Betamipron reduces cisplatin nephrotoxicity in rodents without modifying its antileukemic activity in mice.
Protective effects of betamipron (BP, N-benzoyl-beta-alanine), one of a series of N-acyl amino acids, on cisplatin-induced nephrotoxicity were examined. Since the damage observed in the kidney is localized to the proximal tubule cells, we investigated the influence of BP on urinary enzymes and excreta. Male Wistar rats and ddY mice were injected i.p. with 6 mg/kg and 16 mg/kg, respectively, of cisplatin combined with an i.p. 250 mg/kg BP dose. The toxicity of cisplatin as indicated by body weight gain, blood urea nitrogen, and serum creatinine levels was significantly (p < 0.05) suppressed by administration of BP after cisplatin treatment. The increase in urinary N-acetyl-beta-D-glucosaminidase activity, increase and subsequent decrease in gamma-glutamyl transferase activities, and increase in beta 2-microglobulin level observed after treatment with cisplatin were suppressed by administration of BP after cisplatin treatment. The combination of cisplatin and BP had no apparent effect on the efficacy of cisplatin against P388 leukemic cells in mice.
Tokunaga
J
J
Department of Pharmaceutical Services Kumamoto University Hospital, Japan.
Kobayashi
M
M
Nakamura
C
C
Kitagawa
A
A
Arimori
K
K
Nakano
M
M
D000118:Acetylglucosaminidase / Q000652:urine; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000627:therapeutic use / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000627:therapeutic use / Q000633:toxicity*; D003404:Creatinine / Q000097:blood / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology; D007941:Leukemia P388 / Q000188:drug therapy / Q000401:mortality; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D001613:beta 2-Microglobulin / Q000652:urine; D005723:gamma-Glutamyltransferase / Q000652:urine
D000970:Antineoplastic Agents; D001613:beta 2-Microglobulin; C047207:N-benzoylalanine; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D000118:Acetylglucosaminidase; D000409:Alanine; D002945:Cisplatin