice

    SciTech Connect

    Rowe, Alexander M.; Brundage, Kathleen M.; Schafer, Rosana; Barnett, John B. . E-mail: jbarnett@hsc.wvu.edu

    2006-07-01

    Atrazine is a widely used herbicide applied to corn, sugar and other crops as a broad leaf weed inhibitor. Using the Balb/c mouse model, we have determined that prenatal/lactational exposure to atrazine alters adult immune function. Pregnant Balb/c dams were exposed subcutaneously for 21 days via time release pellets to 700 {mu}g per day of atrazine beginning between days 10 and 12 of pregnancy. Prenatal/Lactational exposure caused no overt physical malformations in the offspring and had no effect on the number of litters carried to term or the litter size. Upon reaching early adulthood (approximately 3 months of age), the state of their immune system was evaluated. There were no changes in body weight or in the organ to body weight ratio of the spleen. Additionally, no changes were observed in the number of CD8{sup +} T cell, CD4{sup +} T cell, or B220{sup +} B cell subpopulations in the spleen. T cell function was assessed by measuring proliferation and cytolytic activity after in vitro allogeneic stimulation. Male mice which had been prenatally/lactationally exposed to atrazine had an increase in both T cell proliferation and cytolytic activity. The humoral immune response was assessed after immunization with heat killed Streptococcus pneumoniae (HKSP). There was a significant increase in the number of HKSP-specific IgM secreting B cells in the spleen of prenatal/lactational exposed male mice. Inasmuch as atrazine is a widespread environmental contaminant, this immunopotentiation raises concerns that it may potentiate clinical diseases, such as autoimmune disease and hypersensitivity, and needs to be carefully monitored and studied.

  6. Chronic MPTP treatment produces hyperactivity in male mice which is not alleviated by concurrent trehalose treatment.

    PubMed

    Ferguson, Sherry A; Law, C Delbert; Sarkar, Sumit

    2015-10-01

    The chronic MPTP+probenecid treatment paradigm has been used to successfully model the neurochemical, neuropathological, and behavioral effects associated with Parkinson's disease. Here, adult male C57Bl/6 mice were injected ip with 25 mg/kg MPTP and 250 mg/kg probenecid (MPTPp) or saline twice weekly for a total of 10 injections. Behavioral assessments included motor coordination, grip strength, spatial learning/memory, locomotor activity, and anhedonia. Those assessments were repeated up to 8 weeks post-treatment. In a subsequent experiment, adult male mice were treated with saline or MPTPp as described above. One-half of each group was allowed access to 1% trehalose in the water bottle. Trehalose intake averaged 1.90-2.34 g/kg. Behavioral assessments included locomotor activity, olfaction, motor coordination, grip strength, and exploratory behavior. Those assessments were repeated 4 weeks post-treatment. The strongest MPTPp effect was hyperactivity as exhibited in the open field. This increased activity was apparent in both experiments and occurred at all time points post-treatment. Assessments of grip strength, water maze performance, olfaction, and exploratory behavior did not indicate MPTPp-related alterations. When the specifications for the motor coordination test were made somewhat easier in the second experiment, there were deficits exhibited by the MPTPp group, the MPTPp+trehalose group and the trehalose group. The addition of trehalose did not alleviate any of the MPTPp-induced behavioral alterations; however, trehalose treatment significantly attenuated the striatal decreases in DA, DOPAC, HVA and 5-HIAA. These results provide a more comprehensive description of the behavioral alterations resulting from the chronic MPTPp treatment regimen and suggest that trehalose at this concentration does not act as a complete neuroprotectant.

