Project 5: Effect of Underlying Liver Diseases on Fibrosis Induced by Superfund T
Seki, E
HERO ID
3490818
Reference Type
Journal Article
Year
2014
Language
English
| HERO ID | 3490818 |
|---|---|
| In Press | No |
| Year | 2014 |
| Title | Project 5: Effect of Underlying Liver Diseases on Fibrosis Induced by Superfund T |
| Authors | Seki, E |
| Abstract | Carbon tetrachloride (CCI{4}) is a superfund toxicant (CERCLA Priority #47) that usually escapes into the environment as a gas. or it is sometimes found in water and soil. The liver is a primary target of the toxicity of CCI4. Exposure to high levels of CCI{4} induces liver damage, inflammation and fibrosis. In healthy people CCI{4} -induced liver injury and fibrosis can reverse when the exposure is discontinued. However, the response of people with underlying liver diseases, such as chronic hepatitis and fatty liver disease, may change, and their livers could be more susceptible to toxicants than healthy livers. Importantly, the health concerns, including chronic liver disease, are often raised regarding vulnerable communities near the Superfund sites. Therefore, the biological response for Superfund toxicants needs to be studied and eariy detection systems need to be developed for identifying these toxicants released into the environment and accumulating in organisms, including the human body. In this context, we will use mouse models with underlying liver diseases, such as Tak1[deltaHEP] mice which have been developed by our laboratory, which mimic human chronic liver disease with liver fibrosis and cancer and mice fed high fat diet that induce obesity and fatty liver disease. Using experimental murine models of liver diseases, we will examine the effect of underlying liver diseases on long-term continuous exposure to CCI{4} with respect to liver fibrosis and cancer. In addition to the evaluation of liver fibrosis by established methodology, we will create a sensitive new detection system for monitoring liver fibrosis using a new fluorescent protein and gene reporter system. This system will also evaluate the effect of another Superfund toxicant in the initiation of liver fibrosis. This project will provide new insights into the effect of environmental CCI{4} exposure on people with underlying liver diseases, including chronic hepatitis and fatty liver. Underlying liver disease is a serious health concern in vulnerable communities, including tribal and low-income border communities that are the targets of our Superfund Research Program. We will share and disseminate our results through the Research Translation and Community Engagement Cores. |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Journal: ISSN: |
| Is Public | Yes |
| Language Text | English |
| Keyword | Animals; antibody conjugate; Antioxidants; Bilirubin; Carbon Tetrachloride; Characteristics; Chronic Hepatitis; chronic liver disease; Cirrhosis; Collaborations; Communities; CYP2E1 gene; Detection; Disease; Disease Progression; Early Diagnosis; Environment; Exposure to; Fatty acid glycerol esters; Fatty Liver; feeding; Fibroblasts; Fibrosis; Free Radicals; Gene Proteins; Generations; Healthcare; Hepatic Stellate Cell; Hepatocyte; Human body; Hyperbilirubinemia; In Vitro; in vivo imaging; Individual; Inflammation; insight; Instruction; Kupffer Cells; Laboratories; Lipid Peroxidation; Liver diseases; Liver Fibrosis; liver injury; Low income; Malignant neoplasm of liver; Malignant Neoplasms; MAP3K7 gene; Mediating; Metabolism; Modeling; mouse model; Mutant Strains Mice; Myofibroblast; Necrosis; Neptune; non-alcoholic fatty liver; Obese Mice; Predisposition; Primary carcinoma of the liver cells; programs; Promotor (Genetics); protein profiling; Proteins; Reactive Oxygen Species; receptor; Reporter; Reporting; Research; Resolution; response; Superfund; superfund site; Testing; TGFB1 gene; toxicant; Toxicant exposure; Transgenic Mice; Translational Research; tumor growth; tumor microenvironment; UGT1A1 gene; Xenobiotics |