Table 1.
Studies linking the effect of environmental toxins on the gut, lungs, and circulatory system and their consequences for stroke risk.
| Environmental Toxins | Compound/ Substance |
Model | Dosage | Exposure Method and Duration | Effect | References |
|---|---|---|---|---|---|---|
| Gut | ||||||
| Heavy Metal | Cadmium | Sprague–Dawley rats | 5 mg/kg | Gastric infusion daily for 30 days | ↓ Expression of the tight junction protein ZO-1 ↑ Expression of TNF-α, and IL-6 in the gut |
[25] |
| Heavy Metals | Cadmium/Arsenic | C57BL/6 mice | 50 ppm | Dietary exposure through drinking water for 2 weeks | ↓ Alpha diversity of the microbiota | [26] |
| Heavy Metal | Arsenic | Participants in cohort study | <50 μg/L | 20-year exposure window |
Higher incidence of stroke | [27] |
| Microplastics and nanoplastics | Micro/nanoplastics | C57/B6 mice | 0.2 and 2 mg/kg | 28 days | High dose led to morphological changes along the GI including the followings: -Absence of villi -Damaged crypts ↓ Mucosa wall lining ↓ Tight junction expression. ↓ Microbial diversity and ratio of bacteria |
[15] |
| Microplastics | Polyethylene terephthalate (PET) | In vitro simulation | 0.166 g/intake | 72 h | Shift in the relative abundance of bacteria in the upper region of the colon. Specifically, ↑ Desulfobacterota and ↓ Proteobacteria over time. ↓ Viable bacterial count |
[28] |
| Microplastics | PS-MPs | Male mice | 0.1mg/day of 5 or 20 μm PS-MPs | 28 days via oral gavage | Accumulation of PS-MPs in the gut, liver, and kidney. ↑ Inflammation and lipid accumulation in the liver |
[29] |
| PAH | BaP | C57BL/6 mice | 10 mL/kg of BW | 28 days oral exposure | ↑ Inflammation in ileal segments -Altered relative abundance of fecal and mucosa associated microbiota ↓ Lactobacillus |
[12] |
| PCBs | PCB153, PCB138, and PCB180 | C57BL/6 mice | 150 µmol/kg | 2 days | ↓ Proteobacteria | [30] |
| PCBs | Prospective population based Follow up | Middle-aged and elderly women | Passive dietary exposure | 12 years of follow-up | Positive association observed between stroke risk and PCB exposure. | [31] |
| PCB | PCB 126 | Ldlr−/− mice | 1 μmol/kg of PCB 126 | 14-week atherogenic diet and exposed to PCB 126 (1 μmol/kg) at weeks 2 and 4 | ↑ Expression of TNF-α, IL-6, and interleukin IL-18 in the jejunum ↑ Tight junction proteins: Occludin and claudin in the colon ↓ Expression of PPAR-δ in the colon ↓ Abundance of Clostridiales, Bifidobacterium, Lactobacillus, Ruminococcus, and Oscillospira. ↑ Abundance of Akkermansia. ↓ Alpha diversity in cecum contents |
[32] |
| PCB | PCB153 | C57BL/6 mice | 300 μmol/kg | 1× per day for 2-days | ↑ Expression of TNF-α and IL-6 in the intestinal epithelial cells of the small intestines -Activates NF-κB pathway -Induces DNA damage |
[33] |
| Particulate matter | Urban particulate matter | C57BL/6 mice | 40 μg course particulate matter/mL | Mice were placed 4 h/day or 5 days/week for 2 weeks in inhalation chamber | ↑ Expression of TNF-α, IFN-γ, CXCL10, and IL-10 ↓ Expression of IL-5 |
[34] |
| Particulate matter | Urban particulate matter | C57BL/6 mice | 200 μg | Gastric gavage | ↑ ROS production ↑ Colonic epithelial cell death |
[35] |
| Particulate matter | Atmosphericparticulate matter | Intestinal tissue | 50–500 µg/cm2 | 1 week and 2 weeks | ↓ ZO−1 and claudin−1 expression level | [36] |
| Lungs | ||||||
| Nanoparticles | Nickel Oxide Nanoparticles | Rats | 50 and 150 cm2 for 10 min | Intratracheally instilled 1 day and 4 weeks | -Narrowed alveolar ducts and alveoli ↑ Levels of neutrophils and cytokines -Induced pulmonary microbiome dysbiosis in the acute phase |
[37] |
| Nano and microplastics | Polyethylene particles | BALB/c mice | 10 mg/kg 1× daily for 1 week | Oral administration | ↑ Percentage of Th17, Tregs, and Th2 cells ↓ Colon length ↑ Percentages of IL-4+, Foxp3+(Tregs), and IL-17 in CD4+T cells ↑ Secretion of IL-4 and IL-17 cytokines |
