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Pharmacol Res. 2009 Nov;60(5):373-81. doi: 10.1016/j.phrs.2009.05.007. Epub 2009 May 23.

Angiotensin-converting enzyme inhibition and angiotensin AT(1)-receptor antagonism equally improve doxorubicin-induced cardiotoxicity and nephrotoxicity.

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  • 1Department of Pharmacology, Minia University, Egypt.


Doxorubicin (Dox) is a potent anticancer agent; its clinical use is limited for its marked cardiotoxicity and nephrotoxicity. The present study investigated the possible protective effect of telmisartan, an angiotensin AT(1)-receptor blocker versus captopril, an angiotensin-converting enzyme inhibitor, on Dox-induced cardiotoxicity and nephrotoxicity in rats. Rats were allocated into four groups. Control group, Dox group, Dox+telmisartan group, and Dox+captopril group. Cardiotoxicity and nephrotoxicity were assessed biochemically and histopathologically. Frozen heart and kidney specimens were used for estimation of lipid peroxides product (MDA), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and nitric oxide (NO). Expression of induced nitric oxide synthase (iNOS) was detected by immunohistochemistry. Coadministration of either telmisartan or captopril with Dox equally decreased the biochemical markers of both cardiotoxicity (LDH and CK-MP) and nephrotoxicity (urea and creatinine). Both telmisartan and captopril attenuated the effects of Dox on oxidative stress parameters and NO. Histopathologically, coadministration of either drug with Dox was able to attenuate Dox-induced myocardial fibrosis and renal tubular damage. Immunohistochemistry, expression of iNOS was increased in both cardiac and renal tissues. Both telmisartan and captopril significantly and equally attenuated the effect of Dox on all measured parameters. These results suggested that telmisartan has protective effects equal to that of captopril against Dox-induced cardiotoxicity and nephrotoxicity; implying that angiotensin II pathway plays a role in Dox-induced cardiac and renal damage. The protective effect of either drug relies, at least in part, on their antioxidant effects and decreased the expression of iNOS.

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