Abstract
The liver is an organ of vital importance in the body; it is the center of metabolic activities and acts as the primary line of defense against toxic compounds. Exposure to environmental toxicants is an unavoidable fallout from rapid industrialization across the world and is even higher in develo** countries. Technological development and industrialization have led to the release of toxicants such as pollutant toxic gases, chemical discharge, industrial effluents, pesticides and solvents, into the environment. In the last few years, a growing body of evidence has shed light on the potential impact of environmental toxicants on liver health, in particular, on non-alcoholic fatty liver disease (NAFLD) incidence and progression. NAFLD is a multifactorial disease linked to metabolic derangement including diabetes and other complications. Environmental toxicants including xenobiotics and pollutants may have a direct or indirect steatogenic/fibrogenic impact on the liver and should be considered as risk factors associated with NAFLD. This review discusses the contribution of environmental toxicants toward the increasing disease burden of NAFLD.
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Abbreviations
- NASH:
-
Non-alcoholic steatohepatitis
- NAFLD:
-
Non-alcoholic fatty liver disease
- HCC:
-
Hepatocellular carcinoma
- ALT:
-
Alanine transaminase
- POPs:
-
Persistent organic pollutants
- PCB:
-
Poly chlorinated biphenyls
- PAHs:
-
Poly aromatic hydrocarbons
- DDT:
-
Dichlorodiphenyltrichloroethane
- ROS:
-
Reactive oxygen species
- BPA:
-
Bis phenol A
- CVD:
-
Cardiovascular disease
- TG:
-
Triglyceride
- T2D:
-
Type 2 diabetes
- HFD:
-
High fat diet
- VOCs:
-
Volatile organic compounds
- HSC:
-
Hepatic stellate cells
- BAP:
-
Benzo alpha pyrene
- PXR:
-
Pregnane X receptor
- AhR:
-
Aryl hydrocarbon receptors
- PPAR:
-
Peroxisome proliferator-activated receptor
- SREBP:
-
Sterol regulatory element-binding proteins
- TCDD:
-
2,3,7,8-Tetrachlorodibenzo-p-dioxin
- CAR:
-
Constitutive androstane receptor
- HNF4α:
-
Hepatocyte nuclear factor 4 alpha
- PFAS:
-
Per- and polyfluoroalkyl substances
- TAFLD:
-
Toxicant-associated fatty liver diseases
- NF-κB:
-
Nuclear factor-κB
- TLR4:
-
Toll-like receptor 4
- IR:
-
Insulin resistance
References
Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15:11–20. https://doi.org/10.1038/nrgastro.2017.109.
Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016;65:1038–1048. https://doi.org/10.1016/j.metabol.2015.12.012.
Mendez-Sanchez N, Cruz-Ramon VC, Ramirez-Perez OL, Hwang JP, Barranco-Fragoso B, Cordova-Gallardo J. New Aspects of Lipotoxicity in Nonalcoholic Steatohepatitis. Int J Mol Sci. 2018. https://doi.org/10.3390/ijms19072034.
Raza S, Rajak S, Anjum B, Sinha RA. Molecular links between non-alcoholic fatty liver disease and hepatocellular carcinoma. Hepatoma Res. 2019;5:42. https://doi.org/10.20517/2394-5079.2019.014.
Zhang X, Ji X, Wang Q, Li JZ. New insight into inter-organ crosstalk contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Protein Cell. 2018;9:164–177. https://doi.org/10.1007/s13238-017-0436-0.
Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement: Executive Summary. Crit Pathw Cardiol. 2005;4:198–203. https://doi.org/10.1097/00132577-200512000-00018.
Perez-Martinez P, Mikhailidis DP, Athyros VG, Bullo M, Couture P, Covas MI et al. Lifestyle recommendations for the prevention and management of metabolic syndrome: an international panel recommendation. Nutr Rev. 2017;75:307–326. https://doi.org/10.1093/nutrit/nux014.
