Chemopreventive Effects of Naringin against Valproic Acid-Induced Reproductive Toxicity in Male Wistar Rats

Abstract

Valproic acid (VA) is an anticonvulsant widely used for the treatment of seizures and other neurological disorders but limited by reproductive toxicity. Naringin (NGN), a flavanone glycoside commonly found in fruits and vegetables has been shown to modulate and interact with signaling pathways and molecules resulting in its pharmacological activities, however, reports on its chemopreventive effects against VA-induced reproductive toxicity in male Wistar rats is limited. This study investigated the modulatory potential of NGN against reproductive toxicity induced by VA in male Wistar rats. Animals were grouped into six (n= 6) treatments to receive oral administration of; normal saline (1 mL/kg), VA (500 mg/kg), NGN (10 mg/kg), VA (500 mg/kg) + (Sildenafil (SDF), 100 mg/kg), VA (500 mg/kg) + NGN (10 mg/kg), and VA (500 mg/kg) + NGN (20 mg/kg) respectively for 28 days. Reproductive hormones, semen parameters, biochemical indices, testis and epididymis histology were assessed. Also, immunohistochemical evaluation of inducible nitric oxide (iNOS) levels in the testis was investigated. VA significantly decreased testis weight (32.9%), serum testosterone (80.2%), follicle stimulating hormone (47.7%), sperm count (75.5%) and motility (80.2%) and elevated cyclooxygenase-2 and malondialdehyde levels in the testes when compared with the control. Histology showed vascular congestion. Immunohistochemical evaluation of iNOS showed positive reaction in the testes of VA treated rats. However, NGN administrations reversed VA induced toxicity in the treated rats. Antioxidant levels increased in the testes and the epididymis of NGN treated rats. Further, NGN prevented structural abnormalities in the VA treated rats. Overall, these results provide evidence of a chemopreventive potential of NGN that may serve an adjuvant purpose for clinical uses.