6.1 Introduction

Environmental pollutants affecting human health have been a grave concern. Particulate matter is a most ubiquitous air pollutant with serious consequences to health. With their diversity in chemical composition, these minute pollutants are difficult to track and minimize. Microplastics are an emerging group of pollutants to be intensively studied owing to their small size and widespread use of non-biodegradable plastics. Both particulate matters and microplastics are implicated in various disease conditions. Not surprisingly, both these pollutants are able to positively affect the hallmarks of cancer and aid in cancer progression. Mitochondria are crucial to cells’ energy metabolism and normal homeostasis. Particulate matter and microplastics have an impact on mitochondrial health. This chapter aims to understand the nature of particulate pollutants and microplastics, their toxicity and their effects on various pathological conditions, and the impact of these potent pollutants on mitochondrial health.

6.2 Particulate Matter

Human civilization has long been victims of pollutants that surround them, causing serious threats to survival. Air pollution is one prominent health disrupter, and the World Health Organization (WHO) states that air pollution is responsible for causing 4.2 million deaths annually. Particulate matter (PM) contributes significantly to polluting the air and deteriorating human health. Particulate matter as a potent threat to human life was first evident from increased mortality due to smog in early 1900 in Belgium, Pennsylvania, and the UK (Stanek et al. 2011). Particulate matter has been associated with causing cardiovascular and respiratory distress. In addition, it blocks solar radiation, modulates climate, and seriously affects air visibility apart from influencing ozone production and impacting precipitation (Liu et al. 2020; Zeb et al. 2018). Particulate matter is a heterogenous mixture of minute differently sized particles with varying physio-chemical properties and suspension of liquid droplets in the air. The chemical composition of PM mainly consists of carbonaceous particles with various chemicals and metals attached to them. The inorganic matters of concern including silicates, nitrates, sulfates, and organic components like polyaromatic hydrocarbons also pose a threat. The presence of heavy metals adsorbed to their surface (Fe, Cu, Ni, Zn) enhances the toxicity of PM (Hamanaka and Mutlu 2018; Zhang et al. 2018). PM is also reported to harbor spores and pathogenic cell fragments which can cause opportunistic infections (Miri et al. 2018).

Based on their aerodynamic diameter, particulate matter is characterized as coarse particles, having diameter greater than 2.5 μm; fine particles with diameter 0.1–2.5 μm and ultra-fine particulate matter with diameter less than 0.1 μm (Xiao et al. 2018). Coarse particulate matters are formed from mechanical or physical processes such as grinding. PM2.5 are byproducts of combustion reactions either from anthropogenic sources like emissions from traffic, fossil fuel burning, industrial effluents, or natural sources like forest fires, dust storms, and volcanic eruptions (Miri et al. 2018; Wu et al. 2018a, b). PM has been reported to sustain in the air for a substantial time frame and is also reported to cause serious health effects to human being, in addition to causing modulations in climate (Deng et al. 2019; Miri et al. 2018; Zhang et al. 2018).

6.3 Particulate Matter: Impact on Human Health

Particulate matters are a serious threat to human health. Coarse particulate matter is reported to deposit in upper respiratory tracts. Fine particulate matter gets deposited in the lungs and is a potent respiratory irritant. PM2.5–10 are associated with respiratory diseases. Asthma, chronic obstructive pulmonary disease (COPD), pneumonia, and allergic rhinitis are linked to short-term exposure to particulate matters, and emphysema, bronchitis, and pleuritis are associated with long-term exposures (Cho and Choi 2021; Wu et al. 2018a, b). Respiratory distress is an aftermath of inflammatory reactions caused due to oxidative stress or direct toxicity brought about by particulate matters as evidence points out exposure to PM leads to the release of inflammatory mediator (Delfino et al. 2010). PM2.5 are inducers of neutrophils and eosinophils, which account for allergic rhinitis in addition to promoting TH2-and TH13-mediated allergic responses (Wu et al. 2018a, b). Oxidative stress has been reported in lung epithelial cells upon exposure to PM which in turn results in apoptosis of the cells (Huang et al. 2014).

