锗与烟酸配合物对实验性阿霉素慢性中毒大鼠心脏和肝脏蛋白氧化修饰的影响

V. Narokha
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引用次数: 1

摘要

蒽环类抗肿瘤抗生素广泛用于恶性肿瘤的治疗,但这类药物以其细胞毒性作用,特别是心脏毒性而闻名。已经证明,蒽环类药物对组织的不良影响是基于活性氧的形成,促进氧化应激的发展。在人体生物分子中,蛋白质对过氧化反应最为敏感;在细胞水平上,它们是决定这种病理过程的主要标志。识别和预防氧化应激对防止进一步的组织凋亡和坏死具有重要意义。本研究旨在探讨烟酸及锗-烟酸复合物(MIGU-1)对实验性阿霉素(CID)慢性中毒大鼠心肌和肝脏蛋白氧化修饰的影响。确定了大鼠心肌细胞和肝细胞中蛋白质过氧化产物(中性和碱性2,4-二硝基苯肼)含量的变化模式;显示CID中氧化应激的加剧。烟酸在10 mg/kg / d剂量下对CID无肝保护作用。实验证明,以10 mg/kg / d的剂量使用锗与烟酸的新型配合物可减弱CID大鼠心肌细胞和肝细胞中的蛋白质过氧化。研究结果表明,MIGU-1可能是一种具有细胞保护作用的药物,其进一步研究具有一定的局域性和前瞻性。
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The effect of the germanium complex with nicotinic acid on oxidative modification of cardiac and hepatic proteins in the experimental chronic intoxication with doxorubicin in rats
Anthracycline antitumor antibiotics are widely used for the treatment of malignancies, but this group of drugs is known for their cytotoxic effects, especially cardiotoxicity. It has been proven that the adverse effect of anthracyclines on tissues is based on formation of the reactive oxygen species that enhance development of the oxidative stress. Among the body biomolecules proteins are the most sensitive to peroxidation; they can be the primary markers in determining this pathological process at the cellular level. To identify and prevent the oxidative stress is important for prevention of further tissue apoptosis and necrosis. The aim of the study was to investigate the effect of nicotinic acid and the complex compound of germanium with nicotinic acid (MIGU-1) on oxidative modification of myocardial and hepatic proteins in the experimental chronic intoxication with doxorubicin (CID) in rats. The pattern of modifications in the content of protein peroxidation products (neutral and basic 2,4-dinitrophenylhydrazine) in cardiomyocytes and hepatocytes in rats has been determined; it shows intensification of the oxidative stress in CID. Nicotinic acid in the dose of 10 mg/kg daily did not exhibit the hepatoprotective effect in CID. It has been proven that the use of the new complex compound of germanium with nicotinic acid in the dose of 10 mg/kg daily provide attenuation of protein peroxidation in rats’ cardiomyocytes and hepatocytes in CID. The results obtained allow considering MIGU-1 as a drug with a possible cytoprotective activity, and its further study may be topical and prospective.
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