Angiotensin-converting enzyme inhibition and novel cardiovascular risk biomarkers (original) (raw)
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Pharmacological Research, 2009
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.
Protective effects of telmisartan against acute doxorubicin-induced cardiotoxicity in rats
Pharmacological reports : PR
The therapeutic usefulness of doxorubicin (DXR), an anthracycline antibiotic, is limited by its cardiotoxicity. The present study investigated the effects of telmisartan, an angiotensin II receptor (AT1) antagonist against doxorubicin-induced cardiotoxicity in rats using biochemical and histopathological approaches. Doxorubicin (20 mg/kg) was injected intraperitoneally (ip) as a single dose and telmisartan (10 mg/kg) was administered orally for 7 days. Rats treated with DXR showed cardiotoxicity as evidenced by elevation of serum lactate dehydrogenase (LDH) activity, tissue malondialdehyde (MDA) level, catalase activity and a decrease in the level of glutathione (GSH). Pre- and post-treatment with telmisartan elicited a significant decrease in the activities of LDH and catalase in comparison with DXR-treated group. Furthermore, pretreatment with telmisartan also decreased lipid peroxidation (MDA level) and increased the GSH content in comparison with DXR group. However, the differen...
2005
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.
Effect of telmisartan in limiting the cardiotoxic effect of daunorubicin in rats
Journal of Pharmacy and Pharmacology, 2010
Objectives Studies have suggested that angiotensin receptor blockers may exert a protective role towards doxorubicin-induced cardiotoxicity, but they have not been extensively investigated in this area. We therefore investigated whether the co-treatment of telmisartan, an angiotensin (Ang II) type-1 receptor blocker, might offer protection against daunorubicin cardiotoxic properties in rats. Methods Daunorubicin was administered at 3 mg/kg/day every other day for 12 days. Telmisartan was administered orally every day for 12 days. Key findings Daunorubicin-treated rats showed cardiac toxicity, evidenced by worsening cardiac function, evaluated by haemodynamic status and echocardiography, elevation of malondialdehyde level and a decreased level of total glutathione peroxidase activity in the heart tissue. These changes were reversed by treatment with telmisartan. Furthermore, telmisartan also downregulated matrix metalloproteinase-2 expression, attenuated the increased protein express...
Experimental and therapeutic medicine, 2011
Chronic inflammation, oxidative stress and the renin-angiotensin system (RAS) play a significant role in chemotherapy-induced cardiotoxicity (CTX). Telmisartan (TEL), an antagonist of the angiotensin II type-1 receptor, was found to reduce anthracycline (ANT)-induced CTX. We carried out a phase II placebo (PLA)-controlled randomized trial to assess the possible role of TEL in the prevention of cardiac subclinical damage induced by epirubicin (EPI). Forty-nine patients (mean age ± SD, 53.0±8 years), cardiovascular disease-free with cancer at different sites and eligible for EPI-based treatment, were randomized to one of two arms: TEL n=25; PLA n=24. A conventional echocardiography equipped with Tissue Doppler imaging, strain and strain rate (SR) was performed, and serum levels of proinflammatory cytokines, IL-6 and TNF-α, and oxidative stress parameters, reactive oxygen species (ROS) and glutathione peroxidase were determined. All assessments were carried out at baseline, after every...
Ameliorative Potential of Rosuvastatin on Doxorubicin-induced Cardiotoxicity
Ameliorative Potential of Rosuvastatin on Doxorubicin-induced Cardiotoxicity , 2022
Objectives: The study aimed to explore the in vivo protective potential of rosuvastatin (ROSS), an oral antihyperlipidemic drug against doxorubicin (DOXO) induced cardio toxicity in rats. Materials and Methods: Cardiac toxicity was induced by DOXO injection (10 mg/kg, i.p.), once on the 20 th day of the experiment. Except for the control rats, all were received DOXO and the study was continued for up to 21 days. The influence of ROSS on acute treatment was analyzed by quantification of cardiac marker enzymes such as creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and liver marker enzymes like aspartate aminotransferase (AST), alanine aminotransferase (ALT) along with the measurement of in vivo antioxidants like superoxide dismutase and catalase. To observe histological changes of myocardial tissue hematoxylin and eosin staining were used. Results: Acute administration of DOXO resulted in a marked rise of cardiac marker enzymes that confirms the myocardial damage compared to control animals whereas administration of ROSS (10 mg/kg, p.o.) resulted in the significant reduction of CK-MB, LDH levels (p<0.05) and AST, ALT levels to a remarkable extent. Moreover, ROSS administration significantly increased the activities of various in vivo antioxidant levels. Conclusion: From the results, the acute administration of ROSS showed significant cardioprotective property, which was evidenced by a significant reduction of cardiac and liver marker enzymes along with significant improvement of in vivo antioxidant activities. Furthermore the results were supported with histopathological observations. Hence, it can be concluded that cardioprotective potential of ROSS may be through attenuation of oxidative stress by modulating oxidative damage in rats.