Preventive effect of α-linolenic acid-rich flaxseed oil against ethanol-induced liver injury is associated with ameliorating gut-derived endotoxin-mediated inflammation in mice

• α-linolenic acid-rich flaxseed oil alleviates ethanol-induced liver injury.
• Flaxseed oil decreases the elevation of plasma endotoxin level.
• Flaxseed oil ameliorates ethanol-induced intestinal barrier dysfunction.
• Flaxseed oil suppresses gut-derived endotoxin-triggered inflammation in liver.
• This inhibitory effect is associated with blocking TLR4/MyD88/NF-κB signalling.

The effects of α-linolenic acid (ALA)-rich flaxseed oil (FDO) against ethanol-induced liver injury and the probable molecular mechanisms in a mouse model of chronic-plus-single-binge ethanol feeding were evaluated. Mice were fed Lieber-DeCarli ethanol or control liquid diets with corn oil (CNO) or flaxseed oil for 10 days. On day 11, mice are gavaged with a single dose of ethanol or maltose dextrin. Ethanol exposure with CNO caused severe liver injury, inflammation and oxidative stress in liver, which were remarkably ameliorated by FDO. FDO supplementation decreased the elevation of plasma endotoxin level, which might be attributed to ameliorating ethanol-induced intestinal barrier dysfunction via upregulating the expressions of tight junction proteins. Additionally, FDO supplementation suppressed endotoxin-triggered inflammation via blocking TLR4/MyD88/NF-κB cascades in liver. These findings suggest that ALA-rich flaxseed oil may have potential to be developed as an effective agent for ethanol-induced liver injury.