The Preventive Effect of Dexrazoxane and Pentoxifylline on Adriamycin Induced Cardiomyopathy

Ling, Zhu; Bae, Eun Jung; Ha, Il Soo; Seo, Jung Wook; Noh, Chung Il; Choi, Jung Yun; Yun, Yong Soo

Abstract

PURPOSE
We hypothesized dexrazoxane (DXR) and pentoxifylline (PTX) may prevent myocardial damage in adriamycin (ADR) -induced cardiomyopathic rat model. We also investigated their effects on the myocardial apoptosis and fibrosis in ADR induced cardiomyopathy. METHODS: The six-week old female Spregue-Dawley rats were divided into control group (CNT, n= 4), ADR group (n=6), ADR+DXR group (DXR, n=5), ADR+PTX group (PTX, n=6), ADR+DXR+PTX group (DXPT, n=5). ADR (5 mg/week, twice) was administrated intravenously to rats except CNT group to induce cardiomyopathy. The PTX (50 mg/kg/day) was administered daily from day-0 to Day-21. The DXR (100 mg/kg) was administered 30 minutes before each ADR injection. On day 21, the rats were sacrificed and the degree of histopathologic changes of hypercontraction band necrosis, cytoplasmic vacuolar change and fibrosis were scored. Immunohistochemical staining for Bcl-2 expression and RT-PCR for TNF-alpha and CTGF were performed. RESULTS: Histopathological scores of myocardial damage were significantly higher in ADR rats than CNT rats (P< 0.05), and significantly lower in DXPT rats than ADR rats (P< 0.01). Myocardial fibrosis was prevented in both PTX rats and DXPT rats. The expression of Bcl-2 was weaker in ADR rats than that in CNT rats (P< 0.05), and stronger in both DXR and DXPT rats than that in ADR rats (P< 0.05). TNF-alpha concentration of ADR rats was not different from that of treated groups. CONCLUSION: DXR prevented myocyte apoptosis with increased Bcl-2 expression, and PTX prevented myocardial fibrosis in ADR induced cardiomyopathic rats. The combination therapy of DXR and PTX showed prevention of cardiomyopathy in ADR induced cardiomyopathy rat model.