Air pollution affects the human body at the level of metabolites


A new University at Buffalo study based on levels before, during and after the Beijing Olympics reveals how air pollution affects the human body at the level of metabolites.

Researchers found that 69 metabolites changed significantly when air pollution changed.

Their results were published today (May 29) in the journal Environmental Health Perspectives.

The study identified two major metabolic signatures, one consisting of lipids and a second that included dipeptides, polyunsaturated fatty acids, taurine, and xanthine.

Many of those metabolites are involved in oxidative stress, inflammation, cardiovascular and nervous systems, researchers note.

The findings are based on the Beijing Olympics Air Pollution study, conducted during the 2008 Olympic Games in China, when temporary air pollution controls were implemented. The study was led by UB epidemiologist Lina Mu.

The study enrolled 201 adults prior to Beijing’s air quality improvement initiative, when air pollution was high.

Researchers followed them during the Games, when air pollution was low, and afterward, when levels returned to their usual high in the city of 21 million people.

A subset of 26 non-smokers aged 30 to 65 was selected for the metabolomics analysis.

Metabolites are small molecules that are the end products of environmental exposures, such as air pollution, and body metabolism.

“Think of our body as a society.

These metabolites fulfill different positions, such as teacher, farmer, worker, soldier.

We need each one functioning properly in order to maintain a healthy system,” said Mu, Ph.D., associate professor of epidemiology and environmental health in UB’s School of Public Health and Health Professions.

“Our study found that the human body had systemic changes at the metabolite level before, during and after the 2008 Beijing Olympics, when ambient air pollution changed drastically,” said Zhongzheng Niu, a Ph.D. candidate and a paper co-author.

The molecules mostly belonged to the lipid and dipeptide families.

The study provides researchers with a broader view of the molecular mechanism underlying the impact of air pollution on the human body.

Most previous studies only looked at a small number of molecules.

However, the human body is complex and molecules affect one another.

Mu and her colleagues used the “omics” method, a new platform that can measure a whole collection of all detectable metabolites – 886 in their study – simultaneously.

Instead of examining these molecules one by one, Mu and her team used network analysis to analyze them all together.

“We found that these metabolites together depicted a relatively comprehensive picture of human body responses to air pollution,” said paper co-author Rachael Hageman Blair, associate professor of biostatistics at UB. She and her team developed the novel analysis method used in the study

The responses include cellular stability, oxidative stress, anti-oxidation and inflammation.

Researchers measured metabolomics repeatedly when air pollution was high, low and high.

All terrestrial animals with lungs are dependent on the supply of oxygen from air, and pollution of air can result in the inadvertent intake of many undesired components with adverse consequences.

According to the World Health Organization (WHO), air pollution caused the death of 6.5 million people worldwide in 2012.1 

Of this global mortality, about 3 million deaths were caused by outdoor air pollution, but this varied markedly according to geographic location, with the highest values recorded in the Democratic People’s Republic of Korea (238.4 deaths per 100,000 population) and the lowest values recorded in Brunei Darussalam and in Australia/Sweden (0.2 and 0.4 per 100,000 population, respectively).1 

However, WHO has attributed an even greater number of deaths to indoor air pollution, and, in 2012, they estimated this to be about 4 million people globally, largely resulting from heating and cooking with solid fuels in an indoor environment without adequate ventilation.2

Pollutants may be natural or man-made, and they may occur as gases, liquid droplets, or solid particles as summarized in Table 1.

Gaseous components of air pollution include carbon dioxide and carbon monoxide, sulfur oxides, nitrogen oxides, ammonia, and ground-level ozone.13

Particulate matter (PM) includes dust, soil, acids, organic molecules, and some metals.4 

It is categorized according to the size of the particles, with particles of diameter 2.5–10 µm considered coarse (PM10), <2.5 µm fine (PM2.5), and <0.1 µm ultrafine (PM0.1).4 

Distributed between the gaseous and particulate phases are also a range of organic pollutant molecules which may exist as volatile organic compounds (VOCs) or semi-volatile organic compounds (SVOCs) in gaseous form or which may attach to PM.

