# Oxidative and Inflammatory Damage by Environmental Polyethylene Microplastics in Caco‐2 Cells Is Prevented by Polyphenol‐Rich Limoncella Apple Extract

**Authors:** Stefania Lama, Massimo Venditti, Alessandra Biasi, Carmen Lenti, Hana Najahi, Mohamed Banni, Gian Carlo Tenore, Ettore Novellino, Paola Stiuso

PMC · DOI: 10.1155/omcl/3136395 · Oxidative Medicine and Cellular Longevity · 2026-02-24

## TL;DR

This study shows that polyethylene microplastics harm intestinal cells, but a polyphenol-rich apple extract can protect against this damage.

## Contribution

The study demonstrates the protective effect of Limoncella apple extract against microplastic-induced cellular damage for the first time.

## Key findings

- Polyethylene microplastics reduced cell viability and increased oxidative stress in intestinal cells.
- Limoncella apple extract counteracted the harmful effects of microplastics by reducing inflammation and oxidative damage.
- The extract preserved cell structure and function, suggesting potential as a nutraceutical intervention.

## Abstract

Humans are constantly exposed to environmental microplastic (MP) particles, which can be absorbed through the gut and exert adverse health effects. This study aimed to investigate the harmful effects of environmental polyethylene MPs (PE, 2.6 μm) on differentiated Caco‐2 (D‐Caco‐2) intestinal epithelial cells and to assess the protective potential of Limoncella apple polyphenol extract (LAPE).

D‐Caco‐2 cells were exposed to PE, LAPE, or their combination. Cell viability and lipid peroxidation were evaluated using MTT and TBARS assays, respectively. The organization of F‐actin and alkaline phosphatase proteins was evaluated by immunofluorescence, whereas occludin and NF‐κB were evaluated by Western blot analysis.

PE reduced D‐Caco‐2 viability and impaired cell differentiation by increasing lipid peroxidation. In addition, PE destructured F‐actin organization and altered the expression of occludin, a tight‐junction protein.

Our findings show that PE increases oxidative stress, triggering epithelial–mesenchymal transition and dedifferentiation in Caco‐2 cells. Interestingly, LAPE, owing to its antioxidant and anti‐inflammatory properties, counteracted the harmful effects of PE, suggesting its potential as a nutraceutical strategy to prevent MP‐induced damage in the gastrointestinal (GI) tract.

## Linked entities

- **Proteins:** Act5C (Actin 5C), si:ch73-61d6.3 (uncharacterized si:ch73-61d6.3), NFKB1 (nuclear factor kappa B subunit 1)

## Full-text entities

- **Genes:** MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, OCLN (occludin) [NCBI Gene 100506658] {aka BLCPMG, PPP1R115, PTORCH1}, SLC11A2 (solute carrier family 11 member 2) [NCBI Gene 4891] {aka AHMIO1, DCT1, DMT1, NRAMP2}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}
- **Diseases:** colorectal adenocarcinoma (MESH:D003110), intestinal dysfunction (MESH:D007410), liver injury (MESH:D017093), inflammatory bowel disease (MESH:D015212), cytotoxic (MESH:D064420), colitis (MESH:D003092), cancer (MESH:D009369), Inflammatory (MESH:D007249)
- **Chemicals:** MP (MESH:D000080545), DAPI (MESH:C007293), polyethylene (MESH:D020959), chlorogenic acid (MESH:D002726), ethanol (MESH:D000431), poly (ethylene terephthalate) (MESH:D011093), TBARS (MESH:D017392), PVDF (MESH:C024865), acetic acid (MESH:D019342), SDS (MESH:D012967), Tween-20 (MESH:D011136), alpha-MEM (MESH:C420642), resveratrol (MESH:D000077185), polypropylene (MESH:D011126), thiobarbituric acid (MESH:C029684), lactulose (MESH:D007792), catechin (MESH:D002392), Lipid (MESH:D008055), L-glutamine (MESH:D005973), mannitol (MESH:D008353), PS (MESH:D011137), free radicals (MESH:D005609), Polyphenol (MESH:D059808), water (MESH:D014867), Alexa Fluor 488 (MESH:C000711379), polyacrylamide (MESH:C016679), DNBS (MESH:C007488), oil (MESH:D009821), streptomycin (MESH:D013307), MTT (MESH:C070243), quercetin (MESH:D011794), MDA (MESH:D015104), amino acids (MESH:D000596), hydroxycinnamic acids (MESH:D003373), penicillin (MESH:D010406), NaCl (MESH:D012965), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MESH:C022616), sodium deoxycholate (MESH:D003840), curcumin (MESH:D003474), epigallocatechin-3-gallate (MESH:C045651), D (MESH:D003903), flavan-3-ols (MESH:C404987), metal (MESH:D008670), LAPE (-), H2O2 (MESH:D006861)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Malus domestica (apple, species) [taxon 3750]
- **Cell lines:** D — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_IZ09), DH — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_2483), Caco-2 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0025)

## Full text

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## References

29 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932969/full.md

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Source: https://tomesphere.com/paper/PMC12932969