# Brevetoxin PbTx2 Modulates Oxidative Stress and Inflammatory Response in an In Vitro Human Immune Cell Line

**Authors:** Ambbar Aballay-González, Claudia Melo, Alejandra Rivera, Miquel Martorell, Viviana Ulloa, Juan José Gallardo-Rodriguez, Allisson Astuya-Villalón

PMC · DOI: 10.3390/toxics14030238 · Toxics · 2026-03-10

## TL;DR

This study shows that brevetoxin PbTx2 affects immune cell function by altering oxidative stress and inflammation in human cells, even at non-lethal doses.

## Contribution

The study reveals new evidence that sublethal brevetoxin exposure modulates immune and oxidative pathways in human immune cells.

## Key findings

- PbTx-2 exposure altered catalase, glutathione reductase, IL-8, IL-1β, and TNF-α expression in THP-1 cells.
- Catalase and Cu/Zn-superoxide dismutase activity decreased after 8 h of PbTx-2 exposure.
- Sublethal PbTx-2 concentrations modulate redox and inflammatory pathways without affecting cell viability.

## Abstract

Brevetoxins (PbTx) exert detrimental effects on marine organisms and humans, mainly through alterations in immune cell function. This study evaluated the immunotoxic potential of sublethal concentrations of PbTx-2 using the THP-1 human monocyte cell line as an in vitro model. Cell viability assessed by the MTT assay revealed an IC50 of 8.99 µM at 24 h, while exposures to 2.8 and 5.6 µM for 4 and 8 h did not affect viability. Immune and oxidative responses were examined through antioxidant activity and transcript expression by qPCR. PbTx-2 exposure altered the expression of catalase, glutathione reductase, interleukin IL-8, IL-1β, and TNF-α. Although reactive oxygen species (ROS) levels remained unchanged, catalase activity and Cu/Zn-superoxide dismutase activity decreased after 8 h. These results indicate that PbTx-2 modulates redox and inflammatory pathways in THP-1 cells, even under non-cytotoxic conditions. The observed sublethal effects suggest potential immunomodulatory consequences of brevetoxin exposure. More studies are needed to determine whether chronic low-level exposure to brevetoxins could contribute to immune dysfunction or inflammatory pathologies in humans and marine mammals.

## Linked entities

- **Proteins:** Cat (Catalase), GR (glutathione reductase), Sod1 (Superoxide dismutase 1)
- **Chemicals:** brevetoxin PbTx2 (PubChem CID 2432), PbTx-2 (PubChem CID 2432)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, EIF2B2 (eukaryotic translation initiation factor 2B subunit beta) [NCBI Gene 8892] {aka EIF-2Bbeta, EIF2B, EIF2Bbeta, VWM2}, GSR (glutathione-disulfide reductase) [NCBI Gene 2936] {aka CNSHA10, GR, GSRD, HEL-75, HEL-S-122m}, CAT (catalase) [NCBI Gene 847], TXN (thioredoxin) [NCBI Gene 7295] {aka TRDX, TRX, TRX1, TXN1, Trx80}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, IL9 (interleukin 9) [NCBI Gene 3578] {aka HP40, IL-9, P40}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, NAIP (NLR family apoptosis inhibitory protein) [NCBI Gene 4671] {aka BIRC1, NLRB1, psiNAIP}, IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}, IL16 (interleukin 16) [NCBI Gene 3603] {aka LCF, NIL16, PRIL16, prIL-16}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}
- **Diseases:** gastrointestinal and neurologic symptoms (MESH:D012817), tissue injury (MESH:D017695), dry cough (MESH:D003371), asthma (MESH:D001249), Inflammatory (MESH:D007249), injury to (MESH:D014947), myeloma (MESH:D009101), pulmonary inflammation (MESH:D011014), monocytic human leukemia (MESH:D007951), neurotoxic (MESH:D020258), immune dysfunction (MESH:D007154), cytotoxic (MESH:D064420), leukemic T (MESH:D001260), chronic obstructive pulmonary disease (MESH:D029424)
- **Chemicals:** 2',7'-dichlorofluorescein diacetate (MESH:C029569), ROS (MESH:D017382), sodium (MESH:D012964), GSSG (MESH:D019803), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MESH:C022616), GSH (MESH:D005978), cysteine (MESH:D003545), PBS (MESH:D007854), H2O2 (MESH:D006861), penicillin (MESH:D010406), dimethyl sulfoxide (MESH:D004121), methanol (MESH:D000432), CO2 (MESH:D002245), LPS (MESH:D008070), MOPS (MESH:C008550), MESNA (MESH:D015080), glucose (MESH:D005947), MTT (MESH:C070243), water (MESH:D014867), Brevetoxin-2 (MESH:C546611), agarose (MESH:D012685), RPMI 1640 medium (-), H2DCFDA (MESH:C110400), streptomycin (MESH:D013307), superoxide (MESH:D013481), thiol (MESH:D013438), L-glutamine (MESH:D005973), peroxide (MESH:D010545), PbTx-2 (MESH:C051732), brevetoxin B (MESH:C043466), formazan (MESH:D005562), Brevetoxin (MESH:C053342), lipid (MESH:D008055), amphotericin B (MESH:D000666)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Trachemys scripta (pond slider, species) [taxon 34903], Karenia brevis (species) [taxon 156230], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006), PbTx-2 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_A628), Jurkat E-6 — Homo sapiens (Human), Childhood T acute lymphoblastic leukemia, Cancer cell line (CVCL_0367), MH-S — Labeo rohita (Indian major carp), Spontaneously immortalized cell line (CVCL_A8VR), U-937 — Homo sapiens (Human), Adult acute monocytic leukemia, Cancer cell line (CVCL_0007), Jurkat — Homo sapiens (Human), Childhood T acute lymphoblastic leukemia, Cancer cell line (CVCL_0065), SP2/O — Mus musculus (Mouse), Mouse multiple myeloma, Cancer cell line (CVCL_2199), CHO-K1-BH4 — Cricetulus griseus (Chinese hamster), Spontaneously immortalized cell line (CVCL_Y502)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC13030196/full.md

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13030196/full.md

## References

55 references — full list in the complete paper: https://tomesphere.com/paper/PMC13030196/full.md

---
Source: https://tomesphere.com/paper/PMC13030196