Attenuation the Side Effects of Adriamycin- induced Cardiotoxicity and Nephrotoxicity in Rats by Fermented Punica granatum (Pomegranate) Peel Extract

Abstract

Most pomegranate (Punica granatum Linn., Punicaceae) fruit parts are known to possess enormous antioxidant activity. The present study used Kluyveromyces marxianus NRRL Y-8281, as yeast candidate to enhance the anti-oxidant activities of pomegranate peel by modulating polyphenolic substances during solid state fermentation, in an attempt to examine the protective effects of either methanolic extract of unfermented (UFPP) or fermented (FPP) pomegranate peels on adriamycin-induced myocardial and renal toxicities in rats. Both extracts were found to contain a large amount of polyphenols and exhibit enormous antioxidant activity. UFPP and FPP extracts showed 92% and 93% antioxidant activity in DPPH model system respectively, while the phenolic content recorded 160 and 211 mg gallic acid/ g dry peel for UFPP and FPP respectively at concentration of 125 µg /ml. Administration of adriamycin (10 mg/Kg body weight /day, i.p. for 3 days) caused significant rise in the levels of diagnostic markers [serum creatine kinase (CK) for heart and blood urea nitrogen (BUN) for kidney] as well as lipid peroxidation and total antioxidant status in the heart and kidney tissues. Concomitant decline in the level of tissues reduced glutathione and the activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) were observed. Administration of either UFPP or FPP extracts at 1/10 of lethal dose, two doses before and two doses after ADR, significantly prevented all the adriamycin adverse effects, through diminution the activity of CK and the level of BUN as well as the level of cardiac and renal lipid peroxidation comparing with ADR group. At the same time, the levels of glutathione, total antioxidant and the activities of antioxidant enzymes were increased. The most significant effects were obtained with FPP extract which could thus relate to their high total phenolic content. In conclusion, the protective effect of pomegranate might be ascribable to its membrane stabilizing property and/or antioxidant nature which might serve as novel combination chemotherapeutic agent with ADR to limit free radical-mediated organ injury.