Persistence of Liver Cirrhosis in Association with Proliferation of Nonparenchymal Cells and Altered Location of <i>α</i>-Smooth Muscle Actin-Positive Cells

Kang, Jin Seok; Morimura, Keiichirou; Salim, Elsayed I.; Wanibuchi, Hideki; Yamaguchi, Shuji; Fukushima, Shoji

doi:10.1080/01926230590922901

Cited by 17 publications

(11 citation statements)

References 47 publications

(43 reference statements)

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“…Thioacetamide (TAA) in drinking water (0.03%) or by intraperitoneal injection induces fibrosis in rats and mice over a period of 2-3 months, which may be secondary to the oxidant properties of TAA and the induction of hepatic oxidative stress [134,146,147]. Acute liver injury and subsequent fibrosis can be created by administration of D-galactosamine (GalN), a hepatotoxin that induces liver damage by depleting uridine nucleotides and therefore diminishing RNA and protein synthesis [148].…”

Section: Chemically-induced Fibrosis and Hepatocarcinogenesismentioning

confidence: 99%

Experimental models of hepatocellular carcinoma

Newell

Villanueva

Friedman

et al. 2008

Journal of Hepatology

205

168

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Hepatocellular carcinoma (HCC) is a common and deadly cancer whose pathogenesis is incompletely understood. Comparative genomic studies from human HCC samples have classified HCCs into different molecular subgroups; yet, the unifying feature of this tumor is its propensity to arise upon a background of inflammation and fibrosis. This review seeks to analyze the available experimental models in HCC research and to correlate data from human populations with them in order to consolidate our efforts to date, as it is increasingly clear that different models will be required to mimic different subclasses of the neoplasm. These models will be instrumental in the evaluation of compounds targeting specific molecular pathways in future preclinical studies.

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Section: Chemically-induced Fibrosis and Hepatocarcinogenesismentioning

confidence: 99%

Experimental models of hepatocellular carcinoma

Newell

Villanueva

Friedman

et al. 2008

Journal of Hepatology

205

168

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“…These effects occur due to the existence of two distinct isoforms of COX enzymes, COX-1 (constitutive) and COX-2 (inducible) (Lichtenstein and Wolfe 2000;Halpin et al 2000;Harworth et al 2005). While the first maintains the homeostasis of our body with the physiological production of PGs, especially those related to the integrity of gastric mucosa (Kargman 1996;Zhang et al 2002), COX-2 is mainly activated by cytokines and growth factors involved in inflammatory conditions (Needelman and Isakson 1997).…”

Section: Introductionmentioning

confidence: 98%

Short-term administration of non-selective and selective cox-2 nsaids do not interfere with bone repair in rats

et al. 2008

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Selective cyclooxygenase-2 non-steroidal anti-inflammatory drugs are known to inhibit bone repair, especially when long-term administration is required due to chronicle inflammatory diseases. In order to evaluate the action of this drug in bone repair during short-term administration, 48 rats underwent surgical bone defects in their tibias, being randomly distributed into three groups: (Group 1) negative control; (Group 2) animals treated with celecoxib, and (Group 3) animals treated with ketoprofen, both experimental groups at 1 mg/kg dose, beginning 1 h before the surgical procedure and after every 12 h for the following 3 days, or until the day of sacrifice. The animals were killed after 48 h, 7, 14, and 21 days. The tibias were removed for morphological, morphometric, and immunohistochemistry analysis for COX-2. No statistical significant differences were observed in the quality of bone repair and quantity of formed bone among the groups. COX-2 immunoreactivity of the celecoxib treated specimens was more intense in the first analyzed period, and no longer observed in the periods of 14 and 21 days. Such results suggest that the administration of the analyzed drugs in short periods does not interfere with the process of bone repair in the tibia of rats.

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“…Thioacetamide (TAA) induced liver cell damage, fibrosis and/or cirrhosis, associated with increase of oxidative stress and activation of hepatic stellate cells (Kang et al 2005;Li et al 2002;Muller et al 1988;Porter et al 1979). It was metabolized via CYP450, and induced hepatocellular toxicities including hepatic cell necrosis (James et al 2003;Porter et al 1979).…”

Section: Introductionmentioning

confidence: 99%

Comparing In Vitro and In Vivo Genomic Profiles Specific to Liver Toxicity Induced by Thioacetamide

Kang¹,

Jeong²,

Shin³

et al. 2007

Biomolecules and Therapeutics

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− As it is needed to assay possible feasibility of extrapolation between in vivo and in vitro systems and to develop a new in vitro method for toxicity testing, we investigated global gene expression from both animal and cell line treated with thioacetamide (TAA) and compared between in vivo and in vitro genomic profiles. For in vivo study, mice were orally treated with TAA and sacrificed at 6 and 24 h. For in vitro study, TAA was administered to a mouse hepatic cell line, BNL CL.2 and sampling was carried out at 6 and 24 h. Hepatotoxicity was assessed by analyzing hepatic enzymes and histopathological examination (in vivo) or lactate dehydrogenase (LDH) assay and morphological examination (in vitro). Global gene expression was assessed using microarray. In high dose TAA-treated group, there was centrilobular necrosis (in vivo) and cellular toxicity with an elevation of LDH (in vitro) at 24 h. Statistical analysis of global gene expression identified that there were similar numbers of altered genes found between in vivo and in vitro at each time points. Pathway analysis identified several common pathways existed between in vivo and in vitro system such as glutathione metabolism, bile acid biosynthesis, nitrogen metabolism, butanoate metabolism for hepatotoxicty caused by TAA. Our results suggest it may be feasible to develop toxicogenomics biomarkers by comparing in vivo and in vitro genomic profiles specific to TAA for application to prediction of liver toxicity.

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Persistence of Liver Cirrhosis in Association with Proliferation of Nonparenchymal Cells and Altered Location of α-Smooth Muscle Actin-Positive Cells

Cited by 17 publications

References 47 publications

Experimental models of hepatocellular carcinoma

Experimental models of hepatocellular carcinoma

Short-term administration of non-selective and selective cox-2 nsaids do not interfere with bone repair in rats

Comparing In Vitro and In Vivo Genomic Profiles Specific to Liver Toxicity Induced by Thioacetamide

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