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A pilot study of the effect of curcumin on epigenetic changes and DNA damage among patients with non-alcoholic fatty liver disease: A randomized,double-blind,placebo-controlled,clinical trial
Affiliation:1. Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran;2. Department of Epidemiology & Biostatistics, School of Public Health, Neyshabur University of Medical Sciences, Neyshabur, Iran;3. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;4. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran;5. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran;1. Nursing Care Research Center, Semnan University of Medical Sciences, Semnan, Iran;2. Department of Nursing, Faculty of Nursing and Midwifery, Semnan University of Medical Sciences, Semnan, Iran;3. Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran;4. Neuromuscular Rehabilitation Research Center, Semnan University of Medical Sciences, Semnan, Iran;5. Department of Physiotherapy, School of Rehabilitation Sciences, Semnan University of Medical Sciences, Semnan, Iran;6. Social Determinants of Health Research Center, Semnan University of Medical Sciences, Semnan, Iran;7. Department of Epidemiology and Biostatistics, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran;1. Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran;2. Department of Endocrinology, Baqiyatallah University of Medical Sciences, Tehran, Iran;3. Department of Clinical Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran;4. Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;5. Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia;1. Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;2. Department of otolaryngology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;3. Ph.D of Pharmacognosy;4. MPH Department, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran;5. Department of Traditional Medicine, Faculty of Iranian Traditional Medicine, Shahid Sadoughi University of Medical Sciences, Ardakan, Iran;1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;2. Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;3. Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;4. Department of Infectious Diseases, The First Affiliated Hospital of Xi ''an Jiaotong University, Xi’an, 710061 China;5. Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, 44195, USA;6. Departrment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA;7. Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, Philadelphia, USA;1. Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran;2. Gastroenterology and Hepatology Subdivision of Internal Medicine, Imam Khomeini Hospital, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran;3. Food and Beverages Safety Research Center, Urmia University of Medical Sciences, Urmia, Iran;4. Department of Nutrition, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran;1. Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran;2. Department of Community Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran;3. Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran;4. Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
Abstract:BackgroundThe enhancement of oxidative stress in non-alcoholic fatty liver disease (NAFLD) patients may cause mutation in DNA by deamination of cytosine to 5-hydroxyuracil or uracil. This study aimed to discover the effects of curcumin on NAFLD progress, DNA damage caused by oxidative stress, and promoter methylation of mismatch repair enzymes.Material and methodsin this study, 54 NAFLD patients were randomly devided into two groups, according to a double blind parallel design either phytosomal curcumin (250 mg/day) or placebo for 8 weeks. Fasting blood samples and anthropometric measures were taken twice, once at the baseline and once at the end of the study. Promoter methylation and 8-hydroxy-2′ -deoxyguanosine (8−OHdG) concentration as DNA damage mediator were measured by restriction enzymes and enzyme-linked immunosorbent assay, respectively.ResultAnalysis was performed on 44 patients. According to our between groups analysis, curcumin significantly reduced the methylation in MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) promoter regions. The within-group comparison revealed that anthropometric variables significantly decreased. However, the result of the between groups comparison indicated no significant changes in the anthropometric variables except for BMI. Liver enzymes and 8−OHdG did not significantly change at the end of the study, neither in curcumin group nor in placebo group.ConclusionCurcumin might be able to reduce the risk of mismatch base pair in DNA among the NAFLD patients. However, it did not change the DNA damage mediator and liver enzymes. For confirming these results, more studies with longer duration, more numbers of examined genes, higher dose of curcumin, and larger sample size are required.
Keywords:Non-alcoholic fatty liver  Promoter methylation  Epigenetic  Liver enzymes
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