The Effect of CB1 Antagonism on Hepatic Oxidative/Nitrosative Stress and Inflammation in Nonalcoholic Fatty Liver Disease

2020 ◽  
Vol 28 (1) ◽  
pp. 169-180 ◽  
Author(s):  
Bojan Jorgačević ◽  
Danijela Vučević ◽  
Janko Samardžić ◽  
Dušan Mladenović ◽  
Milena Vesković ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Cell Activation ◽  
Nitrosative Stress ◽  
Experimental Studies ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Cb1 Receptors ◽  
Nonalcoholic Fatty Liver

: Dysfunction of the endocannabinoid system (ES) has been identified in nonalcoholic fatty liver disease (NAFLD) and associated metabolic disorders. Cannabinoid receptor type 1 (CB1) expression is largely dependent on nutritional status. Thus, individuals suffering from NAFLD and metabolic syndrome (MS) have a significant increase in ES activity. Furthermore, oxidative/ nitrosative stress and inflammatory process modulation in the liver are highly influenced by the ES. Numerous experimental studies indicate that oxidative and nitrosative stress in the liver is associated with steatosis and portal inflammation during NAFLD. On the other hand, inflammation itself may also contribute to reactive oxygen species (ROS) production due to Kupffer cell activation and increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The pathways by which endocannabinoids and their lipid-related mediators modulate oxidative stress and lipid peroxidation represent a significant area of research that could yield novel pharmaceutical strategies for the treatment of NAFLD. Cumulative evidence suggested that the ES, particularly CB1 receptors, may also play a role in inflammation and disease progression toward steatohepatitis. Pharmacological inactivation of CB1 receptors in NAFLD exerts multiple beneficial effects, particularly due to the attenuation of hepatic oxidative/nitrosative stress parameters and significant reduction of proinflammatory cytokine production. However, further investigations regarding precise mechanisms by which CB1 blockade influences the reduction of hepatic oxidative/nitrosative stress and inflammation are required before moving toward the clinical phase of the investigation.

scholarly journals Macrophages as Key Players during Adipose Tissue–Liver Crosstalk in Nonalcoholic Fatty Liver Disease

2019 ◽  
Vol 39 (03) ◽  
pp. 291-300 ◽  
Author(s):  
Hannelie Korf ◽  
Markus Boesch ◽  
Lore Meelberghs ◽  
Schalk van der Merwe
Keyword(s):  
Adipose Tissue ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Disease Progression ◽  
Fatty Liver Disease ◽  
Metabolic Profile ◽  
Cell Activation ◽  
Immune Cell ◽  
Nonalcoholic Fatty Liver

AbstractNonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that could lead to serious health problems including liver failure, cancer, or death. The term NAFLD includes a spectrum of disease states with histological features ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). A key aspect within this research field is the identification of pathogenic factors that trigger inflammation, thus fueling the transition from nonalcoholic fatty liver to NASH. These inflammatory triggers may originate from within the liver as a result of innate immune cell activation and/or hepatocyte injury. Additionally, they may originate from other sites such as adipose tissue or the intestinal tract. In the current review, the authors will primarily focus on events within adipose tissue which may be of importance in triggering the disease progression. They specifically focus on the role of adipose tissue macrophages during NAFLD pathogenesis and how microenvironmental factors may shape their metabolic profile. They further dissect how redirecting the macrophage's metabolic profile alters their immunological functions. Finally, they discuss the opportunities and challenges of targeting macrophages to interfere in disease progression.

Dynamics of oxidative/nitrosative stress in mice with methionine–choline-deficient diet-induced nonalcoholic fatty liver disease

2013 ◽  
Vol 33 (7) ◽  
pp. 701-709 ◽  
Author(s):  
B Jorgačević ◽  
D Mladenović ◽  
M Ninković ◽  
V Prokić ◽  
MN Stanković ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nitrosative Stress ◽  
Control Group ◽  
Standard Diet ◽  
Deficient Diet ◽  
Acute Phase Reactants ◽  
Nonalcoholic Fatty Liver

