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      Identification of Environmental Chemicals Associated with the Development of Toxicant-associated Fatty Liver Disease in Rodents

      , , , , , ,
      Toxicologic Pathology
      SAGE Publications

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          Abstract

          Toxicant-associated fatty liver disease (TAFLD) is a recently identified form of nonalcoholic fatty liver disease (NAFLD) associated with exposure to industrial chemicals and environmental pollutants. Numerous studies have been conducted to test the association between industrial chemicals/environmental pollutants and fatty liver disease both in vivo and in vitro.

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          P450 genes: structure, evolution, and regulation.

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            Animal models of NASH: getting both pathology and metabolic context right.

            Non-alcoholic fatty liver disease (NAFLD) is the most common cause of referral to liver clinics, and its progressive form, non-alcoholic steatohepatitis (NASH), can lead to cirrhosis and end-stage liver disease. The main risk factors for NAFLD/NASH are the metabolic abnormalities commonly observed in metabolic syndrome: insulin resistance, visceral obesity, dyslipidemia and altered adipokine profile. At present, the causes of progression from NAFLD to NASH remain poorly defined, and research in this area has been limited by the availability of suitable animal models of this disease. In the past, the main models used to investigate the pathogenesis of steatohepatitis have either failed to reproduce the full spectrum of liver pathology that characterizes human NASH, or the liver pathology has developed in a metabolic context that is not representative of the human condition. In the last few years, a number of models have been described in which the full spectrum of liver pathology develops in an appropriate metabolic context. In general, the underlying cause of metabolic defects in these models is chronic caloric overconsumption, also known as overnutrition. Overnutrition has been achieved in a number of different ways, including forced feeding, administration of high-fat diets, the use of genetically hyperphagic animals, or a combination of these approaches. The purpose of the present review is to critique the liver pathology and metabolic abnormalities present in currently available animal models of NASH, with particular focus on models described in approximately the last 5 years.
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              Polychlorinated Biphenyls, Lead, and Mercury Are Associated with Liver Disease in American Adults: NHANES 2003–2004

              Background High-level occupational exposures to some industrial chemicals have been associated with liver diseases, including nonalcoholic fatty liver disease (NAFLD). However, the potential role of low-level environmental pollution on liver disease in the general population has not been evaluated. Objective We determined whether environmental pollutants are associated with an elevation in serum alanine aminotransferase (ALT) activity and suspected NAFLD in U.S. adults. Methods This cross-sectional cohort study evaluated adult participants without viral hepatitis, hemochromatosis, or alcoholic liver disease from the National Health and Nutrition Examination Survey (NHANES) for 2003–2004. ALT elevation was defined in men as ≥ 37 IU/L (age18–20 years) and ≥ 48 IU/L (age ≥ 21 years) and in women as ≥ 30 IU/L (age 18–20 years) and ≥ 31 IU/L (age ≥ 21 years). Adjusted odds ratios (ORs) for ALT elevation were determined across exposure quartiles for 17 pollutant subclasses comprising 111 individual pollutants present with at least a 60% detection rate. Adjustments were made for age, race/ethnicity, sex, body mass index, poverty income ratio, and insulin resistance. Individual pollutants from subclasses associated with ALT elevation were subsequently analyzed. Results The overall prevalence of ALT elevation was 10.6%. Heavy metals and polychlorinated biphenyls (PCBs) were associated with dose-dependent increased adjusted ORs for ALT elevation. Within these subclasses, increasing whole-blood levels of lead and mercury and increasing lipid-adjusted serum levels of 20 PCBs were individually associated with ALT elevation. Conclusions PCB, lead, and mercury exposures were associated with unexplained ALT elevation, a proxy marker of NAFLD, in NHANES 2003–2004 adult participants.
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                Author and article information

                Journal
                Toxicologic Pathology
                Toxicol Pathol
                SAGE Publications
                0192-6233
                1533-1601
                April 12 2015
                October 16 2014
                : 43
                : 4
                : 482-497
                Article
                10.1177/0192623314549960
                4501484
                25326588
                22bfb568-32bd-4440-b8e1-9bd80adbf799
                © 2015
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