Huaiqihuang (HQH) granule alleviates cyclophosphamide-induced nephrotoxicity via suppressing the MAPK/NF-κB pathway and NLRP3 inflammasome activation. (1st January 2021)

• Record Type: Journal Article
• Authors: Zhang, Yueming; Chang, Jian; Gao, Huan; Qu, Xiaoyu; Zhai, Jinghui; Tao, Lina; Sun, Jingmeng; Song, Yanqing
• Is Part Of: Pharmaceutical biology. Volume 59:Number 1(2021)
• Page Start: 1423
• Page End: 1429
• Publication Date: 2021-01-01
• Subjects: Chinese medicine -- chemotherapeutic agent -- oxidative stress -- apoptosis -- inflammation; Pharmacognosy -- Periodicals; Materia medica, Vegetable -- Periodicals; 615.321
• DOI: 10.1080/13880209.2021.1990356
• Languages: English
• ISSNs: 1388-0209

Abstract

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.