Insulin resistance, oxidative stress, and proinflammatory cytokines play a key role in pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of our study was to investigate the dynamics of oxidative/nitrosative stress in methionine–choline-deficient (MCD) diet -induced NAFLD in mice. Male C57BL/6 mice were divided into following groups: group 1: control group on standard diet; group 2: MCD diet for 2, 4, and 6 weeks (MCD2, MCD4, and MCD6, respectively). After treatment, liver and blood samples were taken for histopathology, alanine- and aspartate aminotransferase, acute phase reactants, and oxidative/nitrosative stress parameters. Liver malondialdehyde level was higher in all MCD-fed groups versus control group ( p < 0.01), while nitrites + nitrates level showed a progressive increase. The activity of total superoxide dismutase and its isoenzymes was significantly lower in all MCD-fed groups ( p < 0.01). Although catalase activity was significantly lower in MCD-fed animals at all intervals ( p < 0.01), the lowest activity of this enzyme was evident in MCD4 group. Liver content of glutathione was lower in MCD4 ( p < 0.05) and MCD6 group ( p < 0.01) versus control.Ferritin and C-reactive protein serum concentration were significantly higher only in MCD6 group. Our study suggests that MCD diet induces a progressive rise in nitrosative stress in the liver. Additionally, the most prominent decrease in liver antioxidative capacity is in the fourth week, which implies that application of antioxidants would be most suitable in this period, in order to prevent nonalcoholic steatohepatitis but not the initial NAFLD phase.

scholarly journals Urinary Phthalate Levels Associated with the Risk of Nonalcoholic Fatty Liver Disease in Adults: The Korean National Environmental Health Survey (KoNEHS) 2012–2014

2021 ◽  
Vol 18 (11) ◽  
pp. 6035
Author(s):  
Yun-Jung Yang ◽  
Taehyen Kim ◽  
Yeon-Pyo Hong
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Environmental Health ◽  
Nonalcoholic Fatty Liver Disease ◽  
Health Survey ◽  
Fatty Liver Disease ◽  
Experimental Studies ◽  
Nonalcoholic Fatty Liver ◽  
Korean Adults ◽  
National Environmental

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Recent experimental studies suggested that phthalates might induce NAFLD. Therefore, this study aimed to investigate the relationship between phthalates metabolites and NAFLD in the human population. This cross-sectional analysis was performed using data from the Korean National Environmental Health Survey II (2012–2014) among Korean adults (n = 5800). NAFLD was diagnosed using the hepatic steatosis index (HSI) in the absence of other causes of chronic liver diseases. Among the participants (mean age 46 years, 47.5% male), the prevalence of NAFLD was associated with urinary levels of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, mono-benzyl phthalate (MBzP), and mono-n-butyl phthalate (MnBP) compared to the reference group. In the multivariate model, the odds ratios (ORs), 95% confidence interval (CI) for NAFLD were 1.33 (1.00–1.78) and 1.39 (1.00–1.92) in the 3rd and 4th quartile of MEHHP, respectively. Based on the study findings, high levels of urinary phthalates are associated with the prevalence of NAFLD in Korean adults. Further investigation is required to elucidate the causal relationship.

scholarly journals Phloroglucinol Strengthens the Antioxidant Barrier and Reduces Oxidative/Nitrosative Stress in Nonalcoholic Fatty Liver Disease (NAFLD)

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Krzysztof Drygalski ◽  
Katarzyna Siewko ◽  
Andrzej Chomentowski ◽  
Cezary Odrzygóźdź ◽  
Anna Zalewska ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nitrosative Stress ◽  
Diet Change ◽  
Nonalcoholic Fatty Liver ◽  
Nonenzymatic Antioxidants ◽  
Stress Models