Ultra-fine particulate matter could diffuse out of alveoli and even penetrate to circulation through blood vessels (Mannucci et al. 2015). Particulate matters from wildfires are reported to be linked to pulmonary edema and cardiovascular diseases (Ghio et al. 2012). Cardiovascular diseases associated with particulate matter exposure include ischemic heart disease, myocardial infarction, congestive heart failure, and carotid artery thrombosis (Wu et al. 2018a, b). Endothelial inflammation due to particulate matters in circulation results in increase in incidences of atherosclerosis (Dutta et al. 2012). Another cause of concern is evidence of premature death incidents due to particulate matter exposure.

Ultra-fine particulate matter sustains for a longer time in the air and is reported to be a carrier of pathogenic microbes and viruses (Setti et al. 2020). PM is reported to be the carriers of viruses acting as vectors of pathogenicity (Alonso et al. 2015; Yang et al. 2011). A report from Italy hypothesizes the presence of SARs-CoV2 on particulate matter (Setti et al. 2020). It is also found that chronic exposure to PM could make the population susceptible to SARs-CoV2 (Yao et al. 2020). Reports also suggest that the mechanism of action of particulate matter by recruiting inflammatory mediators and affecting the airways can impact the prognosis of COVID patients (Kelly and Fussell 2011; Yao et al. 2020). These findings suggest that in the present scenario of rising COVID cases, particulate matter pollution will further worsen pandemic-associated morbidity.

Particulate matters are also associated with cancer progression. It acquired the status of being a carcinogen in 2013 as proclaimed by the WHO and International Agency for Research on Cancer (IARC). Increased particulate matter in the atmosphere has risked human life to lung cancers predominantly (Turner et al. 2011). PM2.5 is also associated with cancers of the breast, colorectal, bladder, kidney, stomach, liver, pancreas, and cervix (Deng et al. 2019; Turner et al. 2020; Wu et al. 2019). Hodgkin lymphoma and leukemia are also reported to be linked to particulate matter exposure (Coleman et al. 2020). Particulate matters are implicated to affect all major hallmarks of cancer (Santibanez-Andrade et al. 2019). They are reported to activate proliferation in lung cancer lines (Yang et al. 2016). PM2.5 prevents bronchial cell apoptosis (Ferecatu et al. 2010). Components associated with particulate matters like PAHs and heavy metals activate anti-apoptotic signaling pathways (Lovera-Leroux et al. 2015; Shang et al. 2017). PM2.5 is reported to inhibit the mTOR pathway in lung cell lines and hence induce autophagy (Liu et al. 2015). Particulate matters accelerate angiogenesis and help in tumor growth (Yang et al. 2018). They aid in epithelial-mesenchymal transition, which further increases the invasiveness of cancer and by means of reactive oxygen species (ROS) cause DNA damage (Wang et al. 2020a, b, c; Wei et al. 2017). Particulate matters as epigenetic modifiers are yet to be studied conclusively. However, reports suggest that exposure to particulate matter led to changes in methylation status and caused alterations in the expression of micro-RNAs and long non-coding RNAs inducing malignant genes and pathways sustaining the tumor growth and progression (Hesselbach et al. 2017; Liu et al. 2015). Mitochondrial health is also compensated when exposed to ultra-fine particulate matters leading to changes in mitochondrial membrane potential, mtDNA content, and energy metabolism (Bhargava et al. 2018).

6.4 Microplastics

Plastics are one of the most ubiquitous commodities that humans use. The fact that they are non-biodegradable is overlooked without any check on their production or proper disposal. Plastics are so prevalent that they are now used as indicator of Anthropocene, evident from deposits which remarkedly act as indicators of stratigraphy (Zalasiewicz et al. 2016). Basically, polymers of various chemicals like polyethylene, polystyrene, and polyvinyl chloride are made from non-renewable resources like fossil fuels or are bio-based. Plastics pose a threat to life and nature alike. A recent UN report points to the fact that there is an increasing trend in the number of publications on plastic debris. Not surprisingly, WEF also revealed the observation that plastic particles in oceans will surpass the marine fish population by 2050.

