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坎地沙坦通过 GDF-15 途径保护顺铂诱导的肾脏损伤。

Candesartan protects from cisplatin-induced kidney damage via the GDF-15 pathway.

机构信息

Department of Medical Oncology, Medical Point Hospital, University of Economy, Izmir, Turkey.

出版信息

Eur Rev Med Pharmacol Sci. 2024 Feb;28(3):1103-1110. doi: 10.26355/eurrev_202402_35347.

Abstract

OBJECTIVE

The aim of this study was to explore the protective effect of candesartan against cisplatin-induced kidney damage, with a specific focus on the growth differentiation factor 15 (GDF-15) pathway.

MATERIALS AND METHODS

24 adult female Wistar rats, with a weight range of 200-210 grams, were enrolled in the study. Eight rats were included as a normal control group and did not receive any medication. 16 rats were administered cisplatin at a dosage of 2.5 mg/kg/day twice a week for 4 weeks (total dose 20 mg/kg). Then, they were randomly divided into two groups and treated with 1 ml/kg/day tap water or 8 mg/kg/day candesartan via oral gavage daily for 4 weeks. At the end of the treatment period, animals were sacrificed, and their kidneys were assessed histologically. In addition, plasma malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), creatinine, and GDF-15 levels were assessed.

RESULTS

Treatment with candesartan resulted in a significant rise in serum GDF-15 levels and a significant reduction in levels of serum MDA, TNF-α, IL-6, and creatinine compared to the cisplatin and saline group. Candesartan treatment effectively protected the kidney injury, and histopathological examinations of the kidneys confirmed these results.

CONCLUSIONS

This study demonstrates that candesartan alleviates cisplatin-induced renal toxicity by further increasing GDF-15, downregulating inflammatory markers, and reducing oxidative stress.

摘要

目的

本研究旨在探讨坎地沙坦对顺铂诱导的肾损伤的保护作用,特别关注生长分化因子 15(GDF-15)途径。

材料和方法

24 只成年雌性 Wistar 大鼠,体重范围为 200-210 克,纳入本研究。8 只大鼠作为正常对照组,不给予任何药物。16 只大鼠每周两次给予顺铂 2.5mg/kg/天,共 4 周(总剂量 20mg/kg)。然后,它们被随机分为两组,分别给予 1ml/kg/天的自来水或 8mg/kg/天的坎地沙坦通过口服灌胃每天 4 周。在治疗期末,处死动物并评估其肾脏的组织学变化。此外,评估了血浆丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、肌酐和 GDF-15 水平。

结果

与顺铂和生理盐水组相比,坎地沙坦治疗导致血清 GDF-15 水平显著升高,血清 MDA、TNF-α、IL-6 和肌酐水平显著降低。坎地沙坦治疗有效保护了肾损伤,肾脏的组织学检查结果证实了这一点。

结论

本研究表明,坎地沙坦通过进一步增加 GDF-15、下调炎症标志物和减轻氧化应激,减轻顺铂诱导的肾毒性。

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