  7. Chronic MPTP treatment produces hyperactivity in male mice which is not alleviated by concurrent trehalose treatment.

    PubMed

    Ferguson, Sherry A; Law, C Delbert; Sarkar, Sumit

    2015-10-01

    The chronic MPTP+probenecid treatment paradigm has been used to successfully model the neurochemical, neuropathological, and behavioral effects associated with Parkinson's disease. Here, adult male C57Bl/6 mice were injected ip with 25 mg/kg MPTP and 250 mg/kg probenecid (MPTPp) or saline twice weekly for a total of 10 injections. Behavioral assessments included motor coordination, grip strength, spatial learning/memory, locomotor activity, and anhedonia. Those assessments were repeated up to 8 weeks post-treatment. In a subsequent experiment, adult male mice were treated with saline or MPTPp as described above. One-half of each group was allowed access to 1% trehalose in the water bottle. Trehalose intake averaged 1.90-2.34 g/kg. Behavioral assessments included locomotor activity, olfaction, motor coordination, grip strength, and exploratory behavior. Those assessments were repeated 4 weeks post-treatment. The strongest MPTPp effect was hyperactivity as exhibited in the open field. This increased activity was apparent in both experiments and occurred at all time points post-treatment. Assessments of grip strength, water maze performance, olfaction, and exploratory behavior did not indicate MPTPp-related alterations. When the specifications for the motor coordination test were made somewhat easier in the second experiment, there were deficits exhibited by the MPTPp group, the MPTPp+trehalose group and the trehalose group. The addition of trehalose did not alleviate any of the MPTPp-induced behavioral alterations; however, trehalose treatment significantly attenuated the striatal decreases in DA, DOPAC, HVA and 5-HIAA. These results provide a more comprehensive description of the behavioral alterations resulting from the chronic MPTPp treatment regimen and suggest that trehalose at this concentration does not act as a complete neuroprotectant. PMID:26111725

  8. The testicular form of hormone-sensitive lipase HSLtes confers rescue of male infertility in HSL-deficient mice.

    PubMed

    Vallet-Erdtmann, Virginie; Tavernier, Geneviève; Contreras, Juan Antonio; Mairal, Aline; Rieu, Cécile; Touzalin, Anne-Marie; Holm, Cecilia; Jégou, Bernard; Langin, Dominique

    2004-10-01

    Inactivation of the hormone-sensitive lipase gene (HSL) confers male sterility with a major defect in spermatogenesis. Several forms of HSL are expressed in testis. HSLtes mRNA and protein are found in early and elongated spermatids, respectively. The other forms are expressed in diploid germ cells and interstitial cells of the testis. To determine whether the absence of the testis-specific form of HSL, HSLtes, was responsible for the infertility in HSL-null mice, we generated transgenic mice expressing HSLtes under the control of its own promoter. The transgenic animals were crossed with HSL-null mice to produce mice deficient in HSL in nongonadal tissues but expressing HSLtes in haploid germ cells. Cholesteryl ester hydrolase activity was almost completely blunted in HSL-deficient testis. Mice with one allele of the transgene showed an increase in enzymatic activity and a small elevation in the production of spermatozoa. The few fertile hemizygous male mice produced litters of very small to small size. The presence of the two alleles led to a doubling in cholesteryl ester hydrolase activity, which represented 25% of the wild type values associated with a qualitatively normal spermatogenesis and a partial restoration of sperm reserves. The fertility of these mice was totally restored with normal litter sizes. In line with the importance of the esterase activity, HSLtes transgene expression reversed the cholesteryl ester accumulation observed in HSL-null mice. Therefore, expression of HSLtes and cognate cholesteryl ester hydrolase activity leads to a rescue of the infertility observed in HSL-deficient male mice. PMID:15292223

  9. The testicular form of hormone-sensitive lipase HSLtes confers rescue of male infertility in HSL-deficient mice.

    PubMed

    Vallet-Erdtmann, Virginie; Tavernier, Geneviève; Contreras, Juan Antonio; Mairal, Aline; Rieu, Cécile; Touzalin, Anne-Marie; Holm, Cecilia; Jégou, Bernard; Langin, Dominique

    2004-10-01

    Inactivation of the hormone-sensitive lipase gene (HSL) confers male sterility with a major defect in spermatogenesis. Several forms of HSL are expressed in testis. HSLtes mRNA and protein are found in early and elongated spermatids, respectively. The other forms are expressed in diploid germ cells and interstitial cells of the testis. To determine whether the absence of the testis-specific form of HSL, HSLtes, was responsible for the infertility in HSL-null mice, we generated transgenic mice expressing HSLtes under the control of its own promoter. The transgenic animals were crossed with HSL-null mice to produce mice deficient in HSL in nongonadal tissues but expressing HSLtes in haploid germ cells. Cholesteryl ester hydrolase activity was almost completely blunted in HSL-deficient testis. Mice with one allele of the transgene showed an increase in enzymatic activity and a small elevation in the production of spermatozoa. The few fertile hemizygous male mice produced litters of very small to small size. The presence of the two alleles led to a doubling in cholesteryl ester hydrolase activity, which represented 25% of the wild type values associated with a qualitatively normal spermatogenesis and a partial restoration of sperm reserves. The fertility of these mice was totally restored with normal litter sizes. In line with the importance of the esterase activity, HSLtes transgene expression reversed the cholesteryl ester accumulation observed in HSL-null mice. Therefore, expression of HSLtes and cognate cholesteryl ester hydrolase activity leads to a rescue of the infertility observed in HSL-deficient male mice.

