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Journal Article 2004; 25(3): 178-183 PubMed PMID: 15349082 Citation  Keywords:  Amines:pharmacology, Analgesics:pharmacology, Animals, Antimanic Agents:pharmacology, Body Weight:drug effects, Cyclohexanecarboxylic Acids:pharmacology, Female, Fertility:drug effects, Follicle Stimulating Hormone:blood, Male, Organ Size:drug effects, Pr.   

PURPOSE: A case control study was conducted to assess the effect of Sabril (Vigabatrin), Lamictal (Lamotrigine) and Neurontin (Gabapentin) on fertility in male rats. Their effect on the body and organs weight and certain biochemical profiles including total serum protein, cholesterol, triglycerides, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum testosterone, and FSH levels were also measured.

METHODS: several parameters, concerning fertility were measured in 40 albino male rats of Sprague Dawley strain, they were divided into 4 groups, group one received vehicle (distilled water), group two received Vigabatrin in a dose of 200 mg/kg body weight, group three received Lamotrigine in a dose of 30 mg/kg body weight, and group four received Gabapentin 100 mg/kg body weight. All the male rats in these groups received the different medications for a complete reproductive cycle (60 days). After 24 hours of the last dose, the animals were weighed and autopsied under light ether anesthesia. Parameter of fertility that has been measured in this study includes: sperm count and motility, weight of different reproductive organs, germ cell and interstitial cell population, serum testosterone and FSH levels and assessment of pregnancies in females mixed with tested males. Biochemical profiles such as serum cholesterol, serum triglycerides, serum bilirubin, SGOT, SGPT level are all measured. The results of the histological, histometerical studies and biochemical profiles were compared to that of the control group, and the significance of these results was measured using student's "t" test.

RESULTS: There was significant reduction in the body weight and the weight of the testes, epididymis, seminal vesicles, ventral prostate, and vas deferens in the antiepileptic fed male rats in comparison to the control group (p > 0.001). There was significant reduction in testicular cells population dynamics including both germinal cell types and interstitial cell types in the antiepileptic fed male rats in comparison to the control group. There was also significant reduction in histometrical parameters and sperm dynamics in the antiepileptic fed male rats histologies in comparison to the control group. There was significant reduction in both testosterone and FSH levels (p < 0.001) in the antiepileptics fed male rats in comparison to the control group. There was also significant reduction in pregnancy rate observed in female rats exposed to the tested male rats among antiepileptic fed male rats compared to controls. The results of biochemical profiles assessment showed significant reduction in serum glucose, serum cholesterol, serum triglycerides levels and significant increase in serum bilirubin, SGOT, and SGPT levels in antiepileptics fed male rats in comparison to the control group.

CONCLUSIONS: Fertility rate and other parameters concerned with fertility, sex hormones and certain biochemical profiles were significantly disturbed in male rats fed with three of the second-generation antiepileptic drugs Vigabatrin, Lamotrigine, and Gabapentin, indicating a possible toxic effect of these three medications on sexual organs, liver, and lipid metabolism....

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Journal Article 2003; 24(3-4): 241-248 PubMed PMID: 14523364 Citation  Keywords:  Adipocytes:drug effects, Adipose Tissue:physiology, Animals, Animals, Newborn:physiology, Blood Glucose:metabolism, Body Weight:drug effects, Cells, Cultured, Corticosterone:blood, Estradiol:blood, Female, Follicle Stimulating Hormone:blood, Glucose:pharm.   

UNLABELLED: It is recognized that there exists a link between hyperandrogenicity and insulin resistance.

OBJECTIVE: By using the neonatally androgenized female rat we explored whether this treatment modifies peripheral insulin sensitivity and visceral fat function at adulthood.

EXPERIMENTAL DESIGNS: On day 5 of age, female Sprague-Dawley pups were injected, sub cutaneous, with either 50 ml of sterile corn oil alone (CT) or containing 1.25 mg of testosterone propionate (TP) and further used for experimentation on day 100 of age. CT and TP rats were killed by decapitation in non-fasting condition and blood samples were kept frozen for measurement of different metabolites. Immediately after sacrifice, freshly dissected visceral fat pads were used for isolation of adipocytes, these cells were then incubated with medium alone or containing different concentrations of insulin in order to determine leptin secreted into the medium. Additionally, in vivo metabolic responses to intravenous high glucose load were performed in, 24 hour-fasting, CT and TP rats.

RESULTS: We found that neonatal androgenization induced adult animals displaying higher visceral adiposity mass, body weight and leptinemia than CT rats. No group differences were found in basal circulating levels of several hormones and metabolic parameters. The results of the high glucose load 90-min test indicated that TP and CT rats developed similar glycemia but this accounted because of an early significantly higher peak values of circulating insulin in TP than in CT rats, regardless of similar enhancement in circulating glucocorticoid concentrations in both groups. While high glucose load significantly increased, over the baseline, circulating leptin concentrations as early as 30 min post-glucose in CT rats, in TP animals, it significantly enhanced leptinemia only by the end of the test. Finally, results of in vitro incubations of isolated visceral adipocytes indicated that cells from androgenized rats spontaneously released more leptin than control cells, although they were less responsive than CT cells to insulin-induced leptin output.

CONCLUSION: Our study strongly supports the hypothesis that development of insulin resistance seems to be dependent on early hyperandrogenicity....

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Journal Article 2001; 22(6): 449-452 PubMed PMID: 11781543 Citation  Keywords:  Animals, Body Weight, Circadian Rhythm:physiology, Leptin:blood, Male, Melatonin:metabolism, Pineal Gland:metabolism, Rats, Rats, Wistar,.   

OBJECTIVES: Exogenous and endogenous melatonin decrease leptin release. It is not known whether melatonin also has an effect on circadian release pattern of leptin. So, this study was planned to investigate the possible changes in the circadian release of leptin following pinealectomy.

METHODS: A group of rats were surgically pinealectomized while some others were exposed to sham operation. The animals were decapitated at 13.30 p.m. and 01.30 a.m. Serum leptin levels were measured by radioimmunoassay.

RESULTS: Serum leptin levels at 13.30 p.m. were lower than the values at 01.30 a.m. in both pinealectomized (P<0.002) and sham rats P<0.001). Serum leptin levels measured at 13.30 p.m. and 01.30 a.m. were significantly elevated (P<0.05 and P<0.01, respectively) in the pinealectomized rats in comparison to sham animals.

CONCLUSION: The circadian release of leptin does not seem to be regulated by melatonin release from the pineal gland whereas melatonin, physiologically released, may have a decreasing effect on leptin release....

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