Oxidative stress in the pathogenesis of nonalcoholic fatty liver disease, in rats fed with a choline‐deficient diet

Abstract

Background Aim: The pathogenesis of Nonalcoholic Fatty Liver Disease remains largely unknown, but oxidative stress seems to be involved. The aim of this study was to evaluate the role of oxidative stress in experimental hepatic steatosis induced by a choline-deficient diet. Methods: Fatty liver disease was induced in Wistar rats by a cholinedeficient diet. The animals were randomized into three groups: I (G1) and II (G2), n=6 each -fed with a cholinedeficient diet for four and twelve weeks respectively; Group III (control-G3; n=6) -fed with a standard diet for twelve weeks. Samples of plasma and liver were submitted to biochemical, histological and oxidative stress analysis. Variables measured included serum levels of aminotransferases (AST, ALT), cholesterol and triglycerides. Oxidative stress was measured by lucigenin-enhanced luminescence and the concentration of hydroperoxides (CE-OOHcholesteryl ester) in the liver tissue. Results: We observed moderate macro-and microvesicular fatty change in periportal zones G1 and G2 as compared to controls (G3). In G2, fatty change was more severe. The inflammatory infiltrate was scanty and no fibrosis was seen in any group. There was a significant increase of AST and triglycerides in G1 and G2 as compared to control group G3. The lucigenin-amplified luminescence (cpm/mg/min x 10 3 ) was significantly increased in G1 (1393±790) and G2 (7191±500) as compared to controls (513±170), p<0.05. The concentrations of CE-OOH were higher in G1 (5.7±0.9 nmol/mg protein) as compared to control (2.6±0.7 nmol/mg protein), p<0.05. Conclusion: 1) Oxidative stress was found to be increased in experimental liver steatosis; 2) The production of reactive oxygen species was accentuated when liver steatosis was more severe; 3) The alterations produced by oxidative stress could be an important step in the pathogenesis of nonalcoholic fatty liver disease.

Differential alterations in mitochondrial function induced by a choline-deficient diet: Understanding fatty liver disease progression

“…This paper further recognizes that fat accumulation in the liver is associated with decreased efficiency of the phosphorylative system, in concordance with our previous studies in another animal model of fatty liver (Teodoro et al, 2006). Although other studies have been conducted with the choline-deficient model of fatty liver disease (Vendemiale et al, 2001;Oliveira et al, 2002;Grattagliano et al, 2003;Zafrani, 2004), this work proved invaluable since it is the first of its kind to apply a timeline approach. The mitochondrial function, mainly at the bioenergetic level, was found to be impaired due to fat accumulation.…”

Dietary choline regulates antibacterial activity, inflammatory response and barrier function in the gills of grass carp (Ctenopharyngodon idella)

“…In the present study, relative to choline deficiency, dietary choline supplementation markedly decreased pro-inflammatory cytokines IL-1b, TNF-a, IFN-g and IL-8 and increased anti-inflammatory cytokines IL-10 and TGFb1 mRNA levels in the gills of grass carp, suggesting that choline could reduce the inflammation in the gills of fish. Although research in rat has implied that choline could attenuate the liver inflammation [56], but the exact mechanisms which choline regulates the inflammation remains largely unknown. To our knowledge, production of cytokine could be regulated by the signaling pathway of TOR and NF-kB [12].…”

Experimental induction of steatosis in different tissues after the ingestion of a carbohydrate-rich diet: effect on the liver, on the heart and on indicators of oxidation

“…This fact may have occurred because hepatic fibrogenesis probably was not present, as observed by histological analysis. Oxidative stress occurring within a context of triacyglyceride deposition inside the hepatocytes appears to be important for the progression of steatosis to steatohepatitis and fribrosis (19,20) . Several studies have demonstrated that reactive oxygen species are increase in steatohepatitis, whereas antioxidant (vitamin E and glutathione) levels are decreased (10,11) .…”