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An ?-3-enriched diet alone does not attenuate CCl4-induced hepatic fibrosis.

ABSTRACT: Exposure to the halogenated hydrocarbon carbon tetrachloride (CCl4) leads to hepatic lipid peroxidation, inflammation and fibrosis. Dietary supplementation of ?-3 fatty acids has been increasingly advocated as being generally anti-inflammatory, though its effect in models of liver fibrosis is mixed. This raises the question of whether diets high in ?-3 fatty acids will result in a greater sensitivity or resistance to liver fibrosis as a result of environmental toxicants like CCl4. In this study, we fed CCl4-treated mice a high ?-3 diet (using a mix of docosahexaenoic acid and eicosapentaenoic acid ethyl esters). We also co-administered an inhibitor of soluble epoxide hydrolase, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), which has been shown to boost anti-inflammatory epoxy fatty acids that are produced from both ?-3 and ?-6 dietary lipids. We showed that soluble epoxide inhibitors reduced CCl4-induced liver fibrosis. Three major results were obtained. First, the ?-3-enriched diet did not attenuate CCl4-induced liver fibrosis as judged by collagen deposition and collagen mRNA expression. Second, the ?-3-enriched diet raised hepatic tissue levels of several inflammatory lipoxygenase metabolites and prostaglandins, including PGE2. Third, treatment with TPPU in drinking water in conjunction with the ?-3-enriched diet resulted in a reduction in liver fibrosis compared to all other groups. Taken together, these results indicate that dietary ?-3 supplementation alone did not attenuate CCl4-induced liver fibrosis. Additionally, oxylipin signaling molecules may play role in the CCl4-induced liver fibrosis in the high ?-3 diet groups.

SUBMITTER: Harris TR

PROVIDER: S-EPMC5102762 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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An ω-3-enriched diet alone does not attenuate CCl4-induced hepatic fibrosis.

Harris Todd R TR Kodani Sean S Yang Jun J Imai Denise M DM Hammock Bruce D BD

The Journal of nutritional biochemistry 20160914

Exposure to the halogenated hydrocarbon carbon tetrachloride (CCl4) leads to hepatic lipid peroxidation, inflammation and fibrosis. Dietary supplementation of ω-3 fatty acids has been increasingly advocated as being generally anti-inflammatory, though its effect in models of liver fibrosis is mixed. This raises the question of whether diets high in ω-3 fatty acids will result in a greater sensitivity or resistance to liver fibrosis as a result of environmental toxicants like CCl4 ...[more]

PMID: 27732914

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Project description:ContextOur previous studies indicated that Yiguanjian decoction (YGJ) has an anti-hepatic-fibrosis effect and could regulate macrophage status.ObjectiveTo elucidate the mechanism of YGJ in regulating macrophages.Materials and methodsLiver cirrhosis was induced by CCl4 for 12 weeks combined with 2-acetylaminofluorene (2-AAF) for the last 4 weeks in male Wistar rats. YGJ (3.56 mg/kg) orally administered in the last 4 weeks, and SORA (1 mg/kg) as control. In vitro, RAW264.7 cells were treated with lipopolysaccharides (LPSs) to induce macrophage polarization to the M1 phenotype, and they were co-cultured with WB-F344 cells and allocated to M group, YGJ group (2 μg/mL) and WIF-1 group (1 μg/mL) with untreated cells as control. The differentiation direction of WB-F344 cell line was observed in the presence or absence of YGJ. Pathology, fibrosis-related cytokines, macrophage polarization-related components, and Wnt signalling pathway components were detected.ResultsIn vivo, the expression levels of α-SMA, Col (1), OV6, SOX9, EpCAM and M1 macrophage-related components (STAT1, IRF3, IRF5, IRF8, SOCS3) significantly decreased in the YGJ group compared with those in the 2-AAF/CCl4 group (p < 0.01 or 0.05). In vitro, the expression levels of M1 macrophage-related components, including STAT1, NF-κB, IRF3, IRF5, and SOCS3, in RAW264.7 cells decreased significantly in the YGJ group compared with those in the M group (p < 0.05 or p < 0.01). The expression levels of Wnt3A, FZD5, LRP-5/-6, and β-catenin significantly increased in the YGJ group compared with those in the M group (p < 0.05 or p < 0.01). In addition, the expression levels of Wnt-4/-5A/-5B, and FZD2 significantly decreased in the YGJ group compared with those in the M group (p < 0.05 or p < 0.01).ConclusionThis study suggests that the anti-cirrhosis effect of YGJ is associated with its ability to inhibit macrophage M1-polarization, which provides a scientific basis for the clinical application of YGJ.

Project description:BackgroundThe increase in demand and consumption of single clove garlic or 'Solo garlic' (Allium sativum) has resulted in an increase in research on its therapeutic properties. The present study aims to evaluate the antioxidant activities, oxidant-scavenging efficiency and preventive effects of SCG (single clove garlic) and MCG (multi clove garlic) on CCl4-induced acute hepatotoxicity in male rabbits.MethodsFor this purpose, rabbits were orally administered with 3 ml of CCl4 /kg of body weight, followed by 0.8 g of MCG or SCG/kg twice a week for three successive weeks. Oxidative hepatotoxicity was then assessed.ResultsSCG extracts exhibited higher antioxidant capacity than the MCG extract. Scavenging ability of SCG showed significant (p < 0.05) elevation against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals in comparison to MCG. In addition, total phenolic content of SCG was significantly elevated (p < 0.001), thereby suggesting that the composition of garlic storage constituents varies with the number of cloves present. CCl4-induced hepatotoxicity demonstrated histological changes including severe damage in the structure of liver tissues which correlated well to oxidative stress levels. Simultaneously, administration of SCG resulted in a significant reduction of serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TB) levels in addition to improvement in some histological parameters. Low levels of lipid peroxidation (malondialdehyde, MDA) (p < 0.001), along with a huge reduction in peroxidase (POx) (p < 0.001) revealed protection against oxidative toxicity in the liver homogenate. Higher levels of catalase (CAT) (p < 0.001) and superoxide dismutase (SOD) (p < 0.05) when compared to the MCG test (TM) group indicates that removal of H2O2 is based on CAT activity in SCG test (TS) group rather than the POx activity demonstrated in the former group.ConclusionThe present study indicates that SCG possesses more protective ability than MCG against CCl4-induced liver injury and might be an effective alternative medicine against acute oxidative liver toxicity.

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An ?-3-enriched diet alone does not attenuate CCl4-induced hepatic fibrosis.

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An ω-3-enriched diet alone does not attenuate CCl<sub>4</sub>-induced hepatic fibrosis.

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