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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Effect of alpha-tocopherol and OTR-4131 on muscle degeneration after rotator cuff tear in rats: An experimental protocol
Stavros Stamiris, Angeliki Cheva, Michael Potoupnis, Elissavet Anestiadou, Dimitrios Stamiris, Chryssa Bekiari, Antonia Loukousia, Papavasiliou Kyriakos, Eleftherios Tsiridis, Ioannis Sarris
Stavros Stamiris, Dimitrios Stamiris, Department of Orthopaedics, 424 General Military Hospital, Thessaloniki 56429, Greece
Stavros Stamiris, Michael Potoupnis, Dimitrios Stamiris, Papavasiliou Kyriakos, Eleftherios Tsiridis, Ioannis Sarris, Third Academic Department of Orthopaedics, Papageorgiou General Hospital, Thessaloniki 56403, Greece
Angeliki Cheva, Antonia Loukousia, Department of Pathology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
Elissavet Anestiadou, Fourth Academic Department of Surgery, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
Chryssa Bekiari, Laboratory of Anatomy and Histology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
Chryssa Bekiari, Experimental and Research Center, Papageorgiou General Hospital, Thessaloniki 56403, Greece
Author contributions: Stamiris S, Stamiris D, and Sarris I conceived and designed the experimental study; Stamiris S, Stamiris D, and Bekiari C developed the study protocol and supervised its scientific integrity; Stamiris S, Stamiris D, and Anestiadou E performed the pilot surgical procedures; Cheva A and Loukousia A provided methodological input for histological and pathological assessments and critically revised the manuscript; Potoupnis M, Papavasileiou K, Tsiridis K, and Sarris I critically revised the study protocol for clinical relevance, contributed to manuscript drafting, and ensured scientific accuracy; Stamiris S and Anestiadou E wrote the first draft of the manuscript; all authors participated in reviewing, editing, and finalizing the manuscript. All authors have read and approved the final version of the manuscript and agree to be accountable for all aspects of the work.
Institutional animal care and use committee statement: The research protocol was reviewed and approved by Ethics and Bioethics Committee of the School of Medical, Aristotle University of Thessaloniki.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All data are available upon request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Elissavet Anestiadou, MD, Fourth Academic Department of Surgery, School of Medical, Aristotle University of Thessaloniki, Leoforos Papanikolaou, Thessaloniki 54124, Greece.
elissavetxatz@gmail.com
Received: February 21, 2025
Revised: April 27, 2025
Accepted: June 27, 2025
Published online: December 20, 2025
Processing time: 166 Days and 13.5 Hours
BACKGROUND
Massive rotator cuff tears (RCTs) result in impaired shoulder function and quality of life. These tears lead to structural changes in the rotator cuff muscles, which compromise recovery after repair and increase re-tear rates.
AIM
To investigate the potential inhibitory effects of alpha-tocopherol (vitamin E) and OTR-4131 on muscle atrophy, fatty infiltration, and fibrosis in rotator cuff muscles following a massive RCT using a Wistar rat model, and establish a standardized methodology for evaluating potential therapeutic agents.
METHODS
This protocol outlines a controlled animal study using 40 male Wistar rats, randomized into five groups. The experimental groups will receive either systemic administration of alpha-tocopherol or local administration of OTR-4131 via intramuscular injection into the supraspinatus and infraspinatus muscles. Two sham groups will receive systemic and local saline injections respectively, while a control group will undergo no intervention. The interventions will be administered after surgical transection of the supraspinatus and infraspinatus tendons. Outcomes will be assessed via wet muscle weight measurements, muscle fiber diameter, fatty infiltration percentage, and fibrosis evaluation using histological methods.
RESULTS
The study anticipates that alpha-tocopherol and OTR-4131 will reduce muscle atrophy, fatty infiltration, and fibrosis compared to control and sham groups, supporting their potential protective role in rotator cuff muscle degeneration.
CONCLUSION
The results are expected to improve the understanding on the role of alpha-tocopherol and OTR-4131 in rotator cuff muscle protection after massive RCT and may serve as a foundation for further preclinical and clinical research aimed at improving rotator cuff repair outcomes.
Core Tip: This experimental protocol outlines a novel approach to investigating the use of therapeutic agents, following massive rotator cuff tears in a rat model. By systematically assessing muscle atrophy, fatty infiltration, and fibrosis, this study aims to establish a standardized methodology for evaluating potential therapeutic agents. The findings from this protocol could provide critical insights into muscle preservation strategies, potentially informing future preclinical and clinical interventional studies for rotator cuff repair.
