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Table 2 Review of reported effects on oxidative stress in varying skin models upon exposure to PM

From: Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

Model PM type Dose and application Exposure time Main findings Ref.
Ex vivo human skin SRM® 1649b 2 mg/cm2, topical 24 h - Lipid peroxidation. [119]
Mice, C-57 Diesel PM 4.5, 11.1 and 26.7 mg/cm2, topical 80 h - Increased DNA adduct formation. [166]
Mice, FVB/N SRM® 1650b 1 mg/time (PAH extracted), topical 12 h - Increased CYP1B1 mRNA expression. [167]
Mice, HR-1 SRM® 1650b 100 μg/mL, topical 7 d - Increased protein carbonylation and lipid peroxidation. [168]
SRM® 1650b 100 μg/mL, topical 7 d - ER stress: upregulation protein expression of CHOP and GRP78.
- Lipid peroxidation: increased expression of HNE protein.
- Mitochondrial and ER swelling.
- Increased protein carbonylation.
- Apoptosis: increased protein expression of BAX, active caspase-3, and caspase-9, and DNA breakage.
- Autophagy: increased protein expression of LC3B-II.
[123]
SRM® 1650b 100 μg/mL, topical 7 d - Increased protein carbonylation.
- Increased NOX4 protein expression.
[169]
HSE SRM® 2975 200 μg/mL, systemic 2 d repetitive exposure, 6 d total - Increased protein expression of cleaved caspase-3. [125]
HEE CAPs, PM2.5 0.5 and 2.0 μg/cm2, topical 24 and 48 h - Increased isoprostanes protein level.
- Increased HNE protein expression.
- Increased CYP1A1 protein expression.
- Increased DNA fragmentation.
[128]
CAPs, PM2.5 25 μg/mL, topical 24 and 48 h - Increased protein carbonylation. [170]
PM0.3–2.5 from Benin, West-Africa 30 μg/cm2, topical 24 h - Increased HNE protein expression.
- Increased HMOX1, metallothionein 1G and 1E, cyclin dependent kinase inhibitor 2A, and caspase 3 mRNA expression.
- Decreased BIRC5 mRNA expression.
[133]
CRM no. 28 25 mg, topical 6 h - Upregulated mRNA expression of CYP1A1, CYP1B1, and SOD2. [129]
SRM® 1975 5 mg/mL, topical 48 h - Increased level of carbonylated proteins [171]
SRM® 1648a 2.2, 8.9, and 17.9 μg/cm2, topical 24 and 48 h - Decreased AhR and increased NOTCH1 protein expression. [131]
NHDF SRM® 2787 30 μg/cm2, systemic 24 h - Autophagy: accumulation of LC3-II.
- Mitochondrial stress: deformed mitochondria.
- Increased CYP1A1 and CYP1B1 mRNA expression.
[135]
ERM-CZ100 50–400 μg/mL, systemic 3.3 h - Increased levels of intracellular ROS. [136]
The pre-conditioned medium of HaCaT treated with CRM no. 28 125 μg/mL, systemic 30 m, 48 h post-incubation - Increased levels of intracellular ROS.
- Increased number of apoptotic bodies.
[137]
SRM® 1649b 50 μg/mL, systemic 24 h - Increased intracellular ROS levels.
- Activation of AhR (XRE activity).
- Upregulation of CYP1A1 mRNA expression.
[119]
SRM® 1649b 100–400 μg/mL, systemic 24 h - Nuclear translocation of AhR.
- Increased mRNA expression of CYP1A1.
- Induced apoptosis.
[172]
NHEK Diesel PM or vapour 0.05% (v/v), systemic 20 d - Increased Nrf2 protein expression.
- Mitochondrial dysfunction: overexpression of proteins from mitochondrial complex I and IV.
[127]
SRM® 1975 5 mg/mL, systemic 1 and 24 h - Increased intracellular ROS levels.
- Increased of CYP1A1 mRNA expression.
- Nuclear translocation of AhR.
[171]
ERM-CZ120 3, 10, 30 and 100 μg/mL, systemic 24 and 48 h - Increased ROS levels after 24 h.
- Increased NOX1 and NOX2 mRNA expression after 24 h.
[173]
PM ≤1 μm from Seoul, Korea 40 μg/cm2, systemic 24 h - Increased ROS production.
- Inhibition of ROS inhibited cytokine secretion.
