S-allylcysteine ameliorates doxorubicin toxicity in the heart and liver inmice

Doxorubicin, a patent anticancer drug, is effective against a wide range of human neoplasms. However, the clinical uses of doxorubicin have been limit ed due to its serious cardiotoxic effects, which are likely the result of g eneration of free radicals and lipid peroxidation. S-Allylcysteine (SAC), a n organosulfur compound purified from garlic, has been reported to have ant ioxidant and radical scavenging effects. Thus, we examined the effect of SA C on doxorubicin toxicity in mice. Severe doxorubicin toxicity was induced in mice by a single intraperitoneal injection (15 mg/kg body weight), SAC ( 30 mg/kg) was injected intraperitoneally daily for 5 days, starting two day s prior to the administration of doxorubicin. Body weight was measured ever y alternate day. A measurement of serum creatine phosphokinase (CPK) and a histopathological analysis of the heart and liver was performed 6 days afte r the administration of doxorubicin. Death of any of the animals was record ed during the observation period. Doxorubicin injection induced a mortality rate of 58%, with SAC treatment reducing the doxorubicin-induced mortality rate to 30%. The severe body weight loss caused by doxorubicin (13%) was a lso significantly attenuated by SAC treatment (9%). Although an elevation o f the level of serum CPK was observed Following doxorubicin injection (5472 +/- 570 i.u./L), treatment with SAC significantly reduced the level of CPK (1923 +/- 635 i.u./L). Histological analysis demonstrated that heart and l iver damage was significantly less severe in SAC treated mice than in mice receiving only doxorubicin. These results suggest that SAC research may ult imately lead to a resolution of the adverse effects of doxorubicin treatmen t in cancer chemotherapy.