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大蒜素对庆大霉素致大鼠肾毒性的保护作用。

Protective effect of allicin against gentamicin-induced nephrotoxicity in rats.

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.

出版信息

Int Immunopharmacol. 2015 Dec;29(2):679-686. doi: 10.1016/j.intimp.2015.09.010. Epub 2015 Sep 29.

Abstract

In this study, the modulator effect of allicin on the oxidative nephrotoxicity of gentamicin in the kidneys of rats was investigated by determining indices of lipid peroxidation and the activities of antioxidant enzymes, as well as by histological analyses. Furthermore, the effect of allicin on gentamicin induced hypersensitivity of urinary bladder rings to ACh was estimated. Twenty-four male Wistar albino rats were randomly divided into three groups, control, gentamicin (100mg/kg, i.p.) and gentamicin+allicin (50mg/kg, orally). At the end of the study, all rats were sacrificed and then urine, blood samples and kidneys were taken. Gentamicin administration caused a severe nephrotoxicity as evidenced by an elevated kidney/body weight ratio, serum creatinine, blood urea nitrogen (BUN), serum lactate dehydrogenase (LDH) and proteinuria with a reduction in serum albumin and creatinine clearance as compared with control group. In addition, a significant increase in renal contents of malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NOx) and tumor necrosis factor-alpha (TNF-α) concomitantly with a significant decrease in renal reduced glutathione (GSH) and superoxide dismutase (SOD) activities was detected upon gentamicin injection. Exposure to gentamicin increased the sensitivity of isolated urinary bladder rings to ACh and induced acute renal tubular epithelial cells necrosis. Administration of allicin significantly decreased kidney/body weight ratio, serum creatinine, LDH, renal MDA, MPO, NOx and TNF-α while it significantly increased creatinine clearance, renal GSH content and renal SOD activity when compared to gentamicin-treated group. Additionally, allicin significantly reduced the responses of isolated bladder rings to ACh and ameliorated tissue morphology as evidenced by histological evaluation. Our study indicates that allicin exerted protection against structural and functional damage induced by gentamicin possibly due to its antioxidant, anti-inflammatory and immunomodulatory properties in addition to its ability to retaining nitric oxide level.

摘要

在这项研究中,通过测定脂质过氧化指标和抗氧化酶活性以及组织学分析,研究了大蒜素对庆大霉素在大鼠肾脏氧化肾毒性的调节剂作用。此外,还评估了大蒜素对庆大霉素诱导的膀胱环对 ACh 超敏反应的影响。将 24 只雄性 Wistar 白化大鼠随机分为三组:对照组、庆大霉素(100mg/kg,腹腔注射)和庆大霉素+大蒜素(50mg/kg,口服)。研究结束时,处死所有大鼠,然后采集尿液、血液样本和肾脏。庆大霉素给药导致严重的肾毒性,表现为肾/体重比、血清肌酐、血尿素氮(BUN)、血清乳酸脱氢酶(LDH)和蛋白尿升高,同时血清白蛋白和肌酐清除率降低与对照组相比。此外,与对照组相比,庆大霉素注射后肾脏丙二醛(MDA)、髓过氧化物酶(MPO)、一氧化氮(NOx)和肿瘤坏死因子-α(TNF-α)含量显著增加,同时肾脏还原型谷胱甘肽(GSH)和超氧化物歧化酶(SOD)活性显著降低。庆大霉素给药增加了分离的膀胱环对 ACh 的敏感性,并诱导急性肾小管上皮细胞坏死。与庆大霉素治疗组相比,大蒜素给药显著降低了肾/体重比、血清肌酐、LDH、肾 MDA、MPO、NOx 和 TNF-α,同时显著增加了肌酐清除率、肾 GSH 含量和肾 SOD 活性。此外,大蒜素还显著降低了分离的膀胱环对 ACh 的反应,并通过组织学评估改善了组织形态。我们的研究表明,大蒜素对庆大霉素引起的结构和功能损伤具有保护作用,这可能是由于其抗氧化、抗炎和免疫调节特性,以及维持一氧化氮水平的能力。

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