Treatment Of Albino Rats With Oltipraz (4-MethyL-5-PyrazinyL-3H-1,2-Dithiole-3-Thione Protects Against Doxorubicin-Induced Cardiotoxicity

G. Jagetia, Kanan Ramthianghlima
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Abstract

Doxorubicin is an anthracycline group of antibiotics that is frequently used in the treatment of various human neoplasias clinically. However, its adverse effect on the human heart is of major concern and limits its full clinical utilization. The present study was undertaken to alleviate the doxorubicin-induced myocardial toxicity by oltipraz an Nrf-2 inducer in albino rats. The albino rats were orally administered with 10 mg/kg body weight of oltipraz daily for three days before treatment with 15 mg/kg body weight of doxorubicin. The doxorubicin-induced myocardial stress indicated by an increase in the CK-MB activity, and lipid peroxidation accompanied by a reduction in the glutathione, glutathione-s-transferase, catalase and superoxide dismutase in the rat heart. The administration of 10 mg/kg oltipraz for three days before doxorubicin treatment reduced the CK-MB activity and lipid peroxidation significantly followed by the significant elevation in the activities of glutathione-s-transferase, catalase and superoxide dismutase and glutathione in the rat heart. Our study demonstrates that oltipraz an Nrf-2 inducer reduced doxorubicin-induced myocardial stress in the rats.
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Oltipraz(4-甲基-5-吡嗪基- 3h -1,2-二硫基-3-硫酮)治疗白化大鼠抗阿霉素诱导的心脏毒性
阿霉素是一种蒽环类抗生素,临床上常用于治疗各种人类肿瘤。然而,它对人体心脏的不良影响是人们关注的主要问题,限制了它的充分临床应用。本研究旨在减轻多柔比星诱导的白化大鼠心肌毒性。白化大鼠每日口服奥替普拉10 mg/kg体重,连续3天,然后口服阿霉素15 mg/kg体重。阿霉素诱导的心肌应激表现为CK-MB活性升高,脂质过氧化反应伴随着大鼠心脏谷胱甘肽、谷胱甘肽s-转移酶、过氧化氢酶和超氧化物歧化酶的减少。在阿霉素治疗前3天给药10 mg/kg奥替普拉可显著降低CK-MB活性和脂质过氧化,随后显著升高谷胱甘肽-s转移酶、过氧化氢酶、超氧化物歧化酶和谷胱甘肽的活性。我们的研究表明,作为Nrf-2诱导剂的oltipraz可以减轻阿霉素引起的大鼠心肌应激。
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