Plastic particles with a diameter of less than 5 mm are now widely acknowledged as a threat to the environment and a health risk to human populations, ranging from oxidative stress to DNA damage (Rochman et al., 2013; Katsnelson 2015; Smith et al., 2018; Prata et al., 2020; Ibrahim et al., 2021; Blackburn and Green 2022). There are two major sources of microplastics (MPs):

1) cosmetics, detergents, sunscreens, and medicine delivery systems all containing plastic powders or particles (Galloway 2015) and

MPs have been found in various settings and media, such as rivers, sewage, sediments, soil, and even table salt (Rillig 2012; Imhof et al., 2013; Jabeen et al., 2015; Lechner and Ramler 2015; Lusher et al., 2015).

MPs can reach human populations either directly through the environment or indirectly through food. According to numerous studies (Thompson et al., 2009; Cole et al., 2013) and food chains (Setälä et al., 2014), a variety of marine organisms (bivalves, fish, etc.) consume MPs. MPs are therefore anticipated to accumulate in the environment and increase the risk of exposure for wild creatures and human populations over time due to their extensive use and durability.

Studies demonstrating the potential health risk and tissue accumulation of MPs in mammals are scarce, although most research on the toxic effects of MPs has been on aquatic creatures. Accumulation of MPs in tissues can have various negative effects, which include physical harm. This is because the majority of these plastics have been detected in the marine animals examined, and it has been hypothesized that malnutrition contributes to their death, which is the rupture of the stomach from being trapped by debris (De Stephanis et al., 2013). Many species of birds, reptiles, and fish were found to directly ingest plastic, which may block their stomach and intestines (Hämer et al., 2014). This may cause inhibition of growth and development (Koelmans et al., 2014) and energy deficiency (Galloway 2015). Among the cellular impacts were modifications to immunological responses, the lysosomal compartment, peroxisome proliferation, antioxidant system, neurotoxic effects, and the start of genotoxicity (Avio et al., 2015; Hamed et al., 2019; Hamed et al. 2020; Hamed et al. 2021; Sayed et al., 2021; Ammar et al., 2022; Sayed et al., 2022; Sayed et al., 2022). Microplastic-induced reactive oxygen species (ROS) has been shown to be an inducer of oxidative stress in some marine organisms (Wright et al., 2013). It has been found to have severe effects on the feeding and water behavior as well as the metabolism of fish. Hence, it has been concluded that polystyrene nanoparticles have severe effects on both behavior and metabolism (Mattsson et al., 2015). Therefore, information on MP tissue accumulation in mammalian models would be crucial for determining the risk of MPs to human health (Prata et al., 2020; Ibrahim et al., 2021; Blackburn and Green 2022).

The toxic effects of MPs on erythrocytes (RBCs) are yet to be verified. Hence, the current study determined how exposure to different MP concentrations influenced haematological changes and biochemical indicators of liver and kidney function as a proxy for the effects that microplastics on human health.

In recent years, a significant increase in the negative impact of environmental contaminants on human health (Inhorn and Patrizio. 2015) is seen. High MP concentrations have been found in freshwater (0-1 106 items/m³) and marine (0-1 104 items/m³) waterbodies. MPs have also been seen in various animal species such as mussels and fish that humans consume (Desforges et al., 2014; Deng et al., 2017). MPs can spread through the aquatic food chain, which will likely cause a biological buildup of the substance. Microplastics (MPs), an environmental pollutant, cause toxicity in the liver, kidneys, and gastrointestinal system (Hou et al., 2021; Wang et al., 2021; Zhao et al., 2021) in animals and aquatic organisms. A recent study has shown that MPs harm the male reproductive system (Hou et al., 2021). However, little is known regarding how microplastics affect vascular biology or humans/mammals. A recent study has revealed that MPs fundamentally impact the hematological system in mice and that these alterations in gene expressions were connected (Sun et al., 2021). However, further research is needed to determine how MPs impact blood cells and other hematological variables. Red blood cell deformability has a significant impact on blood circulation at the microcirculation level. Consequently, any reduction in RBC deformability could impact flow resistance, tissue perfusion, and oxygenation (Nader et al., 2019). In this investigation, we discovered that MP particle accumulation was primarily dose dependent in the gastrointestinal system. Their particle size highly influences their distribution and the tissue accumulation kinetics, and they accumulate in the liver, kidneys, and gut (Deng et al., 2017). The cellular components in the plasma—an aqueous solution which includes organic compounds, proteins, and salts—make up the whole blood, a two-phase liquid (Baskurt and Meiselman 2003). The blood’s erythrocytes, leukocytes, and platelets make up its cellular phase. The white blood cells and platelets impact blood rheology, but under typical circumstances, erythrocytes (RBCs) have the most significant impact (Pop et al., 2002) The physical characteristics of these two phases and their proportional contributions to the total blood volume determine the rheological characteristics of the blood. Additionally, hematocrit, plasma viscosity, RBCs’ capacity to deform under flow, and RBC aggregation–disaggregation characteristics all affect blood viscosity (Baskurt and Meiselman 2003; Cokelet et al., 2007).

