Cardio-nephrotoxicity mediated by Echis ocellatus venom and its amelioration through kaempferol’s suppressive effect on oxidative stress, inflammation, and apoptosis expression

Abstract

Abstract Background Echis ocellatus venom toxins have the ability to impact multiple organ systems subsequent to envenomation. Kaempferol have been reported to have several therapeutic benefits. In this study, the therapeutic value of kaempferol was investigated in relation to the cardio-nephrotoxicity in rats resulting from E. ocellatus envenoming. Methods Fifty male wistar rats were allotted unbiased into five groups ( n = 10) for this study. Group 1 was the control, while rats in groups 2 to 5 were envenomed with LD 50 of E. ocellatus venom (0.22 mg/kg bw; i.p.). Group 2 was not treated after envenomation while groups 3, 4 and 5 were treated with polyvalent antivenom, 4 and 8 mg/kg of kaempferol, respectively. Results E. ocellatus envenomation caused considerable reduction in organ weight and relative organ weight in the envenomed untreated rats. The venom induced intense oxidative stress, inflammation, apoptotic damage to the cardiac and renal tissues accompanied with severe histomorphology in the organ tissues of untreated envenomed rats. In contrast, kaempferol treatment post-envenomation attenuated the venom-induced cardio-nephrotoxic responses in a dose dependent effect. Kaempferol substantially ( p < 0.05) decreased malondialdehyde levels while enhancing reduced glutathione levels and superoxide dismutase and glutathione peroxidase activities in the heart and kidney of envenomed treated rats. Treatment of envenomed rats with kaempferol successfully decreased nitric oxide levels and myeloperoxidase activity. Overexpression of apoptotic caspase 3 and caspase 9 in cardiac and renal tissues were suppressed by kaempferol ( p < 0.05). The histopathological result supports kaempferol’s ameliorative ability by convalescing the severe morphological alterations of cardiac and renal tissues induced by the venom. Conclusion Findings elucidate the significance of kaempferol as promising agent in the management of cardio-nephrotoxicity resulting from snakebite envenoming.