Protective effects of betamipron on renal toxicity during repeated cisplatin administration in rats and protective mechanism.
The protective effects of betamipron (BP, N-benzoyl-beta-alanine) against nephrotoxicity induced by repeated cisplatin injections were examined. The ratio of the kidney weight to body weight and the lipid peroxide level after treatment with cisplatin plus BP tended to be larger and lower than those after treatment with cisplatin plus alkaline solution, respectively. The blood urea nitrogen, serum creatinine and glutathione levels in the animals treated with cisplatin plus BP differed significantly from those in the animals treated with cisplatin plus alkaline solution. Furthermore, the mechanism of the preventive effects of BP was analyzed for cisplatin-induced nephrotoxicity. The concentration of cisplatin in the renal cortex significantly decreased with concomitant BP. BP inhibited the uptake of cisplatin into the renal cortex in a competitive manner in the same way as an anionic transport inhibitor, probenecid. The treatment with BP appears to be useful for the renal toxicity induced by repeated cisplatin administration.
Tokunaga
J
J
Department of Pharmaceutical Services, Kumamoto University Hospital, Japan.
Kobayashi
M
M
Kitagawa
A
A
Nakamura
C
C
Arimori
K
K
Nakano
M
M
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D002945:Cisplatin / Q000493:pharmacokinetics / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects*; D007672:Kidney Cortex / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D008054:Lipid Peroxides; C047207:N-benzoylalanine; D002374:Catalase; D005978:Glutathione; D000409:Alanine; D002945:Cisplatin