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Effect of Vinyl Chloride Exposure on Cardiometabolic Toxicity

View ORCID ProfileIgor N. Zelko, View ORCID ProfileBreandon S. Taylor, Trinath P. Das, View ORCID ProfileWalter H. Watson, Israel D. Sithu, View ORCID ProfileBanrida Wahlang, View ORCID ProfileMarina V. Malovichko, Matthew C. Cave, Sanjay Srivastava
doi: https://doi.org/10.1101/2021.08.31.458366
Igor N. Zelko
1Superfund Research Center, University of Louisville, KY 40202
2Envirome Institute, University of Louisville, KY 40202
3Department of Medicine, Division of Environmental Medicine, University of Louisville, KY 40202
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  • For correspondence: igor.zelko@louisville.edu
Breandon S. Taylor
1Superfund Research Center, University of Louisville, KY 40202
2Envirome Institute, University of Louisville, KY 40202
3Department of Medicine, Division of Environmental Medicine, University of Louisville, KY 40202
4Department of Pharmacology and Toxicology, University of Louisville, KY 40202
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Trinath P. Das
1Superfund Research Center, University of Louisville, KY 40202
2Envirome Institute, University of Louisville, KY 40202
3Department of Medicine, Division of Environmental Medicine, University of Louisville, KY 40202
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Walter H. Watson
4Department of Pharmacology and Toxicology, University of Louisville, KY 40202
5Hepatobiology and Toxicology Program, University of Louisville, KY 40202
6Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, KY 40202
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Israel D. Sithu
1Superfund Research Center, University of Louisville, KY 40202
2Envirome Institute, University of Louisville, KY 40202
3Department of Medicine, Division of Environmental Medicine, University of Louisville, KY 40202
4Department of Pharmacology and Toxicology, University of Louisville, KY 40202
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Banrida Wahlang
1Superfund Research Center, University of Louisville, KY 40202
4Department of Pharmacology and Toxicology, University of Louisville, KY 40202
5Hepatobiology and Toxicology Program, University of Louisville, KY 40202
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Marina V. Malovichko
1Superfund Research Center, University of Louisville, KY 40202
2Envirome Institute, University of Louisville, KY 40202
3Department of Medicine, Division of Environmental Medicine, University of Louisville, KY 40202
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Matthew C. Cave
1Superfund Research Center, University of Louisville, KY 40202
2Envirome Institute, University of Louisville, KY 40202
4Department of Pharmacology and Toxicology, University of Louisville, KY 40202
5Hepatobiology and Toxicology Program, University of Louisville, KY 40202
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Sanjay Srivastava
1Superfund Research Center, University of Louisville, KY 40202
2Envirome Institute, University of Louisville, KY 40202
3Department of Medicine, Division of Environmental Medicine, University of Louisville, KY 40202
4Department of Pharmacology and Toxicology, University of Louisville, KY 40202
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ABSTRACT

Vinyl chloride is an organochlorine mainly used to manufacture its polymer polyvinyl chloride, which is extensively used in the manufacturing of consumer products. Recent studies suggest that chronic low dose vinyl chloride exposure affects glucose homeostasis in high fat diet-fed mice. Our data suggest that even in the absence of high fat diet, exposure to vinyl chloride (0.8 ppm, 6h/day, 5day/week, for 12 weeks) induces glucose intolerance (1.0 g/kg, i.p) in male C57BL/6 mice. This was accompanied with the depletion of hepatic glutathione and a modest increase in lung interstitial macrophages. Vinyl chloride exposure did not affect the levels of circulating immune cells, endothelial progenitor cells, platelet-immune cell aggregates, and cytokines and chemokines. The acute challenge of vinyl chloride-exposed mice with LPS did not affect lung immune cell composition or plasma IL-6. To examine the effect of vinyl chloride exposure on vascular inflammation and atherosclerosis, LDL receptor-KO mice on C57BL/6 background maintained on western diet were exposed to vinyl chloride for 12 weeks (0.8 ppm, 6h/day, 5day/week). Unlike the WT C57BL/6 mice, vinyl chloride exposure did not affect glucose tolerance in the LDL receptor-KO mice. Plasma cytokines, lesion area in the aortic valve, and markers of lesional inflammation in vinyl chloride-exposed LDL receptor-KO mice were comparable with the air-exposed controls. Collectively, despite impaired glucose tolerance and modest pulmonary inflammation, chronic low dose vinyl chloride exposure does not affect surrogate markers of cardiovascular injury, LPS-induced acute inflammation in C57BL/6 mice, and chronic inflammation and atherosclerosis in the LDL receptor-KO mice.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 01, 2021.
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Effect of Vinyl Chloride Exposure on Cardiometabolic Toxicity
Igor N. Zelko, Breandon S. Taylor, Trinath P. Das, Walter H. Watson, Israel D. Sithu, Banrida Wahlang, Marina V. Malovichko, Matthew C. Cave, Sanjay Srivastava
bioRxiv 2021.08.31.458366; doi: https://doi.org/10.1101/2021.08.31.458366
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Effect of Vinyl Chloride Exposure on Cardiometabolic Toxicity
Igor N. Zelko, Breandon S. Taylor, Trinath P. Das, Walter H. Watson, Israel D. Sithu, Banrida Wahlang, Marina V. Malovichko, Matthew C. Cave, Sanjay Srivastava
bioRxiv 2021.08.31.458366; doi: https://doi.org/10.1101/2021.08.31.458366

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