linoleic-acid and Chemical-and-Drug-Induced-Liver-Injury

Oxylipins are metabolites of polyunsaturated fatty acids that mediate cardiovascular health by attenuation of inflammation, vascular tone, hemostasis, and thrombosis. Very low-density lipoproteins (VLDL) contain oxylipins, but it is unknown whether the liver regulates their concentrations. In this study, we used a perfused liver model to observe the effect of inflammatory lipopolysaccharide (LPS) challenge and soluble epoxide hydrolase inhibition (sEHi) on VLDL oxylipins. A compartmental model of deuterium-labeled linoleic acid and palmitic acid incorporation into VLDL was also developed to assess the dependence of VLDL oxylipins on fatty acid incorporation rates. LPS decreased the total fatty acid VLDL content by 30% [6%,47%], and decreased final concentration of several oxylipins by a similar amount (13-HOTrE, 35% [4%,55%], -1.3 nM; 9(10)-EpODE, 29% [3%,49%], -2.0 nM; 15(16)-EpODE, 29% [2%,49%], -1.6 nM; AA-derived diols, 32% [5%,52%], -2.4 nM; 19(20)-DiHDPA, 31% [7%,50%], -1.0 nM). However, the EPA-derived epoxide, 17(18)-EpETE, was decreased by 75% [49%,88%], (-0.52 nM) with LPS, double the suppression of other oxylipins. sEHi increased final concentration of DHA epoxide, 16(17)-EpDPE, by 99% [35%,193%], (2.0 nM). Final VLDL-oxylipin concentrations with LPS treatment were not correlated with linoleic acid kinetics, suggesting they were independently regulated under inflammatory conditions. We conclude that the liver regulates oxylipin incorporation into VLDL, and the oxylipin content is altered by LPS challenge and by inhibition of the epoxide hydrolase pathway. This provides evidence for delivery of systemic oxylipin signals by VLDL transport.

Topics: Adamantane; Animals; Chemical and Drug Induced Liver Injury; Enzyme Inhibitors; Epoxide Hydrolases; In Vitro Techniques; Kinetics; Lauric Acids; Linoleic Acid; Lipopolysaccharides; Lipoproteins, VLDL; Liver; Male; Oxylipins; Palmitic Acid; Perfusion; Rats, Sprague-Dawley

A rapid method had been used for comparative study on Artemisia halodendron Turcz. and its two related plants by gas phase-mass spectrometry (GC-MS). The comparison of the volatile oils obtained in three plants by GC-MS were similar in 20 compositions. However, n-Hexadecanoic acid (10.40%), Biphenyl (7.867%) and 9,12-Octadecadienoic acid (7.25%) were the predominant in the volatile oils of A. halodendron Turcz., whereas these constituents did not exist in the other two plants. And the study investigated the effect of three plants against CCl

Topics: Animals; Artemisia; Biphenyl Compounds; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Gas Chromatography-Mass Spectrometry; Linoleic Acid; Male; Mice; Oils, Volatile; Protective Agents

In the present study, in vitro antioxidant, antioxidative stress and hepatoprotective activity of Moringa oleifera Lam. seed oil (Ben oil; BO) was evaluated against carbon tetrachloride (CCl(4) ) induced lipid peroxidation and hepatic damage in rats. The oil at 0.2 and 0.4 mL/rat was administered orally for 21 consecutive days. The substantially elevated serum enzymatic (GOT, GPT, ALP, GGT) and bilirubin levels were significantly restored towards normalization by the oil. There was a significant elevation in the level of malondialdehyde (MDA), non-protein sulfhydryl (NP-SH), and total protein (TP) contents in the liver tissue. The results obtained indicated that BO possesses potent hepatoprotective action against CCl(4) -induced hepatic damage by lowering liver marker enzymes, MDA concentration, and elevating NP-SH and TP levels in liver tissue. The biochemical observations were supplemented with histopathological examination of rat liver. The results of this study showed that treatment with Ben oil or silymarin (as a reference) appears to enhance the recovery from hepatic damage induced by CCl(4) . The pentobarbital induced narcolepsy prolongation in mice was retarded by the Ben oil. Acute toxicity test in mice showed no morbidity or mortality. In vitro DPPH radical scavenging and β-carotene-linolic acid assay tests of the BO exhibited a moderate antioxidant activity in both tests used. The possible mechanism(s) of the liver protective activity of Ben oil activity may be due to free radical scavenging potential caused by the presence of antioxidant component(s) in the oil. Consequently, BO can be used as a therapeutic regime in treatment of some hepatic disorders.