Al-Eryani L, Wahlang B, Falkner KC, Guardiola JJ, Clair HB, Prough RA et al. Identification of environmental chemicals associated with the development of toxicant-associated fatty liver disease in rodents. Toxicol Pathol. 2015;43:482–497. https://doi.org/10.1177/0192623314549960.
Cave M, Appana S, Patel M, Falkner KC, McClain CJ, Brock G. Polychlorinated biphenyls, lead, and mercury are associated with liver disease in American adults: NHANES 2003–2004. Environ Health Perspect. 2010;118:1735–1742. https://doi.org/10.1289/ehp.1002720.
Lin YC, Lian IB, Kor CT, Chang CC, Su PY, Chang WT et al. Association between soil heavy metals and fatty liver disease in men in Taiwan: a cross sectional study. BMJ Open. 2017;7:e014215. https://doi.org/10.1136/bmjopen-2016-014215.
Wahlang B, Appana S, Falkner KC, McClain CJ, Brock G, Cave MC. Insecticide and metal exposures are associated with a surrogate biomarker for non-alcoholic fatty liver disease in the National Health and Nutrition Examination Survey 2003–2004. Environ Sci Pollut Res Int. 2020;27:6476–6487. https://doi.org/10.1007/s11356-019-07066-x.
Frediani JK, Naioti EA, Vos MB, Figueroa J, Marsit CJ, Welsh JA. Arsenic exposure and risk of nonalcoholic fatty liver disease (NAFLD) among U.S. adolescents and adults: an association modified by race/ethnicity, NHANES 2005–2014. Environ Health. 2018;17:6. https://doi.org/10.1186/s12940-017-0350-1.
Straub AC, Stolz DB, Ross MA, Hernandez-Zavala A, Soucy NV, Klei LR et al. Arsenic stimulates sinusoidal endothelial cell capillarization and vessel remodeling in mouse liver. Hepatology. 2007;45:205–212. https://doi.org/10.1002/hep.21444.
Ditzel EJ, Li H, Foy CE, Perrera AB, Parker P, Renquist BJ et al. Altered hepatic transport by fetal arsenite exposure in diet-induced fatty liver disease. J Biochem Mol Toxicol. 2016;30:321–330. https://doi.org/10.1002/jbt.21796.
Tan M, Schmidt RH, Beier JI, Watson WH, Zhong H, States JC et al. Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice. Toxicol Appl Pharmacol. 2011;257:356–364. https://doi.org/10.1016/j.taap.2011.09.019.
Qiu T, Pei P, Yao X, Jiang L, Wei S, Wang Z et al. Taurine attenuates arsenic-induced pyroptosis and nonalcoholic steatohepatitis by inhibiting the autophagic-inflammasomal pathway. Cell Death Dis. 2018;9:946. https://doi.org/10.1038/s41419-018-1004-0.
Wei S, Qiu T, Wang N, Yao X, Jiang L, Jia X et al. Ferroptosis mediated by the interaction between Mfn2 and IREα promotes arsenic-induced nonalcoholic steatohepatitis. Environ Res. 2020;188:109824. https://doi.org/10.1016/j.envres.2020.109824.
Berrahal AA, Lasram M, El Elj N, Kerkeni A, Gharbi N, El-Fazaa S. Effect of age-dependent exposure to lead on hepatotoxicity and nephrotoxicity in male rats. Environ Toxicol. 2011;26:68–78. https://doi.org/10.1002/tox.20530.
Milosevic N, Maier P. Lead stimulates intercellular signalling between hepatocytes and Kupffer cells. Eur J Pharmacol. 2000;401:317–328. https://doi.org/10.1016/s0014-2999(00)00473-8.
Bernard A. Renal dysfunction induced by cadmium: biomarkers of critical effects. Biometals. 2004;17:519–523. https://doi.org/10.1023/b:biom.0000045731.75602.b9.
