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

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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 LD_<50> 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-β-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 1eukemia 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.
日本トキシコロジー学会の論文
1993-02-25