Microplastics are considered as a particulate pollutant owing to their minute sizes and have earned ample interest in terms of threatening human health. Marine ecologist Richard Thomas coined the term in 2004 although the earliest literature on these minute contaminants dates to the 1990s. There isn’t any conclusive definition of microplastics, but their signature is of particles having sizes in the range of 1 nm—<5 mm. Microplastics may be artificially synthesized or are formed from natural or chemical modification of plastics. Microplastics are in market, incorporated in scrubs, cosmetic products, and detergents. These are classified as primary microplastics. Secondary microplastics are formed from plastic by means of their degradation or modification by exposure to UV radiations, and weathering of physio-chemical treatments. Microplastics are widespread in oceans, and dumping of industrial sewage into water bodies can be a major cause. Combustion of plastics on large scale can increase the microplastic content in the atmosphere. The main sources of microplastics in the atmosphere are synthetic cloth fibers, tire industry, industrial effluents, and combustion of chemicals. Microplastics are also found in various food products like honey, for example (Liebezeit and Liebezeit 2013). Use of canned foods and storing drinking water in plastic cans (El-Ziney 2016) are major cause of concern for the presence of microplastics in water and food. The accumulations of microplastics in soil alter their biochemical properties which can affect flora and fauna dependent upon the soil (de Souza Machado et al. 2018). The leaching of such particles into the ocean or water bodies again harm aquatic life and is even reported to enter the food chain endangering the lives of animals as well (Waring et al. 2018).

Microplastic toxicity is being studied in terrestrial and marine life. Elucidating the harmful effects of microplastics is still a challenge, owing to the fact they are of varied shapes and sizes with no proper detection methods, studies are inconclusive with regard to how to tackle the burden of microplastics, how to determine their age and biochemistry, routes of exposure to marine and terrestrial life.

6.5 Microplastics and Human Health

Microplastics are a silent threat to human health, minuscule but with immense potential to cause harm. Aptly put by Rachal Carson in his book Silent spring, “If we are going to live so intimately with these chemicals - eating and drinking them, taken them into the very marrow of our bones, we had better know something about their nature and power” (Carson 2002). Microplastics are omnipresent, recorded in the very air we breathe in, the soil, in the oceans, associated with microbes and even in unimaginable conditions as the Polar Regions (Campanale et al. 2020b; Pabortsava and Lampitt 2020; Peeken et al. 2018). The very same reason without doubt validates the exposure of humans to microplastics.

The major ways in which microplastics pave their way into human system include inhalation of these minute particles from the atmosphere (Prata 2018), ingestion of some microparticles through food (Bernatsky et al. 2016) or drinking water (Koelmans et al. 2019), absorption of microparticles via skin (De-la-Torre 2020). Though very few reports point to the absorption of microparticles via skin, it cannot be overlooked. Microparticles find their way to our system through glands of skin or skin follicles and even act as opportunistic attackers through cuts or injuries in skin. It is reported that microparticles are inhaled in concentrations of 0.4–56.5 ppm indoors and 0.3–1.2 ppm concentrations outdoors (Dris et al. 2017). Microplastics are found to enter the food chain, especially through marine ecosystem and they tend to accumulate with each passing hierarchy of the food chain to finally culminate into human system (Rist et al. 2018). Marine fauna such as the mollusks and other sea foods are reported sources of entry to human through their dining. The organism accumulates microplastics in their digestive tracks and the consumption of fish as whole or even dry fishes pose a threat of exposure to these chemicals (Bernatsky et al. 2016).

6.6 Respiratory System

Airway exposure of microparticles results in accumulation in the respiratory pathway leading to irritation, inflammation mainly in bronchioles, alveoli, and lungs. This in turn can cause serious consequences in the form of respiratory diseases like asthma, bronchitis, and lung cancer (Valavanidis et al. 2013). Additives used in microplastics like phthalates are a major concern with respect to asthma and allergic reactions (Ait Bamai et al. 2014). Although un-noticed even cloth fibers cause respiratory distress or difficulty in breathing, dyspnea (Prata 2018). Polyvinyl chloride polymers are found to cause cytotoxicity in human lung. In the COVID era with the increasing use of PPE made of polyvinyl polymers, there is a greater risk of respiratory distress due to microplastics (Fadare and Okoffo 2020).

6.7 Digestive System

Through drinking water or routine food intake, especially sea foods (Bernatsky et al. 2016), we ingest microparticles. Microparticles get caught in mucous layers but many of these get transported and lodged in the intestine (Prata 2018). They are reported to be found in human stool (Schwabl et al. 2019). Microparticles are said to even penetrate the barriers of the intestinal epithelium and get translocated to other organs via the lymphatic system or the circulatory system (Rahman et al. 2021).

