Reduction of cisplatin toxicity and lethality by sodium malate in mice. 1998

H Ueda, and K Sugiyama, and M Yokota, and K Matsuno, and T Ezaki
Institute of Traditional Chinese Medicines, School of Pharmaceutical Sciences, University of Shizuoka, Yada, Japan.

The effects of oral treatment with sodium malate, an active ingredient of Juzen-taiho-to, on the nephrotoxicity, bone marrow toxicity, hepatotoxicity and gastrointestinal toxicity caused by i.p. administration of 9 doses of 3.0 mg/kg/d cisplatin (CDDP) (on days 3, 4, 5, 6, 7, 8, 10, 11 and 12) were examined in ddY mice inoculated with sarcoma 180 (S-180) cells on day 1 of the study. The CDDP-induced increases in blood urea nitrogen, serum creatinine, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminases and relative stomach weight and the decreases in food intake and body weight were inhibited nearly to the control levels without reducing the antitumor activity of CDDP against S-180 by the oral treatment with sodium malate of 12 doses of more than the equimolar amount of CDDP (on days 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14 and 15). However, the CDDP-induced decreases in white blood cell and platelet counts and relative spleen and thymus weight could not be inhibited completely by combination with sodium malate, even at a dose of twice the equimolar amount of CDDP. The sodium malate-induced reduction of CDDP-induced nephrotoxicity and hepatotoxicity was observed after oral administration, as well as with i.p., s.c. and i.v. administration, and the effect was almost the same for each route of administration. Sodium malate also reduced the toxicity induced by high doses of CDDP (4.5, 6.0, 7.5, 9.0 and 12.0 mg/kg/d) at doses of twice the equimolar amount of CDDP. Sodium malate at a dose of 10.68 mg/kg/d (twice as high as carboplatin, CBDCA) did not reduce the nephrotoxicity, bone marrow toxicity, hepatotoxicity and gastrointestinal toxicity caused by i.p. administration of 9 doses of 15.0 mg/kg/d CBDCA on days 3, 4, 5, 6, 7, 8, 10, 11 and 12 in ddY mice inoculated with sarcoma 180 (S-180) cells on day 1 of the study. From this study, it was suggested that sodium malate could become a useful agent for the reduction of CDDP-induced toxicity, particularly nephrotoxicity and hepatotoxicity.

UI MeSH Term Description Entries
D008293 Malates Derivatives of malic acid (the structural formula: (COO-)2CH2CHOH), including its salts and esters.
D008297 Male Males
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D001772 Blood Cell Count The number of LEUKOCYTES and ERYTHROCYTES per unit volume in a sample of venous BLOOD. A complete blood count (CBC) also includes measurement of the HEMOGLOBIN; HEMATOCRIT; and ERYTHROCYTE INDICES. Blood Cell Number,Blood Count, Complete,Blood Cell Counts,Blood Cell Numbers,Blood Counts, Complete,Complete Blood Count,Complete Blood Counts,Count, Blood Cell,Count, Complete Blood,Counts, Blood Cell,Counts, Complete Blood,Number, Blood Cell,Numbers, Blood Cell
D001774 Blood Chemical Analysis An examination of chemicals in the blood. Analysis, Blood Chemical,Chemical Analysis, Blood,Analyses, Blood Chemical,Blood Chemical Analyses,Chemical Analyses, Blood
D001855 Bone Marrow Diseases Diseases involving the BONE MARROW. Bone Marrow Disease,Disease, Bone Marrow,Diseases, Bone Marrow,Marrow Disease, Bone,Marrow Diseases, Bone
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
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D016190 Carboplatin An organoplatinum compound that possesses antineoplastic activity. cis-Diammine(cyclobutanedicarboxylato)platinum II,Blastocarb,CBDCA,Carboplat,Carbosin,Carbotec,Ercar,JM-8,NSC-241240,Nealorin,Neocarbo,Paraplatin,Paraplatine,Platinwas,Ribocarbo,JM 8,JM8,NSC 241240,NSC241240

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