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石榴通过减轻氧化应激改善庆大霉素诱导的大鼠肾病的肾功能。

Punica granatum improves renal function in gentamicin-induced nephropathy in rats via attenuation of oxidative stress.

作者信息

Mestry Snehal N, Gawali Nitin B, Pai Sarayu A, Gursahani Malvika S, Dhodi Jayesh B, Munshi Renuka, Juvekar Archana R

机构信息

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, NP Marg Matunga, Mumbai 400019, Maharashtra, India.

Department of Clinical Pharmacology, TN Medical College & BYL Nair Ch. Hospital, Mumbai Central, Mumbai 400008, India.

出版信息

J Ayurveda Integr Med. 2020 Jan-Mar;11(1):16-23. doi: 10.1016/j.jaim.2017.09.006. Epub 2018 Mar 17.

Abstract

BACKGROUND

Gentamicin is widely used as an antibiotic for the treatment of gram negative infections. Evidences indicates that oxidative stress is involved in gentamicin-induced nephrotoxicity. In Ayurvedic medicine, Punica granatum Linn. is considered as 'a pharmacy unto itself". It has been claimed in traditional literature, to treat various kidney ailments due to its antioxidant potential.

OBJECTIVE

To explore the possible mechanism of action of methanolic extract of P.granatum leaves (MPGL) in exerting a protective effect on gentamicin-induced nephropathy.

MATERIAL AND METHODS

Animals were administered with gentamicin (80 mg/kg/day i.m.) and simultaneously with MPGL (100, 200 and 400 mg/kg p.o.) or metformin (100 mg/kg p.o.) for 8 days. A satellite group was employed in order to check for reversibility of nephrotoxic effects post discontinuation of gentamicin administration. At the end of the study, all the rats were sacrificed and serum-urine parameters were investigated. Antioxidant enzymes and tumor necrosis factor alpha (TNF-α) levels were determined in the kidney tissues along with histopathological examination of kidneys.

RESULTS

Increase in serum creatinine, urea, TNF-α, lipid peroxidation along with fall in the antioxidant enzymes activity and degeneration of tubules, arterioles as revealed by histopathological examination confirmed the manifestation of nephrotoxicity caused due to gentamicin. Simultaneous administration of MPGL and gentamicin protected kidneys against nephrotoxic effects of gentamicin as evidenced from normalization of renal function parameters and amelioration of histopathological changes.

CONCLUSION

Data suggests that MPGL attenuated oxidative stress associated renal injury by preserving antioxidant enzymes, reducing lipid peroxidation and inhibiting inflammatory mediators such as TNF-α.

摘要

背景

庆大霉素作为一种抗生素被广泛用于治疗革兰氏阴性菌感染。有证据表明,氧化应激参与了庆大霉素诱导的肾毒性。在阿育吠陀医学中,石榴被视为“一座自成体系的药房”。传统文献称,由于其抗氧化潜力,石榴可治疗各种肾脏疾病。

目的

探讨石榴叶甲醇提取物(MPGL)对庆大霉素诱导的肾病发挥保护作用的可能作用机制。

材料与方法

给动物注射庆大霉素(80毫克/千克/天,肌肉注射),同时给予MPGL(100、200和400毫克/千克,口服)或二甲双胍(100毫克/千克,口服),持续8天。设立一个卫星组,以检查停止注射庆大霉素后肾毒性作用的可逆性。在研究结束时,处死所有大鼠并检测血清-尿液参数。测定肾组织中的抗氧化酶和肿瘤坏死因子α(TNF-α)水平,并对肾脏进行组织病理学检查。

结果

血清肌酐、尿素、TNF-α升高,脂质过氧化增加,同时抗氧化酶活性下降,组织病理学检查显示肾小管和小动脉变性,证实了庆大霉素引起的肾毒性表现。MPGL与庆大霉素同时给药可保护肾脏免受庆大霉素的肾毒性作用,这从肾功能参数的正常化和组织病理学变化的改善得到证明。

结论

数据表明,MPGL通过保留抗氧化酶、减少脂质过氧化和抑制TNF-α等炎症介质,减轻了与氧化应激相关的肾损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1be0/7125389/6397a2bac01d/fx1.jpg

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