The Treatment with Antibody of TNF-α Reduces the Inflammation, Necrosis and Fibrosis in the Non-alcoholic Steatohepatitis Induced by Methionine- and Choline-deficient Diet

Koca, Süleyman Serdar; Bahçecıoğlu, İbrahim Halil; Poyrazoğlu, Orhan Kürşat; Ozercan, İbrahim Hanifi; Şahin, Kazım; Üstündağ, Bilal

doi:10.1007/s10753-007-9053-z

Cited by 124 publications

(88 citation statements)

References 35 publications

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“…The study by Koca et al also did not report a significant improvement in hepatocyte ballooning, in contrast to our observation of a significant improvement in hepatocyte ballooning in the MCD+infliximab group (27,28).…”

Section: Discussioncontrasting

confidence: 99%

A comparison of the effects of infliximab, adalimumab, and pentoxifylline on rats with non-alcoholic steatohepatitis

Yalçın

Akarsu²,

Çelik³

et al. 2015

Turk J Gastroenterol

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Background/Aims: Non-alcoholic steatohepatitis (NASH) lacks effective medical treatment.Since tumor necrosis factor alpha (TNF-α) plays an important role in NASH pathogenesis, we aimed to investigate drugs affecting TNF-α as possible treatment options during the development of NASH. Materials and Methods: A total of 35 rats were divided into five groupsand evaluated over a 6week period. One group received a normal diet alone or in combination with the administration of infliximab, adalimumab or pentoxifylline Results: NASH was successfully established in the MCD diet group. Levels of TNF-α were effectively suppressed in the three groups that received anti-TNF agents. No statistically significant differences were observed between the three agents in terms of the histological NASH score. Conclusion: Our study showed that the anti-TNF agents infliximab, adalimumab, and pentoxifylline effectively suppress TNF-α. Although these drugs did not prevent the development of NASH, they were able to slightly reverse the NASH histopathology score and positively affect liver function tests

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Section: Discussioncontrasting

confidence: 99%

A comparison of the effects of infliximab, adalimumab, and pentoxifylline on rats with non-alcoholic steatohepatitis

Yalçın

Akarsu²,

Çelik³

et al. 2015

Turk J Gastroenterol

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“…However, the MCH1R antagonist did not affect MCP-1 levels in the MCD diet-induced model, suggesting that MCP-1 might have a more important role in obese-than in lean steatohepatitis. On the other hand, it is reported that leptin and TNFa are also important factors in the progression of fibrogenesis or inflammation in MCD diet-induced NASH (Sahai et al 2004, Koca et al 2008. In accordance with these reports, we showed that plasma leptin levels and hepatic TNFa mRNAs were significantly reduced in obese and lean NASH models.…”

Section: Discussionsupporting

confidence: 91%

Antagonism of central melanin-concentrating hormone 1 receptor alleviates steatohepatitis in mice

Ito¹,

Gomori²,

Suzuki³

et al. 2008

Journal of Endocrinology

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Blockade of brain melanin-concentrating hormone 1 receptor (MCH1R) significantly ameliorates fatty liver as well as obesity. However, the mode of action of this effect is unknown. This study examined the effect of a MCH1R antagonist in murine steatohepatitis models with and without obesity and clarified whether these pharmacological effects were attributed to anti-obesity effects. Steatohepatitis with concomitant obese phenotypes was developed after 52-week exposure to a high-fat diet, and steatohepatitis with reduced body weight was developed by exposure to a methionine-and choline-deficient diet for 10 days. Chronic intracerebroventricular infusion of a peptidic MCH1R antagonist reduced hepatic triglyceride contents and ameliorated steatohepatitis on histological observations in both mice models.Improvement of steatohepatitis was concomitant with amelioration of obese phenotypes such as hyperinsulinemia and hyperleptinemia in the case of the obese model, whereas body weight reduction was not associated with amelioration of steatohepatitis by the antagonist in the lean model. Reduction of hepatic gene expressions encoding cytochromes P450 4A was identified by treatment with the antagonist in both the obese and lean models. These results suggest that brain blockade of MCH1R could alleviate steatohepatitis independently from anti-obesity effects. In conclusion, MCH1R antagonist could have a new therapeutic potential for the treatment of human nonalcoholic steatohepatitis.

