Hepatoprotective activity of ethanol root extract and fractions of Hippocratea africana against doxorubicin-induced liver toxicity

Abstract

Doxorubicin (DOX) is an anthracycline glycoside antibiotic with high efficacy against various forms of cancer, whose clinical usefulness has been limited by associated undesirable organs toxicities such as cardiomyopathy, nephrotoxicity and hepatotoxicity despite its high therapeutic index. Hippocratea africana root used locally in the treatment of poisoning was evaluated for antidotal potentials against DOX-induced liver toxicity in rats. Hippocratea africana ethanol root extract as well as  dichloromethane and aqueous fractions were evaluated for hepatoprotective activity against doxorubicin-induced liver injury in rats at various doses of the crude extract (200-600 mg/kg)  and 400 mg/kg each of dichloromethane (DCM) and aqueous fractions respectively. Liver function parameters, liver oxidative stress markers and liver histology were used to assess the liver protective potential of the extract and fractions. The root extract and fractions significantly (p<0.05-0.01) reduced the serum levels of AST, ALT, ALP, total and direct bilirubin that were elevated by doxorubincin. Also, the levels of total protein and albumin reduced by doxorubicin were increased by the extract coadministration. The levels of GSH, GST, SOD, GPx, and CAT that were decreased by doxorubicin were significantly (p<0.01) elevated and raised MDA level was reduced by the leaf extract. Histology of the liver sections of extract -treated animals showed reductions in the pathological features compared to the DOX-treated animals. The observed histopathological changes were consistent with chemical pathological observations suggesting marked hepatoprotective potential.  The anti-toxic effect of this plant may in part be mediated through the chemical constituents of the plant.  The plant, Hippocratea africana possesses anti-toxicant properties which can be exploited in the treatment of doxorubicin related toxicities.