  10. Identification of a tyrosinase (TYR) exon 4 deletion in albino ferrets (Mustela putorius furo).

    PubMed

    Blaszczyk, W M; Distler, C; Dekomien, G; Arning, L; Hoffmann, K-P; Epplen, J T

    2007-08-01

    Albinism is due to a lack of pigmentation in hair, skin and eye, and has been shown to occur in several animal species. Mutations of the tyrosinase (TYR) gene account for albinism in domestic cats, rabbits, cattle, mice and rats. In this study, we demonstrate that a TYR mutation accounts for albinism in the ferret (Mustela putorius furo). The coding sequence of the five exons of TYR was determined in genomic DNA from wild-type pigmented 'sable' coloured and albino ferrets. It was not possible to amplify TYR exon 4 in albino ferrets originating from different breeds. The deletion of exon 4 in albino ferrets was confirmed by Southern blot hybridization of genomic DNA from albino and pigmented ferrets. This is the first report of a deletion of a TYR exon in a non-human mammal. PMID:17655555

  11. Inhalation reproductive toxicology studies: Male dominant lethal study of n-hexane in Swiss (CD-1) mice: Final report

    SciTech Connect

    Mast, T.J.; Rommereim, R.L.; Evanoff, J.J.; Sasser, L.B.; Decker, J.R.; Stoney, K.H.; Weigel, R.J.; Westerberg, R.B.

    1988-08-01

    The straight-chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent routinely used in industrial environments; consequently, the opportunity for industrial, environmental or accidental exposure to hexane vapors is significant. Although myelinated nerve tissue is the primary target organ of hexane, the testes have also been identified as being sensitive to hexacarbon exposure. The objective of this study was to evaluate male dominant lethal effects in Swiss (CD-1) mice after exposure to 0, 200, 1000, or 5000 ppM n-hexane, 20 h/day for 5 consecutive days. Each exposure concentration consisted of 30 randomly selected, proven male breeders; 4 groups. The mice were weighed just prior to the first day of exposure and at weekly intervals until sacrifice. Ten males in each dose group were sacrificed one day after the cessation of exposure, and their testes and epididymides were removed for evaluation of the germinal epithelium. The remaining male mice, 20 per group, were individually housed in hanging wire-mesh breeding cages where they were mated with unexposed, virgin females for eight weekly intervals; new females were provided each week. The mated females were sacrificed 12 days after the last day of cohabitation and their reproductive status and the number and viability of the implants were recorded. The appearance and behavior of the male mice were unremarkable throughout the study period and no evidence of n-hexane toxicity was observed. 18 refs., 3 figs., 11 tabs.

  12. Maternal separation facilitates extinction of social fear in adult male mice.

    PubMed

    Zoicas, Iulia; Neumann, Inga D

    2016-01-15

    Early life stress, such as child abuse or neglect, is a risk factor for the development of psychopathologies characterized by abnormal social and emotional behaviors. In rodents, long-lasting changes in stress coping and emotional behavior can be induced by separating pups from their mother. We used maternal separation (MS; 3h daily on postnatal days 1-14) to test whether early life stress alters acquisition and extinction of social fear in adult male mice as studied in a specific model of social fear, i.e., in the social fear conditioning paradigm. We show that MS facilitated extinction of social fear without altering acquisition or expression of social fear. This facilitatory effect of MS on social fear extinction was not due to improved social learning and memory abilities or to increased social interest, as MS rather impaired social memory in the social discrimination test and did not alter social preference in the social preference-avoidance test. In contrast, MS did not alter acquisition and extinction of non-social, cued fear, or non-social memory as assessed in the object discrimination test and non-social anxiety as assessed in the elevated plus-maze. These results suggest that a social stress like MS in early life may improve coping with and recovery from a traumatic social experience in adulthood in mice. PMID:26497106

  13. Immune Alterations in Male and Female Mice after 2-Deoxy-D-Glucose Administration

    NASA Technical Reports Server (NTRS)

