Dietary extra virgin olive oil down regulates oxidized lipid mediators in CCl4 induced liver injury

Abstract

Dietary oils rich in unsaturated fatty acids demonstrate various effects in chronic liver injury. Some reports indicated that extra virgin olive oil has better benefits against carbon tetrachloride (CCl4) induced liver injury, but the details are still unclear. It is well established part of liver injury induced by CCl4 is mediated by lipid peroxidation. In this study we investigated the effect of different dietary fat in rats with and without CCl4. Oxidized lipid mediators of arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid and cholesterol liberated through lipoxygenase and cytochrome P450 enzymatic and non-enzymatic pathways were determined. Fischer 344 male rats were fed normal laboratory chow plus 20% (w/w) corn oil (CO) or extra virgin olive oil (EVOO) or lard (LD). The animals in each dietary group were hypodermically given CCl4 (1:1 with soybean oil, 0.1 ml/100g bodyweight) twice a week for 4 weeks and the control with soybean oil only. Oxidized lipid mediators (OLM) namely 5(S)-, 8(S)-, 11(S)-, 12(S)-, 15(S) and 20-HETEs, F2-isoprostanes, F3-isoprostanes, resolvin D1, 7β-hydroxycholesterol, 7-ketocholesterol, 27-hydroxycholesterol and the precursor levels were measured by liquid chromatography tandem mass spectrometry. Liver of rats fed with EVOO had significantly reduced (p<0.01) HETE products, F2-isoprostanes, 7 β -hydroxycholesterol and 7-ketocholesterol levels compared to control, CO and LD. Treatment of CCl4 alone substantially elevated (p<0.01) liver OLM in particular 5(S)- and 9(S)-HETEs, F2-isoprostanes, 7 β -hydroxycholesterol and 7-ketocholesterol compared to the control. However, some of these OLM in rat livers fed with EVOO significantly (p<0.01) reduced (HETE products, F2-isoprostanes, F3--hydroxycholesterol) below the control levels. The levels remained low even when adjusted by the precursor concentration. This effect was not seen in rat livers fed with CO or LD where OLM levels remained high. This study showed dietary EVOO is capable of reducing oxidized lipid mediators in rat liver even when injured by CCl4.