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白杨素调节 Wistar 大鼠乙醇代谢:一种对抗器官毒性的有前景作用。

Chrysin modulates ethanol metabolism in Wistar rats: a promising role against organ toxicities.

机构信息

Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.

出版信息

Alcohol Alcohol. 2011 Jul-Aug;46(4):383-92. doi: 10.1093/alcalc/agr038. Epub 2011 Apr 29.

Abstract

AIMS

Hepato- and nephro-protective efficacy of chrysin was investigated against sequential increase of ethanol intake on the alteration of alcohol metabolizing enzymes-alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP 2E1), xanthine oxidase (XO) and oxidant/anti-oxidant status.

METHODS

Thirty female Wistar rats segregated into five groups, each with six animals, were put to different doses. Group I as control followed by Group II, III and IV were treated with ethanol (5,8,10 and 12 g/kg body weight per week respectively) for 4 weeks. While Group III and IV were administered with chrysin at 20 mg (D1) and 40 mg/kg body weight (D2), respectively, prior to ethanol administration. Group V was given only chrysin (D2). Various oxidative stress and ethanol metabolizing enzymes were estimated in hepatic and renal tissues.

RESULTS

Ethanol administration significantly induced CYP 2E1, ADH and XO in liver and kidneys, respectively, along with an enhancement in levels of malondialdehyde and serum alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine and lactate dehydrogenase when compared with the control group and this enhancement is significantly normalized with chrysin administration. Oxidative stress markers: reduced glutathione, glutathione peroxidase, catalase and glutathione reductase were significantly (P < 0.001) depleted in the ethanol-treated group, while chrysin administration significantly restored all of these. Only chrysin administration did not show any adverse effect.

CONCLUSION

Results demonstrate that chrysin administration prevents the liver and kidney of Wistar rats against oxidative damage during chronic ethanol consumption by inhibiting the activities of ADH, CYP 2E1, XO and catalase.

摘要

目的

研究白杨素对乙醇摄入逐渐增加引起的肝、肾损伤的保护作用,观察其对乙醇代谢酶(醇脱氢酶[ADH]、细胞色素 P450 2E1[CYP 2E1]、黄嘌呤氧化酶[XO])和氧化应激/抗氧化状态的影响。

方法

将 30 只雌性 Wistar 大鼠分为 5 组,每组 6 只,给予不同剂量的药物。第 1 组为对照组,第 2、3、4 组分别给予 5、8、10、12 g/kg 体重/周的乙醇,连续 4 周。第 3、4 组在给予乙醇前分别给予白杨素 20 mg(D1)和 40 mg/kg 体重(D2),第 5 组仅给予白杨素(D2)。检测肝、肾组织中各种氧化应激和乙醇代谢酶的变化。

结果

与对照组相比,乙醇处理组肝脏和肾脏中的 CYP 2E1、ADH 和 XO 显著增加,血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、血尿素氮、肌酐和乳酸脱氢酶水平也显著升高,而用白杨素处理后这些变化均得到显著改善。氧化应激标志物:与对照组相比,乙醇处理组大鼠肝、肾组织中还原型谷胱甘肽、谷胱甘肽过氧化物酶、过氧化氢酶和谷胱甘肽还原酶水平显著降低(P<0.001),而用白杨素处理后这些酶的水平均显著升高。仅给予白杨素处理没有显示出任何不良反应。

结论

结果表明,白杨素通过抑制 ADH、CYP 2E1、XO 和过氧化氢酶的活性,可防止 Wistar 大鼠在慢性乙醇摄入期间的肝、肾氧化损伤。

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