    Dreau, Didier; Morton, Darla S.; Foster, Mareva; Swiggett, Jeanene P.; Sonnenfeld, Gerald

    1995-01-01

    Administration of 2-deoxy-D-glucose (2-DG), an analog of glucose which inhibits glycolysis by competitive antagonism for phosphohexose isomerase, results in acute periods of intracellular glucoprivation and hyperglycemia resulting in hyperphagia. In addition to these changes in the carbohydrate metabolism, injection of 2-DG results in alterations of both the endocrine and neurological systems as suggested by modifications in oxytocin and glucocorticoid levels and norepinephrine production. Moreover, alterations of the immune response, such as a decrease in the in vitro proliferation of splenocytes after mitogen-stimulation, were observed in mice injected with 2-DG. Sex, genotype and environment are among the factors that may modulate effects of catecholamines and hypothalamo-pituitary-adrenal axis on these immune changes. Sexual dimorphism in immune function resulting from the effects of sex hormones on immune effector cells has been shown in both animals and humans. These observations have important implications, especially with regard to higher incidence of many autoimmune diseases in females. Evidence exists that reproductive hormones influence the immune system and increase the risk of immunologically related disorders in both animals and humans. Indeed, immunological responses in stressful situations may also be confounded by fluctuations of sex hormones especially in females. Lymphocyte distribution, cytoldne production, and the ability of lymphocyte to proliferate in vitro were analyzed in male and female mice to determine if sex influenced 2-DG immunomodulation. In addition, the influence of hormones, especially sex hormones, on these changes were evaluated.

  14. Cimetidine and Clobenpropit Attenuate Inflammation-Associated Colorectal Carcinogenesis in Male ICR Mice

    PubMed Central

    Tanaka, Takuji; Kochi, Takahiro; Shirakami, Yohei; Mori, Takayuki; Kurata, Ayumi; Watanabe, Naoki; Moriwaki, Hisataka; Shimizu, Masahito

    2016-01-01

    Histamine and histamine receptors (Hrhs) have been identified as critical molecules during inflammation and carcinogenesis. This study was conducted to determine the effects of Hrh1-Hrh3 antagonists on inflammation-associated colorectal carcinogenesis. Male ICR mice were treated with azoxymethane (AOM, 10 mg/kg bw, i.p.) and 1.5% dextran sodium sulfate (DSS, drinking water for 7 days) to induce colorectal carcinogenesis. The mice were then fed diets containing test chemical (500 ppm terfenadine, 500 ppm cimetidine or 10 ppm clobenpropit) for 15 weeks. At week 18, feeding with the diets containing cimetidine (Hrh2 antagonist) and clobenpropit (Hrh3 antagonist/inverse agonist) significantly lowered the multiplicity of colonic adenocarcinoma. Terfenadine (Hrh1 antagonist) did not affect AOM-DSS-induced colorectal carcinogenesis. Adenocarcinoma cells immunohistochemically expressed Hrh1, Hrh2, Hrh3 and Hrh4 with varied intensities. Because clobenpropit is also known to be a Hrh4 receptor agonist, Hrh2, Hrh3 and Hrh4 may be involved in inflammation-related colorectal carcinogenesis. Additional data, including the mRNA expression of pro-inflammatory cytokines and inducible inflammatory enzymes in the colonic mucosa, are also presented. PMID:26907350

  15. Cimetidine and Clobenpropit Attenuate Inflammation-Associated Colorectal Carcinogenesis in Male ICR Mice.

    PubMed

    Tanaka, Takuji; Kochi, Takahiro; Shirakami, Yohei; Mori, Takayuki; Kurata, Ayumi; Watanabe, Naoki; Moriwaki, Hisataka; Shimizu, Masahito

