Journal
ENVIRONMENTAL TOXICOLOGY
Volume 37, Issue 2, Pages 245-255Publisher
WILEY
DOI: 10.1002/tox.23394
Keywords
atherosclerosis; glucose homeostasis; inflammation; oxidative stress; vinyl chloride
Categories
Funding
- Jewish Heritage Fund for Excelence [OGMN190574L]
- National Institutes of Health [P42ES023716 1R01HL149351-01 1R01HL138992 1R01HL137229 P20GM113226 R35ES028373 R01ES032189 T32ES011564 P30ES030283 R21ES031510 1R01HL149351]
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Chronic low dose exposure to vinyl chloride may lead to impaired glucose tolerance and a slight increase in lung inflammation, but does not affect surrogate markers of cardiovascular injury and atherosclerosis.
Vinyl chloride (VC) 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 VC exposure affects glucose homeostasis in high fat diet-fed mice. Our data suggest that even in the absence of high fat diet, exposure to VC (0.8 ppm, 6 h/day, 5 day/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. VC 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 VC-exposed mice with LPS did not affect lung immune cell composition or plasma IL-6. To examine the effect of VC exposure on vascular inflammation and atherosclerosis, LDL receptor-KO mice on C57BL/6 background maintained on western diet were exposed to VC for 12 weeks (0.8 ppm, 6 h/day, 5 day/week). Unlike the WT C57BL/6 mice, VC 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 VC-exposed LDL receptor-KO mice were comparable with the air-exposed controls. Collectively, despite impaired glucose tolerance and modest pulmonary inflammation, chronic low dose VC 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.
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