Journal
DRUG DEVELOPMENT RESEARCH
Volume 73, Issue 3, Pages 154-165Publisher
WILEY
DOI: 10.1002/ddr.21006
Keywords
aloin; doxorubicin; heart function tests; antioxidants; inducible nitric oxide synthase; histological studies; rat
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In the present study, the cardiotoxicity of aloin, a naturally occurring anthraquinone glycoside with antiproliferative activitywas compared with doxorubicin, a cardiotoxic anthracyline drug, in rats. The antioxidant and iron- chelating activities of aloin and doxorubicin in vitro were also evaluated. Rats treated with aloin ( 50 mg/ kg body weight, intramuscular)) twice weekly over 2 weeks showed no signs of cardiotoxicity as assessed by an absence of changes in relative heart weight, serum level of heart function enzymes, and a lack of degeneration in the myocardium of the left ventricle. Acute doxorubicin administration ( 30 mg/ kg body weight, intraperitoneal) to rats produced severe cardiotoxicity as supported by biochemical and histological studies. Aloin did not induce oxidative stress or enhance the endogenous antioxidant defense system in the heart. In vitro antioxidant tests showed that aloin, in contrast to doxorubicin, had substantial antioxidant activity represented by scavenging of 1,1- diphenyl 2- picrylhydrazyl and nitric oxide radicals, inhibition of lipid peroxidation, and ferric- reducing antioxidant activity in addition to iron chelating potential. Ventricular inducible nitric oxide synthase protein expression was unaffected by either aloin and doxorubicin treatments. In conclusion, repeated aloin treatment, in contrast to that of doxorubicin, failed to produce oxidative stress- induced cardiotoxicity in the rats.
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