[121]
PM2.5 from Seoul, Korea 25 μg/mL, systemic 24 h - Top upregulated genes from transcriptomics analysis are CYP1A1 and CYP1B1. [132]
PM2.5 from Xi’an, China 50 μg/mL, systemic 24 h - Top upregulated genes from transcriptomics analysis are CYP1A1 and SOD2. [134]
Asian dust storm particles from Seoul, Korea 25 μg/mL, systemic 24 h - Increased CYP1A1, CYP1A2, and CYP1B1 mRNA expression. [139]
Diesel PM 30 and 60 μg/mL, systemic 24 h - Increased ROS production.
- Increased HMOX1 mRNA and protein expression.
- Increased Nrf2 mRNA expression.
[138]
SRM® 2786 1 mg/mL, systemic 6 h - RNA-Seq analysis: Downregulation of ER stress apoptosis-related genes such as ATF4 and CHOP. No activation of BCL2, BAX, caspase 3, and caspase 8.
- Upregulation of HMOX1, CYP1A1, CYP1B1, and NQO1.
[141]
SRM® 1650b and 2975 10 and 100 μg/mL, systemic 1 and 24 h - Increased radical production. [174]
NHEK, HaCaT, and HEK001 SRM® 1650b 50 μg/mL, systemic 72 h - Induced senescence: increased β-galactosidase activity. [124]
NHEK and HaCaT SRM® 1650b 50 μg/mL, systemic 0.5–48 h - Increased intracellular ROS levels.
- Nuclear translocation of AhR (0.5 h).
- Induced senescence: upregulation of P16INK4A and increased number of SAHF/nuclei. Decreased colony-forming ability.
- Senescence is AhR dependent.
- Transcriptional regulation of P16INK4A correlates with DNA demethylation: lower methylation of the P16INK4A promoter region.
[124]
NHDF and HaCaT SRM® 1650b 50 μg/mL, systemic 30 m and 24 h - Increased levels of lipid peroxidation and protein carbonylation after 24 h.
- Increased levels of superoxide anion, hydroxyl radicals, and intracellular ROS (30 m).
- Increased intracellular and mitochondrial calcium levels after 24 h.
- Increased protein expression of CHOP, GRP78, active caspase-3, caspase-9, PARP, and BAX after 24 h.
- Downregulated protein expression of Bcl-1 and Mcl-1 after 24 h.
- Increased mitochondrial permeability after 24 h.
- Reduced ATP levels after 24 h.
- Increased DNA degradation and the number of apoptotic bodies after 24 h.
[175]
HaCaT PM2.5 from Bangkok, Thailand 100 μg/mL, systemic 30 m - Increased intracellular ROS levels. [176]
PM2.5 from Taoyuan, China 25, 50, 100 and 200 μg/mL, systemic 24 h - Increased intracellular ROS levels.
- Decreased SOD activity.
- Increased lipid peroxidation: accumulation of MDA protein.
- Induced formation of apoptotic bodies.
- Induced protein expression of cytochrome c, active caspase-3, and caspase-9.
- DNA damage.
[177]
SRM® 1648a 50–200 ppm, systemic 24 and 48 h - Increased ROS production. [130]
SRM® 1648a SRM® 1649b 50 μg/cm2, systemic 24 h - Nuclear translocation of AhR.
- Increased CYP1A1 and CYP1B1 mRNA expression.
[178]
SRM® 1649b 50 μg/cm2, systemic 1 h - Increased levels of intracellular ROS. [142]
SRM® 1649b 50 μg/cm2, systemic 2 and 24 h - Increased cellular and mitochondrial ROS levels after 2 h.
- Increased HMOX1 protein expression after 24 h.
[143]
SRM® 1649b 25 and 50 μg/cm2, systemic 4 and 24 h - Increased ROS production.
- Increased NOX activity.
[122]
SRM® 1649b 25–100 μg/cm2, systemic 4 and 24 h - Increased NOX2 protein expression.
- Increased ROS production.
[179]
SRM® 1649b 25 μg/mL, systemic 2 and 24 h - Increased ROS production. [180]
SRM® 1649b 50 μg/cm2, systemic 1 and 4 h - Increased ROS production.
- Increased NOX2 activity.
[181]
SRM® 1649b 25 and 50 μg/cm2, systemic 4 and 24 h - Increased ROS production
- Increased NOX activity.
[122]
SRM® 1649b 100–400 μg/mL, systemic 24 h - Nuclear translocation of AhR.
- Increased CYP1A1 mRNA expression.
- Induced apoptosis.
