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

Abstract

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 100mg/kg for DT827A-treated animals and more than 800mg/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 ≒ 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.