Study on mechanism of multistep hepatotumorigenesis in rat: development of hepatotumorigenesis

Ha, Woo Song; Kim, Chi Kyeong; Song, Sang Hwa; Kang, Chung Boo

doi:10.4142/jvs.2001.2.1.53

Cited by 84 publications

(39 citation statements)

References 11 publications

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“…In the later period, a complete collapse of hepatic architecture happened, the presence of HCC was verified and on the MRI images the signal heterogeneity of the liver became more significant and nodules with various diameters and signal intensities could be seen clearly. A similar pathological result was described in S.D rat model (Ha et al 2001).…”

Section: Discussionsupporting

confidence: 71%

“…An in vivo 1 H-MRS research of healthy individuals (Tarasow et al 2002) showed that there was positive correlation between the gender, body mass index (BMI) and total lipid concentration (TL). Also, in the formation of carcinoma in animal models the speed of tumor development was not synchronous (Ha et al 2001). In the late treated group of the current study, though some 1 H-MRS results were from HCC nodules which were confirmed by pathology, others, instead of cancerous tissues, were from severe hepatic lesions, which could contribute to the different results with other studies.…”

Section: Discussionmentioning

confidence: 99%

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In vivo detection of metabolic changes by 1 H-MRS in the DEN-induced hepatocellular carcinoma in wistar rat

Zhao

Guan

Zhou

et al. 2005

J Cancer Res Clin Oncol

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

In vivo detection of metabolic changes by 1 H-MRS in the DEN-induced hepatocellular carcinoma in wistar rat

Zhao

Guan

Zhou

et al. 2005

J Cancer Res Clin Oncol

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“…ALT is recognised to be a largely liver specific enzyme. Conversely, AST might be a non-specific index in the liver because AST is present in the heart, skeletal muscle, kidney, and brain [38]. LDH is a highly sensitive marker for solid neoplasm.…”

Section: Discussionmentioning

confidence: 98%

Apoptotic effects of dipyrido [3,2-a:2′,3′-c] phenazine (dppz) Au(III) complex against diethylnitrosamine/phenobarbital induced experimental hepatocarcinogenesis in rats

et al. 2014

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We evaluated the effects of dipyrido [3,2-a:2',3'-c] phenazine (dppz) Au(III) complex ([Au(dppz)Cl2]Cl) on apoptosis during chemically induced hepatocellular carcinoma. 48 male Spraque-Dawley rats were divided into six groups; group I (control), group II [Dimethyl sulfoxide (DMSO)], group III ([Au(dppz)Cl2]Cl), group IV [diethylnitrosamine + Phenobabital (DEN + PB)], group V (DEN + PB + [Au(dppz)Cl2]Cl (2nd week)), and group VI (DEN + PB + [Au(dppz)Cl2]Cl (7th week). The rats in groups IV through VI were administrated with DEN in a single dose of intraperitoneal 175 mg/kg. After 2 weeks of DEN administration, these groups of rats were given daily PB in a dose of 500 ppm. In group V, after two weeks of DEN administration, [Au(dppz)Cl2]Cl complex (2 mg/kg) was given once a week by intraperitoneal injection. In the group VI, the rats were given a dose of 2 mg/kg [Au(dppz)Cl2]Cl complex once a week, 7 weeks after DEN administration. At the end of the study, blood and tissue samples were collected from the rats to determine levels of serum AST, ALT, and LDH, and caspase 3, p53, Bax, Bcl-2 and DNA fragmentation in liver. AST, ALT, LDH, and Bcl-2 levels were higher in group IV, compared to group I, but caspase 3 and p53 levels were lower. In group V, caspase 3, p53, Bax, and DNA fragmentation levels were higher than those of group IV. Caspase 3 and p53 levels increased in group VI compared with group IV. In conclusion, [Au(dppz)Cl2]Cl complex induced apoptosis by elevating levels of caspase 3, p53, Bax, and DNA fragmentation.

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“…DEN, a genotoxic carcinogen, is typically used in a single dose paradigm with analysis of the results coming weeks or month later; however, there are several reports that chronic treatment results in hepatocellular vacuolation and steatosis (Braunbeck et al, 1992;Dunsford et al, 1989;Goldfarb et al, 1983;Ha et al, 2001). Most evidence points to mitochondrial permeability transition (MPT) and induction of apoptosis as the primary mechanism of microcystin LR-induced hepatotoxicity (Ding and Nam Ong, 2003;Ding et al, 2001); although, there are reports of this compound inducing lipid changes and/or steatosis (Guzman and Solter, 1999;Sturgeon and Towner 1999).…”

Section: Discussionmentioning

confidence: 98%

Investigating the Mechanistic Basis for Hepatic Toxicity Induced by an Experimental Chemokine Receptor 5 (CCR5) Antagonist Using a Compendium of Gene Expression Profiles

Cornwell

Ulrich²

2007

Toxicol Pathol

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A compendium of hepatic gene expression signatures was used to identify a mechanistic basis for the hepatic toxicity of an experimental CCR5 antagonist (MrkA). Development of MrkA, a potential HIV therapeutic, was discontinued due to hepatotoxicity in preclinical studies. Rats were treated with MrkA at 3 dose levels (50, 250, and 500 mg/kg) for 1, 3, or 7 days. Hepatic toxicity (vacuolation, consistent with steatosis, and elevated serum transaminase levels) was observed at 250 and 500 mg/kg, but not at 50 mg/kg. Hepatic gene expression profiles were compared to a compendium of hepatic expression profiles. MrkA was similar to 3 beta-oxidation inhibitors (valproate, cyclopropane carboxylate, pivalate), 8 PPARalpha agonists (fenofibrate, bezafibrate and 6 fibrate analogues), and 3 other diverse compounds (diethylnitrosamine, microcystin LR & actinomycin D). These data indicate MrkA to be a mitochondrial inhibitor, and activation of PPARalpha-regulated transcription was thought to be due to an accumulation of endogenous ligands. While mitochondrial inhibition was likely responsible for steatosis, canonical pathway analysis revealed that progression to liver injury may be mediated by activation of the innate immune system primarily through NF-kB pathways. These results demonstrate the utility of a gene expression response compendium in developing transcriptional biomarkers and identifying the mechanistic basis for toxicity.

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Study on mechanism of multistep hepatotumorigenesis in rat: development of hepatotumorigenesis

Cited by 84 publications

References 11 publications

In vivo detection of metabolic changes by 1 H-MRS in the DEN-induced hepatocellular carcinoma in wistar rat

In vivo detection of metabolic changes by 1 H-MRS in the DEN-induced hepatocellular carcinoma in wistar rat

Apoptotic effects of dipyrido [3,2-a:2′,3′-c] phenazine (dppz) Au(III) complex against diethylnitrosamine/phenobarbital induced experimental hepatocarcinogenesis in rats

Investigating the Mechanistic Basis for Hepatic Toxicity Induced by an Experimental Chemokine Receptor 5 (CCR5) Antagonist Using a Compendium of Gene Expression Profiles

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