Contribution of Cyclooxygenase End Products and Oxidative Stress to Intrahepatic Endothelial Dysfunction in Early Non-Alcoholic Fatty Liver Disease
| Autor: | Dalia Morales Arraez, Manuel Hernández-Guerra, Francisco Javier Gonzalez-Paredes, Enrique Quintero, Goretti Hernández Mesa, Eduardo Salido, Raquel Reyes, Beatriz Abrante, Felicitas Diaz-Flores |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Steatosis Thromboxane Indomethacin lcsh:Medicine Blood Pressure Pathology and Laboratory Medicine medicine.disease_cause Nitroarginine Biochemistry Vascular Medicine Rats Sprague-Dawley Cytopathology chemistry.chemical_compound 0302 clinical medicine Non-alcoholic Fatty Liver Disease Medicine and Health Sciences Medicine Splanchnic Circulation Lipid Hormones Endothelial dysfunction lcsh:Science Immune Response Multidisciplinary biology Liver Diseases Fatty liver Neurochemistry Thromboxane B2 Hydrazines medicine.anatomical_structure Fatty Acids Unsaturated 030211 gastroenterology & hepatology Neurochemicals Research Article medicine.medical_specialty Endothelium Immunology Gastroenterology and Hepatology Nitric Oxide Cyclic N-Oxides 03 medical and health sciences Signs and Symptoms Diagnostic Medicine Internal medicine Animals Inflammation business.industry lcsh:R Biology and Life Sciences Cell Biology Bridged Bicyclo Compounds Heterocyclic medicine.disease Dietary Fats Fibrosis Acetylcholine Hormones Rats Fatty Liver Oxidative Stress 030104 developmental biology Endocrinology chemistry Anatomical Pathology biology.protein lcsh:Q Spin Labels Cyclooxygenase Metabolic syndrome business Oxidative stress Neuroscience Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 5, p e0156650 (2016) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0156650 |
| Popis: | Introduction Metabolic syndrome induces endothelial dysfunction, a surrogate marker of cardiovascular disease. In parallel, metabolic syndrome is frequently associated with non-alcoholic fatty liver disease (NAFLD), which may progress to cirrhosis. The aim of the present study was to evaluate intrahepatic endothelial dysfunction related to cyclooxygenase end products and oxidative stress as possible mechanisms involved in the pathophysiology of NAFLD. Materials and Methods Sprague-Dawley rats were fed standard diet (control-diet, CD) or high-fat-diet (HFD) for 6 weeks. Metabolic syndrome was assessed by recording arterial pressure, lipids, glycemia and rat body weight. Splanchnic hemodynamics were measured, and endothelial dysfunction was evaluated using concentration-effect curves to acetylcholine. Response was assessed with either vehicle, L-NG-Nitroarginine (L-NNA), indomethacin, tempol, or a thromboxane receptor antagonist, SQ 29548. We quantified inflammation, fibrosis, oxidative stress, nitric oxide (NO) bioavailability and thromboxane B2 levels. Results HFD rats exhibited metabolic syndrome together with the presence of NAFLD. Compared to control-diet livers, HFD livers showed increased hepatic vascular resistance unrelated to inflammation or fibrosis, but with decreased NO activity and increased oxidative stress. Endothelial dysfunction was observed in HFD livers compared with CD rats and improved after cyclooxygenase inhibition or tempol pre-incubation. However, pre-incubation with SQ 29548 did not modify acetylcholine response. Conclusions Our study provides evidence that endothelial dysfunction at an early stage of NAFLD is associated with reduced NO bioavailability together with increased cyclooxygenase end products and oxidative stress, which suggests that both pathways are involved in the pathophysiology and may be worth exploring as therapeutic targets to prevent progression of the disease. |
| Databáze: | OpenAIRE |
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