Habeebu SS, Liu J, Liu Y, Klaassen CD. Metallothionein-null mice are more sensitive than wild-type mice to liver injury induced by repeated exposure to cadmium. Toxicol Sci. 2000;55:223–232. https://doi.org/10.1093/toxsci/55.1.223.
Hyder O, Chung M, Cosgrove D, Herman JM, Li Z, Firoozmand A et al. Cadmium exposure and liver disease among US adults. J Gastrointest Surg. 2013;17:1265–1273. https://doi.org/10.1007/s11605-013-2210-9.
Werder EJ, Beier JI, Sandler DP, Falkner KC, Gripshover T, Wahlang B et al. Blood BTEXS and heavy metal levels are associated with liver injury and systemic inflammation in Gulf states residents. Food Chem Toxicol. 2020;139:111242. https://doi.org/10.1016/j.fct.2020.111242.
He X, Gao J, Hou H, Qi Z, Chen H, Zhang XX. Inhibition of mitochondrial fatty acid oxidation contributes to development of nonalcoholic fatty liver disease induced by environmental cadmium exposure. Environ Sci Technol. 2019;53:13992–14000. https://doi.org/10.1021/acs.est.9b05131.
Rosales-Cruz P, Dominguez-Perez M, Reyes-Zarate E, Bello-Monroy O, Enriquez-Cortina C, Miranda-Labra R et al. Cadmium exposure exacerbates hyperlipidemia in cholesterol-overloaded hepatocytes via autophagy dysregulation. Toxicology. 2018;398–399:41–51. https://doi.org/10.1016/j.tox.2018.02.007.
Go YM, Orr M, Jones DP. Actin cytoskeleton redox proteome oxidation by cadmium. Am J Physiol Lung Cell Mol Physiol. 2013;305:L831–L843. https://doi.org/10.1152/ajplung.00203.2013.
Yang JS, Park Y. Insecticide exposure and development of nonalcoholic fatty liver disease. J Agri Food Chem. 2018;66:10132–10138. https://doi.org/10.1021/acs.jafc.8b03177.
Chargui I, Grissa I, Bensassi F, Hrira MY, Haouem S, Haouas Z et al. Oxidative stress, biochemical and histopathological alterations in the liver and kidney of female rats exposed to low doses of deltamethrin (DM): a molecular assessment. Biomed Environ Sci. 2012;25:672–683. https://doi.org/10.3967/0895-3988.2012.06.009.
Giray B, Gurbay A, Hincal F. Cypermethrin-induced oxidative stress in rat brain and liver is prevented by vitamin E or allopurinol. Toxicol Lett. 2001;118:139–146. https://doi.org/10.1016/s0378-4274(00)00277-0.
Peyre L, Zucchini-Pascal N, de Sousa G, Rahmani R. Effects of endosulfan on hepatoma cell adhesion: epithelial-mesenchymal transition and anoikis resistance. Toxicology. 2012;300:19–30. https://doi.org/10.1016/j.tox.2012.05.008.
Teimouri F, Amirkabirian N, Esmaily H, Mohammadirad A, Aliahmadi A, Abdollahi M. Alteration of hepatic cells glucose metabolism as a non-cholinergic detoxication mechanism in counteracting diazinon-induced oxidative stress. Hum Exp Toxicol. 2006;25:697–703. https://doi.org/10.1177/0960327106075064.
Tuzmen N, Candan N, Kaya E, Demiryas N. Biochemical effects of chlorpyrifos and deltamethrin on altered antioxidative defense mechanisms and lipid peroxidation in rat liver. Cell Biochem Funct. 2008;26:119–124. https://doi.org/10.1002/cbf.1411.
Wasef L, Nassar AMK, El-Sayed YS, Samak D, Noreldin A, Elshony N et al. The potential ameliorative impacts of cerium oxide nanoparticles against fipronil-induced hepatic steatosis. Sci Rep. 2021;11:1310. https://doi.org/10.1038/s41598-020-79479-5.
