caa a22 4500 467954623 CHVBK 20180405193746.0 cr unu---uuuuu 170328e20040101xx s 000 0 eng 10.1007/s00280-003-0706-9 doi (NATIONALLICENCE)springer-10.1007/s00280-003-0706-9 (NATIONALLICENCE)springer-10.1007/BF02665350 Citrate enhances the protective effect of orally administered bismuth subnitrate against the nephrotoxicity of cis -diamminedichloroplatinum [Elektronische Daten] [Yukihiro Kondo, Seiichiro Himeno, Masahiko Satoh, Akira Naganuma, Taiji Nishimura, Nobumasa Imura] Attenuation of the renal toxicity of cis-diamminedichloroplatinum (CDDP) is important in the use of this effective but cytotoxic anticancer agent. We have previously shown that the renal toxicity of CDDP can be efficiently reduced by the induction of metallothionein (MT) by preadministration of bismuth compounds in mice. Bismuth subnitrate (BSN) is used as an antigastric ulcer agent and as an antidiarrheic agent, and is suitable for inducing MT in the kidney in cancer patients. However, due to the low absorption rate of Bi from the gastrointestinal tract, the efficacy of BSN in inducing renal MT is low. In the present study, we examined the effects of citrate as a vehicle for oral administration of BSN on the tissue distribution of Bi and induction of MT in the kidneys and tumors in mice inoculated with Meth-A fibrosarcoma. Renal levels of MT and Bi were markedly increased in the mice given BSN dissolved in citrate solution compared with those given BSN suspended in saline. On the other hand, the use of citrate increased Bi accumulation in the tumor only slightly and did not increase tumor MT levels. Administration of BSN with citrate efficiently depressed the renal toxicity of CDDP, but did not affect its antitumor activity. Since both BSN and citrate are used clinically as pharmaceuticals, the combination regimen of BSN and citrate may be readily applicable as a countermeasure against the adverse side effects of CDDP without affecting its antitumor activity. Springer-Verlag, 2003 Cisplatin nationallicence Metallothionein nationallicence Bismuth nationallicence Nephrotoxicity nationallicence Kondo Yukihiro Department of Urology, Nippon Medical School, Bunkyo-ku, 114, Tokyo, Japan aut Himeno Seiichiro School of Pharmaceutical Sciences, Kitasato University, Minato-ku, 108, Tokyo, Japan aut Satoh Masahiko School of Pharmaceutical Sciences, Kitasato University, Minato-ku, 108, Tokyo, Japan aut Naganuma Akira School of Pharmaceutical Sciences, Kitasato University, Minato-ku, 108, Tokyo, Japan aut Nishimura Taiji Department of Urology, Nippon Medical School, Bunkyo-ku, 114, Tokyo, Japan aut Imura Nobumasa School of Pharmaceutical Sciences, Kitasato University, Minato-ku, 108, Tokyo, Japan aut Cancer Chemotherapy and Pharmacology Springer-Verlag 53/1(2004-01-01), 33-38 0344-5704 53:1<33 2004 53 280 https://doi.org/10.1007/s00280-003-0706-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00280-003-0706-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kondo Yukihiro Department of Urology, Nippon Medical School, Bunkyo-ku, 114, Tokyo, Japan aut NATIONALLICENCE 700 1- Himeno Seiichiro School of Pharmaceutical Sciences, Kitasato University, Minato-ku, 108, Tokyo, Japan aut NATIONALLICENCE 700 1- Satoh Masahiko School of Pharmaceutical Sciences, Kitasato University, Minato-ku, 108, Tokyo, Japan aut NATIONALLICENCE 700 1- Naganuma Akira School of Pharmaceutical Sciences, Kitasato University, Minato-ku, 108, Tokyo, Japan aut NATIONALLICENCE 700 1- Nishimura Taiji Department of Urology, Nippon Medical School, Bunkyo-ku, 114, Tokyo, Japan aut NATIONALLICENCE 700 1- Imura Nobumasa School of Pharmaceutical Sciences, Kitasato University, Minato-ku, 108, Tokyo, Japan aut NATIONALLICENCE 773 0- Cancer Chemotherapy and Pharmacology Springer-Verlag 53/1(2004-01-01), 33-38 0344-5704 53:1<33 2004 53 280 NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02665350 text/html Onlinezugriff via DOI Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE NATIONALLICENCE NL-springer