[Effect of azosemide (SK-110) and its metabolites on mouse liver].
The effect of azosemide (SK-110), and its metabolites, 5-(2'-amino-4'-chloro-5'-sulfamoylphenyl)-tetrazole (M-1), 2-thiophenecarboxylic acid (TC), on mouse liver was investigated using biochemical and pathological parameters as indices of hepatotoxicity. The effects were compared with that of furosemide (FM) administration. A single dose of each compound was administered orally, or intraperitoneally, while multiple oral dosing was carried out once daily for a week. The results are summarized as follows: 1) SK-110 did not produce hepatotoxicity even after a single p.o. dose as high as 5000 mg/kg, a single i.p. dose of 400 mg/kg, or multiple p.o. doses of 700 mg/kg/day. 2) M-1 also did not produce hepatotoxicity even after a single p.o. dose of 4000 mg/kg or multiple p.o. doses of 550 mg/kg/day. TC did not exert hepatotoxicity after a single i.p. dose of 150 mg/kg or multiple p.o. doses of 250 mg/kg/day, but did produce hepatotoxicity after a single p.o. dose of more than 1000 mg/kg. However, it was presumed that, in vivo, TC formed as a metabolite of administered SK-110 would hardly produce hepatotoxicity. 3) FM produced hepatotoxicity after a single p.o. dose of more than 800 mg/kg, or a single i.p. dose of more than 200 mg/kg, but not after multiple p.o. doses of 700 mg/kg/day. Based on these findings, it was concluded that, in contrast to FM, SK-110 had no hepatotoxic effect on the mouse liver.
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002264:Carboxylic Acids; D004232:Diuretics / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000633:toxicity; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D013424:Sulfanilamides / Q000008:administration & dosage / Q000633:toxicity*; D013876:Thiophenes / Q000008:administration & dosage / Q000633:toxicity*; D013777:Tetrazoles; D000096926:Benzenesulfonamides
D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D002264:Carboxylic Acids; D004232:Diuretics; D005665:Furosemide; D013424:Sulfanilamides; D013876:Thiophenes; C550746:2-thiophene carboxylic acid; C018222:azosemide; D013777:Tetrazoles; D000096926:Benzenesulfonamides