EVALUATION OF PROTECTIVE POTENTIAL OF CITRUS AURANTIFOLIA (CHRISTM) SWINGLE PEEL EXTRACT IN ATTENUATING DOXORUBICIN-INDUCED HEPATOTOXICITY IN EXPERIMENTAL MODELS

Abstract

Citrus aurantifolia is a very common, and widely cultivated and consumed for its antioxidant properties due to its robust flavonoids content. Doxorubicin (DOX) is an antibiotic broadly used in the treatment of different types of solid tumours, but its use also comes at a cost, organ toxicity. The curative and preventive properties of Citrus aurantifolia  peel extract (CAPE) in doxorubicininduced hepatotoxicity in Wistar rats were evaluated. Thirty female rats were divided into six groups of five (5) rats each in both curative and preventive studies. In curative study, five groups of rats (II – VI) received Doxorubicin (mixed with normal saline, 15 mg/kg body weight i.p) on day one, 24 hours after, graded doses of CAPE and alpha-lipoic acid (A.L.A.) were administered to groups II- V and VI respectively for 7 consecutive days. For the prophylactic study, groups II – V and VI received graded doses of CAPE and A.L.A. respectively, 24 hours after Doxorubicin was administered to groups II-VI. Groups treated with D.W. and A.L.A. were used as a negative and positive control, respectively Liver enzymes such as A.S.T., A.L.T. and A.L.P., including liver samples, were examined for histopathological changes. A significant reduction (p< 0.05) in serum A.S.T. and A.L.T. levels was observed in animals treated with CAPE 200 and 400mg/kg in the preventive study, while in curative, a significant reduction in an expected rise in serum A.S.T., A.L.T. and A.L.P. (p<0.05) was observed in animals treated with CAPE 400mg/kg when compared to the group treated with DOX + distilled water. Hepatocellular necrosis was observed in the histology of DOX- distilled water treated group. Besides, the hepatocytes of groups treated with CAPE (200 and 400mg/kg) in this study showed narrow foci of mild vacuolar change as compared with groups treated with the lowest dose of CAPE (100mg.kg) and distilled water, which revealed random foci of mild vacuolar change. This study has provided information that DOX damaged liver tissue due to an increase in liver enzymes and histopathological results showing tissue damaged in groups treated with lower doses of CAPE and distilled water.  This study further demonstrates that groups treated with CAPE 200, 400 mg/kg and A.L.A. protect hepatic damage induced by DOX.