6.8 Immunology

Microplastics have the ability to affect the immune system by perturbing the immune cells. They reach the lymphatic and circulatory system crossing epithelial and lung barriers (Campanale et al. 2020a). They trigger allergic reaction by up-regulating histamines (Hwang et al. 2019). Macrophages are reported to accumulate toxic polymers from microplastic like polystyrene and result in autophagy causing cytotoxicity in lung epithelium and macrophages. The cytotoxic effect of microplastics is an aftermath of excessive ROS production caused by oxidative stress (Geiser et al. 2005). They are also reported to get into secondary immune cells like M cells and dendritic cells. By stimulating the overproduction of cytokines, microplastics play a major role in causing chronic inflammatory reactions which lead to cytotoxicity and are also related to cancer (Prata 2018). Other less-studied potential health hazards from microplastic exposure include autoimmune diseases like SLE (Fernandes et al. 2015), Rheumatoid arthritis (Bernatsky et al. 2016), and immune suppression (Prata et al. 2020) (Fig. 6.1).

Fig. 6.1
An illustrative semi-circle spoke diagram lists the effects of microplastics on distinct organs. Some of them include neurotoxicity, asthma, lung cancer, disturbed gut microbiota, and deposits in the intestine.

Impact of microplastics on human health

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6.9 Reproductive Disorders

Additives used in the production of microplastics like bisphenol (BPA) are reported to be toxic to the reproductive system (Campanale et al. 2020a). Polybrominated diphenyl ether (PBDE), a class of additive used as flame retardant, is a known endocrine modulator (Linares et al. 2015). Microplastics can be considered as a new class of teratogen. Recently, microplastics are found to cross the human placenta causing retardation of fetal growth (Ragusa et al. 2021).

6.10 Neurotoxicity

There are very few conclusive studies on how microplastics affect the nervous system. Studies of microplastics affecting cerebral epithelial cells indicate some level of oxidative stress (Barboza et al. 2018). Neurotoxicity, resulting from increased cytokine production by microplastics, is a cause of concern (Mohan Kumar et al. 2008).

6.11 Pathogenicity

Microplastics harbor harmful microorganisms on their surface forming a biofilm. These biofilms are pathogenic (Lobelle and Cunliffe 2011). The presence of antibiotic-resistant bacteria in microplastics is a reason to worry for sure and must be studied extensively (Zhang et al. 2020). Association of microplastic with gut microbiome referred as plastisphere can alter the microbiome of the gut. This has been reported to have endotoxic effects in addition to that it results in various opportunistic diseases (Zettler et al. 2013).

6.12 Cancer

The ability of microplastics to cause chronic inflammation is the major cause of cancers due to microplastics (Prata 2018). DNA damage by microplastics is also a reported strategy (Prata 2018). Heavy metals used as additives in microplastics production are reported to be potent carcinogens (Tchounwou et al. 2012). Arsenic toxicity has been linked to cancers of lung, liver, kidney, and bladder (Hahladakis et al. 2018; Jan et al. 2015). Metals, like antimony and aluminum, are associated with breast cancer (Byrne et al. 2013; Hahladakis et al. 2018; Byrne et al. 2013). Additives like phthalate (Böckers et al. 2021) and tri-cresyl phosphate (Bockers et al. 2020) have been reported to be tumorigenic in MCF-7 lines. Various chemicals used as additives in microplastics have endocrine-modulating function and are implicated in breast cancer, prostate, and testicular cancers (Böckers et al. 2021). Evidence indicates occupational exposure of microplastics with the development of lung cancer, hematopoietic cancer, colorectal cancer, esophageal cancer, cancers of cervix, and gastric cancer (Cho and Choi 2021; Ibrahim et al. 2021; Prata 2018; Yan et al. 2020). Report suggests possible gene mutation due to long-term exposure of microplastics as a cue for developing cancers (Hu et al. 2021).

