Protecting cisplatin-induced nephrotoxicity with cimetidine does not affect antitumor activity. 2010

Hiromu Katsuda, and Mariko Yamashita, and Hideyuki Katsura, and Jia Yu, and Yoshihiro Waki, and Naoto Nagata, and Yoshimichi Sai, and Ken-Ichi Miyamoto
Department of Medicinal Informatics, Graduate School of Medical Science, Kanazawa University, 13–1 Takara-machi, Kanazawa 920–8641, Japan.

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.

UI MeSH Term Description Entries
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008297 Male Males
D010984 Platinum A heavy, soft, whitish metal, resembling tin, with atomic number 78, atomic weight 195.084, symbol Pt. It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". Platinum Black
D012076 Renal Agents Drugs used for their effects on the kidneys' regulation of body fluid composition and volume. The most commonly used are the diuretics. Also included are drugs used for their antidiuretic and uricosuric actions, for their effects on the kidneys' clearance of other drugs, and for diagnosis of renal function. Agents, Renal
D001859 Bone Neoplasms Tumors or cancer located in bone tissue or specific BONES. Bone Cancer,Cancer of Bone,Cancer of the Bone,Neoplasms, Bone,Bone Neoplasm,Neoplasm, Bone
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002927 Cimetidine A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output. Altramet,Biomet,Biomet400,Cimetidine HCl,Cimetidine Hydrochloride,Eureceptor,Histodil,N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine,SK&F-92334,SKF-92334,Tagamet,HCl, Cimetidine,Hydrochloride, Cimetidine,SK&F 92334,SK&F92334,SKF 92334,SKF92334
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D000111 Acetylcysteine The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. Mercapturic Acid,Acemuc,Acetabs,Acetylcystein AL,Acetylcystein Atid,Acetylcystein Heumann,Acetylcystein Trom,Acetylcysteine Hydrochloride,Acetylcysteine Sodium,Acetylcysteine Zinc,Acetylcysteine, (D)-Isomer,Acetylcysteine, (DL)-Isomer,Acetylcysteine, Monoammonium Salt,Acetylcysteine, Monosodium Salt,Acetylin,Acetyst,Acétylcystéine GNR,Airbron,Alveolex,Azubronchin,Bisolvon NAC,Bromuc,Broncho-Fips,Broncholysin,Broncoclar,Codotussyl,Cystamucil,Dampo Mucopect,Eurespiran,Exomuc,Fabrol,Fluimucil,Fluprowit,Frekatuss,Genac,Hoestil,Ilube,Jenacystein,Jenapharm,Lantamed,Larylin NAC,Lindocetyl,M-Pectil,Muciteran,Muco Sanigen,Mucomyst,Mucosil,Mucosol,Mucosolvin,N-Acetyl-L-cysteine,N-Acetylcysteine,NAC AL,NAC Zambon,Optipect Hustengetränk,Siccoral,Siran,Solmucol,acebraus,durabronchal,mentopin Acetylcystein,Acetylcystein, mentopin,Acid, Mercapturic,Broncho Fips,BronchoFips,Hustengetränk, Optipect,Hydrochloride, Acetylcysteine,M Pectil,MPectil,Monoammonium Salt Acetylcysteine,Monosodium Salt Acetylcysteine,Mucopect, Dampo,N Acetyl L cysteine,N Acetylcysteine,NAC, Bisolvon,Sanigen, Muco,Sodium, Acetylcysteine,Zambon, NAC,Zinc, Acetylcysteine

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