A Long-term Treatment with Silybin in Patients with Non-alcoholic Steatohepatitis Stimulates Catalase Activity in Human Endothelial Cells (original) (raw)
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Evaluation of Oxidant and Antioxidant Levels in Nonalcoholic Fatty Liver Disease (NAFLD)
Archives of Diabetes and Endocrine System, 2018
Aim: Oxidative stress (OS) plays an important role in the pathogenesis of Nonalcoholic fatty liver disease (NAFLD). The aim is to determine the levels of oxidants, antioxidants and oxidative stress index (OSI) in NAFLD and its relation with disease severity and steatohepatitis. Materials/Methods: Sixty patients with liver steatosis in ultrasonography (USG) and 20 healthy volunteers were included. NAFLD patients were classified as grade1, grade2 and grade3 based on the increase in echogenicity in USG. Total Oxidant Status (TOS), Total Antioxidant Status (TAS), Superoxide Dismutase (SOD) and Lipid Hydro Peroxidase (LPO) levels and Oxidative Stress Index (OSI) were evaluated. Results: Body mass index (BMI), waist circumference (WC), systolic/diastolic blood pressures, TOS levels was significantly higher in the NAFLD group (p<0.05). While the LPO level was higher than the control group, the difference was not significant (p=0.33). TAS and SOD levels were lower with no significance (p=0.91, p=0.49, respectively). OSI was significantly higher in NAFLD (p<0.05). Although TOS/LPO levels increased and TAS/SOD decreased with the increasing severity of fatty liver, no significant differences were between the two groups (p > 0.05). Higher TOS and LPO levels and OSI levels were correlated with high levels of ALT Conclusion: OS increases in patients with NAFLD. The oxidation of proteins and lipids created under OS can have an important role in the pathogenesis of NAFLD, and treatment options that reduce OS, ie reduce TOS levels or increase TAS levels, may be considered as a therapeutic option.
Clujul Medical, 2016
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. It affects about 1 billion individuals worldwide. While people with simple steatosis have no higher risk of death than the general population, people with non-alcoholic steatohepatitis are at increased risk of death compared to general population. Current management for NAFLD includes diet and lifestyle changes, management of underlying metabolic risk factors and pharmacological therapies. The objective of therapy is to prevent the complications. The problem with dietary and lifestyle interventions is that they are hard to implement. Compliance is the key. Until now, there is still no approved drug for the treatment of NAFLD. Insulin resistance is the main target of pharmacological therapy, but the question that we ask ourselves as physicians is who should receive medical treatment among NAFLD patients and for how long.
Journal of Hepatology, 2015
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that is predicted to become also the most frequent indication for liver transplantation by 2030. Over the last decade, it has been shown that the clinical burden of NAFLD is not only confined to liver-related morbidity and mortality, but there is now growing evidence that NAFLD is a multisystem disease, affecting extra-hepatic organs and regulatory pathways. For example, NAFLD increases risk of type 2 diabetes mellitus (T2DM), cardiovascular (CVD) and cardiac diseases, and chronic kidney disease (CKD). Although the primary liver pathology in NAFLD affects hepatic structure and function to cause morbidity and mortality from cirrhosis, liver failure and hepatocellular carcinoma, the majority of deaths among NAFLD patients are attributable to CVD. This narrative review focuses on the rapidly expanding body of clinical evidence that supports the concept of NAFLD as a multisystem disease. The review discusses the factors involved in the progression of liver disease in NAFLD and the factors linking NAFLD with other extra-hepatic chronic diseases, such as T2DM, CVD, cardiac diseases and CKD. The review will not discuss NAFLD treatments as these are discussed elsewhere in this issue of the Journal. For this review, PubMed was searched for articles using the keywords ''non-alcoholic fatty liver disease'' or ''fatty liver'' combined with ''diabetes'', ''cardiovascular (or cardiac) disease'', ''cardiovascular mortality'' or ''chronic kidney disease'' between 1990 and 2014. Articles published in languages other than English were excluded.
