# Cytoarchitectural modifications and antiinflammatory strategies in tendinopathy recovery

**Authors:** Marta Ramos-Barbero, Eva E. Rufino-Palomares, Sergio Serrano-Carmona, Cristina E. Trenzado, Khalida Mokhtari, José Antonio Lupiáñez, Amalia Pérez-Jiménez

PMC · DOI: 10.1371/journal.pone.0335977 · 2025-11-03

## TL;DR

This study explores how combining a specific therapy with nutritional supplements can improve recovery from tendon injuries, particularly in a rat model of Achilles tendinitis.

## Contribution

The study introduces a novel combination of percutaneous intratissue electrolysis and nutritional supplementation for treating tendinopathy.

## Key findings

- Combining EPI with nutritional supplements significantly improved tendon recovery compared to EPI alone.
- Hydroxytyrosol showed the most potent anti-inflammatory effects among the tested compounds.
- Nutritional supplementation may serve as a non-invasive alternative when EPI is not possible.

## Abstract

Tendinopathies (TPs) are complex conditions marked by inflammation, pain, and impaired function, often due to tendon overuse. Achilles tendinitis, a prevalent TP, affects both athletes and the general population. Despite available treatments, effective tissue regeneration remains elusive. This study investigates the molecular cytoarchitecture and protein expression in TP-related inflammation and evaluates the therapeutic potential of hydroxytyrosol (HT), maslinic acid (MA), glycine/aspartic acid (AA), and their combination with percutaneous intratissue electrolysis (EPI) in a Wistar rat model of induced TP. Animals received a diet supplemented by incorporating the compounds directly into the chow with MA (0.65 g/kg of diet), HT (3 g/kg of diet), and Gly/Asp (Gly: 28.125 g/kg of diet; Asp: 9.375 g/kg of diet). Tendon samples were collected at different TP phases (I, I-II, II, III). Histological analysis (H&E and Masson’s staining) assessed collagen fiber orientation, fibroblast density, and inflammation. Western blotting quantified inflammatory and apoptotic proteins (GST, Hsp60, JNK, NF-κB, PPAR‐γ, p53), while MDA levels indicated oxidative tissue damage. Results demonstrated that combining EPI with nutritional supplementation significantly improved recovery compared to EPI alone. Among the compounds tested, HT showed the most potent effects, followed by MA, reducing inflammation markers and enhancing tendon regeneration. Additionally, MDA levels significantly decreased in the HT group, indicating reduced oxidative stress. In cases where EPI is contraindicated, nutritional supplementation may serve as a viable non-invasive alternative, promoting faster healing and improved long-term outcomes. These findings highlight the potential of integrating EPI and targeted nutritional strategies to optimize TP treatment.

## Linked entities

- **Proteins:** SLCO6A1 (solute carrier organic anion transporter family member 6A1), HSPD1 (heat shock protein family D (Hsp60) member 1), MAPK8 (mitogen-activated protein kinase 8), NFKB1 (nuclear factor kappa B subunit 1), PPARG (peroxisome proliferator activated receptor gamma), TP53 (tumor protein p53)
- **Chemicals:** hydroxytyrosol (PubChem CID 82755), maslinic acid (PubChem CID 73659), glycine (PubChem CID 750), aspartic acid (PubChem CID 424), MDA (PubChem CID 1614)
- **Diseases:** tendinopathy (MONDO:0100010)

## Full-text entities

- **Genes:** Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 116554] {aka JNK}, p53-ps (Wistar clone pR53P1 p53 pseudogene) [NCBI Gene 301300], Pparg (peroxisome proliferator-activated receptor gamma) [NCBI Gene 25664] {aka PPARgamma2}, Hspd1 (heat shock protein family D (Hsp60) member 1) [NCBI Gene 63868] {aka Hsp60, Hspd1-30p}
- **Diseases:** inflammation (MESH:D007249), impaired function (MESH:D003072), pain (MESH:D010146), tendon overuse (MESH:D012090), Achilles tendinitis (MESH:D052256)
- **Chemicals:** Asp (MESH:D001224), MA (MESH:C412811), HT (MESH:C005975), AA (-), MDA (MESH:D015104), Gly (MESH:D005998), H&amp;E (MESH:D006371)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]
- **Mutations:** glycine/aspartic acid

## Figures

13 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12582488/full.md

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Source: https://tomesphere.com/paper/PMC12582488