    2016-02-20

    Histamine and histamine receptors (Hrhs) have been identified as critical molecules during inflammation and carcinogenesis. This study was conducted to determine the effects of Hrh1-Hrh3 antagonists on inflammation-associated colorectal carcinogenesis. Male ICR mice were treated with azoxymethane (AOM, 10 mg/kg bw, i.p.) and 1.5% dextran sodium sulfate (DSS, drinking water for 7 days) to induce colorectal carcinogenesis. The mice were then fed diets containing test chemical (500 ppm terfenadine, 500 ppm cimetidine or 10 ppm clobenpropit) for 15 weeks. At week 18, feeding with the diets containing cimetidine (Hrh2 antagonist) and clobenpropit (Hrh3 antagonist/inverse agonist) significantly lowered the multiplicity of colonic adenocarcinoma. Terfenadine (Hrh1 antagonist) did not affect AOM-DSS-induced colorectal carcinogenesis. Adenocarcinoma cells immunohistochemically expressed Hrh1, Hrh2, Hrh3 and Hrh4 with varied intensities. Because clobenpropit is also known to be a Hrh4 receptor agonist, Hrh2, Hrh3 and Hrh4 may be involved in inflammation-related colorectal carcinogenesis. Additional data, including the mRNA expression of pro-inflammatory cytokines and inducible inflammatory enzymes in the colonic mucosa, are also presented.

  16. Protective effect of allicin against glycidamide-induced toxicity in male and female mice.

    PubMed

    Wang, En-Ting; Chen, Dong-Yan; Liu, Huang-You; Yan, Hai-Yang; Yuan, Yuan

    2015-04-01

    Acrylamide is known to be a neurotoxic, genotoxic, and carcinogenic compound. Glycidamide has a close relationship to the toxic mechanism of acrylamide. In order to explore the toxic mechanism of acrylamide, we further discussed the effects of oral administration of allicin on glycidamide-induced toxicity by determining the hematological parameters like AST, ALT, LDH, BUN, creatinine, ROS, and 8-OHdG, and biochemical parameters such as MDA, MPO, SOD, GST and GSH in the kidney, liver, brain and lung of male and female mice for the first time. We found that the same dose of glycidamide had more toxic effects and damage effects to the mice compared to the previous study of acrylamide. It could markedly increase the level of AST, ALT, LDH, BUN, ROS, 8-OHdG, MDA, MPO while decrease the SOD, GST and GSH. However, our data showed the oral administered allicin with a concentration of 5, 10, and 20 mg/kg b.w./day could significantly decrease the damage indexes of AST, ALT, LDH, BUN, ROS, 8-OHdG, MDA, and MPO, while increase the antioxidant indicators of SOD, GST and GSH. Thus allicin could be used as an effective dietary supplement for the chemoprevention of glycidamide genotoxicity internally, and to prevent the tissue damage and toxicity induced by glycidamide. PMID:25730897

  17. Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment.

    PubMed

    Adeniyi, Philip A; Ishola, Azeez O; Laoye, Babafemi J; Olatunji, Babawale P; Bankole, Oluwamolakun O; Shallie, Philemon D; Ogundele, Olalekan M

    2016-02-01

    The interaction between MDMA and Nicotine affects multiple brain centres and neurotransmitter systems (serotonin, dopamine and glutamate) involved in motor coordination and cognition. In this study, we have elucidated the effect of prolonged (10 days) MDMA, Nicotine and a combined Nicotine-MDMA treatment on motor-cognitive neural functions. In addition, we have shown the correlation between the observed behavioural change and neural structural changes induced by these treatments in BALB/c mice. We observed that MDMA (2 mg/Kg body weight; subcutaneous) induced a decline in motor function, while Nicotine (2 mg/Kg body weight; subcutaneous) improved motor function in male periadolescent mice. In combined treatment, Nicotine reduced the motor function decline observed in MDMA treatment, thus no significant change in motor function for the combined treatment versus the control. Nicotine or MDMA treatment reduced memory function and altered hippocampal structure. Similarly, a combined Nicotine-MDMA treatment reduced memory function when compared with the control. Ultimately, the metabolic and structural changes in these neural systems were seen to vary for the various forms of treatment. It is noteworthy to mention that a combined treatment increased the rate of lipid peroxidation in brain tissue.

  18. Pairmate-dependent pup retrieval as parental behavior in male mice.

    PubMed

    Liang, Mingkun; Zhong, Jing; Liu, Hong-Xiang; Lopatina, Olga; Nakada, Ryusuke; Yamauchi, Agnes-Mikiko; Higashida, Haruhiro

