Research Article Details
| Article ID: | A13069 |
| PMID: | 30153476 |
| Source: | Free Radic Biol Med |
| Title: | Molecular mechanisms related to the hepatoprotective effects of antioxidant-rich extra virgin olive oil supplementation in rats subjected to short-term iron administration. |
| Abstract: | 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 (200 mg iron/kg diet) versus a control diet (CD; 50 mg iron/kg diet) with alternate AR-EVOO supplementation (100 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. |
| DOI: | 10.1016/j.freeradbiomed.2018.08.030 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D258 | Omega 3 PUFA | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Hypolipidemic drug | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D504 | Polyunsaturated Fatty Acids | Supplement | -- | -- | -- | Under clinical trials | Details |
| D201 | L-Carnitine | Supplement | DB00583 | SLC22A4; SLC22A5; CRAT; MPO | -- | Under clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D178 | Hydroxytyrosol | Chemical drug | DB12771 | -- | Antioxidant | Under clinical trials | Details |
| D062 | Carnitine complex | Supplement | DB00583 | SLC22A4; SLC22A5; CRAT; MPO | -- | Under clinical trials | Details |
| D125 | Epanova | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Enhance lipid metabolism | Under clinical trials | Details |
| D158 | Glutathione | Chemical drug | DB00143 | MGST3; HPGDS; GSTM2; GSTM5; GPX7 cofactor; MGST2; GSS; GSTM1; GSTK1; GSTM3; GSTM4; GPX1 cofactor; GPX2 cofactor; GPX3 cofactor | -- | Under clinical trials | Details |
| D255 | Olive oil | Biological drug | DB09567 | -- | -- | Under clinical trials | Details |