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Angiotensin-converting enzyme inhibition and angiotensin AT(1)-receptor antagonism equally improve doxorubicin-induced cardiotoxicity and nephrotoxicity.
Pharmacol Res. 2009 Nov; 60(5):373-81.PR

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology, Minia University, Egypt. maim69@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19467331

Citation

Ibrahim, Mohamed A., et al. "Angiotensin-converting Enzyme Inhibition and Angiotensin AT(1)-receptor Antagonism Equally Improve Doxorubicin-induced Cardiotoxicity and Nephrotoxicity." Pharmacological Research, vol. 60, no. 5, 2009, pp. 373-81.
Ibrahim MA, Ashour OM, Ibrahim YF, et al. Angiotensin-converting enzyme inhibition and angiotensin AT(1)-receptor antagonism equally improve doxorubicin-induced cardiotoxicity and nephrotoxicity. Pharmacol Res. 2009;60(5):373-81.
Ibrahim, M. A., Ashour, O. M., Ibrahim, Y. F., El-Bitar, H. I., Gomaa, W., & Abdel-Rahim, S. R. (2009). Angiotensin-converting enzyme inhibition and angiotensin AT(1)-receptor antagonism equally improve doxorubicin-induced cardiotoxicity and nephrotoxicity. Pharmacological Research, 60(5), 373-81. https://doi.org/10.1016/j.phrs.2009.05.007
Ibrahim MA, et al. Angiotensin-converting Enzyme Inhibition and Angiotensin AT(1)-receptor Antagonism Equally Improve Doxorubicin-induced Cardiotoxicity and Nephrotoxicity. Pharmacol Res. 2009;60(5):373-81. PubMed PMID: 19467331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin-converting enzyme inhibition and angiotensin AT(1)-receptor antagonism equally improve doxorubicin-induced cardiotoxicity and nephrotoxicity. AU - Ibrahim,Mohamed A, AU - Ashour,Osama M, AU - Ibrahim,Yasmin F, AU - El-Bitar,Hussian I, AU - Gomaa,Wafaey, AU - Abdel-Rahim,Salama R, Y1 - 2009/05/23/ PY - 2009/01/17/received PY - 2009/04/28/revised PY - 2009/05/18/accepted PY - 2009/5/27/entrez PY - 2009/5/27/pubmed PY - 2009/11/18/medline SP - 373 EP - 81 JF - Pharmacological research JO - Pharmacol Res VL - 60 IS - 5 N2 - 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. SN - 1096-1186 UR - https://www.unboundmedicine.com/medline/citation/19467331/Angiotensin_converting_enzyme_inhibition_and_angiotensin_AT_1__receptor_antagonism_equally_improve_doxorubicin_induced_cardiotoxicity_and_nephrotoxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-6618(09)00149-2 DB - PRIME DP - Unbound Medicine ER -