[172]
SRM® 1650b 50 μg/mL, systemic 24 h - Increased cellular and mitochondrial ROS levels and mitochondrial stress.
- Increased lipid peroxidation and protein carbonylation.
- Increased cleaved caspase-3 and BAX and decreased Bcl-2 protein expression.
- Induced DNA damage.
- Increased number of apoptotic bodies.
[182]
SRM® 1650b 50 μg/mL, systemic 1 and 24 h - Increased intracellular ROS and superoxide anion levels.
- Increased levels of protein carbonylation and lipid peroxidation after 24 h.
- Induced DNA damage and apoptotic body formation.
- Increased mitochondrial permeability after 24 h.
- Increased BAX, active caspase-3, and PARP and decreased Bcl-2 protein expression.
[183]
SRM® 1650b 50 μg/mL, systemic 24 h - Increased intracellular ROS and calcium levels.
- Increased levels of lipid peroxidation and protein carbonylation.
- DNA damage.
- Increased mitochondrial ROS, calcium, and permeability.
- Apoptosis: increased protein expression of ATF6, GRP78, p-IRE1, BAX, and active caspase-3 and caspase-9. Decreased protein expression of Bcl2. Increased number of apoptotic bodies.
- Autophagy: autophagic lysosomes. Increased protein expression of LC3B-II and beclin-1.
[168]
SRM® 1650b 50 μg/mL, systemic 24 h - Increased intracellular ROS and superoxide levels.
- Induced NOX activity.
- Increased intracellular calcium levels and mitochondrial membrane permeability.
- Induced lipid peroxidation and protein carbonylation.
- DNA damage.
- Increased number of apoptotic bodies.
[184]
SRM® 1650b 50 μg/mL, systemic 1, 4, 8, 12, and 24 h - Increased intracellular ROS.
- Increased levels of intracellular calcium.
- ER stress: Increased protein expression of CHOP, GRP78, and p-PERK.
- Increased mitochondrial permeability.
- DNA damage.
- Increased lipid peroxidation and protein carbonylation.
- Apoptosis: Increased protein expression of BAX, DNA breakage, apoptotic body formation, and increased expression of active caspase-3 and caspase-9.
- Autophagy: Increased protein expression of LC3B-II.
[123]
SRM® 1650b 50 μg/mL, systemic 30 m, 1 h, and 24 h - Increased ROS production.
- Increased levels of intracellular calcium.
- Induced senescence.
[185]
SRM® 1650b 50 μg/mL, systemic 24 h - Increased ROS production.
- Increased lipid peroxidation.
- Increased number of apoptotic bodies.
[186]
SRM® 1650b and 2975 10 and 100 μg/mL, systemic 1 and 24 h - No changes in radical production. [174]
SRM® 2975 100 and 200 μg/mL, systemic 24 h - Increased protein expression of cleaved caspase-3 and PARP.
- Increased protein expression of BAX and p53.
[125]
CRM no. 28 125 μg/mL, systemic 30 m, 24 h post-incubation - Increased levels of intracellular ROS. [137]
ERM-CZ120 100 μg/mL, systemic 30 m - Increased intracellular ROS production. [126]
ERM-CZ120 25–100 μg/mL, systemic 3 and 24 h - Increased CYP1A1 protein expression.
- Decreased AhR protein expression.
- Increased LC3-II and p62 protein expression.
[187]
CAPs, PM2.5 5–25 μg/mL, systemic 1, 3, 6, and 24 h - Increased HNE protein adduct formation.
- Increased nuclear translocation of Nrf2.
- No changes in GPX, GR, and NPQO1 mRNA expression.
[145]
  1. Abbreviations: h, hour; d, day; m, minute; HSE, human skin equivalent; HEE, human epidermal equivalent; NHEK, normal human epidermal keratinocyte; SRM, standard reference material; PM, particulate matter; CAP, concentrated ambient particles; ppm, parts per million; CRM, certified reference material; ROS, reactive oxygen species; PARP, poly (ADP-ribose) polymerase; Nrf2, nuclear factor erythroid 2-related factor 2; AhR, aryl hydrocarbon receptor; LC3-II, light-chain 3 II; BIRC5, baculoviral IAP repeat containing 5; NQO1, NAD(P) H quinone dehydrogenase 1; HMOX1, heme oxygenase 1; NOX, NADPH oxygenase; HNE, 4-hydroxy-2-nonenal; ER, endoplasmic reticulum; CYP1A1, cytochrome P450 family 1 subfamily A member 1