The protective effect of 4-hydroxy-2-methyl-N-[2-(tetrazol-5-yl)- phenyl]-2H-1, 2-benzothiazine-3-carboxamide-1, 1-dioxide monosodium salt (HX-1920) on cisplatin-induced toxicity in rats.
The protective effect of 4-hydroxy-2-methyl-N-[2-(tetrazol-5-yl)-phenyl]-2H-1, 2-benzothiazine-3-carboxamide-1, 1-dioxide monosodium salt (HX-1920) on the nephrotoxicity of cisplatin was studied in rats. Effects of HX-1920 on antitumor activity and emesis induced by cisplatin were also examined using mice and ferrets, respectively. All 10 rats injected with both HX-1920 and LD50 of cisplatin survived for 14 days. After 24 hr, co-administration of HX-1920 significantly increased the urinary excretion of cisplatin in rats. HX-1920 also significantly inhibited the cisplatin-induced elevation of urinary N-acetyl-beta-D-glucosaminidase, blood urea nitrogen and plasma creatinine concentrations in rats. HX-1920 had no effect on the number of white blood cell. HX-1920 tended to reduce the emesis induced by cisplatin in ferrets. Furthermore, there was no difference in the survival curve between the cisplatin group and the HX-1920 plus cisplatin group in mice inoculated with P 388 leukemia cells. Thus, HX-1920 did not modify the antitumor activity of cisplatin. These results suggest that HX-1920 has a protective effect on the nephrotoxicity of cisplatin without inhibiting its antitumor activity.
Shiroshita
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Higashi-Nippon-Gakuen University, Hokkaido, Japan.
Minami
M
M
Endo
T
T
Monma
Y
Y
Asaka
M
M
Itoh
H
H
Ikeda
T
T
Matsumoto
H
H
Satoh
T
T
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity* / Q000652:urine; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D005289:Ferrets; D007668:Kidney / Q000187:drug effects*; D007928:Lethal Dose 50; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D013843:Thiazines / Q000494:pharmacology*
D013843:Thiazines; D003404:Creatinine; D000118:Acetylglucosaminidase; D002945:Cisplatin; C100301:sudoxicam