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

Song, Zehai, Chang, Hang, Han, Na, Liu, Zhihui, Liu, Ye, Wang, Hui, Shao, Jingxuan, Wang, Zhonglin, Gao, Hao, Yin, Jun
RSC advances 2017 v.7 no.32 pp. 19794-19807
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
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.