101. Protective effect of sodium L-malate, an active constituent isolated from Angelicae radix, on cis-diamminedichloroplatinum(II)-induced toxic side effect
- Author
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Kiyoshi Sugiyama, Yoshitomo Suhara, Harumi Ueda, Yoshimasa Ichio, Masami Yokota, and Yasuhiro Kajima
- Subjects
Male ,Magnetic Resonance Spectroscopy ,Chemical Phenomena ,Spectrophotometry, Infrared ,Stereochemistry ,Sodium ,Malates ,chemistry.chemical_element ,Sodium malate ,Antineoplastic Agents ,Mice, Inbred Strains ,Pharmacology ,Nephrotoxicity ,chemistry.chemical_compound ,Mice ,White blood cell ,Drug Discovery ,Weight Loss ,medicine ,Animals ,Sarcoma 180 ,Blood urea nitrogen ,Bone Marrow Diseases ,Plants, Medicinal ,Chemistry ,Chemistry, Physical ,Biological activity ,General Chemistry ,General Medicine ,medicine.anatomical_structure ,Toxicity ,Kidney Diseases ,Bone marrow ,Cisplatin ,Neoplasm Transplantation ,Drugs, Chinese Herbal - Abstract
The effects of ingredients of Shi-Quan-Da-Bu-Tang (Juzen-taiho-to) on the nephrotoxicity and bone marrow toxicity caused by i.p. administration of 3 mg/kg cis-diamminedichloroplatinum (II) (CDDP) 9 times (on days 3, 4, 5, 6, 7, 8, 10, 11, 12) were examined in ddY mice s.c. inoculated with sarcoma 180 (S-180) cells on day 1. Angelicae Radix showed the strongest protective effect against the toxicity among the ingredients. The ED50 of a water extract of Angelicae Radix was 17.8 mg/kg for nephrotoxicity (indicated by an increase in blood urea nitrogen) and 59.4 mg/kg for bone marrow toxicity (indicated by a decrease in white blood cell count), when it was administered perorally (p.o.) on days, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15. The water extract did not exert any significant effect on the antitumor activity of CDDP. Bioassay-directed fractionation of the water extract resulted in isolation of a constituent having protective effects against the toxicity: sodium L-malate, C4H4Na2O5, was found to exhibit protective effects against both nephrotoxicity (ED50: 0.4 mg/kg, p.o.) and bone marrow toxicity (ED50: 1.8 mg/kg, p.o.), without reducing the antitumor activity of CDDP. These findings indicate that Angelicae Radix and its constituent sodium L-malate could provide significant protection against CDDP-induced nephrotoxicity and bone marrow toxicity without reducing the antitumor activity.
- Published
- 1994