RESUMO
The administration of iron induces liver oxidative stress and depletion of long-chain polyunsaturated fatty acids (LCPUFAs), n-6/n-3 LCPUFA ratio enhancement and fat accumulation, which may be prevented by antioxidant-rich extra virgin olive oil (AR-EVOO) supplementation. Male Wistar rats were subjected to a control diet (50 mg iron/kg diet) or iron-rich diet (IRD; 200 mg/kg diet) with alternate AR-EVOO for 21 days. Liver fatty acid (FA) analysis was performed by gas-liquid chromatography (GLC) after lipid extraction and fractionation, besides Δ-5 desaturase (Δ-5 D) and Δ6-D mRNA expression (qPCR) and activity (GLC) measurements. The IRD significantly (p < 0.05) increased hepatic total fat, triacylglycerols, free FA contents and serum transaminases levels, with diminution in those of n-6 and n-3 LCPUFAs, higher n-6/n-3 ratios, lower unsaturation index and Δ5-D and Δ6-D activities, whereas the mRNA expression of both desaturases was enhanced over control values, changes that were prevented by concomitant AR-EVOO supplementation. N-6 and n-3 LCPUFAs were also decreased by IRD in extrahepatic tissues and normalized by AR-EVOO. In conclusion, AR-EVOO supplementation prevents IRD-induced changes in parameters related to liver FA metabolism and steatosis, an effect that may have a significant impact in the treatment of iron-related pathologies or metabolic disorders such as non-alcoholic fatty liver disease.
Assuntos
Antioxidantes/administração & dosagem , Ácidos Graxos Dessaturases/genética , Fígado Gorduroso/prevenção & controle , Ferro/efeitos adversos , Linoleoil-CoA Desaturase/genética , Azeite de Oliva/administração & dosagem , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Cromatografia Gasosa , Dessaturase de Ácido Graxo Delta-5 , Modelos Animais de Doenças , Ácidos Graxos/análise , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/epidemiologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Azeite de Oliva/química , Azeite de Oliva/farmacologia , Ratos , Ratos WistarRESUMO
Enhanced iron levels in liver are associated with oxidative stress development and damage with increased fat accumulation. The aim of this work was to assess the hypothesis that antioxidant-rich extra virgin olive oil (AR-EVOO) counteracts iron-rich diet (IRD)-induced oxidative stress hindering hepatic steatosis. Male Wistar rats were fed and IRD (200â¯mg iron/kg diet) versus a control diet (CD; 50â¯mg iron/kg diet) with alternate AR-EVOO supplementation (100â¯mg/day) for 21 days. IRD induced liver steatosis and oxidative stress (higher levels of protein oxidation and lipid peroxidation with glutathione depletion), mitochondrial dysfunction (decreased citrate synthase and complex I and II activities) and loss of polyunsaturated fatty acids (PUFAs), with a drastic enhancement in the sterol regulatory element-binding protein-1c (SREBP-1c)/peroxisome proliferator-activated receptor-α (PPAR-α) ratio upregulating the expression of lipogenic enzymes (acetyl-CoA carboxylase, fatty acid (FA) synthase and stearoyl desaturase 2) and downregulating those involved in FA oxidation (carnitine palmitoyl transferase and acyl-CoA oxidase) over values in the CD group. IRD also upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and its target genes. AR-EVOO supplementation alone did not modify the studied parameters, however, IRD combined with AR-EVOO administration returned IRD-induced changes to baseline levels of the CD group. It is concluded that IRD-induced non-alcoholic fatty liver disease (NAFLD) is prevented by AR-EVOO supplementation, which might be related to the protective effects of its components such as hydroxytyrosol, oleic acid, tocopherols and/or PUFAs, thus representing a suitable anti-steatotic strategy to avoid progression into more severe stages of the disease, underlying NAFLD associated with iron overloading pathologies or obesity.