Reevaluation of Experimental Model of Hepatic Fibrosis Induced by Hepatotoxic Drugs: An Easy, Applicable, and Reproducible Model

Jang, Jae Hwi; Kang, Koo-Jeong; Kim, Y.H.; Kang, Yuna; Lee, I.S.

doi:10.1016/j.transproceed.2008.07.040

Cited by 36 publications

(24 citation statements)

References 8 publications

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“…15,16 With regard to the latter, an enlargement of portal tracts without signs of cholestasis is frequently observed. [17][18][19] TAA is first oxidized to TAA-S-oxide and then to TAA-S,S-oxide ( Figure 2); this process can be carried out by hepatic cytochrome P450 enzymes or FAD-containing monooxygenases. 20 The lethal dose (LD 50 ) in rats and mice after both oral and IP administration was determined to be approximately 300 mg/kg body weight.…”

Section: Mechanisms and Pattern Of Liver Injurymentioning

confidence: 99%

Standard Operating Procedures in Experimental Liver Research: Thioacetamide model in mice and rats

et al. 2015

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In addition to carbon tetrachloride (CCl 4 ), thioacetamide (TAA) represents a second widely used model for the induction of experimental liver fibrosis, but can also be employed for the development of acute liver failure and liver tumours. While TAA itself is not hepatotoxic, its reactive metabolites covalently bind to proteins and lipids thereby causing oxidative stress and centrilobular necrosis. Compared with CCl 4 , TAA leads to more periportal infiltrates and more pronounced ductal proliferation. While TAA has been shown to induce liver fibrosis development in several different mouse strains, wide variations in the administration routes, doses and treatment durations have been reported. Therefore, an adoption of a universal standard operating procedure for the administration of TAA is urgently needed. For that purpose, we are presenting here two TAA models (intraperitoneal administration of 150 mg/kg of TAA three times per week for 11 weeks in rats, and TAA administration in drinking water at 300 mg/L for 2-4 months in mice) with which we have had success in reliably and reproducibly developing chronic liver injury and fibrosis.

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Section: Mechanisms and Pattern Of Liver Injurymentioning

confidence: 99%

Standard Operating Procedures in Experimental Liver Research: Thioacetamide model in mice and rats

et al. 2015

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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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“…Recently, large numbers of research groups have studied the efficacy of human stem cells on liver diseases [2,17]. To evaluate the efficacy and safety of cell therapies in preclinical studies, adequate animal models for human diseases are absolutely necessary for research [12]. However, when we evaluate the efficacy and safety of human cells in laboratory animals, we should consider the difference in immune reaction between human cells and host animals.…”

mentioning

confidence: 99%

“…Some indispensable factors for a suitable animal model are such things as easy applicability, adequate fibrosis, a limited duration of induction, reproducibility and animal hazard to personnel [12]. Mouse models of liver fibrosis can be induced by hepatotoxins, such as carbon tetrachloride (CCl 4 ), thioacetamide (TAA) and dimethylnitrosamine (DMN), or bile duct ligation [19].…”

mentioning

confidence: 99%

“…Establishing an easy and reproducible model for hepatic fibrosis is absolutely essential [12], and an immunodeficient mouse model is necessary for evaluation of various cell therapies. Therefore, we attempted to establish a new animal model of disease for DMN-induced liver fibrosis in NOD/SCID mice and examined the characteristics and recovery of this DMN-induced liver fibrosis model through serum biochemistry, histopathology, immunohistochemistry and Western blot analysis.…”

mentioning

confidence: 99%

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Dimethylnitrosamine-Induced Liver Fibrosis and Recovery in NOD/SCID Mice

Hyon

Kwon

Choi

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. There is a need for a new liver fibrosis model of immunodeficient mice to study the effects of cell therapy on liver disease because there are not many animal models available to study the effects of cell therapy. In this study, we induced liver fibrosis using dimethylnitrosamine (DMN) in NOD/SCID mice to create an animal model for liver disease. DMN (5 mg/kg, i.p.) was injected intraperitoneally for three consecutive days per week for 6 or 8 weeks, and the mice were sacrificed at weeks 0, 4 and 8 after the last DMN injection. The 6-week DMN-treated group gradually recovered from serum biochemical changes, histopathological toxic effects and lesions in the liver at weeks 4 and 8 after the last DMN injection. However, the progression of liver fibrosis and toxic levels were maintained in the 8-week DMN-treated group at week 4 after the last DMN injection. The increases in iron and extracellular matrix (collagen) in the DMN-treated group were confirmed by Prussian blue (PB) and Masson's trichrome (MT) staining, respectively. Additionally, activation of hepatic stellate cells was observed by alpha smooth muscle actin (-SMA) immunostaining and western blot. In conclusion, treatment of NOD/SCID mice with 5 mg/kg of DMN for 8 weeks can be used to induce an appropriate animal model of disease for liver fibrosis. This model may be useful for evaluation of the efficacy and safety of cell therapies such as human mesenchymal stem cell therapy.KEY WORDS: animal model, dimethylnitrosamine, liver fibrosis, NOD/SCID mice.

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Reevaluation of Experimental Model of Hepatic Fibrosis Induced by Hepatotoxic Drugs: An Easy, Applicable, and Reproducible Model

Cited by 36 publications

References 8 publications

Standard Operating Procedures in Experimental Liver Research: Thioacetamide model in mice and rats

Standard Operating Procedures in Experimental Liver Research: Thioacetamide model in mice and rats

Adverse Outcome Pathway on Protein Alkylation Leading to Liver Fibrosis

Dimethylnitrosamine-Induced Liver Fibrosis and Recovery in NOD/SCID Mice

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