6.13 Particulate Matters, Microplastics, and Mitochondrial Health

Mitochondrial health can be a classic marker for exposure to harmful pollutants like particulate matter and microplastics. Most studies point to oxidative stress due to excessive ROS production resulting from exposure to pollutants as a major pathway of cytotoxicity (Wang et al. 2020a, b, c). Reports suggest perturbations in mitochondrial morphology because of particulate matters and microplastics. Changes in morphology are particularly vivid in the form of disruption of mitochondrial membrane, mitochondrial edema, and disappearance of mitochondrial cristae as reported in studies of polystyrene microplastics on rat hepatocytes (Li et al. 2021), particulate exposure on cardiomyocytes (Yang et al. 2018), and macrophages (Wei et al. 2021). Damage to mitochondrial membrane in turn is reported to open mitochondrial permeability transition pore which results in the swelling of mitochondria (Miao et al. 2019). Because of increased ROS, the decline in mitochondrial membrane potential has been observed in various studies (Chew et al. 2020). Exposure to microplastics causes lysosome-induced mitochondrial membrane depolarization (Wang et al. 2020a, b, c). Mitochondrial depolarization has been reported to occur because of microplastics in size-dependent manner in caco2 cells (Wang et al. 2020a, b, c).

Imbalance in mitochondrial membrane potential has a serious impact on mitochondrial respiration as it uncouples the mitochondrial electron transport chain and hence decreases ATP significantly. This is validated in murine macrophages exposed to microplastics (Merkley et al. 2021), and polystyrene exposed to caco2 cells (Wang et al. 2020a, b, c). Particulate matter has the ability to alter mitochondrial electron transport chain (ETC) enzyme complexes and hence deteriorate ATP (Myers et al. 2010). Metabolic alteration due to exposure to microplastics has been implicated in intestinal epithelial cells (Myers et al. 2010). Elevated oxidative stress has a marked impact on decreasing the mtDNA copy number in leucocytes exposed to particulate matters (Wang et al. 2020a, b, c) and is also implicated in studies on exposure of poly aromatic hydrocarbons (Pardo et al. 2020). mtDNA is required for crucial processes and depletion of mtDNA results in a decrease in the biogenesis of mitochondria. Disturbed mitochondrial membrane potential and reduction in mtDNA contribute to excessive ROS production by mitochondria and hence induce apoptosis, as evident from studies on exposure of kidney epithelial cells to microplastics (Wang et al. 2021). Increased ROS is also reported to induce lipid peroxidation of the mitochondrial membrane which aids in the accumulation of toxic particulate matter in mitochondria, further increasing mitochondrial dysfunction (Yang et al. 2018). Particulate matters are reported to modulate mitochondrial dynamics by increasing mitochondrial fission (Wang et al. 2019). Imbalance in the dynamics of mitochondria results in poor mitochondrial quality control. Mitochondria-mediated apoptosis is initiated in most cases of particulate matter exposure. Polystyrene additives in microplastics have been reported to trigger mitophagy (Pan et al. 2021). Till date various studies have elucidated the impact of microplastics and particulate matter on mitochondrial health; however, a conclusive modality to minimize the impact and to what extent these pollutants affect human health is yet to be explored (Fig. 6.2).

Fig. 6.2
An illustrative spoke diagram lists the impact of microplastic and particulate matter. Clockwise, some of them include membrane disruption, swelling, mitophagy, and membrane depolarization. Low levels of mitochondrial D N A and membrane depolarization induce cytotoxicity.

Effect of microplastics and particulate matter on mitochondrial health

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6.14 Conclusions and Future Perspectives

Microplastics and particulate matters are potent pollutants capable of causing harm to human health. The ubiquitous presence of these particles continues to pose a threat. They are also increasing on a day-to-day basis owing to various anthropogenic activities. It is a matter of concern that despite various studies on the impact of microplastics and particulate matter on human health has been conducted, preventive and protective strategies are still underexplored. The heterogeneity of these pollutants makes them difficult to be mapped for studies. Real-time analysis of the presence of these pollutants must be elucidated to avoid a potential threat. Minimizing sources can be a way forward to limiting their release. Reducing and reusing plastics, using proper protective gears to avoid on-site exposure, and proper treatment of drinking water can be few steps toward a greater goal of minimizing human exposure to these toxic chemicals. Keeping the environment free of these pollutants should be a way forward by using sustainable resources and avoiding the unchecked release of plastics and other particulate pollutants.