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益生菌 enterococcus lactis IITRHR1 可预防对乙酰氨基酚引起的肝毒性。

Probiotic Enterococcus lactis IITRHR1 protects against acetaminophen-induced hepatotoxicity.

机构信息

Herbal Research Section, Indian Institute of Toxicology Research (CSIR), Lucknow, Uttar Pradesh, India.

出版信息

Nutrition. 2012 Feb;28(2):173-81. doi: 10.1016/j.nut.2011.02.012. Epub 2011 Jul 20.

Abstract

OBJECTIVE

Acetaminophen (APAP), an antipyretic/analgesic drug, is reported to cause toxicity on overdose. Dietary supplements are currently being explored to decrease toxicity. In the present study, the protective effect of probiotic Enterococcus lactis IITRHR1 was evaluated at different doses (10(7), 10(8), and 10(9) colony-forming units) against APAP-induced liver damage.

METHODS

Male Wistar rats were administered APAP (1 g/kg of body weight orally) for 14 d, and hepatotoxicity was assessed by marker enzymes in serum and observation of histopathologic changes. Rats were pretreated with probiotic E. lactis IITRHR1 for 7 d and modulation of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase), redox ratio, and ferric reducing antioxidant power was assessed. Oxidative damage by APAP to membrane lipids, proteins, and DNA was also observed. Involvement of Bax, Bcl2, cytochrome c (pro-/anti-apoptotic proteins), caspases, and their modulation was assessed by immunoblot analysis and reverse transcriptase polymerase chain reaction.

RESULTS

The E. lactis IITRHR1 pretreatment lowered the level of biomarkers of hepatotoxicity in serum. A significant increase was observed in the level of antioxidant enzymes and redox ratio and decreased oxidative damage to membrane lipids and proteins. Probiotic E. lactis IITRHR1 also modulated key apoptotic/anti-apoptotic proteins such as cytochrome-c, Bcl2, Bax, expression of caspases, and resultant DNA damage.

CONCLUSION

Probiotic strain E. lactis IITRHR1 was found to have antioxidant capacity and afforded protection against APAP-induced hepatotoxicity by modulating antioxidant status, pro-/anti-apoptotic proteins, caspases, and DNA damage.

摘要

目的

醋氨酚(APAP)是一种解热/镇痛药,过量服用会导致毒性。目前正在探索膳食补充剂以降低毒性。本研究评估了不同剂量(10(7)、10(8)和 10(9)个菌落形成单位)的益生菌 Enterococcus lactis IITRHR1 对 APAP 诱导的肝损伤的保护作用。

方法

雄性 Wistar 大鼠口服给予 APAP(1 g/kg 体重)14 天,通过血清标志物酶和组织病理学变化观察评估肝毒性。大鼠用益生菌 E. lactis IITRHR1 预处理 7 天,评估抗氧化酶(超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽-S-转移酶)、氧化还原比和铁还原抗氧化能力的调节。还观察了 APAP 对膜脂质、蛋白质和 DNA 的氧化损伤。通过免疫印迹分析和逆转录聚合酶链反应评估 Bax、Bcl2、细胞色素 c(促凋亡/抗凋亡蛋白)、半胱天冬酶及其调节因子的参与。

结果

E. lactis IITRHR1 预处理降低了血清中肝毒性生物标志物的水平。观察到抗氧化酶和氧化还原比水平显著增加,膜脂质和蛋白质的氧化损伤减少。益生菌 E. lactis IITRHR1 还调节了关键的凋亡/抗凋亡蛋白,如细胞色素 c、Bcl2、Bax、半胱天冬酶的表达和由此产生的 DNA 损伤。

结论

益生菌菌株 E. lactis IITRHR1 具有抗氧化能力,通过调节抗氧化状态、促凋亡/抗凋亡蛋白、半胱天冬酶和 DNA 损伤,为 APAP 诱导的肝毒性提供了保护。

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