Benzene exposure is associated with cardiovascular disease risk

Abplanalp, Wesley; DeJarnett, Natasha; Riggs, Daniel W.; Conklin, Daniel J.; McCracken, James; Srivastava, Sanjay; Xie, Zhengzhi; Rai, Shesh; Bhatnagar, Aruni; O’Toole, Timothy E.

doi:10.1371/journal.pone.0183602

Cited by 62 publications

(48 citation statements)

References 40 publications

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“…Various sources of benzene exposure include drinking contaminated water or food, smoking cigarettes, breathing secondhand cigarette smoke, vehicle exhaust or petroleum fuels, vaping e-cigarettes, using paint or detergent products [6][7][8][9][10][11][12][13][14]. While values of ambient benzene air concentrations in the U.S. have typically been <1 ppm (parts per million), significantly higher levels can be experienced as a result of various environmental factors [15] [16].…”

Section: Introductionmentioning

confidence: 99%

“…A recent study demonstrated an association between levels of urinary benzene metabolites in elderly adults living in polluted areas and insulin resistance (IR) [23]. Additionally, benzene exposure and presence of urinary benzene metabolites are associated with increased cardiovascular risk and dyslipidemia in both smokers and nonsmokers, suggesting that benzene may be linked to cardiovascular injury, even in the absence of exposure to other tobacco smoke constituents [16]. Benzene exposure during pregnancy is strongly associated with gestational diabetes among women belonging to underrepresented minorities in the US [24].…”

Section: Introductionmentioning

confidence: 99%

“…Effect of Acarbose on hepatic gene expression. Hepatic gene expression of (A)Fgf21 (effect of treatment: F1.16 = 15.16, p< 0.0012, η 2 = 2.75%; of diet: F1 16. = 518.99, p < 0.0001, η 2 = 94.33%), (B) Cyp2e1 (effect of treatment: F1.16 = 8.92, p< 0.0087, η 2 = 24.97%; of diet: F1.16 = 4.58, p < 0.0480, η 2 = 12.84%; and treatment x diet F1.16 =6.20, p < 0.0001, η 2 = 17.37%) (C) Il1b(effect of treatment: F1.20 = 10.44, p< 0.0041, η 2 = 20.29%; of diet: F1.20 = 11.62, p < 0.0028, η 2 = 22.59%; and treatment x diet F1.20 = 9.38, p < 0.0061, η 2 = 18.24%), (D) Il6 (effect of treatment: F1.16 = 16.44, p< 0.0009, η 2 = 27.41%; of diet: F1.16 = 11.25 p < 0.0040, η 2 = 18.76%; and treatment x diet F1.16 = 16.27, p < 0.0009, η 2 = 27.13%), (E) G6pc (effect of treatment: F1.16 = 10.39, p< 0.0053, η 2 = 14.87%; of diet: F1.16 = 18.81 p < 0.0005, η 2 = 25.90%; and treatment x diet F1.16 = 24.72, p < 0.0001, η 2 =35.35%), (F) Ppck (effect of treatment: F1.21 = 25.64, p< 0.0001, η 2 = 26.17%; of diet: F1.21 = 21.20, p < 0.0001, η 2 = 21.64 %; and treatment x diet F1.21 = 30.14, p < 0.0001, η 2 = 30.75%), (G) Srebp1c (effect of treatment: F1.21 = 6.08, p< 0.0223, η 2 = 17.59% and treatment x diet F1.21 = 4.89, p < 0.0381, η 2 = 14.16%), (H) Srepb2 (effect of treatment: F1.21 = 8.68, p< 0.0077, η 2 = 15.52%; of diet: F1.21 = 10.31, p < 0.0038, η 2 = 21.27%; and treatment x diet F1.21 = 9.33, p < 0.0060, η 2 = 18.83%), (I) Abca1 (effect of treatment: F1.21 = 7.35, p< 0.0130, η 2 = 14.51%; of diet: F1.21 = 9.97, p < 0.0047, η 2 = 19.69%; and treatment x diet F1.21 = 12.34, p < 0.0020, η 2 = 24.35%), (J) Cpt1 (effect of treatment: F1.21 = 10.37 p< 0.0041, η 2 = 21.66%; of diet: F1.21 = 7.56, p < 0.0119, η 2 = 15.80%; and treatment x diet F1.21 = 8.95, p < 0.0069, η 2 = 18.68%), and (K) Acc (effect of treatment: F1.21 = 15.55 p< 0.0007, η 2 = 28.84%; of diet: F1.21 = 6.99, p < 0.0151, η 2 = 12.98%; and treatment x diet F1.21 = 10.36, p < 0.0041, η 2 = 19.22%), (n = 7-5 per each group).…”

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confidence: 99%

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Acarbose Protects From Central and Peripheral Metabolic Imbalance Induced by Benzene Exposure

