Effect of 1,3-dithia-2-thioxo-cyclopent-4-ene and its derivatives on liver injury induced by carbon tetrachloride and orotic acid in rats.
The protective effect of 1,3-dithia-2-thioxo-cyclopent-4-ene (DT827A) and its two derivatives of 4-phenyl-1,3-dithia-2-thioxo-cyclopent-4-ene (DT827B) and 4-(4-fluorophenyl)-1,3-dithia-2-thioxo-cyclopent-4-ene (DT827C) on liver injury induced by carbon tetrachloride (CCl4) and orotic acid was studied using male rats. The approximate lethal doses were about 100 mg/kg for DT827A-treated animals and more than 800 mg/kg for the other two compounds-treated groups. Single oral administration of the three test compounds at the dose levels of 2 and 10 mg/kg 1 hour before CCl4 exposure revealed a protective effect on the findings of centrolobular necrosis, balloon cells and macrophage infiltration in histopathological findings in livers in the order of DT827B-treated rats > DT827A-treated rats > DT827C-treated rats. Repeated oral administration of the compounds at the dose levels of 2 and 10 mg/kg/day for 10 consecutive days revealed a protective effect against liver injury on the findings of centrolobular necrosis, balloon cells and macrophage infiltration in the order of DT827B-treated rats > DT827A-treated rats [symbol: see text] DT827C-treated rats. Simultaneous administration of the compounds at the dose level of 10 mg/kg/day together with a high sucrose diet containing orotic acid for 12 days revealed an inhibitory effect on fatty liver formation in the order of DT827B-treated rats > DT827C-treated rats > DT827A-treated rats. A hepatoprotective potential of the DT827 series compounds was suggested under the conditions of these studies, and DT827B was considered to be the most effective.
Sadanobu
S
S
Department of Hygienic Chemistry, College of Pharmacy, Nihon University, Chiba, Japan.
Takeuchi
M
M
Tezuka
M
M
D000284:Administration, Oral; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000517:prevention & control*; D056486:Chemical and Drug Induced Liver Injury; D005234:Fatty Liver / Q000139:chemically induced / Q000517:prevention & control; D006573:Heterocyclic Compounds, 1-Ring / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D009963:Orotic Acid / Q000506:poisoning*; D051381:Rats; D017208:Rats, Wistar; D013871:Thiones / Q000008:administration & dosage / Q000494:pharmacology*
C111193:1,3-dithia-2-thioxocyclopent-4-ene; C111195:4-(4-fluorophenyl)-1,3-dithia-2-thioxocyclopent-4-ene; C111194:4-phenyl-1,3-dithia-2-thioxocyclopent-4-ene; D006573:Heterocyclic Compounds, 1-Ring; D013871:Thiones; D009963:Orotic Acid