[13] |
| Microplastics | PS-MPs | C57BL/6 mice | 6.25 mg/kg PS-MPs | Intratracheally instilled 3× per week for 3 weeks | ↑ Expression of collagen ↑ Fibrosis with increased exposure ↑ Oxidative stress |
[38] |
| Ozone | Ozone exposure | C57BL/6 mice | 1 ppm ozone for 1 h | Inhalation chamber 1× | ↑ Barrier disruption and epithelial cell permeability | [39] |
| Ozone | Ozone exposure | C57BL/6 mice | 1 ppm for the acute model and 1.5 ppm for the chronic model. | Acute phase: 1 h Chronic phase: 2 h, 2× per week for 6 weeks |
Acute exposure induced the following: Disrupted tight junctions Desquamation of epithelial layer Chronic exposure to ozone particles remodeled the airway in mice using the following: ↑ Airspace density and diameter ↓ Number of airspaces ↓ Epithelium thickness |
[14] |
| PAH | BaP | Sprague Dawley rats |
0.01 mg/kg | Intratracheally instilled for 7 days | ↑ Neutrophil recruitment ↑ Lung inflammation |
[40] |
| PAH | Atmospheric PAHs | Human lung epithelial cell lines | Low dose | 30 days | Chronic exposure: Induced DNA damage Altered cellular homeostasis and ↑ ROS production |
[41] |
| Particulate matter | PM2.5 | C57BL/6N mice | 1.8, 5.4, and 16.2 mg/kg | Intratracheally instilled for 1 week | PM2.5 exposure led to the following: Infiltration of inflammatory cells, ↑ serum cytokine levels in the serum ↑ Lung microbiome diversity ↓ Relative abundance of proteobacteria post-exposure ↑ Number of goblet cells |
[42] |
| Particulate matter | Various | 18–64 years | Passive exposure | Average daily concentration | Exposure to air pollutants increased the risk for respiratory tract infections. |
[43] |
| Circulatory system | ||||||
| Heavy Metal | Cadmium | Cohort study | Passive exposure | Measured urinary cadmium concentration | May increase the incidence of ischemic stroke | [44] |
| Heavy Metal | Mixed metals | Ischemic stroke patients | Passive exposure | Fasting blood concentration within 48 h post-diagnosis | Higher plasma concentrations of aluminum, arsenic, and cadmium may increase the risk of ischemic stroke. |
[45] |
| Dioxin | TCDD | Primary human aortic endothelial cell | 0.1% TCDD | 24 h | ↑ Hypertension and endothelial dysfunction. | [46] |
| PAH | BaP | Sprague Dawley rats |
0.01 mg/kg | Intratracheally instilled for 7 days | ↑ Systolic and diastolic pressure and heart rate | [40] |
| PAH | BaP | Wistar rats | 20 mg/kg for 4 and 8 weeks | Intra-peritoneal. injection | ↑ Blood pressure after 8 weeks in vivo ↑ Vasoconstriction ex vivo |
[47] |
| POPs | Passive exposure | Aged 70 yrs. in Sweden. 5-year follow-up | Passive exposure | Baseline plasma samples | PCB congeners, organochlorine pesticides, and octachlorodibenzo-p-dioxin showed increased risk of developing stroke in elderly population. | [48] |
| PCBs | Various PCBs | Endothelial cells from porcine pulmonary arteries | PCB 77, PCB 153, and PCB114 | 24 h | Exposure led to the development of atherosclerosis and endothelial barrier dysfunction. ↑ Albumin flux and oxidative stress |
[49] |
BaP, benzo-a-pyrene; CXCL10, interferon gamma-induced protein 10; DNA, deoxyribonucleic acid; Foxp3, forkhead box P3; IFN-γ, interferon-gamma; IL-4, interleukin-4; IL-5, interleukin-5; IL-6, interleukin-6; IL-10, interleukin-10; IL-17, interleukin-17; Ldlr−/−, LDL receptor deficient mouse; NF-κB, nuclear factor-κB; PAH, polycyclic aromatic hydrocarbon; PCB, polychlorinated biphenyls; PET, polyethylene terephthalate; PM2.5, particulate matter ≤ 2.5 μm; PS-MP, polystyrene microplastics; POP, persistent organic pollutant; ROS, reactive oxygen species; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; Th2, T helper 2 cells; Th17, T helper 17 cells; TNF-α, tumor necrosis factor-alpha; Tregs, regulatory T cells; ZO-1, zona occludens 1. Upward and downward arrows indicate an increase or a decrease of the observed effect, respectively.