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Food Chem Toxicol

Title:		Blood BTEXS and heavy metal levels are associated with liver injury and systemic inflammation in Gulf states residents
Author(s):		Werder EJ; Beier JI; Sandler DP; Falkner KC; Gripshover T; Wahlang B; Engel LS; Cave MC;
Address:		"Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, NC, USA. Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh School of Medicine and the Pittsburgh Liver Research Center, Pittsburgh, PA, 15213, USA. Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Louisville School of Medicine, Louisville, KY, 40202, USA. Department Pharmacology & Toxicology, University of Louisville School of Medicine and the UofL Superfund Research Center, Louisville, KY, 40202, USA. Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Louisville School of Medicine and the UofL Superfund Research Center, Louisville, KY, 40202, USA. Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, NC, USA; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. Departments of Medicine, Pharmacology & Toxicology, Biochemistry & Molecular Genetics, University of Louisville School of Medicine, The UofL Superfund Research Center, The UofL Hepatobiology and Toxicology Center, The UofL Alcohol Research Center and the Jewish Hospital Liver Transplant Program, Louisville, KY 40202, USA; Robley Rex Veterans Affairs Medical Center, Louisville, KY, 40206, USA. Electronic address: matt.cave@louisville.edu"
Journal Title:		Food Chem Toxicol
Year:		2020
Volume:		20200320
Issue:
Page Number:		111242 -
DOI:		10.1016/j.fct.2020.111242
ISSN/ISBN:		1873-6351 (Electronic) 0278-6915 (Print) 0278-6915 (Linking)
Abstract:		"INTRODUCTION: Exposures to volatile organic compounds and metals have previously been associated with liver diseases including steatohepatitis, although more data are needed. Benzene, toluene, ethylbenzene, xylenes, styrene (BTEXS) and metals were measured in blood samples collected between May 2012-July 2013 from volunteers participating in home visits for the Gulf Long-term Follow-up (GuLF) Study. This cross-sectional analysis evaluates associations of exposure biomarkers with serum liver injury and adipocytokine biomarkers in a sample of 214 men. METHODS: Adult nonsmoking men without a history of liver disease or heavy alcohol consumption were included. The serologic disease biomarkers evaluated were the hepatocellular injury biomarker, cytokeratin 18 [whole (CK18 M65) and caspase-cleaved fragment (CK18 M30)]; and adipocytokines. Confounder-adjusted beta coefficients were determined using linear regression models for the overall sample (primary endpoints) and for obesity-classified sub-groups (secondary endpoints). A product interaction term between the exposure of interest and a dichotomized indicator of obesity was included to determine the disease modifying effects of obesity on the biomarker associations. RESULTS: The study sample was 57% white and 51% obese. In the overall sample, lead was positively associated with CK18 M30 (beta = 21.7 +/- 6.0 (SE), p = 0.0004); IL-1beta (beta = 32.8 +/- 5.2, p < 0.0001); IL-6 (beta = 72.8 +/- 18.3, p = 0.0001); and IL-8 (beta = 140.8 +/- 42.2, p = 0.001). Cadmium exposures were associated with increased IL-1beta (beta = 77.8 +/- 26.3, p = 0.003) and IL-8 (beta = 419.5 +/- 201.2, p = 0.04). There were multiple significant interactions between obesity and exposure to lead, cadmium, benzene and toluene in relation to outcome biomarkers. Among obese participants (n = 108), benzene, lead, and cadmium were each positively associated with CK18 M30, IL-1beta, IL-6, and IL-8. In obese subjects, lead was also inversely associated with leptin, and toluene was positively associated with IL-1beta. CONCLUSION: For the overall sample, heavy metal exposures were associated with liver injury (lead only) and/or systemic inflammation (lead and cadmium). Obesity modified the associations between BTEXS and heavy metal exposures on several of the outcome variables. In the obesity subgroup, liver injury was positively associated with lead, cadmium and benzene exposures; systemic inflammation was increased with lead, cadmium, benzene, and toluene exposures; and leptin was inversely associated with lead exposures. The cross-sectional design of this study makes it difficult to determine causality, and all results should be interpreted cautiously. Nonetheless, the potential impact of exposures to lead, cadmium, benzene and toluene in steatohepatitis, an obesity-associated inflammatory liver disease, warrants further investigation"
Keywords:		Adipokines/blood Adult Alanine Transaminase/blood Alkaline Phosphatase/blood Aspartate Aminotransferases/blood Benzene/*metabolism/toxicity Benzene Derivatives/*blood/toxicity Bilirubin/blood Biomarkers/blood Cotinine/blood/toxicity Cross-Sectional Studie;
Notes:		"MedlineWerder, Emily J Beier, Juliane I Sandler, Dale P Falkner, Keith C Gripshover, Tyler Wahlang, Banrida Engel, Lawrence S Cave, Matthew C eng R03 DK107912/DK/NIDDK NIH HHS/ P20 GM113226/GM/NIGMS NIH HHS/ K01 DK096042/DK/NIDDK NIH HHS/ P50 AA024337/AA/NIAAA NIH HHS/ ZIA ES102945/ImNIH/Intramural NIH HHS/ R01 DK133454/DK/NIDDK NIH HHS/ R35 ES028373/ES/NIEHS NIH HHS/ P42 ES023716/ES/NIEHS NIH HHS/ T32 ES011564/ES/NIEHS NIH HHS/ R21 ES031531/ES/NIEHS NIH HHS/ England 2020/03/25 Food Chem Toxicol. 2020 May; 139:111242. doi: 10.1016/j.fct.2020.111242. Epub 2020 Mar 20"