Effect of malotilate on chronic liver injury induced by carbon tetrachloride in the rat.
The effect of malotilate, a new drug proposed for the treatment of chronic liver diseases, was studied in carbon tetrachloride (CCl4)-induced chronic liver injury in the rat. Treatment with CCl4 (0.5 ml/kg twice per week, intraperitoneally for 6 or 9 weeks) led to marked necrosis, steatosis and fibrosis, as shown by both biochemical and histological examinations, and a significant decrease of the bromosulfophtaleine (BSP) clearance test. Malotilate (50 mg/kg p.o., 5 days per week given simultaneously with CCl4 for 6 weeks), suppressed the increase of plasma aminotransferase activity and decreased significantly the accumulation of lipid and collagen in the liver; histology confirmed this protective effect of malotilate. The BSP clearance test returned to normal values and the rise in hepatic collagen synthesis activity in the malotilate-treated and intoxicated rats was reduced as compared with intoxicated control rats. The same effect was found when malotilate (100 mg/kg, p.o., 5 days per week), was given for 3 weeks to rats already intoxicated during the 6 previous weeks. Malotilate was able to prevent the increase of hepatic alterations that appeared during the last 3 weeks of CCl4 intoxication. These results show clearly that malotilate can markedly reduce the hepatic disorders induced by a chronic CCl4 intoxication in the rat.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002251:Carbon Tetrachloride; D002908:Chronic Disease; D003094:Collagen / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008314:Malonates / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D051381:Rats
D008314:Malonates; D003094:Collagen; D002251:Carbon Tetrachloride; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate