Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sulphur-containing drug, di-isopropyl-1,3-dithiol-2-ylidenemalonate (Malotilate) protects against the increase in hepatic triglyceride concentration after acute ethanol administration (either 6 g/kg p.o. or 2 g/kg i.p.) in rats. The compound had no influence on the increased hepatic NADH:NAD ratio (measured as the lactate:pyruvate and 3-hydroxybutyrate:acetoacetate ratios) after acute ethanol dosing (2 g/kg i.p.), but was found to lower hepatic acetaldehyde concentrations and prevent some of the disturbances in lipid metabolism observed in liver slices from ethanol-treated animals (e.g. decreased oxidation of [1-14C]palmitate to 14CO2) after this ethanol dose. The drug did not inhibit ethanol metabolism in this acute experiment. Administration of Malotilate to Wistar rats (100 mg/kg/day orally) during chronic feeding of ethanol as 36% of the total calorie intake in a liquid diet, resulted in a lower intake of the alcohol-containing diet by ethanol-fed animals and reduced body weight gain in rats which received the drug, without blood ethanol levels or the ethanol intake (expressed in g/kg body weight/day) being affected. In ethanol-fed animals, Malotilate prevented the production of fatty liver and the adaptive increase in the ethanol elimination rate (EER) normally seen in ethanol-fed animals, although the drug actually caused a slight increase in EER in glucose pair-fed controls. Malotilate did not significantly decrease the degree of induction of microsomal cytochrome P-450 by ethanol, but the increase in aniline hydroxylation was much less marked in animals receiving ethanol and Malotilate, suggesting that the activity of the inducible microsomal ethanol oxidising system (MEOS) may be reduced by the compound. Determination of hepatic acetaldehyde concentrations during ethanol feeding, and during an acute ethanol challenge test following long-term ethanol treatment showed that the compound significantly lowered the level of this ethanol metabolite in the liver under both circumstances. This reduction of hepatic acetaldehyde concentrations, probably resulting in part from the reduced EER as well as increased low-Km aldehyde dehydrogenase activities and glutathione contents seen in the livers of Malotilate-treated rats, are possible mechanisms by which the drug protects against triglyceride accumulation after ethanol administration.
 ...
PMID:The effect of di-isopropyl 1,3 dithiol-2-ylidenemalonate (malotilate) on the hepatic changes induced by ethanol administration in the rat. 314 67

The mode of action of malotilate in normalizing serum cholesterol in hypocholesterolemic rats with fatty liver was examined by determination of biosynthesis, catabolism and excretion of cholesterol. Fatty liver was produced by subcutaneous injection of CCl4 at the dose of 1 ml/kg into male rats (SLC-SD) twice a week for 3 weeks. Daily administration of malotilate (100 mg/kg) in rats with hypocholesterolemia resulted in a rapid normalization of lowered serum cholesterol. Such a recovery of cholesterol level in serum coincided in time with normalization of the decreased cholesterol level of each lipoprotein fraction, VLDL-triglycerides secretion and the decreased apolipoprotein A1 value. Histopathological improvement in liver was also confirmed by a decrease in the size of fat droplets stored within the hepatocytes. The malotilate treatment gave a tendency to facilitate hepatic cholesterol synthesis in rats with fatty liver. Malotilate at a concentration of 0.5-2 micrograms/ml also stimulated cholesterol biosynthesis in cultured normal hepatocytes. The drug had the action to accelerate the catabolic excretion of 3H-labeled cholesterol into feces. These results suggest that the mode of action by which serum cholesterol is normalized in rats with fatty liver is probably due to a stimulative effect of malotilate on hepatic cholesterol synthesis and cholesterol secretion from the liver.
 ...
PMID:Action of malotilate on reduced serum cholesterol level in rats with carbon tetrachloride-induced liver damage. 393 40