Yan S, Tian S, Meng Z, Teng M, Sun W, Jia M et al. Exposure to nitenpyram during pregnancy causes colonic mucosal damage and non-alcoholic steatohepatitis in mouse offspring: the role of gut microbiota. Environ Pollut (Bark Essex: 1987) 2021;271:116306. https://doi.org/10.1016/j.envpol.2020.116306.
Yang D, Zhang X, Yue L, Hu H, Wei X, Guo Q et al. Thiamethoxam induces nonalcoholic fatty liver disease in mice via methionine metabolism disturb via nicotinamide N-methyltransferase overexpression. Chemosphere. 2021;273:129727. https://doi.org/10.1016/j.chemosphere.2021.129727.
Marx-Stoelting P, Ganzenberg K, Knebel C, Schmidt F, Rieke S, Hammer H et al. Hepatotoxic effects of cyproconazole and prochloraz in wild-type and hCAR/hPXR mice. Arch Toxicol. 2017;91:2895–2907. https://doi.org/10.1007/s00204-016-1925-2.
Stellavato A, Lamberti M, Pirozzi AVA, de Novellis F, Schiraldi C. Myclobutanil worsens nonalcoholic fatty liver disease: an in vitro study of toxicity and apoptosis on HepG2 cells. Toxicol Lett. 2016;262:100–104. https://doi.org/10.1016/j.toxlet.2016.09.013.
Pirozzi AV, Stellavato A, La Gatta A, Lamberti M, Schiraldi C. Mancozeb, a fungicide routinely used in agriculture, worsens nonalcoholic fatty liver disease in the human HepG2 cell model. Toxicol Lett. 2016;249:1–4. https://doi.org/10.1016/j.toxlet.2016.03.004.
Heal MR, Kumar P, Harrison RM. Particles, air quality, policy and health. Chem Soc Rev. 2012;41:6606–6630. https://doi.org/10.1039/c2cs35076a.
Furuyama A, Kanno S, Kobayashi T, Hirano S. Extrapulmonary translocation of intratracheally instilled fine and ultrafine particles via direct and alveolar macrophage-associated routes. Arch Toxicol. 2009;83:429–437. https://doi.org/10.1007/s00204-008-0371-1.
Xu X, Yavar Z, Verdin M, Ying Z, Mihai G, Kampfrath T et al. Effect of early particulate air pollution exposure on obesity in mice: role of p47phox. Arterioscler Thromb Vasc Biol. 2010;30:2518–2527. https://doi.org/10.1161/ATVBAHA.110.215350.
Zheng Z, Xu X, Zhang X, Wang A, Zhang C, Huttemann M et al. Exposure to ambient particulate matter induces a NASH-like phenotype and impairs hepatic glucose metabolism in an animal model. J Hepatol. 2013;58:148–154. https://doi.org/10.1016/j.jhep.2012.08.009.
Laing S, Wang G, Briazova T, Zhang C, Wang A, Zheng Z et al. Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues. Am J Physiol Cell Physiol. 2010;299:C736–C749. https://doi.org/10.1152/ajpcell.00529.2009.
Heindel JJ, Blumberg B, Cave M, Machtinger R, Mantovani A, Mendez MA et al. Metabolism disrupting chemicals and metabolic disorders. Reprod Toxicol. 2017;68:3–33. https://doi.org/10.1016/j.reprotox.2016.10.001.
Joshi-Barve S, Kirpich I, Cave MC, Marsano LS, McClain CJ. Alcoholic, nonalcoholic, and toxicant-associated steatohepatitis: mechanistic similarities and differences. Cell Mol Gastroenterol Hepatol. 2015;1:356–367. https://doi.org/10.1016/j.jcmgh.2015.05.006.
