Table 3.

The effects of DEP on inflammation, oxidative stress, blood parameters, and hemostatic changes: Evidence from in vivo studies.

Models	Exposure/Method	Results			Interpretation	References
		Inflammation and Oxidative Stress	Coagulation and Adhesion Molecules	Blood Parameters
Male Wistar rats 175–275 g	Intratracheal instillation of # DEP (SRM 2975) 0.5 mg/animal # Black carbon (BC) 0.5 mg/animal # DQ12 quartz microparticles 0.125 mg/animal Evaluation at 2, 6, and 24 h after exposure	BALF # DEP: ↑ PMN influx ↑ IL-6 ↔ TNF-α, CRP # BC: ↑↑ PMN influx ↑ IL-6 ↔ TNF-α ↑ CRP # DQ12 quarts: ↑↑ PMN influx ↔ IL-6 ↔ TNF-α ↑ CRP	Plasma # DEP ↓ thrombotic occlusion time ↑ PAI-1 ↓ tPA ↓ tPA:PAI-1 ratio ↑ platelet-monocyte aggregation # BC, DQ12 quarts: ↔ thrombotic occlusion time ↑ PAI-1 ↓ tPA ↓ tPA:PAI-1 ratio ↔ platelet-monocyte aggregation		Pulmonary exposure of DEP caused lung inflammation and accelerated arterial thrombus formation through increasing platelet activation, and impaired fibrinolytic function, while IV injection of DEP promoted thrombosis, without evidence of pulmonary inflammatory response.	[50]
	Intravenous injection (IV) of DEP or BC 0.5 mg/kg Evaluation at 2, 6, and 24 h after exposure	# DEP: ↔ inflammatory cells in BALF ↔ BALF TNF-α, CRP ↔ plasma TNF-α, CRP, IL-6 # BC: ↔ inflammatory cells in BALF ↔ BALF TNF-α, CRP ↔ plasma TNF-α, IL-6 ↑ plasma CRP	# DEP: ↓ thrombotic occlusion time ↑ PAI-1 ↓ tPA ↓ tPA:PAI-1 ratio ↑ platelet-monocyte aggregation # BC: ↓ thrombotic occlusion time ↑ PAI-1 ↓ tPA ↓ tPA:PAI-1 ratio ↔ platelet-monocyte aggregation
Hamsters (Pfd Gold) 100–110 g	Intratracheal instillation of DEP (SRM 1650) 5, 50, 500 µg/animal Evaluate at 1 h after PM exposure	BALF ↑ PMN influx ↑ protein, histamine, in a dose-dependent manner ↔ LDH	↑ venous thrombus formation, dose-dependent manner ↑ arterial thrombus formation ↓ PFA100 closure time	↔ platelet	DEP enhanced lung inflammation, platelet activation, and peripheral vascular thrombosis.	[46]
Hamsters 100–110 g	Intratracheal instillation of DEP (SRM 1650) 50 µg/animal Evaluation at 1, 6, 24 h after exposure	↑ BALF PMN influx, time-dependent manner ↑ BALF histamine ↑ plasma histamine	↑ thrombus formation ↓ PFA100 closure time	↔ platelet	Histamine involved in the process of DEP-induced lung inflammation and platelet activation led to a prothrombotic state.	[67]
Hamsters (Pfd Gold) 100–110 g	Intratracheal instillation of # DEP (SRM 1650) 50 µg/animal # Polystyrene particles 400 nm 500 µg/animal Evaluation at 24 h after exposure	# DEP: ↑↑ PMN influx # Polystyrene particles: ↑ PMN influx # DEP and polystyrene particles: ↑ histamine in BALF and plasma	# DEP and polystyrene particles: ↑ thrombus formation ↔ VWF		DEP triggered mast cell degranulation by histamine release and enhanced thrombus formation.	[68]
Male TO mice (HsdOla: TO) 10–12 wk-old DM vs. non-DM mice (Intraperitoneal injection of streptozotocin 200 mg/kg to induced Type 1 DM)	Intratracheal instillation of DEP (SRM 2975) 0.4 mg/kg Evaluation of plasma at 24 h after exposure	# Non-DM mice: ↔ CRP ↔ 8-isoprostane # DM mice: ↑ CRP ↑ 8-isoprostane	# Non-DM mice: ↔ thrombotic occlusion time ↑ PAI-1 ↔ VWF # DM mice: ↓ thrombotic occlusion time ↑↑ PAI-1 ↑ VWF	# Non-DM mice: ↔ WBC ↔ platelet # DM mice: ↑ WBC ↓ platelet	Particulate air pollution activated systemic inflammation, oxidative stress, hypoxemia, hepatotoxicity, coagulation, and interfered with fibrinolytic function, resulting in a procoagulant state. These results were more enhanced in DM mice.	[49]
Male TO mice (HsdOla: TO) 30–35 g	Intratracheal instillation of DEP (SRM 2975) 15 µg/animal on day 0, 2, 4, 6 Evaluation at 48 h after the last exposure	BALF: ↑ PMN influx ↑ macrophages ↑ TNF-α ↔ IL-6 Plasma: ↑ CRP ↑ TNF-α ↔ IL-6	↓ thrombotic occlusion time ↑ D-dimer ↑ PAI-1 ↔ VWF	↓ platelet	Repeated DEP exposure activated systemic inflammation, thrombotic events, and platelet aggregation.	[66]
Male TO mice (HsdOla: TO) 30–35 g	Intratracheal instillation of DEP (SRM 2975) 30 µg/animal Evaluation at 4, and 18 h after exposure	BALF ↑↑ PMN, macrophages ↑↑ IL-6 ↑↑ total protein ↓ superoxide dismutase	↑ IL-6 ↓ thrombotic occlusion time	↑ WBC ↓ platelet	DEP exposure-induced pulmonary inflammation, and enhanced platelet aggregation and thrombosis.	[48]
Male TO mice	Intratracheal instillation of DEP 1 mg/kg Evaluation at 24 h after exposure	↑ TNF-α ↑ IL-1β ↓ superoxide dismutase ↑ glutathione reductase	↓ thrombotic occlusion time	↑ Hb, Hct, RBC, WBC, platelet	DEP exposure activated inflammation, oxidative stress, and promoted thrombosis.	[47]

BALF: bronchoalveolar lavage fluid, BC: black carbon, CRP: C-reactive protein, DEP: diesel exhaust particles, DM: diabetes mellitus, h: hours, Hb: hemoglobin, Hct: hematocrit, IL-1β: interleukin-1beta, IL-6: interleukin-6, IV: intravenous injection, PAI-1: plasminogen activator inhibitor-1, PFA100: platelet function analyzer-100, PM: particulate matter, PMN: polymorphonuclear cells, RBC: red blood cells, SRM: standard reference material, TNF-α: tumor necrotic factor-α, TO mice: Tuck-Ordinary mice, tPA: tissue plasminogen activator, VWF: von Willebrand factor, WBC: white blood cells, wk: week.