Rat liver and kidney post-mitochondrial dysfunction by addition of chronic mixed metal intoxication and hepatorenal wellness mediated by phenolic components from Croton zambiscus leaves

Abstract

Chronic exposure of mixed-metal intoxication has been associated with prolonged oxidative stress and severe hepatorenal damage. This present study demonstrates the hepatoprotective and renoprotective activity of Croton zambesicus (C-ZAMB) leaves, naturally occurring phenolic compounds against chronic mixed-metal (EOMABRSL) induced toxicity. 0.5 ml of EOMABRSL via oral route induced chronic hepatoxicity and nephrotoxicity on exposure for 98 days (non-withdrawal) and 70 days (withdrawal) by abnormal alteration in the levels of endogenous antioxidants. Moreover, EOMABRSL induced hepatorenal damage by increasing the markers of liver toxicity (ALT, AST, ALP, GGT and bilirubin) and kidney failure (creatinine, urea, uric acid, and renal electrolytes-Na⁺ and K⁺). Both non-withdrawal and withdrawal approaches of EOMABRSL-exposed animals exhibited hepatorenal dysfunctions by increasing the activity of eco-5¹-nucleotidase (5¹ENT) followed by the decreased in the activity of lactate dehydrogenase (LDH)-index of cellular ATP. These results were further supported by the histopathological examination of nephritic cells, hepatocytes and splenocytes, manifested by hepatocellular necrosis, swelling or degeneration of tubular kidney epithelial cells as well as coalescing splenic periarteriolar lymphoid sheaths (PALSs) and lymphoid haemosiderin. The chronic EOMABRSL intoxication was ameliorated by administration of phenolic antioxidants from C-ZAMB leaves. Therefore, our study supports the view that phenolic C-ZAMB leaves may mediate hepatorenal wellness on chronic exposure to mixed-metal intoxication.

Keywords: Croton; Damage; Fraction; Hepatorenal; Mixed-metal intoxication; Phenolic antioxidant; zambesicus.