Some of these compounds are now known to have profound effects on the functioning of the endocrine system and have been termed endocrine disrupting chemicals (EDCs).5 

Whilst much has been written over the past two decades of the actions of EDCs from oral and dermal exposure, research is increasingly documenting their presence in air which opens a debate on the potential for adverse consequences from inhalation of EDCs.

This review aims to summarize current knowledge concerning the sources of EDCs in air, measurements of levels of the EDCs in outdoor versus indoor air, and the potential for adverse effects on human endocrine health.

Table 1

Origins of air pollution from natural sources and from human activities

FormCompound(s)Source – naturalSource – human activity
GasesCarbon dioxide (CO2)Natural component – balanced between use in plant photosynthesis and release from animal respirationHuman activity is increasing levels especially through burning of fossil fuels and deforestation
Carbon monoxideWild firesIncomplete combustion of fuel (natural gas, coal, wood, petrol)
Sulfur oxides, especially sulfur dioxide (SO2)VolcanoesIndustrial activities; excess combines with atmospheric water to cause acid rain
Nitrogen oxides, especially nitrogen dioxideThunderstormsHigh-temperature combustion
AmmoniaAgricultural processes
Ground-level ozoneCombustion of fossil fuel
Volatile organic compoundsNatural methane; vegetation; animal and vegetable waste; sewageExcess methane from industrial and agricultural processes; industrial pollutants; waste incineration (including burning of plastics); chlorofluorocarbons (air conditioners, refrigerators, aerosol sprays); consumer products (especially with added fragrance or volatile solvents)
Particulate matter (solid particles and liquid droplets)Dust, soil, acids, organic molecules including persistent organic pollutants, metalsVolcanoes, dust storms, forest fires, sea sprayFuel combustion (motor vehicles, marine vessels, aircraft); power plants; industrial processes; cigarette smoking; consumer products (especially with volatile solvents or added fragrance); aerosol sprays (pesticides, herbicides, household cleaners, paints, glues, personal care products)
Radioactive pollutantsRadon gas from radioactive decayNuclear explosions

Note: Shaded areas indicate sources of EDCs.

Abbreviation: EDCs, endocrine disrupting chemicals.

What are EDCs?

An EDC is defined as “an exogenous substance that causes adverse health effects in an intact organism, and/or its progeny, consequent to changes in endocrine function.”6

 Normal function of the endocrine system is dependent on hormones which act as chemical messengers to regulate physiological functions.

Hormones are secreted by glands distributed around the body and are carried by the blood (as conjugates and/or bound to carrier proteins) to act on target cells of distant organs.

At the target cells, the hormones act through binding to specific cellular receptors which then relay signals into the cell.

Intracellular signaling may involve genomic and/or non-genomic mechanisms.5

By the genomic mechanism, a hormone binds to a receptor, displacing receptor-associated chaperone proteins and enabling dimerization of the receptors.

The receptor dimers then act by binding to specific “response element” nucleotide sequences in the DNA to cause alteration to gene expression.

By the non-genomic mechanisms, a hormone may bind to cell surface receptors triggering intracellular signal transduction pathways.

EDCs can interfere in the action of hormones at many different steps, as illustrated in Figure 1.

They may act by altering hormone synthesis in the endocrine gland, or through altering transport of the hormone to the target organ by interfering with the activity of conjugation enzymes or by competing for binding to carrier proteins.

Alternatively, they may act through altering metabolism/excretion of the hormone or through competing with the hormone for binding to a receptor in target cells and in so doing to mimic action of steroid hormones (particularly, but not exclusively, in relation to the action of estrogens and androgens) and thyroid hormones.5 

Since estrogens and androgens regulate reproductive functions, many of the reported effects of the exposure to EDCs have been on adverse consequences for reproductive health.5 

However, physiological consequences have been demonstrated as resulting from disruption to thyroid function and alterations to thyroid hormone levels.5 

More widely, adverse effects have also been reported as resulting from alterations to adrenocortical function, impairment of the immune system, and the loss of control on energy metabolism including development of obesity, diabetes, and cardiovascular disease.5 

Prior to and just after birth are especially vulnerable times for exposure to EDCs because disruption of hormonal activity in the developing embryo/fetus or young baby can have consequences for health in adult life most notably on reproductive abilities, brain function, immunity, and metabolic programming.5 

For this reason, the passage of EDCs across the placenta from mother to child and postnatal exposure to EDCs in maternal breast milk have become an important topic for research.