Teardrop-like cells (Pollastro and Pillmore, 1987), helmet cells (HE), stomatocytes (Sto), sickle cells (Sic), schistocytes (Sch), folded cells (Gregorio et al., 2009), boat-shaped cells (Bo), ovalocytes Ov), and echinocytes are only a few of the RBC alterations that have been observed in the groups exposed to MPs (Lechner and Ramler). Teardrop-like cells (Pollastro and Pillmore, 1987), which are thought to be a marker for myelofibrosis, significantly increased in the 6 μg/ml MPs and 60 μg/ml MPs groups before reducing on their own after 15 days. The echinocytes are spiculated RBCs in high numbers in the 60 μg/ml MPs blood samples and indicate widespread electrolyte depletion. The distortion of red blood cells into echinocytes is due to the bilayer membrane alterations, which is the result of a protective mechanism (Svetina 2012). On the other hand, there is another explanation mechanism as high ROS levels can easily promote lipid peroxidation because RBC membranes contain a lot of polyunsaturated fatty acids, which further damages RBCs by disrupting membrane integrity and lowering their resistance to injury (Remigante et al., 2022). It is possible to utilize the cationic surfactant benzalkonium chloride as a cell membrane surface state changer since it can integrate into the erythrocyte membrane and change the shape of the erythrocytes in saline solution (Rudenko and Saeid 2010).

A reduction in intracellular erythrocyte potassium (K+) leads to red blood cell dehydration and echinocyte formation (Glader and Sullivan 1979; Gallagher 2017). Most of these alternations in the 6 μg/ml MPs and 60 μg/ml MPs groups were recovered after 15 days, demonstrating the blood’s quick, natural mending process. The recovery time, however, was insufficient for the 600 μg/ml MPs group to return the RBCs to their characteristic morphology. Thus, a 15-day recovery period helped lessen the impacts of microplastics in lower dosages but was insufficient to eliminate them; by contrast, it was never adequate at high concentrations (Table 4). The discovered RBC alternations impacted normal blood flow because they affected their capacity for deformation (Figure 3C) and subsequently led to the formation of cellular aggregations.

Blood viscosity is linearly connected to hematocrit since it depends on the quantity (and number) of erythrocytes in the blood (Nader et al., 2019). At low shear rates (such as in the veins), hematocrit (HT) has a more significant effect on blood viscosity than it does at high shear rates (such as in the arteries) (Cokelet et al., 2007). According to estimates, a one unit increase in hematocrit at high shear rates would result in a 4% increase in blood viscosity (if RBC rheological properties remain the same). In the current investigation, the 60 and 600 μg/ml MPs groups had considerably lower HT levels. Additionally, at the higher MP concentrations (60 and 600 μg/ml MPs), hemoglobin (Hb) levels were much lower, which is thought to be an indication of sickle cell anemia (Magrì et al., 2018). Additionally, RBCs become more fragile and susceptible to hemolysis when they lose their deformability (Connes et al., 2014). Vaso-occlusion and pre-capillary obstruction can both be caused by stiff, sickle-shaped RBCs (Rees et al., 2010).

After exposure to MPs, the biochemical markers (creatinine, AST, ALT, glucose, and total protein) significantly increased. Creatinine can be used as a biomarker for renal impairment and as an indicator of glomerular filtration rate (Lien et al., 2006).

Enzymes (AST and ALT) are found in the cells of several organs throughout the body (Lenaerts et al., 2005). These enzymes’ release and increased blood levels are signs of damaged cell membranes (Lenaerts et al., 2005). According to our findings, paraquat and/or microplastic particles increased the activity of intracellular enzymes (ALT and AST), which may be a sign that cell plasma membranes have been damaged (Cheng et al., 2022). Proteins are essential for preserving physiological homeostasis and in stopping blood leak from the circulatory system (Bergmeier and Hynes 2012). Increased levels of total protein result from MP exposure, and these suggest problems in the kidney and liver functions.

With low MP dosages, when compared to the control group, microplastics buildup and hemato-biochemical changes were improved after the recovery period. However, the high dose group was affected negatively by MPs. The recovery period has an effect ranging from cells to tissues where the defense mechanisms were reported (Hamed et al., 2019; Hamed et al. 2020; Hamed et al. 2021; Sayed et al., 2021; Ammar et al., 2022; Sayed et al., 2022; Sayed et al., 2022).

In C57BL/6 mice, microplastics produced a range of toxic consequences, which included anemia and changes in hemato-biochemical parameters, which may induce severe toxic effects in all organs at higher concentrations and for extended periods. Our findings have shown that MPs had damaging effects on mice’s RBCs, reflecting the dangerous implications of these MPs on human health. The current study may initiate future comprehensive studies on the impacts of MPs on other body systems.