Huaiqihuang (HQH) granule alleviates cyclophosphamide-induced nephrotoxicity via suppressing the MAPK/NF-κB pathway and NLRP3 inflammasome activation
Autor: | Huan Gao, Lina Tao, Jinghui Zhai, Yueming Zhang, Yanqing Song, Xiaoyu Qu, Jian Chang, Jingmeng Sun |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
MAPK/ERK pathway Cyclophosphamide Inflammasomes MAP Kinase Signaling System chinese medicine Pharmaceutical Science Inflammation RM1-950 Pharmacology medicine.disease_cause Nephrotoxicity Rats Sprague-Dawley chemistry.chemical_compound NLR Family Pyrin Domain-Containing 3 Protein Drug Discovery medicine Animals oxidative stress Antineoplastic Agents Alkylating chemotherapeutic agent Granule (cell biology) NF-kappa B apoptosis NF-κB General Medicine Rats Complementary and alternative medicine chemistry Apoptosis inflammation Molecular Medicine Kidney Diseases Therapeutics. Pharmacology medicine.symptom Oxidative stress Drugs Chinese Herbal Research Article medicine.drug |
Zdroj: | Pharmaceutical Biology, Vol 59, Iss 1, Pp 1425-1431 (2021) Pharmaceutical Biology article-version (VoR) Version of Record |
ISSN: | 1744-5116 1388-0209 |
Popis: | 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. |
Databáze: | OpenAIRE |
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