Wahlang B, Beier JI, Clair HB, Bellis-Jones HJ, Falkner KC, McClain CJ et al. Toxicant-associated steatohepatitis. Toxicol Pathol. 2013;41:343–360. https://doi.org/10.1177/0192623312468517.
Jain RB, Ducatman A. Selective associations of recent low concentrations of perfluoroalkyl substances with liver function biomarkers: NHANES 2011 to 2014 data on us adults aged >/=20 years. J Occup Environ Med. 2019;61:293–302. https://doi.org/10.1097/JOM.0000000000001532.
Gallo V, Leonardi G, Genser B, Lopez-Espinosa MJ, Frisbee SJ, Karlsson L et al. Serum perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) concentrations and liver function biomarkers in a population with elevated PFOA exposure. Environ Health Perspect. 2012;120:655–660. https://doi.org/10.1289/ehp.1104436.
Darrow LA, Groth AC, Winquist A, Shin HM, Bartell SM, Steenland K. Modeled perfluorooctanoic Acid (PFOA) exposure and liver function in a mid-ohio valley community. Environ Health Perspect. 2016;124:1227–1233. https://doi.org/10.1289/ehp.1510391.
** R, McConnell R, Catherine C, Xu S, Walker DI, Stratakis N et al. Perfluoroalkyl substances and severity of nonalcoholic fatty liver in Children: an untargeted metabolomics approach. Environ Int. 2020;134:105220. https://doi.org/10.1016/j.envint.2019.105220.
Stratakis N, VC D, ** R, Margetaki K, Valvi D, Siskos AP et al. Prenatal exposure to perfluoroalkyl substances associated with increased susceptibility to liver injury in children. Hepatology. 2020;72:1758–1770. https://doi.org/10.1002/hep.31483.
Das KP, Wood CR, Lin MT, Starkov AA, Lau C, Wallace KB et al. Perfluoroalkyl acids-induced liver steatosis: effects on genes controlling lipid homeostasis. Toxicology. 2017;378:37–52. https://doi.org/10.1016/j.tox.2016.12.007.
Haughom B, Spydevold O. The mechanism underlying the hypolipemic effect of perfluorooctanoic acid (PFOA), perfluorooctane sulphonic acid (PFOSA) and clofibric acid. Biochim Biophys Acta. 1992;1128:65–72. https://doi.org/10.1016/0005-2760(92)90258-w.
Wan HT, Zhao YG, Wei X, Hui KY, Giesy JP, Wong CK. PFOS-induced hepatic steatosis, the mechanistic actions on beta-oxidation and lipid transport. Biochim Biophys Acta. 2012;1820:1092–1101. https://doi.org/10.1016/j.bbagen.2012.03.010.
Tan X, **e G, Sun X, Li Q, Zhong W, Qiao P et al. High fat diet feeding exaggerates perfluorooctanoic acid-induced liver injury in mice via modulating multiple metabolic pathways. PLoS One. 2013;8:e61409. https://doi.org/10.1371/journal.pone.0061409.
Beggs KM, McGreal SR, McCarthy A, Gunewardena S, Lampe JN, Lau C et al. The role of hepatocyte nuclear factor 4-alpha in perfluorooctanoic acid- and perfluorooctanesulfonic acid-induced hepatocellular dysfunction. Toxicol Appl Pharmacol. 2016;304:18–29. https://doi.org/10.1016/j.taap.2016.05.001.
Abe T, Takahashi M, Kano M, Amaike Y, Ishii C, Maeda K et al. Activation of nuclear receptor CAR by an environmental pollutant perfluorooctanoic acid. Arch Toxicol. 2017;91:2365–2374. https://doi.org/10.1007/s00204-016-1888-3.
Yoon K, Kwack SJ, Kim HS, Lee BM. Estrogenic endocrine-disrupting chemicals: molecular mechanisms of actions on putative human diseases. J Toxicol Environ Health B Crit Rev. 2014;17:127–174. https://doi.org/10.1080/10937404.2014.882194.
