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

Abstract

<jats:p> 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 &lt; 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 &lt; 0.01). Although catalase activity was significantly lower in MCD-fed animals at all intervals ( p &lt; 0.01), the lowest activity of this enzyme was evident in MCD4 group. Liver content of glutathione was lower in MCD4 ( p &lt; 0.05) and MCD6 group ( p &lt; 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. </jats:p>

Inulin nanoparticles and silymarin counteract chlorpromazine-induced injury in the liver and kidney of rats

“…These results are in accordance with the previous reports suggested that SIL possess antioxidant, antiapoptotic, anti-inflammatory and immunomodulatory properties (Al-Rasheed et al, 2015Fraschini et al, 2002;Karimi et al, 2011;Pradeep et al, 2007). The hepatoprotective role of SIL was suggested to be due to its enhancement of CYP2E1 activity which has a major role in drug metabolism (Dejanovic et al, 2014;Jorgačević et al, 2014;Mahli et al, 2015;Wong et al, 1998).…”

“…Moreover, the generation of ROS activates the stellate cells in the liver resulting in the deposition of extracellular matrix which contribute to the development of fibrosis or cirrhosis in the liver tissue. The current results also showed that NO was increased in the liver and kidney tissues which may be suggested by the role of ROS in the increase of the synthesis of inducible iNOS (isoform nitric oxide synthase) leading to the increase of the level of NO (Jorgačević et al, 2014).…”

Treatment with baicalein attenuates methionine−choline deficient diet-induced non-alcoholic steatohepatitis in rats

“…MCD-diet led to an increased production of reactive oxygen species and at the same time decreased the activity of antioxidant enzymes (Jorgacevic et al, 2013;Luo et al, 2014). Free fatty acid incubation of HepG2 cells in vitro resulted in swollen mitochondria with increased inner matrix density and loss of cristae (Jun et al, 2011).…”

Is nonalcoholic fatty liver disease an endogenous alcoholic fatty liver disease? – A mechanistic hypothesis

“…These include obstructive sleep apnea-induced hypoxia [71,72], by-products of both carbohydrate [73][74][75][76][77] and lipid metabolism [78][79][80], and gut-derived bacterial toxins [81,82]. Furthermore, nonoxidative metabolites of ethanol [19,83,84], methanol/formaldehyde [27,85,86], and nitrosative stressors [87,88] may also contribute to NAFLD pathogenesis.…”