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“…For example, the induction of TNF␣ was reduced in low TF mice and PAR-1 Ϫ/Ϫ mice fed the MCD diet. Several studies implicate TNF␣ as a mediator of liver inflammation in mice fed the MCD diet, [45][46][47] although this is not the case for all studies. 9 Similarly, TF and PAR-1 contributed to hepatic expression of COX-2, which has been shown to contribute to hepatic inflammatory cell accumulation in mice fed the MCD diet.…”

Section: Discussionmentioning

confidence: 99%

Tissue Factor-Deficiency and Protease Activated Receptor-1-Deficiency Reduce Inflammation Elicited by Diet-Induced Steatohepatitis in Mice

Luyendyk

Sullivan

Guo

et al. 2010

The American Journal of Pathology

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Altered hepatic lipid homeostasis , hepatocellular injury , and inflammation are features of nonalcoholic steatohepatitis , which contributes significantly to liver-related morbidity and mortality in the Western population. A collection of inflammatory mediators have been implicated in the pathogenesis of steatohepatitis in mouse models. However , the pathways essential for coordination and amplification of hepatic inflammation and injury caused by steatosis are not completely understood. We tested the hypothesis that tissue factor (TF)-dependent thrombin generation and the thrombin receptor protease activated receptor-1 (PAR-1) contribute to liver inflammation induced by steatosis in mice. Wild-type C57Bl/6J mice fed a diet deficient in methionine and choline for 2 weeks manifested steatohepatitis characterized by increased serum alanine aminotransferase activity, macrovesicular hepatic steatosis , hepatic inflammatory gene expression , and lobular inflammation. Steatohepatitis progression was associated with thrombin generation and hepatic fibrin deposition. Coagulation cascade activation was significantly reduced in low TF mice , which express 1% of normal TF levels. Non-alcoholic fatty liver disease (NAFLD) is increasingly appreciated as a hepatic feature of the metabolic syndrome. NAFLD may occur in 25% of the Western population and altered hepatic function increases the risk for developing diseases including diabetes and atherosclerosis.1,2 The progression of simple hepatic steatosis to the more severe nonalcoholic steatohepatitis (NASH) contributes significantly to liver-related morbidity and mortality.3 Requisite histological features of NASH include macrovesicular hepatic steatosis, evidence of hepatocellular injury, and lobular inflammation. 4 In a subset of patients with chronic steatohepatitis, stellate cell activation coordinates a fibrogenic response causing fibrosis and cirrhosis.5 Of importance, the mechanisms required for the progression of hepatic inflammation during steatohepatitis are not completely understood.Animal models used to define mechanisms of steatohepatitis have used genetic and dietary modification to induce various features of the disease.2 In particular, feeding mice a diet deficient in methionine and choline (MCD diet) is an established model to study the progression of steatohepatitis and has been extensively used to study mechanisms of hepatic inflammation and fibrosis. Rodents fed an MCD diet for 2 weeks manifest a defect in hepatic ␤ oxidation resulting in accumulation of triglyceride and the induction of steatohepatitis.2,6,7 Prolonged feeding (Ͼ4 weeks) of the MCD diet activates hepatic stellate cells and increases collagen expression and deposition in the liver. Utilization of the MCD diet model has revealed the contribution of hepatic triglyceride, 8 various inflammatory mediators, 9,10

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The Treatment with Antibody of TNF-α Reduces the Inflammation, Necrosis and Fibrosis in the Non-alcoholic Steatohepatitis Induced by Methionine- and Choline-deficient Diet

Cited by 124 publications

References 35 publications

A comparison of the effects of infliximab, adalimumab, and pentoxifylline on rats with non-alcoholic steatohepatitis

A comparison of the effects of infliximab, adalimumab, and pentoxifylline on rats with non-alcoholic steatohepatitis

Antagonism of central melanin-concentrating hormone 1 receptor alleviates steatohepatitis in mice

Tissue Factor-Deficiency and Protease Activated Receptor-1-Deficiency Reduce Inflammation Elicited by Diet-Induced Steatohepatitis in Mice

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