The effect of Vigabatrin, Lamotrigine and Gabapentin on the fertility, weights, sex hormones and biochemical profiles of male rats.
OBJECTIVE
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.
Daoud
A S
AS
Department of Neuroscience, College of Medicine, Jordan University of Science and Technology, Irbid, Jordan. daoud@just.edu.jo
Bataineh
H
H
Otoom
S
S
Abdul-Zahra
E
E
D000588:Amines / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D005260:Female; D005298:Fertility / Q000187:drug effects / Q000502:physiology*; D005640:Follicle Stimulating Hormone / Q000097:blood*; D000077206:Gabapentin; D000077213:Lamotrigine; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood*; D014227:Triazines / Q000494:pharmacology*; D020888:Vigabatrin / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000588:Amines; D000700:Analgesics; D018692:Antimanic Agents; D003509:Cyclohexanecarboxylic Acids; D014227:Triazines; D013739:Testosterone; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D005640:Follicle Stimulating Hormone; D020888:Vigabatrin; D000077213:Lamotrigine