Verstraete SG, Wojcicki JM, Perito ER, Rosenthal P. Bisphenol a increases risk for presumed non-alcoholic fatty liver disease in Hispanic adolescents in NHANES 2003–2010. Environ Health. 2018;17:12. https://doi.org/10.1186/s12940-018-0356-3.
Kim D, Yoo ER, Li AA, Cholankeril G, Tighe SP, Kim W et al. Elevated urinary bisphenol A levels are associated with non-alcoholic fatty liver disease among adults in the United States. Liver Int Official journal Int Assoc Study Liver. 2019;39:1335–1342. https://doi.org/10.1111/liv.14110.
Khalil N, Ebert JR, Wang L, Belcher S, Lee M, Czerwinski SA et al. Bisphenol A and cardiometabolic risk factors in obese children. The Science of the total environment. 2014;470–471:726–732. https://doi.org/10.1016/j.scitotenv.2013.09.088.
Wada K, Sakamoto H, Nishikawa K, Sakuma S, Nakajima A, Fujimoto Y et al. Life style-related diseases of the digestive system: endocrine disruptors stimulate lipid accumulation in target cells related to metabolic syndrome. J Pharmacol Sci. 2007;105:133–137. https://doi.org/10.1254/jphs.fm0070034.
Rochester JR. Bisphenol A and human health: a review of the literature. Reprod Toxicol. 2013;42:132–155. https://doi.org/10.1016/j.reprotox.2013.08.008.
Marmugi A, Ducheix S, Lasserre F, Polizzi A, Paris A, Priymenko N et al. Low doses of bisphenol A induce gene expression related to lipid synthesis and trigger triglyceride accumulation in adult mouse liver. Hepatology. 2012;55:395–407. https://doi.org/10.1002/hep.24685.
Feng D, Zhang H, Jiang X, Zou J, Li Q, Mai H et al. 2020 Bisphenol A exposure induces gut microbiota dysbiosis and consequent activation of gut-liver axis leading to hepatic steatosis in CD-1 mice. Environmental pollution (Barking, Essex: 1987) 1987;265:114880. https://doi.org/10.1016/j.envpol.2020.114880.
Lv Q, Gao R, Peng C, Yi J, Liu L, Yang S et al. Bisphenol A promotes hepatic lipid deposition involving Kupffer cells M1 polarization in male mice. J Endocrinol. 2017;234:143–154. https://doi.org/10.1530/joe-17-0028.
Wang J, Yu P, **e X, Wu L, Zhou M, Huan F et al. Bisphenol F induces nonalcoholic fatty liver disease-like changes: Involvement of lysosome disorder in lipid droplet deposition. Environ Pollut. (Barking, Essex: 1987) 1987;2021:116304. https://doi.org/10.1016/j.envpol.2020.116304.
Huc L, Lemarie A, Gueraud F, Helies-Toussaint C. Low concentrations of bisphenol A induce lipid accumulation mediated by the production of reactive oxygen species in the mitochondria of HepG2 cells. Toxicol In Vitro. 2012;26:709–717. https://doi.org/10.1016/j.tiv.2012.03.017.
Shimpi PC, More VR, Paranjpe M, Donepudi AC, Goodrich JM, Dolinoy DC et al. Hepatic lipid accumulation and nrf2 expression following perinatal and peripubertal exposure to bisphenol a in a mouse model of nonalcoholic liver disease. Environ Health Perspect. 2017;125:087005. https://doi.org/10.1289/ehp664.
Long Z, Fan J, Wu G, Liu X, Wu H, Liu J et al. Gestational bisphenol A exposure induces fatty liver development in male offspring mice through the inhibition of HNF1b and upregulation of PPARγ. Cell Biol Toxicol. 2021;37:65–84. https://doi.org/10.1007/s10565-020-09535-3.
Angrish MM, Dominici CY, Zacharewski TR. TCDD-elicited effects on liver, serum, and adipose lipid composition in C57BL/6 mice. Toxicol Sci. 2013;131:108–115. https://doi.org/10.1093/toxsci/kfs277.
