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Abstract
Resveratrol (RSV), a polyphenolic compound and naturally occurring phytoalexin, has been reported to exert cardio-protective effects in several animal studies. However, the outcome of initial clinical trials with RSV was less effective compared to pre-clinical studies. Therefore, RSV treatment protocols need to be optimized. In this study we evaluated prophylactic versus therapeutic effect of resveratrol (RSV) in mitigating doxorubicin (Dox)-induced cardiac toxicity in rats. To investigate prophylactic effects, RSV was supplemented for 2 weeks along with Dox administration. After 2 weeks, Dox treatment was stopped and RSV was continued for another 4 weeks. To study therapeutic effects, RSV treatment was initiated after 2 weeks of Dox administration and continued for 4 weeks. Both prophylactic and therapeutic use of RSV mitigated Dox induced deterioration of cardiac function as assessed by echocardiography. Also RSV treatment (prophylactic and therapeutic) prevented Dox induced myocardial damage as measured by cardiac enzymes (LDH and CK-MB) in serum. Which was associated with decrease in Dox induced myocardial apoptosis and fibrosis. Interestingly our study also reveals that prophylactic use of RSV was more effective than its therapeutic use in mitigating Dox induced apoptosis and fibrosis in the myocardium. Therefore, prophylactic use of resveratrol may be projected as a possible future adjuvant therapy to minimize cardiotoxic side effects of doxorubicin in cancer patients.
Highlights
Doxorubicin (Dox) is an effective broad spectrum anti-neoplastic agent
Cardiac function further deteriorated at 6 weeks of Dox administration
Another clinical study tested the efficacy of RSV in MI patients, it was reported that treatment with 10 mg/day of RSV had significantly improved diastolic function with a modest increase in systolic function [34]
Summary
Doxorubicin (Dox) is an effective broad spectrum anti-neoplastic agent. The therapeutic index of this highly potent anti-cancer drug is reduced due to cardio-toxic side effects [1,2]. Dox induced deterioration of cardiac function mainly occurs due to myocardial apoptosis [3,4]. Doxorubicin induces cardiac cell apoptosis via intrinsic and extrinsic pathways [5,6]. Both these pathways are linked and that molecules in these two pathways influence each other. Caspase 3 is one such molecule which is involved in both intrinsic and extrinsic pathways [7,8]
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