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香豆素(1,2-苯并吡喃酮)对溴酸钾诱导的Wistar大鼠肾毒性的减轻作用:针对自由基介导的肾脏氧化应激和肿瘤促进反应的化学预防

Attenuation of potassium bromate-induced nephrotoxicity by coumarin (1,2-benzopyrone) in Wistar rats: chemoprevention against free radical-mediated renal oxidative stress and tumor promotion response.

作者信息

Khan Naghma, Sharma Sonia, Sultana Sarwat

机构信息

Section of Chemoprevention and Nutrition Toxicology, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.

出版信息

Redox Rep. 2004;9(1):19-28. doi: 10.1179/135100004225003860.

DOI:10.1179/135100004225003860
PMID:15035824
Abstract

We report the modulatory effect of coumarin (1,2-benzopyrone) on potassium bromate (KBrO(3)) mediated nephrotoxicity in Wistar rats. KBrO(3) (125 mg/kg body weight, i.p.) enhances gamma-glutamyl transpeptidase, renal lipid peroxidation, xanthine oxidase and hydrogen peroxide (H(2)O(2)) generation with reduction in renal glutathione content and antioxidant enzymes. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and [(3)H]-thymidine incorporation into renal DNA. Treatment of rats orally with coumarin (10 mg/kg body weight and 20 mg/kg body weight) resulted in a significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H(2)O(2) generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Renal glutathione content (P < 0.01) and antioxidant enzymes were also recovered to significant level (P < 0.001). These results show that coumarin may be used as an effective chemopreventive agent against KBrO(3)-mediated renal oxidative stress, toxicity and tumor promotion response in Wistar rats.

摘要

我们报道了香豆素(1,2-苯并吡喃酮)对溴酸钾(KBrO₃)介导的Wistar大鼠肾毒性的调节作用。KBrO₃(125毫克/千克体重,腹腔注射)可增强γ-谷氨酰转肽酶、肾脂质过氧化、黄嘌呤氧化酶和过氧化氢(H₂O₂)的生成,同时降低肾谷胱甘肽含量和抗氧化酶活性。它还会提高血尿素氮、血清肌酐、鸟氨酸脱羧酶(ODC)活性以及[³H]-胸腺嘧啶核苷掺入肾DNA的水平。给大鼠口服香豆素(10毫克/千克体重和20毫克/千克体重)后,γ-谷氨酰转肽酶、脂质过氧化、黄嘌呤氧化酶、H₂O₂生成、血尿素氮、血清肌酐、肾ODC活性和DNA合成均显著降低(P < 0.001)。肾谷胱甘肽含量(P < 0.01)和抗氧化酶也恢复到显著水平(P < 0.001)。这些结果表明,香豆素可作为一种有效的化学预防剂,对抗KBrO₃介导的Wistar大鼠肾氧化应激、毒性和肿瘤促进反应。

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