Effects of Pharmacologic Dose of Resveratrol Supplementation on Oxidative/Antioxidative Status Biomarkers in Nonalcoholic Fatty Liver Disease Patients: A Randomized, Double-Blind, Placebo-Controlled Trial
Results: Resveratrol supplementation did not significantly affect neither serum MDA, oxLDL, and TAC levels, nor erythrocyte SOD and GSH-Px activities, compared to placebo group (All P>0.05). [...]changes in serum levels of liver enzymes (ALT, AST, GGT, and ALP) were not significant in neither of...
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Published in: | Advanced pharmaceutical bulletin Vol. 8; no. 2; pp. 307 - 317 |
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Abstract | Results: Resveratrol supplementation did not significantly affect neither serum MDA, oxLDL, and TAC levels, nor erythrocyte SOD and GSH-Px activities, compared to placebo group (All P>0.05). [...]changes in serum levels of liver enzymes (ALT, AST, GGT, and ALP) were not significant in neither of the study groups (All P>0.05). Introduction Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with a prevalence rate of 6-35% in the general population, depending on the assessment methods and the study population.1 Higher prevalences were found among those afflicted with metabolic disorders such as obesity, type 2 diabetes, and metabolic syndrome.1,2 NAFLD represents a spectrum of liver diseases from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), and fibrosis, which may progress to cirrhosis and even hepatocellular carcinoma.3 Insulin resistance and oxidative stress are among the major important risk factors for this disease, and current therapeutic approaches to NAFLD include strategies that could modify these risk factors.4 Insulin resistance leads to increased lipolysis and hepatic uptake of free fatty acids (FFA) and enhances hepatic triglyceride synthesis and accumulation.5 The excessive offer of lipids to the mitochondria would promote production of reactive oxygen species (ROS), which contribute to lipid peroxidation and eventual oxidative stress.6,7 The most remarkable consequence of oxidative stress is the oxidation of lipids, proteins, DNA, and enzymes, leading to cellular damage and acceleration of cell death induced by apoptosis and necrosis.8 Oxidative stress is considered of primary importance in the disease progression from simple steatosis to steatohepatitis and liver damage.9 Lipid peroxidation and ROS can also lead to depletion of nonenzymatic antioxidants as well as antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In another study on fructose-fed rats, resveratrol induced a significant reduction in TBARS levels, indicating a possible role of resveratrol in free radical inactivation.45 There is increasing evidence that antioxidant-rich dietary patterns, induce significant reductions in LDL oxidation.46 A recent trial performed in hypercholesterolemic patients demonstrated that resveratrol at a dose of 8 mg/d significantly reduced serum ox-LDL during 6 months.24 The evidence suggests that resveratrol exerts its antioxidant activities by scavenging ROS and reactive nitrogen species (RNS) and secondary organic radicals formed as a result of the reaction of biomolecules with ROS and RNS.47 The increased lipid peroxidation might be explained by increased oxidative stress as a result of the antioxidant depletion.48 LDL and other biomolecules are protected from oxidative damage by the action of blood antioxidant capacity.49 TAC is an indicator of the overall protection of antioxidants against oxidative stress in body fluids and cell components.50 Plasma antioxidant status includes enzymatic and nonenzymatic antioxidant activities.49 Enzymatic antioxidants like SOD and GSHPx are the first line of defense against ROS and play a vital role in scavenging free radicals. In this study, there were no significant differences in daily dietary intakes of macronutrients and known antioxidants between the two groups, by the end of the study. [...]dietary factors are not likely to have confounded our results. |
