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番茄红素对甲醇中毒大鼠肝组织中 caspase-3 酶激活的影响:与 4-甲基吡唑的比较。

Effect of lycopene on caspase-3 enzyme activation in liver of methanol-intoxicated rats: comparison with fomepizole.

机构信息

Department of Public Health, Faculty of Medicine, Zonguldak Karaelmas University, Zonguldak, Turkey.

出版信息

J Med Food. 2010 Aug;13(4):985-91. doi: 10.1089/jmf.2009.0166.

Abstract

Lycopene is one of the major carotenoids and is found almost exclusively in tomatoes and tomato products. This study was performed to evaluate the effect of lycopene on methanol-induced liver injury and to compare the results with those after fomepizole, which is used in treatment of methanol intoxication. Experiments were carried out with 30 female Wistar rats weighting 180-200 g. Rats were injected with a intraperitoneally dose of 3 g/kg methanol as a 50% solution in isotonic saline once for intoxication. Rats were pretreated with fomepizole (50 mg/kg) and/or lycopene (10 mg/kg) before methanol. After 24 hours all the drug-treated and intoxicated rats were sacrificed under anesthesia. Malondialdehyde (MDA) levels were determined in order to assess lipid peroxidation, and caspase-3 activity was determined by immunostaining of liver tissues to evaluate apoptosis. Methanol administration significantly increased the MDA level and caspase-3 activity in liver. Pretreatment with lycopene and/or fomepizole decreased the MDA levels significantly. Similarly, lycopene and fomepizole decreased methanol-induced caspase-3 activity. The findings of the present study demonstrate that methanol intoxication causes hepatic toxicity in rats and that this is likely a result of reactive oxygen species and apoptosis induction. Lycopene has protective effects against methanol-induced hepatic injury similar to fomepizole. It was demonstrated for the first time that both lycopene and fomepizole prevent methanol-induced hepatic injury by reducing the increase of lipid oxidation and caspase-3 activation.

摘要

番茄红素是类胡萝卜素的主要成分之一,几乎只存在于番茄及其制品中。本研究旨在评估番茄红素对甲醇诱导的肝损伤的影响,并与治疗甲醇中毒的药物依地酸钙钠(fomepizole)的结果进行比较。实验采用 30 只 180-200g 的雌性 Wistar 大鼠进行,通过腹腔注射 3g/kg 的 50%甲醇生理盐水溶液对大鼠进行单次染毒。在甲醇染毒前,大鼠分别用依地酸钙钠(50mg/kg)和/或番茄红素(10mg/kg)预处理。24 小时后,所有接受药物治疗的染毒大鼠均在麻醉下处死。通过测定丙二醛(MDA)水平来评估脂质过氧化,通过免疫组化染色测定肝组织中的 caspase-3 活性来评估细胞凋亡。结果显示,甲醇染毒可显著增加肝组织 MDA 水平和 caspase-3 活性。番茄红素和/或依地酸钙钠预处理可显著降低 MDA 水平。同样,番茄红素和依地酸钙钠也可降低甲醇诱导的 caspase-3 活性。本研究结果表明,甲醇染毒可导致大鼠肝毒性,这可能是由于活性氧和细胞凋亡诱导所致。番茄红素对甲醇诱导的肝损伤具有保护作用,与依地酸钙钠相似。本研究首次证明,番茄红素和依地酸钙钠均可通过降低脂质氧化和 caspase-3 激活来预防甲醇诱导的肝损伤。

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