Topics: Animals; Antioxidants; beta Carotene; Bilirubin; Biphenyl Compounds; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Female; Linoleic Acid; Lipid Peroxidation; Liver; Male; Malondialdehyde; Mice; Moringa oleifera; Picrates; Plant Oils; Rats; Rats, Wistar; Seeds; Silymarin

The in vitro hepatoprotective effect of the methanolic extract from Ficus gnaphalocarpa (Miq.) Steud. ex A. Rich (Moraceae) on the CCl₄-induced liver cell damage as well as the possible antioxidant mechanisms involved in this protective effect, were investigated. The phytochemical investigation of this methanolic extract led to the isolation of six compounds identified as: betulinic acid (1); 3-methoxyquercetin (2); catechin (3); epicatechin (4); quercetin (5); and quercitrin (6). The hepatoprotective activity of these compounds was tested in vitro against CCl₄-induced damage in rat hepatoma cells. In addition, radical-scavenging activity, β-carotene-linoleic acid model system, ferric-reducing antioxidant parameter and microsomal lipid peroxidation assays were used to measure antioxidant activity of crude extract and isolated compounds. Silymarin and trolox were used as standard references and, respectively, exhibited significant hepatoprotective and antioxidant activities. (5), (6) and (2) showed significant antioxidant and hepatoprotective activities as indicated by their ability to prevent liver cell death and lactate dehydrogenase leakage during CCl₄ intoxication. These results suggest that the protective effects of crude extract of F. gnaphalocarpa against the CCl₄-induced hepatotoxicity possibly involve the antioxidant effect of these compounds.

Topics: Animals; Antioxidants; beta Carotene; Cell Death; Cell Line, Tumor; Chemical and Drug Induced Liver Injury; Chromans; Ficus; Free Radical Scavengers; L-Lactate Dehydrogenase; Linoleic Acid; Lipid Peroxidation; Liver; Methanol; Microsomes, Liver; Plant Extracts; Rats; Silymarin

Mice were fed diets with three different ratios of alpha-linolenate (18:3n-3) to linoleate (18:2n-6), and the severity of hepatitis during endotoxic shock was compared. Dietary enrichment with alpha-linolenate increased the severity of hepatitis and the mortality induced by lipopolysaccharide (LPS) in combination with D-galactosamine (GalN). Differences in the dietary alpha-linolenate/linoleate balance were mainly reflected in the levels of arachidonate and eicosapenatenoate in liver phospholipids. Pretreatment of mice with indomethacin was found to also enhance the severity of GalN/LPS-hepatitis. This indicated that cyclooxygenase products of arachidonate may suppress the development of GalN/LPS-hepatitis. The enhancement by high alpha-linolenate diets was not observed when a lethal dose of LPS in the absence of GalN was given. Our results indicate that there are pathophysiological conditions of endotoxin-induced hepatitis under which cyclooxygenase products of arachidonate play protective roles.

Topics: alpha-Linolenic Acid; Animals; Arachidonic Acid; Arachidonic Acids; Chemical and Drug Induced Liver Injury; Dietary Fats, Unsaturated; Eicosapentaenoic Acid; Galactosamine; Indomethacin; Linoleic Acid; Linoleic Acids; Linolenic Acids; Lipopolysaccharides; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Phospholipids

Dietary products of lipid peroxidation cause hepatic dysfunctions such as reductions in activities of aldehyde dehydrogenase (mitochondrial NAD-dependent), succinate dehydrogenase, phosphoglucomutase, glucokinase, and glucose-6-phosphate dehydrogenase, and a depletion of coenzyme A. Toxic products in the peroxidation are considered to be the aldehydes among the decomposed products from hydroperoxides, because the decomposed products were incorporated into the liver but the other products were not when they were administered orally to rats. There are three current ideas on the causes of the dysfunctions: (a) direct attack of the incorporated aldehydes on the enzymes, (b) injury of the bio-membranes by the aldehydes, and (c) disturbance of the synthetic system for enzymes. In this study, to examine these ideas, a reasonable concentration of the peroxidation products to use in vitro was estimated from the amounts present in the liver after an oral dose of lipid peroxidation products. With respect to idea (a), when the peroxidation products were added to subcellular fractions of hepatocytes, the decomposed products specifically inactivated aldehyde dehydrogenase and glucose-6-phosphate dehydrogenase, and destroyed coenzyme A. For ideas (b) and (c), in which the parenchymal hepatocytes isolated from rat were used, the decomposed products did not seem to injure the bio-membrane, but they inhibited induction of glucokinase by hormones in the hepatocytes. It was concluded that in the hepatic dysfunction caused by the dietary products of lipid peroxidation the incorporated decomposed products in the liver directly inactivated the mitochondrial NAD-dependent aldehyde dehydrogenase and glucose-6-phosphate dehydrogenase, destroyed coenzyme A, and disturbed the synthetic system of glucokinase.

Topics: Animals; Cells, Cultured; Chemical and Drug Induced Liver Injury; Dietary Fats; Linoleic Acid; Linoleic Acids; Lipid Peroxidation; Male; Microsomes, Liver; Mitochondria, Liver; Rats; Rats, Inbred Strains

Topics: Chemical and Drug Induced Liver Injury; Cholesterol; Chromatography; Fatty Acids; Fatty Acids, Essential; Fatty Liver; Geriatrics; Hepatitis; Hypervitaminosis A; Linoleic Acid; Lipid Metabolism; Lipids; Liver; Oleic Acid; Palmitic Acid; Phospholipids; Toxicology; Vitamin K

Topics: Biomedical Research; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Hepatitis; Hepatitis A; Linoleic Acid; Lipids; Liver Function Tests; Pharmacology; Rats

Topics: Amino Acids; Blood; Chemical and Drug Induced Liver Injury; Choline; Glycine max; Hepatitis; Linoleic Acid; Lipotropic Agents; Liver Cirrhosis; Liver Cirrhosis, Experimental; Liver Diseases; Phospholipids; Rats; Research; Sulfacetamide; Toxicology