Lefever DE, Xu J, Chen Y, Huang G, Tamas N, Guo TL. TCDD modulation of gut microbiome correlated with liver and immune toxicity in streptozotocin (STZ)-induced hyperglycemic mice. Toxicol Appl Pharmacol. 2016;304:48–58. https://doi.org/10.1016/j.taap.2016.05.016.
Mesnage R, Biserni M, Balu S, Frainay C, Poupin N, Jourdan F et al. Integrated transcriptomics and metabolomics reveal signatures of lipid metabolism dysregulation in HepaRG liver cells exposed to PCB 126. Arch Toxicol. 2018;92:2533–2547. https://doi.org/10.1007/s00204-018-2235-7.
Boucher MP, Lefebvre C, Chapados NA. The effects of PCB126 on intra-hepatic mechanisms associated with non alcoholic fatty liver disease. J Diabetes Metab Disord. 2015;14:88. https://doi.org/10.1186/s40200-015-0218-2.
Gadupudi GS, Klaren WD, Olivier AK, Klingelhutz AJ, Robertson LW. PCB126-induced disruption in gluconeogenesis and fatty acid oxidation precedes fatty liver in male rats. Toxicol Sci. 2016;149:98–110. https://doi.org/10.1093/toxsci/kfv215.
Wahlang B, Song M, Beier JI, Cameron Falkner K, Al-Eryani L, Clair HB et al. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease. Toxicol Appl Pharmacol. 2014;279:380–390. https://doi.org/10.1016/j.taap.2014.06.019.
Sethi S, Morgan RK, Feng W, Lin Y, Li X, Luna C et al. Comparative analyses of the 12 Most Abundant PCB congeners detected in human maternal serum for activity at the thyroid hormone receptor and ryanodine receptor. Environ Sci Technol. 2019;53:3948–3958. https://doi.org/10.1021/acs.est.9b00535.
Sinha RA, Bruinstroop E, Singh BK, Yen PM. Nonalcoholic Fatty Liver Disease and Hypercholesterolemia: Roles of Thyroid Hormones, Metabolites, and Agonists. Thyroid. 2019;29:1173–1191. https://doi.org/10.1089/thy.2018.0664.
Foulds CE, Trevino LS, York B, Walker CL. Endocrine-disrupting chemicals and fatty liver disease. Nat Rev Endocrinol. 2017;13:445–457. https://doi.org/10.1038/nrendo.2017.42.
Tsutsumi T, Adachi R, Matsuda R, Watanabe T, Teshima R, Akiyama H. Concentrations of polycyclic aromatic hydrocarbons in smoked foods in Japan. J Food Prot. 2020;83:692–701. https://doi.org/10.4315/JFP-19-486.
Ortiz L, Nakamura B, Li X, Blumberg B, Luderer U. Reprint of “In utero exposure to benzo[a]pyrene increases adiposity and causes hepatic steatosis in female mice, and glutathione deficiency is protective.” Toxicol Lett. 2014;230:314–321. https://doi.org/10.1016/j.toxlet.2013.11.017.
Neuschafer-Rube F, Schraplau A, Schewe B, Lieske S, Krutzfeldt JM, Ringel S et al. Arylhydrocarbon receptor-dependent mIndy (Slc13a5) induction as possible contributor to benzo[a]pyrene-induced lipid accumulation in hepatocytes. Toxicology. 2015;337:1–9. https://doi.org/10.1016/j.tox.2015.08.007.
Kim KH, Jahan SA, Kabir E, Brown RJ. A review of airborne polycyclic aromatic hydrocarbons (PAHs) and their human health effects. Environ Int. 2013;60:71–80. https://doi.org/10.1016/j.envint.2013.07.019.
