Methyl jasmonate and diphenyl diselenide attenuate diethylnitrosamine and carbon tetrachloride-induced nephrotoxicity in rats via modulation of inflammation and oxidative stress processes

The pathogenesis of toxicity-mediated renal injury has been linked to reactive oxygen species. Therefore, intervention with antioxidant agents as part of therapeutic strategies is necessary. This study investigated the modulatory effects of Diphenyldiselenide (PhSe)2 and Methyl Jasmonate (MJ) against Diethylnitrosamine (DEN) and Carbon tetrachloride (CCL4)-induced nephrotoxicity in male Wistar rats. Forty-eight (48) rats were assigned into six groups of eight animals each. Group 1 served as control, Group 2 received DEN (100mg/kg) + CCL4 (0.5mg/kg), Group 3 received [DEN+CCL4] and treated with MJ (50 mg/kg), Groups 4 and 5 received [DEN+CCL4] and treated with (PhSe)2 (5 mg/kg and 10 mg/kg), and Group 6 received [DEN+CCL4] and treated with quercetin (50mg/kg). Administration of DEN and CCL4 increased serum urea, creatinine and kidney injury molecule-1 (KIM-1) by 97%, 62% and 73%. Furthermore, activities of glutathione-S-transferase, superoxide dismutase and catalase significantly (P<0.05) decreased in [DEN+CCL4] rats. The BCL-2 associated X, caspases -3 and -9 increased in rats administered-[DEN+CCL4]. In addition, TNF-α increased by 117%, myeloperoxidase and nitric oxide level increased by 385% and 65%, respectively in [DEN+CCL4]-administered rats. Histology showed mild vascular congestion and infiltration of inflammatory cells in interstitial spaces in [DEN+CCL4] rats. Interestingly, treatment with methyl jasmonate and diphenyl diselenide attenuated kidney function markers, reduced tissue inflammation and apoptosis status of [DEN+CCL4]-rats. Methyl jasmonate and diphenyldiselenide abate nephrotoxicity caused by combined administration of DEN- and CCL4- via induction of antioxidative and anti-inflammatory activities.