    2014-01-01

    Appropriate parental care by fathers can greatly facilitate healthy human family life. However, much less is known about paternal behavior in animals compared to those regarding maternal behavior. Previously, we reported that male ICR strain laboratory mice, although not spontaneously parental, can be induced to display maternal-like parental care (pup retrieval) when separated from their pups by signals from the pairmate dam (Liu et al., 2013). This parental behavior by the ICR sires, which are not genetically biparental, is novel and has been designated as pairmate-dependent paternal behavior. However, the factors critical for this paternal behavior are unclear. Here, we report that the pairmate-dependent paternal retrieval behavior is observed especially in the ICR strain and not in C57BL/6 or BALB/c mice. An ICR sire displays retrieval behavior only toward his biological pups. A sire co-housed with an unrelated non-pairing dam in a new environment, under which 38-kHz ultrasonic vocalizations are not detected, does not show parenting behavior. It is important for sires to establish their own home territory (cage) by continuous housing and testing to display retrieval behavior. These results indicated that the ICR sires display distinct paternity, including father-child social interaction, and shed light on parental behavior, although further analyses of paternal care at the neuroendocrinological and neurocircuitry levels are required.

  19. Xylitol Affects the Intestinal Microbiota and Metabolism of Daidzein in Adult Male Mice

    PubMed Central

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-01-01

    This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health. PMID:24336061

  20. Middle age has a significant impact on gene expression during skin wound healing in male mice.

    PubMed

    Yanai, Hagai; Lumenta, David Benjamin; Vierlinger, Klemens; Hofner, Manuela; Kitzinger, Hugo-Benito; Kamolz, Lars-Peter; Nöhammer, Christa; Chilosi, Marco; Fraifeld, Vadim E

    2016-08-01

    The vast majority of research on the impact of age on skin wound healing (WH) compares old animals to young ones. The middle age is often ignored in biogerontological research despite the fact that many functions that decline in an age-dependent manner have starting points in mid-life. With this in mind, we examined gene expression patterns during skin WH in late middle-aged versus young adult male mice, using the head and back punch models. The rationale behind this study was that the impact of age would first be detectable at the transcriptional level. We pinpointed several pathways which were over-activated in the middle-aged mice, both in the intact skin and during WH. Among them were various metabolic, immune-inflammatory and growth-promoting pathways. These transcriptional changes were much more pronounced in the head than in the back. In summary, the middle age has a significant impact on gene expression in intact and healing skin. It seems that the head punch model is more sensitive to the effect of age than the back model, and we suggest that it should be more widely applied in aging research on wound healing.

  1. Promotive effect of topical ketoconazole, minoxidil, and minoxidil with tretinoin on hair growth in male mice.

    PubMed

    Aldhalimi, Muhsin A; Hadi, Najah R; Ghafil, Fadaa A

    2014-01-01

    Recently topical use of 2% Ketoconazole solution has been reported to have a therapeutic effect on androgenic alopecia. Minoxidil is a vasodilatory medication used primarily as antihypertensive drug. It was discovered to have the side effect of hair growth and reversing baldness. Tretinoin is commonly used topically for acne treatment and in the treatment of photoaging. It is used by some as hair loss treatment. Objective. To compare the stimulatory effect of Ketoconazole, Minoxidil, and Minoxidil with Tretinoin on hair growth in a mouse model. Materials and Methods. Coat hairs on the dorsal skin of seven weeks old male mice were gently clipped and then stained by using commercial dye. These mice were divided into four groups each of five treated with topical application of ethanol 95%, Ketoconazole solution 2%, Minoxidil solution 5%, and Minoxidil with Tretinoin solution 0.1%, respectively. The drugs were applied once daily for three weeks, the clipped area was photographed, and the ratio of regrown coat area was calculated. Results. The results demonstrated that Ketoconazole, Minoxidil, and Minoxidil with Tretinoin had a significant stimulatory effect on hair growth compared with the control group and Minoxidil was the most effective drug among them. PMID:24734193

  2. Promotive Effect of Topical Ketoconazole, Minoxidil, and Minoxidil with Tretinoin on Hair Growth in Male Mice

    PubMed Central

    Aldhalimi, Muhsin A.; Hadi, Najah R.; Ghafil, Fadaa A.

