Mitochondrial Abnormality and Oxidative Stress in Nonalcoholic Steatohepatitis

Kojima, Hideyuki; Sakurai, Shinya; Uemura, Mamoru; Fukui, Hiroshi; Morimoto, Hiroyo; Tamagawa, Yasuhiro

doi:10.1111/j.1530-0277.2006.00288.x

Cited by 74 publications

(58 citation statements)

References 15 publications

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“…In addition, 4-HNE and 8-OHdG have been reported to be over-expressed in NASH livers (5). However, another study found that ROS was significantly increased in FL as well as NASH livers (22), indicating that FL and NASH are both affected by ROS despite the different clinical outcomes. It has been reported that increased production of ROS occurs very early in the histological spectrum of NAFLD (6), and has also been demonstrated that, even at the earliest stage of Figure 3.…”

Section: Discussionmentioning

confidence: 84%

Neovascularization and oxidative stress in the progression of non-alcoholic steatohepatitis

Kitade

Yoshiji²,

Kojima³

et al. 2008

Mol Med Report

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Abstract. Reactive oxygen species (ROS) is known to play an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH); however, as we previously reported, angiogenesis also plays a pivotal role in NASH progressionthe development of liver fibrosis and hepatocellular carcinoma -in rats. The aim of the current study was to elucidate the role of angiogenesis in the development of fibrosis in NASH. Twenty-six patients with NASH and 11 with simple fatty liver (FL) disease were enrolled in the study and underwent clinicopathological examination. Immunohistochemical analysis of 4-hydroxy-2-noneal (4-HNE) and CD34 was employed for the detection of ROS and angiogenesis in the liver tissues, respectively. Both the NASH and FL samples displayed a marked staining of 4-HNE as compared to the healthy liver. Similar levels of 4-HNE were observed in NASH regardless of the grade of liver fibrosis. In sharp contrast, hepatic neovascularization developed significantly in NASH alone, whereas almost no neovascularization was observed in FL or the healthy liver. The degree of angiogenesis was almost parallel with the development of liver fibrosis. In conclusion, simple FL and NASH cases were both affected by ROS. However, only NASH was associated with marked neovascularization, proportional to the increase in the grade of liver fibrosis development. These results indicate that hepatic neovascularization may play an important role in the onset and progression of NASH.

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Section: Discussionmentioning

confidence: 84%

Neovascularization and oxidative stress in the progression of non-alcoholic steatohepatitis

Kitade

Yoshiji²,

Kojima³

et al. 2008

Mol Med Report

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“…The NF-κB pathway is also one of the most important signalling pathways during development and progression of alcoholic and non-alcoholic steatohepatitis (ASH/NASH) (47,48). All these liver diseases, especially NASH, which is a more advanced form of NAFLD, are characterized by pathogenetic mechanisms including, oxidative stress and redox state imbalance (49)(50)(51).…”

Section: Discussionmentioning

confidence: 99%

Glutathionylation of p65NF-κB correlates with proliferating/apoptotic hepatoma cells exposed to pro- and anti-oxidants

Alisi

Piemonte²,

Pastore³

et al. 2009

Int J Mol Med

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Abstract.Oxidative stress influences a variety of regulatory proteins, including nuclear factor-κB (NF-κB). NF-κB is critical for maintaining the proliferation/apoptosis balance in hepatocytes. In this study we investigated the causal links between glutathione, NF-κB and hepatocyte damage. HepG2 and 3B cells were exposed to different doses of H 2 O 2 or N-acetylcysteine (NAC) and the proliferation/apoptosis rate, glutathione forms, and p65NF-κB glutathionylation and activity were analysed. Our results demonstrate that H 2 O 2 stopped proliferative response at low doses, but induced apoptosis only at high doses. In contrast, NAC exerted, proportionally to its concentration, a dual role simultaneously increasing both proliferation and apoptosis. Interestingly, the levels of proteinbound glutathione were increased by H 2 O 2 and decreased by NAC. Moreover, the antibody recognizing the glutathionylated proteins co-precipitated and -localized with the cytoplasmic inactive form of p65NF-κB in H 2 O 2 -and NAC-treated cells, even when, in 1 mM NAC-treated cells, a part of p65 was glutathione-free and localized into the nucleus. Apoptotic cells were characterised principally by a cytoskeletal staining of glutathionylation and retention of NF-κB in the cytoplasmic region; whereas in proliferating cells, glutathionylated proteins were concentrated into the perinuclear region and p65NF-κB was traslocated into the nucleus. While cytoplasmic NF-κB retention correlated well with an increased apoptotic rate, a greater expression of this protein was observed in association with the NAC-dependent. In conclusion, our findings suggest that glutathionylation inhibits NF-κB activity causing reduced hepatocyte survival, which is common in several liver diseases.

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“…Results from the Biomarkers of Oxidative Stress Study (BOSS) suggested that the most accurate marker to assess lipid peroxidation in vivo is the plasma or urinary iPF 2α -Ⅲ [13] . Elevated plasma or urinary levels of iPF 2α -Ⅲ have been reported in patients [14,15] and in animals with NASH [16] . Information in the literatures with regard to iPF 2α -Ⅲ formation related to hepatic steatosis, however, is limited.…”

Section: Introductionmentioning

confidence: 99%

Blood F2-isoprostanes are significantly associated with abnormalities of lipid status in rats with steatosis

Zhu¹,

Sun²,

Liu³

et al. 2008

WJG

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Mitochondrial Abnormality and Oxidative Stress in Nonalcoholic Steatohepatitis

Cited by 74 publications

References 15 publications

Neovascularization and oxidative stress in the progression of non-alcoholic steatohepatitis

Neovascularization and oxidative stress in the progression of non-alcoholic steatohepatitis

Glutathionylation of p65NF-κB correlates with proliferating/apoptotic hepatoma cells exposed to pro- and anti-oxidants

Blood F2-isoprostanes are significantly associated with abnormalities of lipid status in rats with steatosis

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