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Protecting Cisplatin-induced nephrotoxicity with cimetidine does not affect antitumor activity.
MedLine Citation:
PMID:  21048313     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
The present study examined the influence of cimetidine on the nephrotoxicity and antitumor effects of cisplatin in vitro and in vivo. When the serum concentration of cimetidine was maintained over 20 µg/ml for 4 h by bolus and continuous intravenous infusion, cimetidine prevented nephrotoxicity of cisplatin without influencing antitumor activity. Cimetidine and the antioxidant N-acetylcysteine (NAC) significantly inhibited the in vitro growth inhibition of cisplatin in cells originating from the kidney, but not in SOSN2 osteosarcoma cells. Cimetidine (1 mM) also did not influence platinum concentration in the cells, regardless of whether the organic cation transporter 2 (OCT2) was expressed. Cisplatin did induce reactive oxygen species (ROS) in the KN41 kidney cell line and cimetidine and NAC significantly reduced ROS production. However, cisplatin did not produce ROS in osteosarcoma cells. From these results, cimetidine clearly inhibits nephrotoxicity induced by cisplatin without any influence on the antitumor activity of cisplatin on osteosarcoma in vitro and in vivo.
Authors:
Hiromu Katsuda; Mariko Yamashita; Hideyuki Katsura; Jia Yu; Yoshihiro Waki; Naoto Nagata; Yoshimichi Sai; Ken-Ichi Miyamoto
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  33     ISSN:  1347-5215     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2010  
Date Detail:
Created Date:  2010-11-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  1867-71     Citation Subset:  IM    
Affiliation:
Department of Medicinal Informatics, Graduate School of Medical Science, Kanazawa University, 13–1 Takara-machi, Kanazawa 920–8641, Japan.
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