. 2022 Jul 19;19(14):8771. doi: 10.3390/ijerph19148771

Table 6.

The effect of pharmacological interventions on inflammation, oxidative stress, blood parameters, and hemostatic changes under particulate matter condition: Evidence from in vivo and clinical studies.

Models	Exposure	Intervention	Results			Interpretation	References
Models	Exposure	Intervention	Inflammation and Oxidative Stress	Coagulation and Adhesion Molecules	Blood Parameters	Interpretation	References
Male mice (C57BL/6) 8–12 wk-old	Intratracheal instillation of urban PM (SRM1649a) 200 µg/animal Evaluated at 24 h after exposure	Pretreated with # Vesicular monoamine transporter: Reserpine (chemical sympathectomy) # Propranolol 3 mg/kg IP q 8 h for 48 h	↓ NE in BALF, BAT, adrenal gland, lung ↓ IL-6 in BALF ↓ IL-6 in BALF	↓ plasma TAT complexes ↓ plasma TAT complexes ↑ thrombotic occlusion time		Blocking of the sympathetic nervous system and β₂AR signaling alleviated IL-6 release, lung inflammation, and reduced thrombosis.	[44]
Male mice C57Bl6/j 8–12 wk-old	Inhalation exposure to concentrated ambient particles (CAPs) from downtown Chicago for 8 h/d for 3 d Evaluated at 24 h after exposure	Pretreated with TNF-α inhibitor, Etanercept 10 mg/kg IP. 3 days before, and on the first day of exposure to CAPs		↓ PAI-1/18s mRNA		Blocking TNF-α could promote normal fibrinolytic function, but not alter the PM-induced clotting formation.	[56]
Male mice C57Bl6/j 8–12 wk-old	Intratracheal instillation of urban PM (SRM1649a) 200 µg/animal Evaluate at 24 h after exposure	Pretreated with TNF-α inhibitor, Etanercept 10 mg/kg IP. 3 days before, and on the first day of exposure to PM		↔ Bleeding time ↔ PT, ↔ PTT ↔ TAT complexes ↓ PAI-1/18s mRNA ↓ PAI-1 in BALF			[56]
Hamsters 100–110 g	Intratracheal instillation of DEP (SRM 1650) 50 µg/animal For 1, 3, 6, 24 h after exposure	Pretreated with Antihistamine: Diphenhydramine IP 30 mg/kg for 1 h	BALF ↓ cell count, PMN influx ↓ histamine plasma ↓ histamine	↓ thrombus formation ↑ PFA100 closure time		Pretreatment with diphenhydramine reduced the effects of DEP-induced pulmonary inflammation and peripheral thrombosis.	[67]
Hamsters (Pfd Gold) 100–110 g	Intratracheal instillation of DEP (SRM 1650) 50 µg/animal Evaluation at 24 h after exposure	# Pretreated dexamethasone IP 5 mg/kg # Pretreated dexamethasone IT 0.1 or 0.5 mg/kg # Pretreated Sodium Cromoglycate IP 40 mg/kg for 1 h	# Dexamethasone IP: ↓ BALF cell count, PMN ↓ BALF and plasma histamine # Dexamethasone IT (0.5 mg/kg): ↓ BALF cell count, PMN ↓ BALF histamine ↔ plasma histamine # Sodium cromoglycate: ↓ BALF cell count, PMN ↓ BALF and plasma histamine	# Dexamethasone IP: ↓ thrombus formation # Dexamethasone IT (0.5 mg/kg): ↓ thrombus formation # Sodium cromoglycate: ↑ PFA100 closure time		Dexamethasone prevented PM-induced lung inflammation, histamine release, and thrombosis. Anti-inflammatory pretreatment also helped prevent PM-induced histamine release and reduced the prothrombotic state.	[68]
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	Pretreated with Curcumin (200 µl) oral gavage for 1 h	BALF: ↓ PMN, macrophages ↓ TNF-α ↔ IL-6 Plasma: ↓ CRP ↓ TNF-α ↔ IL-6	↑ thrombotic occlusion time ↓ D-dimer ↓ PAI-1 ↔ VWF	↑ Platelet	Curcumin pretreatment prevented DEP-induced inflammation and promoted fibrinolytic activity, which diminished the prothrombotic state.	[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	Pretreated with anti-inflammatory agent: Thymoquinone IP 6 mg/kg for 1 and 24 h	BALF ↓ PMN, macrophages ↓ IL-6 ↓ total protein Plasma ↓ IL-6 ↑ superoxide dismutase	↑ thrombotic occlusion time	↓ WBC ↑ Platelets	Thymoquinone pretreatment significantly prevented DEP-induced inflammatory response, oxidative stress, and thrombosis.	[48]
Male TO mice	Intratracheal instillation of DEP 1 mg/kg Evaluation at 24 h after exposure	Emodin (antioxidant/anti-inflammation) IP 4 mg/kg twice, 1 h before, and 7 h after exposure	↓ TNF-α ↓ IL-1β ↑ superoxide dismutase ↓ glutathione reductase	↑ thrombotic occlusion time	↓ Hb, Hct, RBC ↓ WBC	Administration of antioxidants prevented DEP-induced inflammatory response, oxidative stress, and thrombotic complications.	[47]
DM type II patients (N = 30) Mean age 56.5 y	Acute exposure to ambient PM in Rochester, NY, USA Evaluated the PM level at 1, 12, 24, 48, 96 h	8 wk sequential therapy with # ASA 81 mg/d for 7 d # Fish oil 4 g/d for 28 d # Combined for 7 d		# ASA, and/or fish oil: ↔ TBXB2 ↔ ADP-, and collagen-induced platelet aggregation		ASA/fish oil blunted the effect of pollution on platelet function and TBXB2.	[78]

ADP: adenosine diphosphate, BAL: bronchoalveolar lavage, BALF: bronchoalveolar lavage fluid, BAT: brown adipose tissue, β₂AR: adrenergic receptor beta-2, CAPs: concentrated ambient particles, CRP: C-reactive protein, d: days, DEP: diesel exhaust particles, DM: diabetes mellitus, h: hours, Hb: hemoglobin, Hct: hematocrit, IL-1β: interleukin-1β, IL-6: interleukin-6, IL-10: interleukin-10, IL-12: interleukin-12, IFN-γ: interferon-γ, IP: intraperitoneal injection, IT: intratracheally instillation, MCP-1: monocyte chemoattractant protein-1, mRNA: messenger ribonucleic acid, NE: norepinephrine, PAI-1: plasminogen activator inhibitor-1, PFA100: platelet function analyzer-100, PM: particulate matter, PM₁₀: particulate matter in diameter <10 µm, PMN: polymorphonuclear cells, PT: prothrombin time, PTT: partial thromboplastin time, RBC: red blood cells, SRM: standard reference material, TAT: thrombin-antithrombin complexes, TBXB2: thromboxane B2, TF: tissue factor, TNF-α: tumor necrotic factor-α, TO mice: Tuck-Ordinary mice, VWF: von Willebrand factor, WBC: white blood cells, wk: weeks, WT mice: wide type mice, y: years.