Nonalcoholic fatty liver disease (NAFLD) is one of the most commonly occurring diseases within western dietary patterns. Usually untreated, it may lead to type 2 diabetes mellitus (T2DM), steatohepatitis (NASH), and hepatocellular carcinoma (HCC). Besides its severe aftermath, up to now, there is no known therapeutic approach to this disease in everyday clinical practice. Most NAFLD patients are encouraged to do physical activities or diet change and remain without pharmacological treatment. In this study, we present phloroglucinol (PHG) as a novel and promising compound in NAFLD treatment. PHG significantly increased the level of enzymatic and nonenzymatic antioxidants both in palmitate and hydrogen peroxide-induced oxidative stress models. Strengthened antioxidative defense reduced the oxidative/nitrosative damage to cell proteins, lipids, and carbohydrates. Furthermore, PHG treatment reduced hepatic steatosis; lowered inflammatory markers, such as NF-κB or HIF-1α; and inhibited cell apoptosis. Moreover, PHG had a more comprehensive effect than other commonly used antioxidants: N-acetylcysteine (NAC) and α-lipoic acid (ALA), suggesting its clinical usability. Therefore, our paper supports the benefits of natural compounds as a therapeutical approach to NAFLD.

scholarly journals Rimonabant Improves Oxidative/Nitrosative Stress in Mice with Nonalcoholic Fatty Liver Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Bojan Jorgačević ◽  
Dušan Mladenović ◽  
Milica Ninković ◽  
Milena Vesković ◽  
Vesna Dragutinović ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nitrosative Stress ◽  
Cannabinoid Receptor ◽  
Control Diet ◽  
Control Group ◽  
Standard Diet ◽  
Nonalcoholic Fatty Liver

The present study deals with the effects of rimonabant on oxidative/nitrosative stress in high diet- (HFD-) induced experimental nonalcoholic fatty liver disease (NAFLD). Male mice C57BL/6 were divided into the following groups: control group fed with control diet for 20 weeks (C;n=6); group fed with HFD for 20 weeks (HF;n=6); group fed with standard diet and treated with rimonabant after 18 weeks (R;n=9); group fed with HFD and treated with rimonabant after 18 weeks (HFR;n=10). Daily dose of rimonabant (10 mg/kg) was administered to HFR and R group by oral gavage for two weeks. Treatment induced a decrease in hepatic malondialdehyde concentration in HFR group compared to HF group(P<0.01). The concentration of nitrites + nitrates in liver was decreased in HFR group compared to HF group(P<0.01). Liver content of reduced glutathione was higher in HFR group compared to HF group(P<0.01). Total liver superoxide dismutase activity in HFR group was decreased in comparison with HF group(P<0.01). It was found that rimonabant may influence hepatic iron, zinc, copper, and manganese status. Our study indicates potential usefulness of cannabinoid receptor type 1 blockade in the treatment of HFD-induced NAFLD.

scholarly journals Spinach consumption and nonalcoholic fatty liver disease among adults: a case–control study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ebrahim Mokhtari ◽  
Hossein Farhadnejad ◽  
Ammar Salehi-Sahlabadi ◽  
Narjes Najibi ◽  
Mina Azadi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Case Control Study ◽  
Experimental Studies ◽  
Case Control ◽  
Inverse Association ◽  
Nonalcoholic Fatty Liver ◽  
Control Study

Abstract Background Spinach has high antioxidants and polyphenols and showed protective effects against liver diseases in experimental studies. We aimed to assess the association between dietary intake of spinach and odds of nonalcoholic fatty liver disease (NAFLD) in a case–control study among Iranian adults. Methods Totally 225 newly diagnosed NAFLD patients and 450 controls, aged 20–60 years, were recruited in this study. Participants’ dietary intakes were collected using a valid and reliable 168-item semi-quantitative food frequency questionnaire (FFQ). The logistic regression test was used for assessing the association between total, raw, and boiled dietary spinach with the odds of NAFLD. Results The mean (SD) age and BMI of participants (53% male) were 38.1 (8.8) years and 26.8 (4.3) kg/m2, respectively. In the final adjusted model for potential confounders, the odds (95% CI) of NAFLD in individuals in the highest tertile of daily total and raw spinach intake was [0.36 (0.19–0.71), P_trend = 0.001] and [0.47 (0.24–0.89), P_trend = 0.008], respectively compared with those in the lowest tertile. Furthermore, in the adjusted analyses, an inverse association was observed between the highest yearly intake versus no raw spinach consumption and odds of NAFLD [(OR 0.41; 95% CI 0.18–0.96), P for trend = 0.013]. However, there was no significant association between higher boiled spinach intake and odds of NAFLD. Conclusions The present study found an inverse association between total and raw spinach intake with the odds of NAFLD.

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