The Role of Tumor Necrosis Factor-α in Liver Toxicity, Inflammation, and Fibrosis Induced by Carbon Tetrachloride

Simeonova, Petia P.; Gallucci, Randle M.; Hulderman, Tracy; Wilson, R. E.; Kommineni, Choudari; Rao, Murali K; Luster, Michael I.

doi:10.1006/taap.2001.9304

Cited by 180 publications

(149 citation statements)

References 36 publications

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“…Second, gene expression has been studied in rodent models of hepatic fibrosis, 8 including hepatic toxins, bile duct ligation, and alcohol administration. Third, mutations generated by gene targeting in mice have re-vealed key genes that modify experimental hepatic fibrosis [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] (Table 1). And finally, the development of powerful techniques to study gene expression profile ("microarray chips") has facilitated the identification of potential candidate genes that are up-regulated in both activated HSCs and the fibrotic liver.…”

Section: Identification Of Candidate Genes Involved In Hepatic Fibrogmentioning

confidence: 99%

Genetic Polymorphisms and the Progression of Liver Fibrosis: A Critical Appraisal

2003

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Liver fibrosis is a highly dynamic process in which multiple genes interact with environmental factors. Recent human epidemiologic studies have identified possible polymorphisms in a number of candidate genes that influence the progression of liver fibrosis. These genetic factors could explain the broad spectrum of responses to the same etiologic agent found in patients with chronic liver diseases. Polymorphisms in genes encoding immunoregulatory proteins, proinflammatory cytokines, and fibrogenic factors may influence disease progression in patients with alcohol-induced liver disease, primary biliary cirrhosis, or chronic hepatitis C. However, some of the studies have yielded contradictory results. For example, conflicting results have been obtained in studies assessing the role of mutations in the hemochromatosis gene on fibrosis progression in patients with chronic hepatitis C. Largescale, well-designed studies are required to clarify the actual role of this factor and other genetic variants in liver fibrosis. (HEPATOLOGY 2003;37:493-503.)

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Section: Identification Of Candidate Genes Involved In Hepatic Fibrogmentioning

confidence: 99%

Genetic Polymorphisms and the Progression of Liver Fibrosis: A Critical Appraisal

2003

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“…18 A pleiotropic cytokine, TNFa, has been shown to induce apoptosis and be involved in acute CCl 4 -induced hepatic injury. [41][42][43] We investigated whether PTD-FNK prevents HepG2 from TNFa/CHX-induced apoptosis. Cells were pretreated with PTD-FNK and incubated with TNFa/CHX in the presence of PTD-FNK.…”

Section: Necrosis In Hepg2 Induced By CCLmentioning

confidence: 99%

Zonal necrosis prevented by transduction of the artificial anti-death FNK protein

et al. 2005

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Protection of cells from necrosis would be important for many medical applications. Here, we show protein transduction domain (PTD)-FNK therapeutics based on protein transduction to prevent necrosis and acute hepatic injury with zonal death induced by carbon tetrachloride (CCl 4 ). PTD-FNK is a fusion protein comprising the HIV/Tat PTD and FNK, a gain-offunction mutant of anti-apoptotic Bcl-x L . PTD-FNK protected hepatoma HepG2 from necrotic death induced by CCl 4 , and additionally, increased the apoptotic population among cells treated with CCl 4 . A concomitant treatment with a pancaspase inhibitor Z-VAD-FMK (N-benzyloxycarbonyl-Val-AlaAsp-fluoromethylketone), which alone could not prevent the necrosis, protected these cells from the apoptosis. When preinjected intraperitoneally, PTD-FNK markedly reduced zonal liver necrosis caused by CCl 4 . Moreover, injection of PTD-FNK accompanied by Z-VAD-FMK suppressed necrotic injury even after CCl 4 administration. These results suggest that PTD-FNK has great potential for clinical applications to prevent cell death, whether from apoptosis or necrosis, and organ failure.

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“…Assuming hepatocyte injury being the crucial KE without which fibrosis could not occur via this AOP, then simple investigation of in vitro hepatotoxicity could provide relevant information for potential fibrosis prediction without the need of highly elaborated cell models. The initial AOP case study was based on data of two prototypic fibrogenic chemicals, namely Carbon Tetrachloride (CCl4) (Basu, 2003;Brattin et al, 1985;Calabrese and Mehendale, 1996;Calabrese et al, 1993;Clawson, 1989Dalu and Mehendale, 1996;EPA, 2010;Feng et al, 2011;Jaeschke et al, 2013;Jang et al, 2008;Lee et al, 2004;Li L. et al, 2012;Li X. et al, 2013;Luster et al, 2000;2001;Lv et al, 2012;Masuda, 2006;Morio et al, 2001;Nagano et al, 2007;Natsume et al, 1999;Neubauer et al, 1998;Nissar et al,2013;Park et al, 2004;Recknagel, 1976;Simeonova et al, 2001;Tipoe et al, 2006;Weber et al, 2003;Zhu and Fung, 2000) and Allyl…”

Section: Uncertainties Inconsistencies and Data Gapsmentioning

confidence: 99%

Adverse Outcome Pathway on Protein Alkylation Leading to Liver Fibrosis

Landesmann

2016

OECD Series on Adverse Outcome Pathways

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The Role of Tumor Necrosis Factor-α in Liver Toxicity, Inflammation, and Fibrosis Induced by Carbon Tetrachloride

Cited by 180 publications

References 36 publications

Genetic Polymorphisms and the Progression of Liver Fibrosis: A Critical Appraisal

Genetic Polymorphisms and the Progression of Liver Fibrosis: A Critical Appraisal

Zonal necrosis prevented by transduction of the artificial anti-death FNK protein

Adverse Outcome Pathway on Protein Alkylation Leading to Liver Fibrosis

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