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标题：Telmisartan Exacerbates Cisplatin-Induced Nephrotoxicity in a Mouse Model
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作者：Atsuki Hosoda ; Yoshio Matsumoto ; Yuuki Toriyama 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2020
卷号：43
期号：9
页码：1331-1337
DOI：10.1248/bpb.b20-00174
出版社：The Pharmaceutical Society of Japan
摘要：Cisplatin (CDDP; cis -diamine dichloroplatinum)-induced nephrotoxicity is the main reason for dose limitations, which can reduce the efficacy of cancer treatment.Lower blood pressure and administration of renin angiotensin system (RAS) inhibitors have been reported as factors that exacerbate CDDP-induced nephrotoxicity; however, the detailed mechanisms remain unknown and the results of previous studies are conflicting.In this study, we examined the influence of various hypotensive drugs, including RAS inhibitors and calcium channel blockers, on CDDP-induced nephrotoxicity in BALB/c mice.The mice were divided into nine groups: (1) CDDP group (15 mg/kg CDDP), (2) AML group (5 mg/kg amlodipine), (3) ENA group (2.5 mg/kg enalapril), (4) telmisartan (TEL) group (10 mg/kg telmisartan), (5) LOS group (10 mg/kg losartan), (6) CDDP AML group, (7) CDDP ENA group, (8) CDDP TEL group, and (9) CDDP LOS group.Nephrotoxicity was evaluated by measuring serum creatinine (CRE) and blood urea nitrogen (BUN) levels.In addition, the kidney sections were stained with Masson’s trichrome and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) to assess the renal fibrosis area and apoptotic area.Serum CRE and BUN levels were increased in the CDDP ENA, CDDP LOS, and CDDP TEL groups compared to those in the CDDP alone group, and the CDDP AML group showed an increasing trend.However, there was no correlation between ∆CRE or ∆BUN levels and ∆ systolic blood pressure.The CDDP TEL group showed a significant increase in the renal fibrosis area.These results suggest that exacerbation of CDDP-induced nephrotoxicity is not correlated with systolic blood pressure but is associated with administration of RAS inhibitors, particularly TEL.
关键词：cisplatin;nephrotoxicity;telmisartan;renin angiotensin system inhibitor;fibrosis