Reproductive toxicity after levetiracetam administration in male rats: Evidence for role of hormonal status and oxidative stress

Abstract

Levetiracetam (LEV) is an antiepileptic drug commonly used in the treatment of epilepsy because of its excellent safety profile in all age groups. It is remarkable that there are no studies evaluating the toxic effects of this drug on the male reproductive system, as it is commonly used in male patients of reproductive age. From this point of view, our aim was to evaluate the possible toxic effects of LEV on the male reproductive system. Therefore, LEV was administered to male rats orally at 50, 150, and 300 mg/kg for 70 consecutive days. At the end of this period, alterations to body and organ weights were calculated, and 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 the testes was carried out. Serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured by ELISAs to determine the effects of hormonal status, while glutathione, superoxide dismutase, catalase, and malondialdehyde levels in the testes were measured by colorimetric assay kits to determine the role of oxidative status in potential toxicity. According to the results, sperm quality was decreased by LEV treatment in a dose-dependent manner. LEV induced significant DNA damage in the 150 and 300 mg/kg LEV-administered groups. Histopathology of the testes showed that LEV resulted in testicular injury in the 300 mg/kg LEV-administered group. Serum testosterone, FSH, and LH levels were significantly decreased in the 300 mg/kg LEV-administered group. Glutathione, superoxide dismutase, and catalase levels were significantly decreased in all experimental groups while malondialdehyde levels were significantly increased in 150 and 300 mg/kg LEV-administered groups. According to these results, it was determined that LEV administration decreased sperm quality and it was alleged that hormonal alteration and oxidative stress are potential contributors to reproductive toxicity.

Toxic Effects of Trazodone on Male Reproductive System via Disrupting Hypothalamic-Pituitary-Testicular Axis and Inducing Testicular Oxidative Stress

“…The right testis was cleared of blood and other contaminants in PBS and fixed for histological examination. The cauda of the right epididymis was used to evaluate sperm parameters [ 46 – 48 ].…”

“…Data were collected by capturing images with a digital camera (Basler, A78075gc, Germany). For motility analysis, eight fields were captured with the SCA system until 200 motile spermatozoa were analyzed, as recommended by WHO (1999) [ 46 – 48 , 51 ].…”

“…A total of 200 sperms/animal were analyzed. The morphometric parameters of head and tail were determined, and abnormal sperms were detected based on previous criteria [ 46 – 48 , 53 – 57 ]. Sperms with banana-shaped head, amorphous head, bent neck, or two-headed and headless sperms were classified as sperms with head abnormalities, whereas sperms with a bent or broken tail were classified as sperms with tail abnormalities ( Figure 1 ).…”

“…Slides were analyzed using Leica DM1000 fluorescence microscope (Leica Microsystems, Wetzlar, Germany) and Comet Assay IV Windows XP Pro software (Perceptive Instruments, Suffolk, United Kingdom). At least 100 cells were analyzed per sample [ 46 – 48 , 58 ].…”

Effect of valproate versus levetiracetam monotherapy on reproductive functions in newly diagnosed epileptic males

“…Moreover, in another animal study, LEV adversely affected sperm parameters by reducing sperm concentration and motility, increasing abnormal sperm morphology and sperm DNA damage, and causing damage in the testicular structure of male rats. It is suggested that the mechanism of LEV toxicity in the male reproductive system arises from the promotion of oxidative stress and alterations in hormonal status [24]. Surges and colleagues, 2008 [6], reported that one of the LEV mechanism as antiepileptic drug is its effect on GABA-ergic system as it was associated with GABA-A receptor modification.…”