Type 2 Diabetes; Non Alcoholic Fatty Liver Disease (Nafld)
The professional medical journal, 2016
To determine the prevalence and the associated risk factors of NAFLD in Type 2 diabetic patients. Study Design: Cross sectional study. Setting: Diabetic clinic of Medical Unit 3, JPMC. Methods: It is a cross sectional study. 262 patients were enrolled between the ages of 18-70 years attending Diabetes Clinic of Medical Unit III, JPMC. Each consenting patient underwent a detailed medical history-taking, physical examination, laboratory assessment and abdominal ultrasonography (US). Fatty liver was diagnosed on abdominal US on the basis of two out of the three criteria: increased hepatic echogenicity, blurring of liver vasculature and deep attenuation of the ultrasonographic signal. In accordance with the guidelines, subjects diagnosed with NAFLD had to fulfill the following criteria: no history of current or past alcohol consumption, other systemic illness known to cause fatty liver disease; absence of history and clinical, biochemical and US findings consistent with cirrhosis. Body mass index (BMI) was calculated. Blood pressures of greater than 130/90 were taken as hypertensive. LFTs, FBS, HbA1c, Lipid profiles were taken. Results: Out of 262 diabetic patients 107 (40.8%) of them were found to be having NFALD. Prevalence was found out to be higher in age group of 41-50 years, females, obese & in Pashtoon subjects.It was also more prevalent in sedentary lifestyle patients and those on oral anti diabetics in contrast to insulin therapy. It was correlating well with US findings when the ALT cutoff value was taken as 30 IU for males and 19 IU for females compared to standard values of ALT. There was association with hypertension, metabolic syndrome and dyslipidemia. Conclusion: Prevalence of NAFLD was higher in our diabetic patients. Middle age, female gender and obesity were found to be statistically strong risk factors in our study.
A placebo-controlled trial of silymarin in patients with nonalcoholic fatty liver disease
2009
Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition that is characterized by significant hepatic lipid deposition with or without necroinflammation and fibrosis. Researchers have proposed that oxidative stress may play a role in pathogenesis of NAFLD, and there is challenging evidence for the efficacy of antioxidant agents in its treatment. Therefore, we tried silymarin as an antioxidant in a randomized controlled trial for a group of patients with NAFLD. Methods: During an 18-month period, a placebo-controlled study was conducted among patients with nonalcoholic steatohepatitis (NASH) referred to the Ahvaz Jundishapur University Hospital (AJSUH) and Hepatitis Clinic from 2007 to 2008. Based on sonography findings and elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels or liver biopsy, we selected 100 NASH patients who were referred to our center for management of liver disease. Patients who had positive viral markers and other hepatic diseases and patients who had ingested ethanol or drugs known to produce fatty liver disease within the previous 6 months were excluded from the study. Patients were randomized to two groups: Group A received a placebo, and Group B received treatment with 280 mg of silymarin. Treatment was continued for 24 weeks, and cases were evaluated every 4 weeks in the outpatient clinic. Results: A total of 100 subjects who met the inclusion and exclusion criteria were included in the analysis. Group A (50 cases, 29 males and 21 females) and Group B (50 cases, 28 males and 22 females). The mean age was 39.0 ± 10.70 years for Group A and 39.28 ± 11.117 years for Group B. The age range for both groups was 20 to 50 years. The mean serum ALT levels in the silymarin group were 113.03 and 73.14 IU/mL before and after treatment, respectively (P = 0.001). ALT normalization (ALT < 40) was observed in 18% and 52% of patients in Groups A and B, respectively (P = 0.001). AST normalization (AST < 40) was observed in 20% of cases in the placebo group and 62% of cases in the silymarin-treated group (P = 0.0001). No significant side effects were reported in our cases. Conclusions: Silymarin treatment appears to be significantly effective in biochemical improvement and decreasing transaminases levels in patients with NAFLD.
Free Radical Biology and Medicine, 2012
The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with Free j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / f r e e r a d b i o m e d improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation.