Debarba

Mulka

Lima

et al. 2020

Preprint

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Abbreviations:CNS, central nervous system; ARC, arcuate nucleus of the hypothalamus; DMH, dorsomedial hypothalamic nucleus; LHA, lateral hypothalamus; PVH, paraventricular hypothalamic nucleus; AbstractBenzene is a well-known human carcinogen that is one of the major components of air pollution. Sources of benzene in ambient air include cigarette smoke, e-cigarettes vaping and evaporation of benzene containing petrol processes. While carcinogenic effects of benzene exposure have been well studied, less is known about metabolic effects of benzene exposure.We show that chronic exposure to benzene at low levels induces severe metabolic imbalance in a sex-specific manner, which is associated with hypothalamic inflammation and endoplasmic reticulum (ER) stress. Benzene exposure rapidly activates hypothalamic ER stress and neuroinflammatory responses in male mice, while pharmacological inhibition of ER stress response by inhibiting IRE1α-XBP1 pathway significantly alleviates benzene-induced glial inflammatory responses. Additionally, feeding mice with Acarbose, a clinically available anti-diabetes drug, protected against benzene induced central and peripheral metabolic imbalance. Acarbose imitates the slowing of dietary carbohydrate digestion, suggesting that choosing a diet with a low glycemic index might be a potential strategy for reducing the negative metabolic effect of chronic exposure to benzene for smokers or for people living/working in urban environments with high concentrations of exposure to automobile exhausts.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Acarbose Protects From Central and Peripheral Metabolic Imbalance Induced by Benzene Exposure

Debarba

Mulka

Lima

et al. 2020

Preprint

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“…Additionally, the effect of VC exposure on existing comorbidities, such as liver disease, is largely unknown 8 . This knowledge gap is especially important today due to the increasing global prevalence of nonalcoholic fatty liver disease (NALFD) 4,6,7,9,10,11,12 . Importantly, VC has recently been shown to be an independent risk factor for liver disease from other causes 13 .…”

Section: Introductionmentioning

confidence: 99%

Vinyl Chloride and High-Fat Diet as a Model of Environment and Obesity Interaction

Lang

Goldsmith

Schnegelberger

et al. 2020

JoVE

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Vinyl chloride (VC), an abundant environmental contaminant, causes steatohepatitis at high levels, but is considered safe at lower levels.Although several studies have investigated the role of VC as a direct hepatotoxicant, the concept that VC modifies sensitivity of the liver to other factors, such as nonalcoholic fatty liver disease (NAFLD) caused by high-fat diet (HFD) is novel. This protocol describes an exposure paradigm to evaluate the effects of chronic, low-level exposure to VC. Mice are acclimated to low-fat or high-fat diet one week prior to the beginning of the inhalation exposure and remain on these diets throughout the experiment. Mice are exposed to VC (sub-OSHA level: <1 ppm) or room air in inhalation chambers for 6 hours/day, 5 days/week, for up to 12 weeks. Animals are monitored weekly for body weight gain and food consumption. This model of VC exposure causes no overt liver injury with VC inhalation alone. However, the combination of VC and HFD significantly enhances liver disease. A technical advantage of this co-exposure model is the whole-body exposure, without restraint. Moreover, the conditions more closely resemble a very common human situation of a combined exposure to VC with underlying nonalcoholic fatty liver disease and therefore support the novel hypothesis that VC is an environmental risk factor for the development of liver damage as a complication of obesity (i.e., NAFLD). This work challenges the paradigm that the current exposure limits of VC (occupational and environmental) are safe. The use of this model can shed new light and concern on the risks of VC exposure. This model of toxicant-induced liver injury can be used for other volatile organic compounds and to study other interactions that may impact the liver and other organ systems.

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“…Benzene is known to be carcinogenic at high concentrations, but its association in causing metabolic diseases particularly T2DM is still emerging. Recent studies demonstrated that benzene non-cancerous health effects at environmental levels include impaired glucose homeostasis and insulin resistance (Abplanalp et al 2017;Amin et al 2018;Debarba et al 2020). We have recently shown that chronic exposure of adult mice to benzene at the levels relevant to human exposures associated with cigarette smoke (50 ppm) induces severe metabolic imbalance associated with central hypothalamic inflammation and endoplasmic reticulum (ER) stress in a sex-specific manner (Debarba et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Metabolic Reprogramming by In Utero Maternal Benzene Exposure

Koshko

Debarba

Sacla

et al. 2020

Preprint

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Environmental chemicals play a significant role in the development of metabolic disorders, especially when exposure occurs early in life. We have recently demonstrated that benzene exposure, at concentrations relevant to a cigarette smoke, induces a severe metabolic imbalance in a sex-specific manner affecting male but not female mice. However, the roles of benzene in the development of aberrant metabolic outcomes following gestational exposure, remain largely unexplored. In this study, we exposed pregnant C57BL/6JB dams to benzene at 50 ppm or filtered air for 5 days/week (6h/day from gestational day 1 to birth) and studied male and female offspring metabolic phenotypes in their adult life. While no changes in body weight or body composition were observed between groups, 4-month-old male and female offspring exhibited reduced parameters of energy homeostasis (VO2, VCO2, and heat production). However, only male offspring from benzene-exposed dams were glucose intolerant and insulin resistant at this age. By six months of age, both male and female offspring displayed glucose and insulin intolerance, associated with elevated expression of hepatic gluconeogenesis and inflammatory genes. Additionally, this effect was accompanied by elevated insulin secretion and increased beta-cell mass only in male offspring. Thus, gestational benzene exposure can reprogram offspring for increased susceptibility to the metabolic imbalance in adulthood with differential sensitivity between sexes.

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Benzene exposure is associated with cardiovascular disease risk

Cited by 62 publications

References 40 publications

Acarbose Protects From Central and Peripheral Metabolic Imbalance Induced by Benzene Exposure

Acarbose Protects From Central and Peripheral Metabolic Imbalance Induced by Benzene Exposure

Vinyl Chloride and High-Fat Diet as a Model of Environment and Obesity Interaction

Metabolic Reprogramming by In Utero Maternal Benzene Exposure

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