Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice

Reyes-Caballero, Hermes; Rao, Xiaoquan; Sun, Qiong; Warmoes, Marc O.; Lin, Penghui; Sussan, Thomas E.; Park, Bong Soo; Fan, Teresa W.‐M.; Maiseyeu, Andrei; Rajagopalan, Sanjay; Girnun, Geoffrey D.; Biswal, Shyam

doi:10.1038/s41598-019-53716-y

Cited by 45 publications

(24 citation statements)

References 79 publications

(89 reference statements)

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“… 183 Although not completely understood, individual and time‐dependent doses influence the mechanisms by which environmental air pollutants result in cancer cell transformation. The impact of air pollution particular carcinogens and their mixtures disrupt several molecular processes through direct or indirect (inflammation and oxidative stress) damage, inducing TSG inactivation and the activation of oncogenes, 184 cell cycle alterations dependent on TP53 activation, 185 activation of energetic dysregulation, 186 chromosome instability, 187,188 the inhibition of apoptosis, 189 and the induction of cell proliferation in somatic cells 190 . Further research will clarify which mechanisms are most relevant and can be used as early biomarkers of air pollution‐related cancer.…”

Section: Biological Mechanisms Of Air Pollution‐derived Carcinogenesismentioning

confidence: 99%

Outdoor air pollution and cancer: An overview of the current evidence and public health recommendations

Turner

Andersen

Baccarelli

et al. 2020

CA A Cancer J Clinicians

558

246

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Outdoor air pollution is a major contributor to the burden of disease worldwide. Most of the global population resides in places where air pollution levels, because of emissions from industry, power generation, transportation, and domestic burning, considerably exceed the World Health Organization's health-based air-quality guidelines. Outdoor air pollution poses an urgent worldwide public health challenge because it is ubiquitous and has numerous serious adverse human health effects, including cancer. Currently, there is substantial evidence from studies of humans and experimental animals as well as mechanistic evidence to support a causal link between outdoor (ambient) air pollution, and especially particulate matter (PM) in outdoor air, with lung cancer incidence and mortality. It is estimated that hundreds of thousands of lung cancer deaths annually worldwide are attributable to PM air pollution. Epidemiological evidence on outdoor air pollution and the risk of other types of cancer, such as bladder cancer or breast cancer, is more limited. Outdoor air pollution may also be associated with poorer cancer survival, although further research is needed. This report presents an overview of outdoor air pollutants, sources, and global levels, as well as a description of epidemiological evidence linking outdoor air pollution with cancer incidence and mortality. Biological mechanisms of air pollution-derived carcinogenesis are also described. This report concludes by summarizing public health/policy recommendations, including multilevel interventions aimed at individual, community, and regional scales. Specific roles for medical and health care communities with regard to prevention and advocacy and recommendations for further research are also described.

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Section: Biological Mechanisms Of Air Pollution‐derived Carcinogenesismentioning

confidence: 99%

Outdoor air pollution and cancer: An overview of the current evidence and public health recommendations

Turner

Andersen

Baccarelli

et al. 2020

CA A Cancer J Clinicians

558

246

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“…Hepatocytes can directly clear LPS from the bloodstream through hepatic uptake via TLR4, indicating their important role in in ammatory responses 33 . Both epidemiologic and controlled exposure studies in humans and animals have demonstrated an association between air pollution exposure and metabolic disorders such as diabetes 34 . It was also found that IL-6 levels were elevated in blood, liver, adipose tissue, and macrophages, which induced activation of the STAT3/SOCS3 pathway in liver 35 .…”

Section: Discussionmentioning

confidence: 99%

TLR4 knock out alleviate both lung and liver inflammation caused by short-time exposure to PM2.5

Jiang¹,

Lu²,

Liu³

et al. 2021

Preprint

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Background: Ambient particulate matter (PM), a principal component of air pollutant, is harmful to human health in many ways. Toll-like receptors (TLRs) are non-catalytic transmembrane protein that can identify conservative molecules from microorganisms. However, the regulatory mechanism of TLR4 and its effects on lung and liver inflammation induced by PM are unknown presently. Method: Wild type mice and TLR4-/- mice (C57BL/10JNju, mixed gender, 8-10 weeks old,), both were randomly divided into two groups. The mice were intratracheally instilled with saline or PM2.5 (4 mg/kg) every other day and continued for 10 days. Result: PM2.5 increased the BCA and Lactate Dehydrogenase (LDH) level and TLR4 KO mice showed lower BCA compared to wild type mice(P=0.08). PM2.5 treatment increased the expression of inflammatory cytokines (HMGB1, TNFα, MCP-1/CCL2, CCR2) significantly compared to the saline treatment (P<0.05) and there is a trend that this could be attenuated in TLR4 knock out mice. HE staining showed that PM2.5 induced severe inflammatory damage, and TLR4 KO could alleviate the process of inflammation. As to the liver, LDH and Alkaline Phosphatase (AKP) significantly increased in PM2.5 treatment only in wild type mice. Similar to the lung tissue, PM2.5 stimulation resulted in robust induction of proinflammatory genes expression levels, and TLR4 KO could alleviate the progression of liver inflammation. Conclusion: Our findings suggest that, TLR4 plays an important role in regulating lung and liver inﬂammatory response caused by PM2.5.

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“…This has been associated with higher oxidative stress and toxicity compared to other sources [ 34 , 36 ]. Oxidative stress may be involved in all PM-induced disorders in multiple organ systems, including the lung, cardiovascular system and liver, which activate the endogenous redox system [ 37 , 38 , 39 , 40 ].…”

Section: Particulate Matter (Pm)—an Intrauterine Toxinmentioning

confidence: 99%

Particulate Matter, an Intrauterine Toxin Affecting Foetal Development and Beyond

et al. 2021

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Air pollution is the 9th cause of the overall disease burden globally. The solid component in the polluted air, particulate matters (PMs) with a diameter of 2.5 μm or smaller (PM2.5) possess a significant health risk to several organ systems. PM2.5 has also been shown to cross the blood–placental barrier and circulate in foetal blood. Therefore, it is considered an intrauterine environmental toxin. Exposure to PM2.5 during the perinatal period, when the foetus is particularly susceptible to developmental defects, has been shown to reduce birth weight and cause preterm birth, with an increase in adult disease susceptibility in the offspring. However, few studies have thoroughly studied the health outcome of foetuses due to intrauterine exposure and the underlying mechanisms. This perspective summarises currently available evidence, which suggests that intrauterine exposure to PM2.5 promotes oxidative stress and inflammation in a similar manner as occurs in response to direct PM exposure. Oxidative stress and inflammation are likely to be the common mechanisms underlying the dysfunction of multiple systems, offering potential targets for preventative strategies in pregnant mothers for an optimal foetal outcome.

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Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice

Cited by 45 publications

References 79 publications

Outdoor air pollution and cancer: An overview of the current evidence and public health recommendations

Outdoor air pollution and cancer: An overview of the current evidence and public health recommendations

TLR4 knock out alleviate both lung and liver inflammation caused by short-time exposure to PM2.5

Particulate Matter, an Intrauterine Toxin Affecting Foetal Development and Beyond

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