Oxidative Medicine and Cellular Longevity, 2019
Nowadays, the nonalcoholic fatty liver disease represents the main chronic liver disease in the Western countries, and the correct medical therapy remains a big question for the scientific community. The aim of our study was to evaluate the effect derived from the administration for six months of silybin with vitamin D and vitamin E (RealSIL 100D®) on metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease markers in nonalcoholic fatty liver disease patients. We enrolled 90 consecutive patients with histological diagnosis of nonalcoholic fatty liver disease and 60 patients with diagnosis of reflux disease (not in therapy) as healthy controls. The nonalcoholic fatty liver disease patients were randomized into two groups: treated (60 patients) and not treated (30 patients). We performed a nutritional assessment and evaluated clinical parameters, routine home tests, the homeostatic model assessment of insulin resistance, NAFLD fibrosis score and fibrosis-...
Journal of Inflammation Research, 2022
Non-alcoholic fatty liver disease (NAFLD) is intimately linked to hepatic steatosis, inflammation, insulin resistance (IR), oxidative stress (OS), and ballooning. A high fat diet (HFD) is considered a major etiological factor that primarily covers the numerous features of NAFLD. Methods: The present study aimed to evaluate the protective effect of safranal on hepatic steatosis, OS, liver index, IR index, liver function enzymes, plasma lipids, TNF-α, malondialdehyde (MDA), advanced oxidation protein products (AOPPs) and nitrite (NO 2-) levels in a NAFLD rat model fed with a HFD for 12 weeks. The ELISA kits were used to measure TNF-α and insulin in serum and plasma, respectively. Results: HFD significantly induced hepatic steatosis, OS, IR, liver, and oxidative enzyme elevation and inflammation in experimental animals. Rats treated with safranal in ascending order of doses 250 and 500 mg/kg orally for 4-weeks showed a reduction in hepatic lipid's accumulation, liver index, hepatic enzymes, collagen, hepatic oxidonitrative stress markers (like AOPP, MDA and NO 2-), and raised the levels of catalase (CAT) and superoxide dismutase (SOD) enzymes. Glutathione system components, namely glutathione (GSH), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) levels were also restored in the safranal-treated groups. The reduction in serum TNF-α and IR provided further support to the anti-NAFLD effect of safranal. Moreover, the histopathological images indicated reverse of NAFLD activity score (NAS) through mild fatty degeneration, ballooning and inflammation in hepatocytes of treated groups. Conclusion: Findings of blood and tissue analysis concluded that safranal can be a good choice in the management and cure of NAFLD.
Oxidative Stress and Pro-Inflammatory Status in Patients with Non-Alcoholic Fatty Liver Disease
Antioxidants, 2020
Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation, especially triglycerides, in hepatocytes. If the pathology is not properly treated, it can progress to nonalcoholic steatohepatitis (NASH) and continue to fibrosis, cirrhosis or hepatocarcinoma. Objective: The aim of the current research was to identify the plasma biomarkers of liver damage, oxidative stress and inflammation that facilitate the early diagnosis of the disease and control its progression. Methods: Antioxidant and inflammatory biomarkers were measured in the plasma of patients diagnosed with NAFLD (n = 100 adults; 40-60 years old) living in the Balearic Islands, Spain. Patients were classified according to the intrahepatic fat content (IFC) measured by magnetic resonance imaging (MRI). Results: Circulating glucose, glycosylated haemoglobin, triglycerides, low-density lipoprotein-cholesterol, aspartate aminotransferase and alanine aminotransferase were higher in patients with an IFC ≥ 2 of NAFLD in comparison to patients with an IFC of 0 and 1. The plasma levels of catalase, irisin, interleukin-6, malondialdehyde, and cytokeratin 18 were higher in stage ≥2 subjects, whereas the resolvin D1 levels were lower. No differences were observed in xanthine oxidase, myeloperoxidase, protein carbonyl and fibroblast growth factor 21 depending on liver status. Conclusion: The current available data show that the severity of NAFLD is associated with an increase in oxidative stress and proinflammatory status. It may be also useful as diagnostic purpose in clinical practice.