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Figure 1

Mechanisms of action of EDCs.

Note: Data from Darbre.5

Abbreviation: EDCs, endocrine disrupting chemicals.

Man-made EDCs are contained within many agricultural, industrial, and consumer products, which due to their widespread use, have become ubiquitous environmental pollutants. This includes components of pesticides and herbicides used both in an agricultural setting and in urban environments.

It includes industrial chemicals and by-products of combustion from vehicles, ships, and aircraft.

It also includes plastics which are used widely in building materials, food containers, water bottles and toys, and detergents used for cleaning in both industrial and domestic applications.

Paints, glues, chemicals used as flame retardants, and stain resistance coatings also form part of the list. EDCs are also widely used in personal care products (PCPs) for purposes of preservation, deodorant, antiperspirant, conditioning, and fragrance.5

Many varied assay strategies have been developed over the years for identifying compounds with endocrine disrupting properties in order to define a series of events at different levels of biological organization along a pathway which may lead to an adverse health outcome.5

Identification of adverse consequences along a pathway may include altered molecular events, changes to cellular actions, consequences for whole organ responses, or even adverse effects at a population level.

Molecular assays include the ability of compounds to bind to specific endocrine receptors followed by assays for genomic actions on gene expression or for non-genomic actions on alterations to defined signal transduction pathways.

Actions at a cellular level are most often defined using proliferation of endocrine-sensitive cells as an easily assayable endpoint. Other more specific assays have been developed to measure alterations to synthesis/transport/metabolism/excretion of steroid and thyroid hormones which may be carried out by measuring the activities of key enzymes or levels of secreted hormones using cellular or animal models.

Animal models are also widely used to try to predict whole body responses albeit with the caveat of consideration to species differences.

It is not always possible to identify actions of every chemical at every step and the challenge for risk assessment is to determine the extent to which early molecular and/or cellular actions may be predictive of later endocrine disease outcomes, and to which effects in animal models can predict for epidemiologically detectable consequences in humans. Specific EDCs which are measurable in air are discussed in the “Sources of exposure to EDCs in air” section together with an outline of the current evidence for their classification as having endocrine disrupting properties.

Such a design mimicked a “natural experiment” while controlling for variations unrelated to air pollution changes. This provided stronger evidence than previous studies.

Air pollution is an environmental exposure that can’t be avoided by people who live in places like Beijing.

The World Health Organization reports that 91 percent of the world’s population lives in places where air quality exceeds WHO guidelines.

Once inhaled, air pollutants stimulate the body’s respiratory system, including the nose and lungs.

Some cells in the body may be directly insulted by these air pollutants, their membrane may be broken, their secretion may be disordered, and they may send out signaling molecules to other organs for subsequent responses, Mu explains.

Metabolites are all these broken membranes, secreted products and signals.

“Capturing these molecules tells us what is going on when people are exposed to air pollution,” Mu said.

Air pollution also induces cellular oxidative stress, which breaks cell membranes.

Researchers found that some molecules that serve as building blocks of cell membranes were elevated when air pollution levels rose.

Broken cell membranes release different kinds of lipid molecules. Some of these lipid molecules, with the help of enzymes, turn to inflammatory molecules, which could be harmful to the body.

“The good thing is that we also found some protective molecules, namely antioxidants, also increased when air pollution is high, indicating our body has a defense system to reduce harm,” Mu said.

Studies such as this one may help identify individuals most vulnerable to air pollution, as well as finding potential biological pathways to guide treatment that reduces harm to the body, Mu said.

More information:Environmental Health Perspectives (2019). DOI: 10.1289/EHP3705

Journal information: Environmental Health Perspectives
Provided by University at Buffalo


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