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番茄红素对万古霉素诱导的肾毒性大鼠的抗氧化、抗炎和抗凋亡作用

Antioxidant, Antiinflammatory and Antiapoptotic Effects of Lycopene in Rats With Vancomycin-Induced Nephrotoxicity.

作者信息

Demirkapı Atik Hülya, Atik Orkun, Aslan Recep, Birdane Yavuz Osman, Eryavuz Abdullah

机构信息

Department of Physiology, Faculty of Veterinary Medicine, University of Afyon Kocatepe, Afyonkarahisar, Türkiye.

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Afyon Kocatepe, Afyonkarahisar, Türkiye.

出版信息

Basic Clin Pharmacol Toxicol. 2025 Aug;137(2):e70084. doi: 10.1111/bcpt.70084.

Abstract

BACKGROUND

The most important side effect of vancomycin (Vanco) is nephrotoxicity (NPT). Lycopene (Lyco) has been reported to have anti-inflammatory and anti-apoptotic properties in addition to its antioxidant activity. The aim is to investigate the protective efficacy of Lyco against the NPT condition that limits the use of Vanco.

METHOD

A total of 48 rats were used in the study in six groups of eight rats each, namely, Corn Oil Control, Lyco 5, Lyco 10, Vanco, Vanco + Lyco 5 and Vanco + Lyco 10.

RESULTS

Vanco (400 mg/kg, intraperitoneal) administered for 7 days elevated serum BUN, creatinine, uric acid levels and renal lipid peroxidation while decreasing renal GSH and the activity of the antioxidant enzymes SOD, CAT and GPx. Vanco also increased the levels of inflammatory markers NF-κB, TNF-α, Bcl-3 and p38α MAPK activity. It decreased the level of AQP-1 and increased the level of NGAL. In addition, it activated apoptosis by decreasing Bcl-2 and Procas-3 expression levels while increasing apoptotic p53, Bax and Cyt-c expression levels. Lyco treatment at both doses (5 and 10 mg/kg, orally) ameliorated NPT by reducing oxidative stress, inflammation and apoptosis, while the higher dose was more effective.

CONCLUSION

The findings showed that Lyco attenuated Vanco-induced NPT.

摘要

背景

万古霉素(Vanco)最重要的副作用是肾毒性(NPT)。据报道,番茄红素(Lyco)除了具有抗氧化活性外,还具有抗炎和抗凋亡特性。目的是研究Lyco对限制Vanco使用的NPT状况的保护作用。

方法

本研究共使用48只大鼠,分为六组,每组8只,即玉米油对照组、Lyco 5组、Lyco 10组、Vanco组、Vanco + Lyco 5组和Vanco + Lyco 10组。

结果

腹腔注射万古霉素(400mg/kg)7天可升高血清尿素氮、肌酐、尿酸水平以及肾脏脂质过氧化水平,同时降低肾脏谷胱甘肽(GSH)以及抗氧化酶超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)的活性。万古霉素还增加了炎症标志物核因子κB(NF-κB)、肿瘤坏死因子-α(TNF-α)、Bcl-3和p38α丝裂原活化蛋白激酶(MAPK)的活性水平。它降低了水通道蛋白-1(AQP-1)的水平,增加了中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的水平。此外,它通过降低Bcl-2和原半胱天冬酶-3(Procas-3)的表达水平,同时增加凋亡相关蛋白p53、Bax和细胞色素c(Cyt-c)的表达水平来激活细胞凋亡。两种剂量(5mg/kg和10mg/kg,口服)的Lyco治疗均通过减轻氧化应激、炎症和细胞凋亡来改善NPT,且较高剂量更有效。

结论

研究结果表明Lyco减轻了万古霉素诱导的NPT。

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