Polyphenolic-enriched olive leaf extract attenuated doxorubicin-induced cardiotoxicity in rats via suppression of oxidative stress and inflammation

Abstract

BackgroundThe therapeutic value of doxorubicin as an effective anti-neoplastic agent is limited by its cardiotoxic side effects. We investigated the effects of ethanolic leaf extracts of olive leaf OL on cardiotoxicity as well as oxidative stress which was induced by doxorubicin (DOX) in Wistar rats. The cardiotoxicity was induced by intraperitoneally injecting a single dose of doxorubicin (10 mg kg−1) after 7 days of OL administration. OL was given by gastric gavage in 250 mg/kg, 500 mg/kg and 1000 mg/kg doses of extract for 10 days.ResultsCardiac toxicity of DOX was evidenced by histopathological changes in cardiac tissues and an increase in the activities of serum markers of heart damage (AST and CK). DOX caused oxidative stress as evidenced by the elevation of malondialdehyde, protein carbonyl content levels, and catalase activity. That stress was also accompanied by a concurrent depletion of the activity of superoxide dismutase within cardiac tissues. The cardiotoxicity and oxidative stress damages caused by DOX also coincided with an increase of myeloperoxidase activity and iNOS expression. Most of these doxorubicin-induced biochemical and histological alterations were effectively attenuated by prior administration of OL. OL combination with DOX significantly increased its cytotoxicity in HepG2 liver cancer cell line and IC50 dropped from 259.35 to 158.12 μg/ml.ConclusionOL potentiated the cytotoxicity of DOX in liver cancer cell line and may play a role in the protection against its cardiotoxicity and thus can be a useful adjuvant therapy where doxorubicin is the common liver cancer-treating drug.