Hosseinimehr Seyed Jalal, Mahmoudzadeh Aziz, Akhlagpour Shahram
Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Cell Biochem Funct. 2007 Jul-Aug;25(4):389-94. doi: 10.1002/cbf.1311.
The radioprotective effects of captopril were investigated by using the micronucleus test for anticlastogenic and cell proliferation activity. A single intraperitoneal administration of captopril at doses of 10, 25 and 50 mg/kg 1 h prior to gamma irradiation (2 Gy) reduced the frequencies of micronuleated polychromatic erythrocytes (MnPCEs). All three doses of captopril significantly reduced the frequencies of MnPCEs and increased polychromatic erythrocytes (PCE)/PCE+NCE (normochromatic erythrocyte) ratio in mice bone marrow compared to the non-drug-treated irradiated control (p < 0.001). The optimum dose for protection in mouse was 10 mg/kg to protect mice bone marrow 2.18-fold against the clastogenic effects of gamma-irradiation with respect to the non-drug-treated irradiated control. There was a drug dose-response effect of captopril in increasing the PCE/PCE+NCE ratio in bone marrow cells. The maximum protective effect of captopril was at a dose of 25 mg/kg for increasing the PCE/PCE + NCE ratio. Captopril exhibited concentration-dependent antioxidant activity, scavenging > 96% of the 1,1-diphenyl-2-picryl hydrazyl free radicals when used at a concentration of 0.2 mM. In this study captopril reduced lipid peroxidation induced by hydrogen peroxide in mice liver. It appears that captopril, due to its free radical scavenging properties, protects mice bone marrow cells from radiation-induced DNA damage and genotoxicity.
通过微核试验研究卡托普利的抗断裂和细胞增殖活性的辐射防护作用。在γ射线照射(2 Gy)前1小时,以10、25和50 mg/kg的剂量腹腔注射卡托普利,可降低微核多染性红细胞(MnPCEs)的频率。与未用药的辐射对照组相比,所有三种剂量的卡托普利均显著降低了小鼠骨髓中MnPCEs的频率,并提高了多染性红细胞(PCE)/PCE+NCE(正染性红细胞)的比例(p<0.001)。在小鼠中,保护骨髓的最佳剂量为10 mg/kg,相对于未用药的辐射对照组,可使小鼠骨髓免受γ射线照射的断裂效应的保护倍数达到2.18倍。卡托普利在增加骨髓细胞中PCE/PCE+NCE比例方面存在药物剂量反应效应。卡托普利在剂量为25 mg/kg时对增加PCE/PCE + NCE比例具有最大保护作用。卡托普利表现出浓度依赖性抗氧化活性,当以0.2 mM的浓度使用时,可清除>96%的1,1-二苯基-2-苦基肼自由基。在本研究中,卡托普利降低了过氧化氢诱导的小鼠肝脏脂质过氧化。看来,卡托普利由于其自由基清除特性,可保护小鼠骨髓细胞免受辐射诱导的DNA损伤和遗传毒性。