Effects of vigabatrin, carbamazepine or its combination on the pituitarygonadal axis in male Wistar rats

Abstract

Objectives: Epilepsy is the most common non-infectious neurologic disease in developing African countries following stroke and Alzheimer's disease. Most conventional antiepileptic drugs, due to their centrally acting potentials have been implicated in the deregulation of reproductive hormones. This study assessed the effect of the single and combined administration of vigabatrin (VIG) and carbamazepine (CBZ) on the pituitary-gonadal axis of male Wistar rats.Methods: Fifty male Wistar rats were randomly divided into 5 groups (n=10). The animals were administered with distilled water (0.1 ml/kg/day), VIG (200 mg/kg/day), CBZ (200 mg/kg/day), VIG-CBZ combination (100 mg/kg/day each) and VIG-CBZ combination (200 mg/kg/day each) for 8 weeks. Twenty-four hours after the last dose, 5 rats from each group were sacrificed, while the remaining 5 eventually sacrificed after another 8 week of drug withdrawal. The level of luteinizing hormone, follicle stimulating hormone and testosterone were determined from the serum. The weight of the reproductive organs and sperm indices were assayed, while the testicular tissue were examined for signs of histological alteration. Results:The results showed significant decrease in the levels of luteinizing hormone, follicle stimulating hormone, testosterone and sperm physiological indices. Morphological alteration was noticed in the testes of all the treated rats. However, there was restoration of these parameters sequelae to 8 weeks cessation of treatment. Conclusion:Single and combined administration of VIG and CBZ resulted into pituitary-gonadal axis hormonal deregulation and alterations in the sperm profile which were however reversible upon cessation of treatment.

Hypothalamic–pituitary–testicular axis derangement following chronic phenytoin–levetiracetam adjunctive treatment in male Wistar rats

“…This finding is in contrast to the report of Akinsomisoye et al. (2017), that carbamazepine–vigabatrin adjunctive treatment had no significant effect on the testicular weight of Wistar rats. The variation in this study relative to Akinsomisoye and co‐worker's report may be dependent on the mechanism of action of the AEDs (carbamazepine–vigabatrin adjunctive treatment).…”

“…Sperm viability study was done according to the method of Akinsomisoye et al. (2017). Briefly uniform spermatozoa smear was done on slides with eosin/nigrosin stain.…”

Toxicity and postwithdrawal effects of ketamine on the reproductive function of male albino rats: Hormonal, histological, and immunohistochemical study

“…It is well known that sperm count is the cumulative result of all phases of spermatogenesis and is one of the most sensitive tests for evaluating the infertility status of animals. 51 In addition, normal sperm motility plays a vital role in sperm fertilizing capability. 52 Ketamine-induced apoptosis, hormonal changes, and increased lipid peroxidation collectively adversely affected the process of spermatogenesis.…”

Carbamazepine adversely altered the pituitary–testicular axis with resultant reproductive dysfunctions than levetiracetam or carbamazepine–levetiracetam adjuvant treatment in male Wistar rat

“…Several studies have revealed the involvement of many antiepileptic drugs in the induction of nervous and endocrine derangements (Falokun et al., 2010; Lee, 2014; Olaibi et al., 2014), with consequential effects on reproductive function (Akinsomisoye et al., 2017; Wisniewski et al., 2015). Additionally, carbamazepine has been reportedly implicated as liver enzyme‐inducing drugs, thereby increasing serum sex hormone‐binding globulin (Verrotti et al., 2011), and thus diminished bioactivity of testosterone (Keerthy et al., 2016).…”

“…However, prolonged AED administration is reportedly associated with a diverse adverse effect such as behavioural/psychiatric disorders (Lee, 2019), metabolic disruption (St Louis, 2009), hepatotoxicity (Ayalew & Muche, 2018), and alterations in bone turnover markers (Arora et al., 2016) to mention but a few. Moreover, sexual dysfunction and reproductive disorders are more common among patients with epilepsy than any typical population (Atif et al., 2016; Isojärvi, 2008; Luef, 2010; Wu et al., 2018), while there are consistent pieces of evidence on the adverse effect of some AEDs particularly on the testicular dysfunction (Akinsomisoye et al., 2017; Osuntokun et al., 2017), deregulation of sex hormones (Herzog et al., 2017), reproductive toxicity (Bairy et al., 2010; Karaduman et al., 2019), and reduction of seminal quality (Falokun et al., 2010).…”