Effect of Vitamin C on the Expression of Apoptosis in the Adriamycin-Treated Rats

Seo, Youn Kyoung; Park, Joon Sup; Youn, Jeehee; Paik, Doo Jin

Abstract

Adriamycin, a member of anthracycline class isolated from the culture medium of Streptomyces peucetius var. caesius, is one of the most effective and useful anti-neoplastic agents for the treatment of hematological and solid malignancy. The efficacy of adriamycin has been shown to mainly rely on free radicals generated during its inhibitory activity of DNA synthesis and its metabolism. However, the production of free radicals elicited side effects including chronic cardiotoxicityits. Such aspect occasionally limits the therapeutic use of adriamycin. This study was aimed to investigate the dose effect of adriamycin on apoptosis induction of the myocardium of left ventricle along with the effect of vitamin C on adriamycin activity. SD rats weighing 250~300 g were injected intraperitoneally with either 20 mg/kg or 5 mg/kg of adriamycin and drunk vitamin C at 1000 mg/animal/day. Rats were sacrificed at days 1, 3, 5, and 14 after injection but rats injected with 20 mg adriamycin died at day 6. The heart were paraffin -sectioned at 6 micrometer thickness, stained following TUNEL methods. Stained cells undergoing apoptotic death in myocardium of left ventricle were counted and statistically analyzed. The results were obtained as follows; 1. The muscular layer of left ventricle from nomal rats contained 4.2+/-12.3 apoptotic cells. 2. Distributions of apoptotic cells from rats treated with 20 mg/kg adriamycin were 26.7+/-43.2, 17.7+/-41.4, and 17.8+/- 31.8 at days 1, 3, and 5, respectively. 3. Distributions of apoptotic cells from rats treated with 5 mg/kg adriamycin were 10.8+/-19.5, 4.1+/-12.4, 5.6+/-10.2, 10.8+/-17.3 at days 1, 3, 5, and 14, respectively. 4. Coadministration of 20 mg/kg adriamycin and vitamin C resulted in 8.8+/-19.5, 4.1+/-12.4, and 16.2+/-33.6 apop-totic cells at days 1, 3, and 5 post administration. 5. Coadministration of 5 mg/kg adriamycin and vitamin C resulted in 17.0+/-32.3, 12.2+/-19.7, 7.1+/-14.0, and 7.2+/-16.7 apoptotic cells at days 1, 3, 5, and 14 post administration. Taken together, these results demonstrated that treatment of rats with 20 mg/kg adriamycin induced more apoptotic cells than that with 5 mg/kg adriamycin and vitamin C reduced such cytotoxic effects of adriamycin.