    2014-01-01

    Recently topical use of 2% Ketoconazole solution has been reported to have a therapeutic effect on androgenic alopecia. Minoxidil is a vasodilatory medication used primarily as antihypertensive drug. It was discovered to have the side effect of hair growth and reversing baldness. Tretinoin is commonly used topically for acne treatment and in the treatment of photoaging. It is used by some as hair loss treatment. Objective. To compare the stimulatory effect of Ketoconazole, Minoxidil, and Minoxidil with Tretinoin on hair growth in a mouse model. Materials and Methods. Coat hairs on the dorsal skin of seven weeks old male mice were gently clipped and then stained by using commercial dye. These mice were divided into four groups each of five treated with topical application of ethanol 95%, Ketoconazole solution 2%, Minoxidil solution 5%, and Minoxidil with Tretinoin solution 0.1%, respectively. The drugs were applied once daily for three weeks, the clipped area was photographed, and the ratio of regrown coat area was calculated. Results. The results demonstrated that Ketoconazole, Minoxidil, and Minoxidil with Tretinoin had a significant stimulatory effect on hair growth compared with the control group and Minoxidil was the most effective drug among them. PMID:24734193

  3. Caloric restriction reveals a metabolomic and lipidomic signature in liver of male mice

    PubMed Central

    Jové, Mariona; Naudí, Alba; Ramírez-Núñez, Omar; Portero-Otín, Manuel; Selman, Colin; Withers, Dominic J; Pamplona, Reinald

    2014-01-01

    Lipid composition, particularly membrane unsaturation, has been proposed as being a lifespan determinant, but it is currently unknown whether caloric restriction (CR), an accepted life-extending intervention, affects cellular lipid profiles. In this study, we employ a liquid chromatography quadrupole time-of-flight-based methodology to demonstrate that CR in the liver of male C57BL/6 mice: (i) induces marked changes in the cellular lipidome, (ii) specifically reduces levels of a phospholipid peroxidation product, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphatidylcholine, (iii) alters cellular phosphoethanolamine and triglyceride distributional profiles, (iv) affects mitochondrial electron transport chain complexes, increasing complex II and decreasing complex III and (v) is associated with specific changes in liver metabolic pathways. These data demonstrate that CR induces a specific lipidome and metabolome reprogramming event in mouse liver which is associated with lower protein oxidative damage, as assessed by mass spectrometry-based measurements. Such changes may be critical to the increased lifespan and healthspan observed in C57BL/6 mice following CR. PMID:25052291

  4. Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment.

    PubMed

    Adeniyi, Philip A; Ishola, Azeez O; Laoye, Babafemi J; Olatunji, Babawale P; Bankole, Oluwamolakun O; Shallie, Philemon D; Ogundele, Olalekan M

    2016-02-01

    The interaction between MDMA and Nicotine affects multiple brain centres and neurotransmitter systems (serotonin, dopamine and glutamate) involved in motor coordination and cognition. In this study, we have elucidated the effect of prolonged (10 days) MDMA, Nicotine and a combined Nicotine-MDMA treatment on motor-cognitive neural functions. In addition, we have shown the correlation between the observed behavioural change and neural structural changes induced by these treatments in BALB/c mice. We observed that MDMA (2 mg/Kg body weight; subcutaneous) induced a decline in motor function, while Nicotine (2 mg/Kg body weight; subcutaneous) improved motor function in male periadolescent mice. In combined treatment, Nicotine reduced the motor function decline observed in MDMA treatment, thus no significant change in motor function for the combined treatment versus the control. Nicotine or MDMA treatment reduced memory function and altered hippocampal structure. Similarly, a combined Nicotine-MDMA treatment reduced memory function when compared with the control. Ultimately, the metabolic and structural changes in these neural systems were seen to vary for the various forms of treatment. It is noteworthy to mention that a combined treatment increased the rate of lipid peroxidation in brain tissue. PMID:26088184

  5. Xylitol affects the intestinal microbiota and metabolism of daidzein in adult male mice.

    PubMed

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-12-10

    This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health.

  6. Caloric restriction reveals a metabolomic and lipidomic signature in liver of male mice.

    PubMed

    Jové, Mariona; Naudí, Alba; Ramírez-Núñez, Omar; Portero-Otín, Manuel; Selman, Colin; Withers, Dominic J; Pamplona, Reinald

    2014-10-01

    Lipid composition, particularly membrane unsaturation, has been proposed as being a lifespan determinant, but it is currently unknown whether caloric restriction (CR), an accepted life-extending intervention, affects cellular lipid profiles. In this study, we employ a liquid chromatography quadrupole time-of-flight-based methodology to demonstrate that CR in the liver of male C57BL/6 mice: (i) induces marked changes in the cellular lipidome, (ii) specifically reduces levels of a phospholipid peroxidation product, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphatidylcholin