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SIRT1/NOX1通路介导迷迭香酸对叶酸诱导的肾损伤的改善作用。

SIRT1/NOX1 pathway mediated ameliorative effects of rosmarinic acid in folic acid-induced renal injury.

作者信息

Mottaghi Maryam, Eidi Akram, Heidari Fatemeh, Movahhed Tahereh Komeili, Moslehi Azam

机构信息

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, I.R. Iran.

Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, I.R. Iran.

出版信息

Res Pharm Sci. 2024 Oct 22;19(5):622-633. doi: 10.4103/RPS.RPS_213_23. eCollection 2024 Oct.

Abstract

BACKGROUND AND PURPOSE

Renal injury is a serious disorder that can be caused by some diseases or agents. Rosmarinic acid (RA) is a natural and safe compound with powerful antioxidant and anti-inflammatory properties. In this study, the ameliorative effects of RA were assayed in folic acid (FA)-induced renal injury by involving the SIRT1/NOX1 pathway.

EXPERIMENTAL APPROACH

Thirty-six male C57/BL6 mice were divided into 6 groups (n = 6) including control, vehicle, FA, RA, FA + RA 50, and FA + RA 100. After 10 days, blood urea nitrogen (BUN), creatinine, and oxidative stress were measured. The expression of SIRT1 and NOX1 proteins was evaluated by western blot. Also, histopathological alterations were assayed by H&E and PAS staining methods.

FINDINGS/RESULTS: BUN and creatinine were significantly higher in the FA group compared to the control group; however, their levels decreased after RA treatment in both doses. A significant decrease was observed in swelling, necrosis, and desquamation of tubular epithelial cells in the FA + RA 50 and FA + RA 100 groups compared to the FA group. RA in the animals receiving FA increased SIRT1 expression and the levels of GSH and SOD compared to the FA group. RA in the animals receiving FA showed a significant decrease in NOX1 expression and MDA level compared to the FA group.

CONCLUSION AND IMPLICATIONS

The findings declared that the administration of RA has positive effects against renal damage induced by FA. The effect might result from involvement in the SIRT1/NOX1 pathway and thereby attenuation of oxidative stress.

摘要

背景与目的

肾损伤是一种严重的病症,可由某些疾病或因素引起。迷迭香酸(RA)是一种天然且安全的化合物,具有强大的抗氧化和抗炎特性。在本研究中,通过涉及SIRT1/NOX1途径,检测了RA对叶酸(FA)诱导的肾损伤的改善作用。

实验方法

将36只雄性C57/BL6小鼠分为6组(n = 6),包括对照组、溶剂组、FA组、RA组、FA + RA 50组和FA + RA 100组。10天后,测量血尿素氮(BUN)、肌酐和氧化应激水平。通过蛋白质印迹法评估SIRT1和NOX1蛋白的表达。此外,采用苏木精-伊红(H&E)和过碘酸-雪夫(PAS)染色法检测组织病理学改变。

研究结果

与对照组相比,FA组的BUN和肌酐显著更高;然而,两种剂量的RA治疗后其水平均下降。与FA组相比,FA + RA 50组和FA + RA 100组的肾小管上皮细胞肿胀、坏死和脱落明显减少。与FA组相比,接受FA的动物体内RA增加了SIRT1表达以及谷胱甘肽(GSH)和超氧化物歧化酶(SOD)水平。与FA组相比,接受FA的动物体内RA使NOX1表达和丙二醛(MDA)水平显著降低。

结论与意义

研究结果表明,给予RA对FA诱导的肾损伤具有积极作用。这种作用可能是由于参与了SIRT1/NOX1途径,从而减轻了氧化应激。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b75b/11648342/d04d31ee5a59/RPS-19-622-g001.jpg

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