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He-Wei granules (HWKL) combat cisplatin-induced nephrotoxicity and myelosuppression in rats by inhibiting oxidative stress, inflammatory cytokines and apoptosis

Author:
Song, Zehai, Chang, Hang, Han, Na, Liu, Zhihui, Liu, Ye, Wang, Hui, Shao, Jingxuan, Wang, Zhonglin, Gao, Hao, Yin, Jun
Source:
RSC advances 2017 v.7 no.32 pp. 19794-19807
ISSN:
2046-2069
Subject:
adverse effects, apoptosis, blood serum, cisplatin, creatinine, drug therapy, granules, humans, interleukin-1beta, intraperitoneal injection, laboratory animals, messenger RNA, mitogen-activated protein kinase, necrosis, neoplasms, nephrotoxicity, oxidative stress, patients, prostaglandin synthase, protective effect, quality of life, rats, tumor necrosis factor-alpha, urea nitrogen
Abstract:
As a highly effective antineoplastic chemotherapeutic drug, cisplatin is widely used clinically to treat a variety of human malignancies. However, its clinical use is severely limited by serious side-effects, of which nephrotoxicity and myelosuppression are considered to be the most important because they significantly reduce patient life quality and hinder effective use. In this study, we investigated whether HWKL, a product obtained from modified Ban-xia xie-xin decoction first described 1700 years ago, exhibits protective effects against cisplatin-induced nephrotoxicity and myelosuppression. After intraperitoneal injection of 7 mg kg⁻¹ cisplatin to Wistar rats, nephrotoxicity and myelosuppression were observed. HWKL reduced cisplatin-induced elevations in blood urea nitrogen (BUN) and serum creatinine (Scr) levels, increased water intake and improved renal tubular lesions. Cisplatin-induced increases in tumor necrosis alpha (TNF-α) protein, interleukin-1 beta (IL-1β) protein, cyclooxygenase-2 (COX-2) protein, extracellular signal-regulated kinase (ERK), TNF-α mRNA and IL-1β mRNA were significantly reduced by HWKL and cisplatin-induced oxidative stress was also inhibited by HWKL. Furthermore, HWKL contributed to increase immunological function to combat cisplatin-induced myelosuppression. Our findings indicate that HWKL inhibits cisplatin-induced nephrotoxicity and myelosuppression via several mechanisms which operate simultaneously and provide basic evidence to confirm that HWKL could be useful in clinical situations as a protective agent to prevent cisplatin-induced nephrotoxicity and myelosuppression.
Agid:
6416239