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坎地沙坦和硫代硫酸钠对肾结石大鼠模型肾组织结石损伤的改善作用。

Amelioration of lithiatic injury to renal tissue by candesartan and sodium thiosulfate in a rat model of nephrolithiasis.

机构信息

Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt.

出版信息

PLoS One. 2021 May 13;16(5):e0251408. doi: 10.1371/journal.pone.0251408. eCollection 2021.

Abstract

AIM

Nephrolithiasis is a chronic metabolic condition affecting 10% of population worldwide. The present study aimed to investigate the possible protective role of candesartan (CAND) and sodium thiosulfate (STS) in ameliorating ethylene glycol (EG) induced nephrolithiasis.

METHODS

One hundred male Wistar rats were divided into five groups: Normal control group, nephrolithiasis (EG) group (1% EG in drinking water), Cystone (CYS) group (EG + 750 mg/kg CYS, orally, once daily), STS group (EG + 0.4 gm/kg STS, intraperitoneally, 3 times/week) and CAND group (EG + 70 μg/mL CAND in drinking water). Treatments and EG administration commenced on the same day and continued for 28 days. CYS was used as reference drug. Urine, blood, and renal tissues were collected at the end of the experiment for assessment of kidney function tests (serum creatinine and urea), urinary (8-hydroxydeoxyguanosine (8-OHdG), calcium and oxalate), inflammatory and oxdative stress biomarkers (transforming growth factor beta (TGF-β), osteopontin (OPN) and ratio of reduced glutathione to oxidized glutathione (GSH/GSSG)) in renal tissue.

RESULTS

Serum (creatinine and urea), urinary (8-OHdG and oxalate) and renal (OPN and TGF-β) were significantly reduced in CAND and STS groups compared to EG group. Furthermore, renal GSH/GSSG and urinary calcium were significantly increased in CAND and STS groups compared to EG group. Histopathological results support the biochemical findings; CAND and STS groups showed less retention of crystals and necrotic damage in kidney. Also, microscopic examination of urine revealed less crystal for CAND and STS groups.

CONCLUSION

Candesartan and sodium thiosulfate exhibited protective effect against nephrolithiasis.

摘要

目的

肾结石是一种影响全球 10%人口的慢性代谢性疾病。本研究旨在探讨坎地沙坦(CAND)和硫代硫酸钠(STS)在改善乙二醇(EG)诱导的肾结石中的可能保护作用。

方法

100 只雄性 Wistar 大鼠分为五组:正常对照组、肾结石(EG)组(饮用水中 1%EG)、结石通(CYS)组(EG+750mg/kg CYS,口服,每日 1 次)、STS 组(EG+0.4gm/kg STS,腹腔内,每周 3 次)和 CAND 组(EG+70μg/mL CAND 在饮用水中)。治疗和 EG 给药于同一天开始,并持续 28 天。CYS 用作参考药物。实验结束时收集尿液、血液和肾脏组织,用于评估肾功能试验(血清肌酐和尿素)、尿液(8-羟基脱氧鸟苷(8-OHdG)、钙和草酸盐)、炎症和氧化应激生物标志物(转化生长因子-β(TGF-β)、骨桥蛋白(OPN)和还原型谷胱甘肽与氧化型谷胱甘肽(GSH/GSSG)的比值)在肾组织中。

结果

与 EG 组相比,CAND 和 STS 组的血清(肌酐和尿素)、尿液(8-OHdG 和草酸盐)和肾脏(OPN 和 TGF-β)均显著降低。此外,CAND 和 STS 组的肾 GSH/GSSG 和尿钙均明显高于 EG 组。组织病理学结果支持生化发现;CAND 和 STS 组在肾脏中保留的晶体和坏死损伤较少。此外,CAND 和 STS 组的尿液显微镜检查显示晶体较少。

结论

坎地沙坦和硫代硫酸钠对肾结石具有保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd74/8118324/deb3eedf22b5/pone.0251408.g003.jpg

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