Long-term exposure to cimetidine induced gonado-toxicity in male rats: Modulating role of Ocimum gratissimum.

BACKGROUND: Available evidence suggests that cimetidine is a reproductive toxicant that induces sexual and testicular dysfunction. Ocimum gratissimum (OG) is globally consumed for medicinal and nutritional purposes. To determine the modulating role of aqueous leaf extract of Ocimum gratissimum on cimetidine-induced gonado-toxicity, sexually mature male rats were randomized into four groups of six (n=6) rats each. Group A: control given 2ml distilled water. Group B received 500mg/kg body weight (bwt) of OG extract, Group C received 50mg/kg bwt cimetidine, and group D received 50mg/kg bwt of cimetidine+500mg/kg bwt OG extract once daily for 8 weeks via gastric gavage. Parameters tested include sperm parameters, testosterone (TT), luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin, testicular alkaline phosphatase (ALP), acid phosphatase (ACP), lactate dehydrogenase (LDH), protein, cholesterol, glycogen, sexual behavioural parameters, and testicular histology. RESULTS: There were depletions in the seminiferous epithelium, decreased sperm quality, TT, LH, and FSH, testicular enzymes, protein, cholesterol, glycogen, and sexual behaviour increase in animals treated with cimetidine only compared to control. OG restored and improved sexual behaviour and libido as evident from increased frequencies of mount, intromission, ejaculation, and ejaculatory latency. Mount latencies, intromission, post-ejaculation, and prolactin were significantly decreased. The significantly decreased testicular activities of ALP, ACP, LDH and protein, cholesterol, glycogen concentrations, TT, LH and FSH were increased by OG administration. CONCLUSION: Ocimum gratissimum attenuated the deleterious effects of cimetidine on the testis, protected the seminiferous epithelium, restored, and boosted sexual competence, and promoted spermatogenesis.

Vitamin B12 ameliorate Tramadol-induced oxidative stress, endocrine imbalance, apoptosis and NO/iNOS/NF-κB expression in Sprague Dawley rats through regulatory mechanism in the pituitary-gonadal axis.

This study aimed at the effect of vitamin B12 (VB12) on tramadol (TRM) induced pituitary-gonadal Axis toxicity. Thirty-two (32) adult male rats were randomized into four groups of eight (n = 8) rats each. Group A served as control was given 1 mL normal saline, group B received 50 mg /kg bwt TRM, group C received 0.5 mg/kg bwt VB12 and group D received 50 mg /kg bwt TRM and 0.5 mg/kg bwt VB12 through gastric gavage daily for 8 weeks. Parameters tested include sperm parameter, male reproductive hormone, testicular histology, glucose, lactate dehydrogenase (LDH), acid phosphate (ACP), and alkaline phosphate (ALP) activity, steroidogenic protein, cytochrome P450 A1, nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor- kappa B (NF-κB), oxidative and antioxidant makers. Tramadol significantly decreases sperm quality, hormone, steroidogenic protein, cytochrome P450 A1, ACP, ALP, and increases glucose, LDH, oxidative stress, mtTFA, and UCP2, p53 expression, NO, iNOS, NF-κB, IL-1ß, IL-6, TNF-α, and caspase-3 activity. Degenerative alterations of the testes' and pituitary architecture and perturbation of spermatogenesis were observed in TRM-treated rats. The intervention of VB12 downregulated testicular oxidative stress, inflammatory markers, glucose, lactate, LDH, p53, caspase-3, mtTFA, and UCP2. And upregulate antioxidant, sperm quality, hormone, and spermatogenic cells. Vitamin B12 exhibited mitigation against TRM-induced testicular dysfunction via its antioxidant, anti-inflammatory and anti-apoptotic effects.

Fluoride-induced testicular degeneration and sperm quality deteriorations: Salutary role of Cyperus esculentus tubers (tiger nut) extract in animal model.

OBJECTIVE: Chronic exposure to fluoride causes tissue damage induced by oxidative imbalance, Cyperus esculentus (CE) possess anti-inflammatory and immunostimulatory properties. This study focused on Salutary role of Cyperus esculentus in sodium fluoride (NaF) induced testicular degeneration and sperm quality deteriorations. METHODS: Sexually mature male Sprague-Dawley rats were randomly divided into four groups (n=6). Animals in control group received 2 mls of normal saline per day; CE group received 500mg/kg bw of CE; NaF group received 5mg/kg bw of NaF; NaF+CE group received 500mg/kg bw of CE (for 14 days pre-treatment) and NaF co-treatment till 56 days via gastric gavage. Parameters tested include: testicular histology, sperm parameters, sex hormone, fertility test, malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione, glutathione peroxidase (GPX), catalase (CAT), testicular fluoride and testicular cholesterol. RESULTS: Sodium fluoride significantly (p<.05) decrease testicular antioxidant (SOD, CAT, GSH and GPx), sperm quality, hormone profiles (TT, FSH, LH, estrogen levels), testicular cholesterol, morphometric parameters, Johnsen's Score and number of implantations in female rats with corresponding (p<.05) increase in oxidative stress makers and abnormal sperm morphology. Also depleted seminiferous epithelium and degenerate spermatogenic cells. Pretreatment with 500mg/kg bw of CE lowered NaF toxicity by significantly reducing the lipid peroxidation products, fluoride accumulation in the testis, histopathological changes of the testes and spermatozoa abnormalities and reverted observed NaF-induced inhibition in antioxidant parameters and weight of accessory sex organs. CONCLUSIONS: Cyperus esculentus attenuated NaF-induced testicular injuries and protected the seminiferous epithelium, reduced oxidative stress and promoted spermatogenesis.

Lamivudine-Induced Liver Injury.

BACKGROUND: Lamivudine is a nucleoside analogue antiretroviral drug, known for its low toxicity at clinically prescribed dose. However, the toxicity or mechanism of toxicity and target tissue effects during prolonged administration of higher doses were hardly given sufficient laboratory attention. AIM: The present work was designed to investigate the biochemical and histopathological changes in the liver of rat administered with prolonged doses of lamivudine. MATERIAL AND METHODS: Lamivudine in multiple doses of five ranging from 4 mg/kg to 2500 mg/kg were administered, in vitro, by injection into the air-sac of 10-day old fertile embryonated eggs of Gallus domesticus. Also, female rats of the Wistar strain received oral doses, up to 500 mg/kg singly or repeatedly for 15 or 45 days, respectively. Spectrophotometric techniques were employed to monitor activities of the aminotransferases (ALT and AST), γ-glutamyltransferase (GGT) and total protein concentration in serum while activities of glutathione S-transferase (GST), GGT and superoxide dismutase (SOD) as well as concentrations of malondialdehyde (MDA) and protein were determined in liver. Histopathological studies were carried out on liver. Data were analysed using ANOVA and were considered significant when p < 0.05. RESULTS: The LD50 for the drug calculated from the incubation experiment was 427 mg/kg. Total serum protein concentration significantly reduced while enzymes activities significantly increased at 500 mg/kg only among the repeat-dosed rats. Hepatic GGT, GST and SOD activities as well as MDA concentration were significantly elevated at 20 mg/kg. Histopathological studies showed multifocal lymphoid cell population in the liver sinusoid of the chicken and hydropic degeneration of hepatocytes were recorded among rats repeatedly exposed to the drug respectively at doses ≥ 100 mg/kg. CONCLUSION: Lamivudine toxicity in rat liver appeared to be mediated by oxidative stress.