Sheng-mai-san reduces adriamycin-induced cardiomyopathy in rats.
The traditional Chinese medicine prescription "sheng-mai-san (SMS)" has been used for treating patients with coronary heart disease for a long time and was found to have antioxidative effects. Here, we applied adriamycin (doxorubicin, ADR), a highly effective anticancer agent, as an inducer to establish the animal model of dose-related cardiomyopathy due to inhibition of nucleic acid as well as protein synthesis, formation of free radicals, and lipid peroxidation. The objective of this study was to investigate the protective effects of SMS on adriamycin-induced cardiomyopathy. Wistar rats were divided into four groups: CONT (control), ADR, SMS, and ADR + SMS. ADR (cumulative dose, 15 mg/kg) was administered to rats in six equal intraperitoneal injections over a period of 2 weeks and SMS was administered via a feeding tube throughout the mouth once a day for 30 days (cumulative dose, 150 g/kg). At the end of the 5-week post-treatment period, the hearts of the rats were surgically removed for the study of synthesis rates of DNA, RNA and proteins. Besides myocardial antioxidants, lipid peroxidation and morphological ultrastructure were also evaluated. Three weeks after the treatment, cardiomyopathy and congestive heart failure were characterized according to assessment in ascites, congested liver, depressed cardiac function and myocardial cell damage. The results demonstrated that nucleic acid as well as protein synthesis was inhibited, while lipid peroxidation was increased. Myocardial glutathione peroxidase (GSHPx) activity was decreased and electron microscopic examination revealed myocardial lesion indicative of ADR-induced cardiomyopathy. In contrast, administration of SMS before and concurrent with ADR significantly attenuated the myocardial effects. It also lowered mortality as well as the amount of ascites. In addition, indexes in myocardial GSHPx, macromolecular biosynthesis and superoxide dismutase activities were increasing, with a concomitant decrease in lipid peroxidation and preserved myocardial ultrastructure. These results indicated that SMS may be partially protective against ADR-induced cardiomyopathy.
Chang Gung University School of Traditional Chinese Medicine, Kweishan, Taoyuan 333, Taiwan. y0606@mail.cgu.edu.tw
Jyh-Sheng
JS
You
Hui-Feng
HF
Huang
Ying-Ling
YL
Chang
Ying-Shiung
YS
Lee
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000188:drug therapy*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004317:Doxorubicin / Q000633:toxicity*; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008854:Microscopy, Electron; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D000970:Antineoplastic Agents; D002316:Cardiotonic Agents; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; D008315:Malondialdehyde; D012313:RNA; D004317:Doxorubicin; D004247:DNA; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase