Effect of D-003, a mixture of high molecular weight primary acids from sugar cane wax, on CL4C-induced liver acute injury in rats.
D-003 is a mixture of very high molecular weight aliphatic primary acids purified from sugar cane (Saccharum officinarum, L.) wax, in which octacosanoic acid is the most abundant component. Previous experimental studies have shown that D-003 not only shows cholesterol-lowering and antiplatelet effects, but also offers strong protection against plasma lipoprotein oxidation. Acute hepatotoxicity induced by CCL4 in rats has been related to an increased rate of lipid peroxidation, and different antioxidant compounds have been revealed to be effective in this model. The aim of this study was to investigate the effects of D-003 in acute hepatotoxicity induced by CCL4 in rats. Male Sprague Dawley rats were randomly distributed in four experimental groups as follows: group 1: negative control rats; group 2: positive control rats (CCL4-treated); groups 3 and 4 rats with liver damage induced by CCL4 and treated with D-003 at 25 and 100 mg/kg, respectively. Acute liver injury was induced by CCL4 suspended in olive oil and intraperitoneally administered at 1 ml/kg. Eighteen hours after CCL4 dosing, the rats were anesthetized with ether and their livers were removed for histopathological studies. D-003 at 25 and 100 mg/kg significantly (p < 0.01) decreased the percentage of ballooned cells and hepatocytes with lipidic inclusions and increased the percentage of normal hepatocytes compared with that in positive controls in a dose-dependent manner. The percent inhibitions of the occurrence of ballooned cells and hepatocytes with lipids were marked (75% and 50%, respectively) with the high dose (100 mg/kg). The percent of turgent hepatocytes was also significantly reduced compared with that in positive controls, but this effect was not dose-dependent. No histological alterations in the liver sections of negative controls were found. Necrotic areas and inflammatory infiltrate were observed in the liver of 7/8 (87.5%) of positive controls. In turn, D-003 dramatically reduced both necrotic areas and inflammatory infiltrate and was present in only 1/8 (12.5%) animals treated with D-003 25 mg/kg and in none (0%) of the animals treated with 100 mg/kg. D-003 protected against the histological changes characteristic of CCL4-induced hepatic injury in rats, in which the process of lipid peroxidation plays the main role. The relationship between this protective action of D-003 on this experimental model and its antioxidant effects needs to be further investigated before definitive conclusions are drawn.
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Center for Natural Products, National Center for Scientific Research, Ave. 25 and 158 Street, Post Box 6990, Havana City, Cuba.
Mendoza
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002251:Carbon Tetrachloride / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury; D005227:Fatty Acids / Q000008:administration & dosage / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000293:injuries; D008107:Liver Diseases / Q000188:drug therapy; D008297:Male; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D031786:Saccharum
D000975:Antioxidants; C418063:D-003 sugarcane wax acid mixture; D005227:Fatty Acids; D002251:Carbon Tetrachloride