Analysis of Gene Expression Profiles in Fatal Hepatic Failure After Hepatectomy in Mice

Makino, Hirochika; Shimada, Hiroshi; Morioka, Daisuke; Kunisaki, Chikara; Morita, Tomoyuki; Matsuyama, Ryusei; Kubota, Takeshi; Shimizu, Daisuke; Ichikawa, Yasushi; Tanaka, Kuniya; Matsuo, Keitaro; Togo, Shinji; Endo, Itaru; Nagashima, Youji; Okazaki, Yasushi; Hayashizaki, Yoshihide

doi:10.1016/j.jss.2009.11.722

Cited by 2 publications

(2 citation statements)

References 47 publications

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“…The significance of gene expression alterations in the absence of data on protein levels is problematic, but efforts were undertaken to identify gene expression profiles in laboratory animals that are indicative of preneoplastic liver disease (Kim and Wang 2003). Various studies included gene expression changes due to nonalcoholic fatty liver disease (NAFLD) (Wang et al 2016) and acute liver failure after CCl4 exposure (Xu et al 2013) or hepatectomy (Makino et al 2011). The utilization of gene expression was suggested as potentially useful in considerations of cyanotoxin NOAEL (Zheng et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Cylindrospermopsin toxicity in mice following a 90-d oral exposure

Chernoff

Hill

Chorus

et al. 2018

Journal of Toxicology and Environmental Health, Part A

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Cylindrospermopsin (CYN) is a toxin associated with numerous species of freshwater cyanobacteria throughout the world. It is postulated to have caused an episode of serious illnesses in Australia through treated drinking water, as well as lethal effects in livestock exposed to water from farm ponds. Toxicity included effects indicative of both hepatic and renal dysfunction. In humans, symptoms progressed from initial hepatomegaly, vomiting, and malaise to acidosis and hypokalemia, bloody diarrhea, and hyperemia in mucous membranes. Laboratory animal studies predominantly involved the intraperitoneal (i.p.) route of administration and confirmed this pattern of toxicity with changes in liver enzyme activities and histopathology consistent with hepatic injury and adverse renal effects. The aim of this study was designed to assess subchronic oral exposure (90 d) of purified CYN from 75 to 300 µg/kg/d in mouse. At the end of the dosing period, examinations of animals noted (1) elevated organ to body weight ratios of liver and kidney at all dose levels, (2) treatment-related increases in serum alanine aminotransferase (ALT) activity, (3) decreased blood urea nitrogen (BUN) and cholesterol concentrations in males, and (4) elevated monocyte counts in both genders. Histopathological alterations included hepatocellular hypertrophy and cord disruption in the liver, as well as renal cellular hypertrophy, tubule dilation, and cortical tubule lesions that were more prominent in males. A series of genes were differentially expressed including Bax (apoptosis), Rpl6 (tissue regeneration), Fabp4 (fatty acid metabolism), and Proc (blood coagulation). Males were more sensitive to many renal end points suggestive of toxicity. At the end of exposure, toxicity was noted at all dose levels, and the 75 µg/kg group exhibited significant effects in liver and kidney/body weight ratios, reduced BUN, increased serum monocytes, and multiple signs of histopathology indicating that a no-observed-adverse-effect level could not be determined for any dose level.

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Section: Discussionmentioning

confidence: 99%

Cylindrospermopsin toxicity in mice following a 90-d oral exposure

Chernoff

Hill

Chorus

et al. 2018

Journal of Toxicology and Environmental Health, Part A

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“…Numerous animal studies have examined the expression of genes related to regeneration following partial hepatectomy [24–27]. Studies also showed evidence illustrating the shift in metabolic function and energy balance in regenerating livers of rodents [28–30].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics microarray analysis and identification of gene expression profiles associated with cirrhotic liver

Chan

et al. 2016

The Kaohsiung J of Med Scie

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Cirrhosis is the endpoint of liver fibrosis that is accompanied by limited regeneration capacity and complications and is the ultimate cause of death in many patients. Despite this, few studies have thoroughly looked at the gene expression profiles in the cirrhotic liver. Hence, this study aims to identify the genes that were differentially expressed in the cirrhotic liver and to explore the putative related signaling pathway and interaction networks. The gene expression profiles of cirrhotic livers and noncirrhotic livers were examined and compared using microarray gene analysis. Proteins encoded by the differentially expressed genes were analyzed for functional clustering and signaling pathway involvement using MetaCore bioinformatics analyses. The Gene Ontology analysis as well as the Kyoto encyclopedia of Genes and Genomes pathway analysis were also performed. A total of 213 significant genes were differentially expressed at more than a two-fold change in cirrhotic livers as compared to noncirrhotic livers. Of these, 105 upregulated genes and 63 downregulated genes were validated through MetaCore bioinformatics analyses. The signaling pathways and major functions of proteins encoded by these differentially expressed genes were further analyzed; results showed that the cirrhotic liver has a unique gene expression pattern related to inflammatory reaction, immune response, and cell growth, and is potentially cancer related. Our findings suggest that the microarray analysis may provide clues to the molecular mechanisms of liver cirrhosis for future experimental studies. However, further exploration of areas regarding therapeutic strategy might be possible to support metabolic activity, decrease inflammation, or enhance regeneration for liver cirrhosis.

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Analysis of Gene Expression Profiles in Fatal Hepatic Failure After Hepatectomy in Mice

Cited by 2 publications

References 47 publications

Cylindrospermopsin toxicity in mice following a 90-d oral exposure

Cylindrospermopsin toxicity in mice following a 90-d oral exposure

Bioinformatics microarray analysis and identification of gene expression profiles associated with cirrhotic liver

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