An assessment of transcriptional changes in porcine skin exposed to bromine vapor

Rogers, James V.; Price, Jennifer A.; Wendling, Morgan Q. S.; Perry, Mark R.; Reid, Frances M.; Kiser, Robyn C.; Graham, John S.

doi:10.1002/jbt.20383

Cited by 18 publications

(14 citation statements)

References 62 publications

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“…Ferritin, by sequestering iron released from heme, and MTs, by sequestering reactive metals and inactivating hydroxyl radicals and superoxide, also protect cells from toxic effects. Though MT‐1 and ferritin levels were not measured, HO‐1 protein levels were significantly elevated after Br 2 inhalation, which correlates with other studies that show that HO‐1 mRNA expression is elevated in pigs exposed to Br 2 vapors . However, it seems that, even though HO‐1 levels are elevated over 24 h after Br 2 inhalation, as shown in our study, the increase is not enough to overcome the toxic effects of the initial Br 2 insult.…”

Section: Role Of Heme In Br2‐induced Lung Injurysupporting

confidence: 77%

“…Though MT-1 and ferritin levels were not measured, HO-1 protein levels were significantly elevated after Br 2 inhalation, which correlates with other studies that show that HO-1 mRNA expression is elevated in pigs exposed to Br 2 vapors. 4 However, it seems that, even though HO-1 levels are elevated over 24 h after Br 2 inhalation, as shown in our study, the increase is not enough to overcome the toxic effects of the initial Br 2 insult. Interestingly, when we treat mice with Hx after Br 2 exposure, the protein levels of HO-1 do not increase in peripheral lung tissue, suggesting that heme is vital in HO-1 regulation.…”

Section: Role Of Heme In Br 2 -Induced Lung Injurycontrasting

confidence: 48%

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Role of heme in bromine‐induced lung injury

Lam

Vetal

Matalon

et al. 2016

Annals of the New York Academy of Sciences

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Bromine (Br2) gas inhalation poses an environmental and occupational hazard resulting in high morbidity and mortality. In this review, we underline the acute lung pathology (within 24 hours of exposure) and potential therapeutic interventions that may be utilized to mitigate Br2-induced human toxicity. We will discuss our latest published data, which suggests that an increase in heme-dependent tissue injury underlies the pathogenesis of Br2 toxicity. Our study was based on previous findings that demonstrated that Br2 upregulates the heme-degrading enzyme heme oxygenase-1 (HO-1), which converts toxic heme into billiverdin. Interestingly, following Br2 inhalation, heme levels were indeed elevated in bronchoalveolar lavage fluid, plasma, and whole lung tissue in C57BL/6 mice. High heme levels correlated with increased lung oxidative stress, lung inflammation, respiratory acidosis, lung edema, higher airway resistance, and mortality. However, therapeutic reduction of heme levels, by either scavenging with hemopexin or degradation by HO-1, improved lung function and survival. Therefore, heme attenuation may prove a useful adjuvant therapy to treat patients after Br2 exposure.

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Section: Role Of Heme In Br2‐induced Lung Injurysupporting

confidence: 77%

Section: Role Of Heme In Br 2 -Induced Lung Injurycontrasting

confidence: 48%

Role of heme in bromine‐induced lung injury

Lam

Vetal

Matalon

et al. 2016

Annals of the New York Academy of Sciences

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“…It has been previously reported that exposure to Br 2 vapors increased the gene expression of the heme degrading enzyme, HO-1 (35), suggesting that heme-dependent toxicity may play a significant role in Br 2 -induced injury. There are two major sources of heme: intravascular hemolysis (red blood cell [RBC] destruction) and extravascular cell death.…”

Section: Figmentioning

confidence: 96%

“…A recent study using the weanling swine burn model demonstrated that cutaneous exposure to Br 2 vapors increased the gene expression of heme oxygenase-1 (HO-1) (35). HO-1 catalyzes the first and rate-limiting step in heme degradation into equimolar amounts of iron, carbon monoxide (CO), and billiverdin (44).…”

