Abstract
Occupational and environmental exposures to industrial chemicals are known to cause hepatotoxicity and liver injury, in humans and in animal models. Historically, research has focused on severe acute liver injury (e.g. fulminant liver failure) or endstage diseases (e.g. cirrhosis and HCC). However, it has become recently recognized that toxicants can cause more subtle changes to the liver. For example, toxicant-associated steatohepatitis, characterized by hepatic steatosis, and inflammation, was recently recognized in an occupational cohort exposed to vinyl chloride. At high occupational levels, toxicants are sufficient to cause liver damage and disease even in healthy subjects with no comorbidities for liver injury. However, it is still largely unknown how exposure to toxicants initiate and possibly more importantly exacerbate liver disease, when combined with other factors, such as underlying non-alcoholic fatty liver disease caused by poor diet and/or obesity. With better understanding of the mechanism(s) and risk factors that mediate the initiation and progression of toxicant-induced liver disease, rational targeted therapy can be developed to better predict risk, as well as to treat or prevent this disease. The purpose of this review is to summarize established and proposed mechanisms of volatile organic compound-induced liver injury and to highlight key signaling events known or hypothesized to mediate these effects.
Funding source: National Institute of Diabetes and Digestive and Kidney Diseases
Award Identifier / Grant number: K01 DK096042
Award Identifier / Grant number: R03 DK107912
Funding source: National Institute of Environmental Health Sciences
Award Identifier / Grant number: P42 ES023716
Funding source: National Institute of General Medical Sciences
Award Identifier / Grant number: P20GM113226
Award Identifier / Grant number: P20GM103492
Funding source: National Institute on Alcohol Abuse and Alcoholism
Award Identifier / Grant number: P50AA024337
Funding statement: Supported by awards from the National Institutes of Health [National Institute of Diabetes and Digestive and Kidney Diseases, Funder id: 10.13039/100000062 (K01 DK096042, R03 DK107912), T32ES011564, and National Institute of Environmental Health Sciences, Funder id: 10.13039/100000066 (P42 ES023716)]. Research was also supported by two Institutional Development Awards (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant numbers P20GM113226 and P20GM103492 as well as the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number P50AA024337 (Funder id: 10.13039/100000027). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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©2018 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Reviews
- Interaction of volatile organic compounds and underlying liver disease: a new paradigm for risk
- Five decades of research on mitochondrial NADH-quinone oxidoreductase (complex I)
- Modifications in small nuclear RNAs and their roles in spliceosome assembly and function
- Minireview
- Transcriptional regulation of human defense peptides: a new direction in infection control
- Research Articles/Short Communications
- Cell Biology and Signaling
- Down-regulated paxillin suppresses cell proliferation and invasion by inhibiting M2 macrophage polarization in colon cancer
- p21Waf1 deficiency does not decrease DNA repair in E1A+cHa-Ras transformed cells by HDI sodium butyrate
- MAC30 knockdown involved in the activation of the Hippo signaling pathway in breast cancer cells
- Inhibition of JAK2/STAT3 signaling suppresses bone marrow stromal cells proliferation and osteogenic differentiation, and impairs bone defect healing
- IL-37 affects the occurrence and development of endometriosis by regulating the biological behavior of endometrial stromal cells through multiple signaling pathways
- Resveratrol alleviates early brain injury following subarachnoid hemorrhage: possible involvement of the AMPK/SIRT1/autophagy signaling pathway
Artikel in diesem Heft
- Frontmatter
- Reviews
- Interaction of volatile organic compounds and underlying liver disease: a new paradigm for risk
- Five decades of research on mitochondrial NADH-quinone oxidoreductase (complex I)
- Modifications in small nuclear RNAs and their roles in spliceosome assembly and function
- Minireview
- Transcriptional regulation of human defense peptides: a new direction in infection control
- Research Articles/Short Communications
- Cell Biology and Signaling
- Down-regulated paxillin suppresses cell proliferation and invasion by inhibiting M2 macrophage polarization in colon cancer
- p21Waf1 deficiency does not decrease DNA repair in E1A+cHa-Ras transformed cells by HDI sodium butyrate
- MAC30 knockdown involved in the activation of the Hippo signaling pathway in breast cancer cells
- Inhibition of JAK2/STAT3 signaling suppresses bone marrow stromal cells proliferation and osteogenic differentiation, and impairs bone defect healing
- IL-37 affects the occurrence and development of endometriosis by regulating the biological behavior of endometrial stromal cells through multiple signaling pathways
- Resveratrol alleviates early brain injury following subarachnoid hemorrhage: possible involvement of the AMPK/SIRT1/autophagy signaling pathway