Abstract

Context

Severe nephrotoxicity greatly limits the clinical use of the common effective chemotherapeutic agent cyclophosphamide (CYP). Huaiqihuang (HQH) is a Chinese herbal complex with various pharmacological activities, widely used for treating kidney disease.

Objective

This study estimates the protective effect of HQH against CYP-induced nephrotoxicity in rats.

Materials and methods

Four groups of 10 Sprague-Dawley rats were pre-treated with once-daily oral gavage of 3 and 6 mg/kg HQH for 5 days before receiving a single dose of CYP (200 mg/kg i.p.) on the 5th day; the control group received equivalent dose of saline. Renal function indices, morphological changes, oxidative stress, apoptosis and inflammatory mediators were measured. In addition, phosphorylation of the NF-κB/MAPK pathway and the activation of the NLRP3 inflammasome were analysed.

Results

Both doses of HQH reduced the levels of serum creatinine (31.27%, 43.61%), urea nitrogen (22.66%, 32.27%) and urine protein (12.87%, 15.98%) in the CYP-treated rats, and improved histopathological aberrations. Additionally, HQH decreased the production of MDA (37.02%, 46.18%) and increased the activities of antioxidant enzyme CAT (59.18%, 112.25%) and SOD (67.10%, 308.34%) after CYP treatment. HQH protected against CYP-induced nephrotoxicity by modulating apoptosis-related protein and suppressing the inflammatory responses. Furthermore, the phosphorylation of the NF-κB/MAPK pathway and the activation of the NLRP3 inflammasome were significantly boosted in CYP-treated rats, which was also abrogated by HQH treatment.

Conclusions

HQH effectively protected against CYP-induced nephrotoxicity, which was associated with regulating oxidative stress, apoptosis and inflammation, and so HQH may be a useful agent for treating nephrotoxicity caused by CYP.

中文翻译：

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怀芪黄颗粒通过抑制 MAPK/NF-κB 通路和 NLRP3 炎性体激活减轻环磷酰胺肾毒性

摘要

语境

严重的肾毒性极大地限制了常用的有效化疗药物环磷酰胺（CYP）的临床应用。怀芪黄（HQH）是一种具有多种药理活性的中药复方，广泛用于治疗肾病。

客观的

本研究估计了 HQH 对大鼠 CYP 诱导的肾毒性的保护作用。

材料和方法

四组 10 只 Sprague-Dawley 大鼠在第 5 天接受单剂量 CYP (200 mg/kg ip) 前，用 3 和 6 mg/kg HQH 每日一次口服管饲法预处理 5 天；对照组给予等剂量生理盐水。测量肾功能指标、形态学变化、氧化应激、细胞凋亡和炎症介质。此外，分析了 NF-κB/MAPK 通路的磷酸化和 NLRP3 炎性体的激活。

结果

两种剂量的 HQH 均降低了 CYP 治疗大鼠的血清肌酐（31.27%、43.61%）、尿素氮（22.66%、32.27%）和尿蛋白（12.87%、15.98%）水平，并改善了组织病理学异常。此外，经CYP处理后，HQH降低了MDA的产生（37.02%、46.18%），增加了抗氧化酶CAT（59.18%、112.25%）和SOD（67.10%、308.34%）的活性。HQH 通过调节细胞凋亡相关蛋白和抑制炎症反应来防止 CYP 诱导的肾毒性。此外，在 CYP 处理的大鼠中，NF-κB/MAPK 通路的磷酸化和 NLRP3 炎性体的激活显着增强，而 HQH 处理也消除了这一点。

结论

HQH 有效地保护免受 CYP 诱导的肾毒性，这与调节氧化应激、细胞凋亡和炎症有关，因此 HQH 可能是治疗 CYP 引起的肾毒性的有用药物。