Section: Innovationmentioning

confidence: 99%

Heme Attenuation Ameliorates Irritant Gas Inhalation-Induced Acute Lung Injury

Aggarwal

Lam

Bolisetty

et al. 2016

Antioxidants & Redox Signaling

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Aims: Exposure to irritant gases, such as bromine (Br 2 ), poses an environmental and occupational hazard that results in severe lung and systemic injury. However, the mechanism(s) of Br 2 toxicity and the therapeutic responses required to mitigate lung damage are not known. Previously, it was demonstrated that Br 2 upregulates the heme degrading enzyme, heme oxygenase-1 (HO-1). Since heme is a major inducer of HO-1, we determined whether an increase in heme and heme-dependent oxidative injury underlies the pathogenesis of Br 2 toxicity. Results: C57BL/6 mice were exposed to Br 2 gas (600 ppm, 30 min) and returned to room air. Thirty minutes postexposure, mice were injected intraperitoneally with a single dose of the heme scavenging protein, hemopexin (Hx) (3 lg/gm body weight), or saline. Twenty-four hours postexposure, saline-treated mice had elevated total heme in bronchoalveolar lavage fluid (BALF) and plasma and acute lung injury (ALI) culminating in 80% mortality after 10 days. Hx treatment significantly lowered heme, decreased evidence of ALI (lower protein and inflammatory cells in BALF, lower lung wet-to-dry weight ratios, and decreased airway hyperreactivity to methacholine), and reduced mortality. In addition, Br 2 caused more severe ALI and mortality in mice with HO-1 gene deletion (HO-1 -/-) compared to wild-type controls, while transgenic mice overexpressing the human HO-1 gene (hHO-1) showed significant protection. Innovation: This is the first study delineating the role of heme in ALI caused by Br 2 . Conclusion: The data suggest that attenuating heme may prove to be a useful adjuvant therapy to treat patients with ALI. Antioxid. Redox Signal. 24, 99-112.

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“…It is produced in central facilities and transported by trains or trucks. A major accident recently occurred during railway Br 2 transport in the city of Chelyabinsk, Russia (pop.1.1 million), resulting in 42 people being hospitalized and over 200 individuals seeking medical attention 33 . A study conducted on human volunteers demonstrated that a small exposure to 0.9 ppm bromine (Br 2 ) for five minutes results in cough, headache, and irritation of the eyes, nose, and upper respiratory tract 34 .…”

Section: Discussionmentioning

confidence: 99%

Mechanisms and Treatment of Halogen Inhalation–Induced Pulmonary and Systemic Injuries in Pregnant Mice

et al. 2017

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Inhalation of oxidant gases has been implicated in adverse outcomes in pregnancy, but animal models to address mechanisms and studies to identify potential pregnancy-specific therapies are lacking. Herein we show that inhalation of bromine at 600 parts per million for 30 minutes by pregnant mice on the 15th day of embryonic development results in significantly lower survival after 96 hours than an identical level of exposure in non-pregnant mice. On the 19th embryonic day, bromine-exposed pregnant mice have increased systemic blood pressure, abnormal placental development, severe fetal growth restriction, systemic inflammation, increased levels of circulating anti-angiogenic short fms-like tyrosine kinase one, and evidence of pulmonary and cardiac injury. Treatment with tadalafil, an inhibitor of type 5 phosphodiesterase, by oral gavage one hour post-exposure and then once daily thereafter, attenuated systemic blood pressures, decreased inflammation, ameliorated pulmonary and cardiac injury, and improved maternal survival (from 36% to 80%) and fetal growth. These pathological changes resemble those seen in preeclampsia. Non-pregnant mice did not exhibit any of these pathological changes, and were not affected by tadalafil. These findings suggest that pregnant women exposed to bromine may require particular attention and monitoring for signs of preeclampsia-like symptoms.

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An assessment of transcriptional changes in porcine skin exposed to bromine vapor

Cited by 18 publications

References 62 publications

Role of heme in bromine‐induced lung injury

Role of heme in bromine‐induced lung injury

Heme Attenuation Ameliorates Irritant Gas Inhalation-Induced Acute Lung Injury

Mechanisms and Treatment of Halogen Inhalation–Induced Pulmonary and Systemic Injuries in Pregnant Mice

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