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AbstractList | Results: Resveratrol supplementation did not significantly affect neither serum MDA, oxLDL, and TAC levels, nor erythrocyte SOD and GSH-Px activities, compared to placebo group (All P>0.05). [...]changes in serum levels of liver enzymes (ALT, AST, GGT, and ALP) were not significant in neither of the study groups (All P>0.05). Introduction Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with a prevalence rate of 6-35% in the general population, depending on the assessment methods and the study population.1 Higher prevalences were found among those afflicted with metabolic disorders such as obesity, type 2 diabetes, and metabolic syndrome.1,2 NAFLD represents a spectrum of liver diseases from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), and fibrosis, which may progress to cirrhosis and even hepatocellular carcinoma.3 Insulin resistance and oxidative stress are among the major important risk factors for this disease, and current therapeutic approaches to NAFLD include strategies that could modify these risk factors.4 Insulin resistance leads to increased lipolysis and hepatic uptake of free fatty acids (FFA) and enhances hepatic triglyceride synthesis and accumulation.5 The excessive offer of lipids to the mitochondria would promote production of reactive oxygen species (ROS), which contribute to lipid peroxidation and eventual oxidative stress.6,7 The most remarkable consequence of oxidative stress is the oxidation of lipids, proteins, DNA, and enzymes, leading to cellular damage and acceleration of cell death induced by apoptosis and necrosis.8 Oxidative stress is considered of primary importance in the disease progression from simple steatosis to steatohepatitis and liver damage.9 Lipid peroxidation and ROS can also lead to depletion of nonenzymatic antioxidants as well as antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In another study on fructose-fed rats, resveratrol induced a significant reduction in TBARS levels, indicating a possible role of resveratrol in free radical inactivation.45 There is increasing evidence that antioxidant-rich dietary patterns, induce significant reductions in LDL oxidation.46 A recent trial performed in hypercholesterolemic patients demonstrated that resveratrol at a dose of 8 mg/d significantly reduced serum ox-LDL during 6 months.24 The evidence suggests that resveratrol exerts its antioxidant activities by scavenging ROS and reactive nitrogen species (RNS) and secondary organic radicals formed as a result of the reaction of biomolecules with ROS and RNS.47 The increased lipid peroxidation might be explained by increased oxidative stress as a result of the antioxidant depletion.48 LDL and other biomolecules are protected from oxidative damage by the action of blood antioxidant capacity.49 TAC is an indicator of the overall protection of antioxidants against oxidative stress in body fluids and cell components.50 Plasma antioxidant status includes enzymatic and nonenzymatic antioxidant activities.49 Enzymatic antioxidants like SOD and GSHPx are the first line of defense against ROS and play a vital role in scavenging free radicals. In this study, there were no significant differences in daily dietary intakes of macronutrients and known antioxidants between the two groups, by the end of the study. [...]dietary factors are not likely to have confounded our results. Purpose: Despite a proposed role for oxidative stress in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), antioxidant approaches have not been sufficiently investigated in human NAFLD management. Resveratrol has been reported to possess a wide range of biological functions, including antioxidant activities. This study aimed to evaluate the effects of resveratrol supplementation on oxidative/anti-oxidative status in patients with NAFLD. Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted on 60 patients with NAFLD (males and females) aged 20 to 60 years, and body mass index (BMI) of 25-35 kg/m2. Subjects were randomly assigned to receive a daily dose of 600 mg resveratrol (2×300 mg pure trans-resveratrol capsules; n=30) or placebo capsules (n=30) for 12 wk. Fasting blood samples, anthropometric measurements, and dietary intakes were collected for all patients at baseline and at the end of the trial. Oxidative stress was evaluated by measurement of serum malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), total antioxidant capacity (TAC), and erythrocyte superoxide dismutase (SOD) as well as glutathione peroxidase (GSH-Px) activities. Changes in the outcomes were analyzed using analysis of covariance (ANCOVA). Results: Resveratrol supplementation did not significantly affect neither serum MDA, ox-LDL, and TAC levels, nor erythrocyte SOD and GSH-Px activities, compared to placebo group (All P>0.05). Moreover, changes in serum levels of liver enzymes (ALT, AST, GGT, and ALP) were not significant in neither of the study groups (All P>0.05). Conclusion: Resveratrol supplementation did not modify oxidative/anti-oxidative status in patients with NAFLD. Purpose: Despite a proposed role for oxidative stress in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), antioxidant approaches have not been sufficiently investigated in human NAFLD management. Resveratrol has been reported to possess a wide range of biological functions, including antioxidant activities. This study aimed to evaluate the effects of resveratrol supplementation on oxidative/anti-oxidative status in patients with NAFLD. Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted on 60 patients with NAFLD (males and females) aged 20 to 60 years, and body mass index (BMI) of 25-35 kg/m2. Subjects were randomly assigned to receive a daily dose of 600 mg resveratrol (2×300 mg pure trans-resveratrol capsules; n=30) or placebo capsules (n=30) for 12 wk. Fasting blood samples, anthropometric measurements, and dietary intakes were collected for all patients at baseline and at the end of the trial. Oxidative stress was evaluated by measurement of serum malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), total antioxidant capacity (TAC), and erythrocyte superoxide dismutase (SOD) as well as glutathione peroxidase (GSH-Px) activities. Changes in the outcomes were analyzed using analysis of covariance (ANCOVA). Results: Resveratrol supplementation did not significantly affect neither serum MDA, ox-LDL, and TAC levels, nor erythrocyte SOD and GSH-Px activities, compared to placebo group (All P>0.05). Moreover, changes in serum levels of liver enzymes (ALT, AST, GGT, and ALP) were not significant in neither of the study groups (All P>0.05). Conclusion: Resveratrol supplementation did not modify oxidative/anti-oxidative status in patients with NAFLD. |
Author | Asghari-Jafarabadi, Mohammad Farzin, Laleh Ghavami, Seyed-Mostafa Somi, Mohammad-Hossein Asghari, Somayyeh Rafraf, Maryam |
AuthorAffiliation | 6 Liver and Gastrointestinal Diseases Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran 1 Students’ Research Committee, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran 2 Nutrition Research Center, Department of Community Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran 5 Department of Radiology, Paramedical school, Tabriz University of Medical Sciences, Tabriz, Iran 4 Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran 3 Road Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran |
AuthorAffiliation_xml | – name: 4 Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran – name: 3 Road Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran – name: 2 Nutrition Research Center, Department of Community Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran – name: 1 Students’ Research Committee, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran – name: 5 Department of Radiology, Paramedical school, Tabriz University of Medical Sciences, Tabriz, Iran – name: 6 Liver and Gastrointestinal Diseases Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran |
Author_xml | – sequence: 1 givenname: Somayyeh surname: Asghari fullname: Asghari, Somayyeh – sequence: 2 givenname: Maryam surname: Rafraf fullname: Rafraf, Maryam – sequence: 3 givenname: Laleh surname: Farzin fullname: Farzin, Laleh – sequence: 4 givenname: Mohammad surname: Asghari-Jafarabadi fullname: Asghari-Jafarabadi, Mohammad – sequence: 5 givenname: Seyed-Mostafa surname: Ghavami fullname: Ghavami, Seyed-Mostafa – sequence: 6 givenname: Mohammad-Hossein surname: Somi fullname: Somi, Mohammad-Hossein |
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Snippet | Results: Resveratrol supplementation did not significantly affect neither serum MDA, oxLDL, and TAC levels, nor erythrocyte SOD and GSH-Px activities, compared... Purpose: Despite a proposed role for oxidative stress in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), antioxidant approaches have not been... Purpose: Despite a proposed role for oxidative stress in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), antioxidant approaches have not been... |
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StartPage | 307 |
SubjectTerms | Clinical trial Double-blind studies Insulin resistance Lipids Liver cirrhosis Nonalcoholic fatty liver disease Oxidation Oxidative stress Resveratrol supplementation Rodents Studies |
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Title | Effects of Pharmacologic Dose of Resveratrol Supplementation on Oxidative/Antioxidative Status Biomarkers in Nonalcoholic Fatty Liver Disease Patients: A Randomized, Double-Blind, Placebo-Controlled Trial |
URI | https://www.proquest.com/docview/2099846366 https://pubmed.ncbi.nlm.nih.gov/PMC6046420 https://doaj.org/article/ce48422c56c04864b473dd526c96f6a4 |
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