Protective effect of juzen-taiho-to against carboplatin-induced toxic side effects in mice.
The effect of an oral treatment with the Kampo formulation Juzen-taiho-to on the toxicity caused by the intraperitoneal administration of 15 mg/kg carboplatin (CBDCA) 9 times (on days 3, 4, 5, 6, 7, 8, 10, 11 and 12) was examined in ddY mice, which were subcutaneously inoculated with sarcoma 180 (S-180) cells on day 1. White blood cell counts, platelet counts, bone marrow cell counts, relative spleen and thymus weight, food intake and body weight decreased significantly, to about 29%, 13%, 14%, 59%, 36%, 42% and 72% of the control levels, respectively, and serum glutamic-oxaloacetatic transaminase, serum glutamic-pyruvic transaminase and relative stomach weight increased significantly, to about 4, 6 and 3 times the control levels, respectively, by the treatment with CBDCA. However, the blood urea nitrogen and serum creatinine were only slightly increased compared to the control value. Co-treatment with 1.7 g/kg of a lyophilized water extract of Juzen-taiho-to once a day 12 times (on days 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14 and 15) prevented both the decreases and increases caused by CBDCA to near the control levels without reducing the antitumor activity of CBDCA against S-180. The inhibitory effect of Juzen-taiho-to against CBDCA-induced myelosuppression was similar to that against 3.0 mg/kg cisplatin (CDDP) 9 times, while CBDCA-induced myelosuppression was more serious in comparison with CDDP. Therefore, these findings indicate that Juzen-taiho-to could be an effective drug for protecting against the side effects induced by CBDCA in the clinic as well as by CDDP.
Sugiyama
K
K
School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Ueda
H
H
Ichio
Y
Y
D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001855:Bone Marrow Diseases / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D016190:Carboplatin / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D004435:Eating / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D012510:Sarcoma 180 / Q000188:drug therapy
D004365:Drugs, Chinese Herbal; D007155:Immunologic Factors; C063587:juzentaihoto; D016190:Carboplatin