Eicosapentaenoic Acid and Vitamin E Against Doxorubicin Induced Cardiac and Renal Damages: Role of Cytochrome c and iNOS.

Background: The current study aimed to evaluate the mechanisms involved in protection against doxorubicin-induced cardiac and renal toxicities upon treatment with eicosapentaenoic acid and vitamin E.

Methods: Rats were randomly assigned to 4 groups: normal control, doxorubicin inducted control, eicosapentaenoic acid treated group and a final group pretreated with vitamin E. Lipid peroxidation, reduced glutathione (GSH) and tumor necrosis factor-alpha (TNF-α) contents as well as glutathione peroxidase (GPx), superoxide dismutase (SOD) and myeloperoxidase (MPO) activities were assessed. Moreover, hearts were used for immunohistochemical detection of the pro-apoptotic protein cytochrome c expression, while the kidneys were used for detection of inducible nitric oxide synthase (iNOS) expression.

Results: Eicosapentaenoic acid and vitamin E produced significant protection from doxorubicin-induced cardiac and renal toxicities. The suggested mechanisms for protection included decreased cytochrome c and iNOS expression as well as markedly decreased lipid peroxides and TNF-α contents accompanied with increased GSH content as compared to the doxorubicin control group. Moreover, there was marked increase in GPx and SOD activities accompanied by significant suppression of MPO activity.

Conclusion: The present study demonstrated the potent protective effects of eicosapentaenoic acid and vitamin E from doxorubicin induced cardiac and renal toxicities through their potent anti-oxidant, anti-inflammatory and anti-apoptotic properties. Hence, eicosapentaenoic acid and vitamin E could be promising protective agents against doxorubicintoxicity.