Hepatotoxicity of DR-3438, tienilic acid, indacrinone and furosemide studied in vitro.
A new diuretic antihypertensive, DR-3438, and marketed diuretic drugs were evaluated for their toxicity in vitro. Hepatocytes were isolated from male rats by the collagenase perfusion method and incubated in Dulbecco's modified Eagle medium containing various doses of DR-3438, tienilic acid, indacrinone or furosemide. Tienilic acid decreased cell viability and glutathione content in hepatocytes and increased lipid peroxidation in the cells. Indacrinone also decreased cell viability, but neither cell viability nor glutathione content was affected by furosemide or DR-3438.
Takagi
S
S
Drug Safety Research Center, Daiichi Seiyako Co., Ltd., Tokyo, Japan.
Takayama
S
S
Onodera
T
T
D000818:Animals; D001578:Benzopyrans / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004232:Diuretics / Q000633:toxicity*; D005665:Furosemide / Q000633:toxicity*; D005978:Glutathione / Q000032:analysis; D066298:In Vitro Techniques; D007189:Indans / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D013989:Ticrynafen / Q000633:toxicity*
D001578:Benzopyrans; D004232:Diuretics; D007189:Indans; C067756:DR 3438; D005665:Furosemide; C013352:indacrinone; D005978:Glutathione; D013989:Ticrynafen