Guo J, Wang C, Guo Z, Zuo Z. Exposure to environmental level phenanthrene induces a NASH-like phenotype in new born rat. Environ Pollut (Barking, Essex: 1987) 1987;2018:261–271. https://doi.org/10.1016/j.envpol.2018.04.030.
Uno S, Nebert DW, Makishima M. Cytochrome P450 1A1 (CYP1A1) protects against nonalcoholic fatty liver disease caused by Western diet containing benzo[a]pyrene in mice. Food Chem Toxicol. 2018;113:73–82. https://doi.org/10.1016/j.fct.2018.01.029.
Franco G. New perspectives in biomonitoring liver function by means of serum bile acids: experimental and hypothetical biochemical basis. Br J Ind Med. 1991;48:557–561. https://doi.org/10.1136/oem.48.8.557.
Franco G, Fonte R, Candura F. Hepatotoxicity of organic solvents. Br J Ind Med. 1986;43:139. https://doi.org/10.1136/oem.43.2.139.
Franco R, Li S, Rodriguez-Rocha H, Burns M, Panayiotidis MI. Molecular mechanisms of pesticide-induced neurotoxicity: relevance to Parkinson’s disease. Chem Biol Interact. 2010;188:289–300. https://doi.org/10.1016/j.cbi.2010.06.003.
Mehta N, Murthy UK, Kaul V, Alpert S, Abruzzese G, Teitelbaum C. Outcome of retinopathy in chronic hepatitis C patients treated with peginterferon and ribavirin. Dig Dis Sci. 2010;55:452–457. https://doi.org/10.1007/s10620-009-0721-8.
Anders LC, Lang AL, Anwar-Mohamed A, Douglas AN, Bushau AM, Falkner KC et al. Vinyl chloride metabolites potentiate inflammatory liver injury caused by LPS in Mice. Toxicol Sci. 2016;151:312–323. https://doi.org/10.1093/toxsci/kfw045.
Anders LC, Yeo H, Kaelin BR, Lang AL, Bushau AM, Douglas AN et al. Role of dietary fatty acids in liver injury caused by vinyl chloride metabolites in mice. Toxicol Appl Pharmacol. 2016;311:34–41. https://doi.org/10.1016/j.taap.2016.09.026.
Lang AL, Beier JI. Interaction of volatile organic compounds and underlying liver disease: a new paradigm for risk. Biol Chem. 2018;399:1237–1248. https://doi.org/10.1515/hsz-2017-0324.
Lang AL, Chen L, Poff GD, Ding WX, Barnett RA, Arteel GE et al. Vinyl chloride dysregulates metabolic homeostasis and enhances diet-induced liver injury in mice. Hepatol Commun 2018;2:270–284. https://doi.org/10.1002/hep4.1151.
Cave M, Falkner KC, Ray M, Joshi-Barve S, Brock G, Khan R et al. Toxicant-associated steatohepatitis in vinyl chloride workers. Hepatology. 2010;51:474–481. https://doi.org/10.1002/hep.23321.
Cotrim HP, De Freitas LA, Freitas C, Braga L, Sousa R, Carvalho F et al. Clinical and histopathological features of NASH in workers exposed to chemicals with or without associated metabolic conditions. Liver Int Official J Int Assoc Study Liver. 2004;24:131–135. https://doi.org/10.1111/j.1478-3231.2004.0897.x.
Acknowledgments
This work was supported by the ICMR (59/05/2019/ONLINE/BMS/TRM), SERB (SRG/2019/000398) awarded to Sinha RA.
Dr. Rohit A. Sinha, Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. Email: anthony.rohit@gmail.com; rasinha@sgpgi.ac.in
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Rajak, S., Raza, S., Tewari, A. et al. Environmental Toxicants and NAFLD: A Neglected yet Significant Relationship. Dig Dis Sci 67, 3497–3507 (2022). https://doi.org/10.1007/s10620-021-07203-y
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DOI: https://doi.org/10.1007/s10620-021-07203-y