Table 7 Experimental studies (2018 and newer) observing induction of oxidative stress (see Results, Induction of oxidative stress and potential consequences for immune health section); modulation of NK-cell activity (see Results, Modulation of NK cell activity section) and investigation of immunoenhancement (see Results, Immunoenhancement section)
From: Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS)
PFAS | Species | Experimental design and doses (mg/kg/day) | Effect | Significant effect level (mg/kg/d) / serum or tissue concentration | Reference |
|---|---|---|---|---|---|
Oxidative stress | |||||
 PFOS | Human lymphocytes (healthy donors) | 75-500 μM PFOS for 12 h (2, 4, 6, 8, 10, 12 h) | ↓ cell viability ↑ ROS, lipid peroxidation, GSH depletion, apoptosis ↑ damage to cell organelles (mitochondria, lysosomes) | IC50: 163.5 μM (12 h) ROS: 75 μM (4 h) | [172] |
 PFOS, PFOA | C57BL/6 Mice pups, Nrf2−/− and wild-type astrocytes | 75-600 μM PFOS for 24 h 400-1000 μM PFOA for 24 h | nrf2−/− astrocytes: ↑ ROS, lipid peroxidation, apoptosis ↓ GSH/GSSG ratio ultrastructural alterations of mitochondria | 600 μM PFOS, 800 μM PFOA | [173] |
 PFOS, PFOA | Adult male C57BL/6 J mice, primary hepatocytes | 0, 0.01, 0.1, 0.5, 1 mM PFOS for 24 h 0, 0.01, 0.1, 0.5, 1 mM PFOA for 24 h | ↑ ROS ↑ SOD ↑ GSH ↓ CAT | 1 mM PFOS, 0.5 mM PFOA 0.5 mM PFOS, 0.5 mM PFOA 0.1 mM PFOS, 0.5 mM PFOA 0.01 mM PFOS, 0.01 mM PFOA | [174] |
 PFOS | ♂ mice (strain not specified), alone or in combination with 100 mg/kg/day naringin, n = 4 per group | 0 or 10, intragastrically for 21 days | ↑ malondialdehyde (MDA), hydrogen peroxide (H2O2) ↓ glutathione (GSH) content; superoxide dismutase (SOD) activity; NRF2 protein; gene expression of Sod, Cat, Ho-1 ↑ liver enzymes (ALT, AST); liver weight ↑ protein levels of p53 and BAX; activity of caspase-3 ↓ protein level of BCL-2 ↑ TNF-α; IL-6 | 10 | [175] |
 PFOA, PFPA, PFDA | Isolated erythrocytes | 10-100 μmol/L for 3 hours | ↑ malondialdehyde (MDA) ↓ glutathione (GSH) content | 100 μmol/L 10 (PFOA and PFDA) 100 μmol/L (PFPA) | [176] |
 PFNA | Pheo-chromocytoma-12 (PC12) cells | 0, 20, 50, 100 μM for 24 h | ↑ MDA content ↓ total antioxidant capacity; glutathione peroxidase activity | 100 μM | [177] |
NK-cell activity | |||||
 PFOA | ♀ Kunning mice, 4 dose groups, n = 6 per group | 0, 2.5, 5, 10 from pregnancy day (PD) 1 to PD 13 | ↓ placental weight Interstitial oedema of placenta blood sinusoids area shrunken ↓ number of NK cells ↑ levels of BAX and cleaved caspase 3 proteins (apoptosis induction) | 5 and 10 2.5 – 10 5 2.5 | [178] |
Immunoenhancement | |||||
 PFOS/PFOA | C57BL/6 M mice | 0, 7, 70 mg/kg TAD PFAS in normal or OVA-induced asthmatic mice | PFOS and PFOA ↑lung inflammation, serum IgE, IL-4 and IL-13 in asthmatic mice ↑ IL-4 and IL-13 in the BALF in asthmatic mice PFOS alone: ↓serum IFNγ; ↑serum IL-13 and IL-4; ↑ IL-4 in the BALF | 7 and/or 70 70 7 and 70 | [184] |
 PFOA | BALB/c M mice | 0, 10, 50 and 100 pg PFOA, intratracheal administration, in OVA sensitised mice | ↑airway hyperresponsiveness and serum IL-4. ↓ serum IFNγ. ↓GR in the lung. | 100 pg | [185] |
 PFOS, PFOA, PFHxS | In vitro, mouse bone marrow derived and human mast cells (HMC-1) | 30 μM for 1 hr | ↑ degranulation ↑ Ca2+ influx ↑LTC4 and PGD2 (lipid mediators) | PFOA and PFOS PFOA and PFOS PFHxS, PFOA and PFOS | [186] |
 PFOS | BALB/c F mice | 10 and 100 μg/kg bw/day for 1 week, intranasal administration | ↓ allergic asthma responses to dust mite, proposed due to the binding and inactivation of the dust mite antigen Der p1 ↓ P. aeruginosa infection, with reduced lung and blood pro-inflammatory cytokines | PFOS | [187] |