Morin attenuates dutasteride/tamsulosin-induced hepatic oxidative stress in rat

Abstract

Dutasteride-Tamsulosin (DUT-TAM) is a combination drug for the treatment of symptoms of prostate enlargement (benign prostatic hyperplasia, BPH). Despite the efficacy, it is associated with some side effects, including hepatotoxicity. Therefore, this study investigated the attenuative effects of morin on DUT-TAMinduced organ toxicity. Twenty four male rats were divided into 4 groups (A-D) consisting of 6 animals each. Group A animals (control) were given olive oil, Group B animals were administered with DUT-TAM (5.4 mg/kg body weight of dutasteride + 3.4 mg/kg body weight of tamsulosin), Group C were given morin (100 mg/kg body weight) while group D animals were administered DUT-TAM and morin (5.4 mg/kg body weight dutasteride + 3.4 mg/kg body weight of Tamsulosin and 100 mg/kg body weight of morin). All the administrations were carried out orally for 14 days. DUT-TAM caused a significant increase in plasma bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) by 62%, 45% and 18% in the DUT-TAM treated group respectively, compared with the control (P˂0.05). However, treatment with morin significantly decreased the DUT-TAM-induced increase in plasma bilirubin concentration as well as AST and ALT activities. Furthermore, DUT-TAM administration decreased the activities of hepatic superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), as well as hepatic concentration of ascorbic acid and reduced glutathione (GSH) by 58%, 54%, 59%, 46% and 63% respectively, but increased malondialdehyde (MDA) level by 49% relative to the control (P˂0.05). However, treatment with morin significantly ameliorated the observed changes in these antioxidant parameters (P˂0.05). These data suggest that morin protects against hepatic toxicity, as well as oxidative stress induced by dutasteride-tamsulosin in rats.

Keywords: Dutasteride, Tamsulosin, Prostate enlargement, Oxidative stress, Liver