Evalution of reproductive toxicity of levetiracetam in male rats

Today, drug-induced reproductive toxic effects including infertility has emerged as a major health problem. For this reason, determining the toxic effects of drugs on male and female reproductive system and evaluating the reflection of these effects on infertility are accepted as important research fields. Levetiracetam (LEV) is a drug commonly used in epilepsy treatment because of its safe profile in all age groups. It is remarkable that there are no studies evaluating the toxic effects of this drug, which is commonly used during reproductive ages, on male reproductive system. From this point of view, our aim was to evaluate the possible toxic effects of LEV on male reproductive system in this study. For this purpose, LEV was administered to 12 weeks old male rats orally in 50, 150 and 300 mg/kg for 70 consecutive days. At the end of this period, alterations of body and organ weights were calculated, sperm concentration, motility and morphology were investigated by a computer assisted sperm analysis system, sperm DNA damage was determined by Comet assay and histopathological examination of testis tissue was carried out. Plasma testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured by ELISAs to determine the effects of hormonal status and Glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels in testes tissue were measured by colorimetric assays to determine the role of oxidative status on the potential toxicity. According to the results, sperm parameters were shown to be decreased with LEV treatment in a dose-dependent manner. LEV induced significant DNA damage in 150 and 300 mg/kg LEV-administered groups. Histopathology of the testis showed that LEV especially resulted in testicular injury in 300 mg/kg LEV-administered group. Plasma testosterone, FSH, and LH levels were significantly decreased in 300 mg/kg LEV-administered group when compared with controls. SOD, CAT ve GSH levels were significantly decreased in all experimental groups while MDA levels were significantly increased in 150 and 300 mg/kg LEV-administered groups when compared with controls. According to these results, it was determined that LEV administration decreased sperm quality and it was alleged that hormonal alteration and oxidative stress in testis tissue are the potential contributors of reproductive toxic effects. Keywords: Levetiracetam, reproductive toxicity, oxidative stress, Comet assay