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The Evaluation of Exogenous Melatonin Administration in Supraspinatus Overuse Tendinopathy in an Experimental Rat Model
Clin Should Elbow 2019;22:79-86
Published online June 1, 2019;  https://doi.org/10.5397/cise.2019.22.2.79
© 2019 Korean Shoulder and Elbow Society.

Onur Kocadal, Murad Pepe1, Nalan Akyurek2, Zafer Gunes3, Hatice Surer4, Ertugrul Aksahin5, Betul Ogut6, Cem Nuri Aktekin7

Department of Orthopedics and Traumatology, Yeditepe University Faculty of Medicine, Istanbul, 1Department of Orthopedics and Traumatology, Alanya Research and Training Hospital, Alanya Alaaddin Keykubat Unversity, Alanya, 2Department of Pathology, Gazi University Medical School, Ankara, 3Department of Orthopedics and Traumatology, Bursa Y?ksek ?htisas Research and Training Hospital, Bursa, 4Department of Biochemistry and Clinical Biochemistry, Ankara Education and Research Hospital, 5Department of Orthopedics and Traumatology, Medical Park Hospital, Ankara, 6Department of Pathology, Gaziantep Cengiz Gokcek Obstetrics and Children's Hospital, Gaziantep, 7Department of Orthopedics and Traumatology, Ankara Education and Research Hospital, Ankara, Turkey
Correspondence to: Onur Kocadal
Department of Orthopedics and Traumatology, Yeditepe University Kozyata?ı Hospital, ??erenk?y Mahallesi Hastane Yolu Sokak no.102-104, Ata?ehir 34752, Istanbul, Turkey
Tel: +90-5323364878, Fax: +90-2164693796, E-mail: onurkocadal@gmail.com, ORCID: https://orcid.org/0000-0002-7390-6888
IRB approval: Ankara Education and Research Hospital (No. 261).
Received January 11, 2019; Revised March 7, 2019; Accepted March 12, 2019.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Background: Increased oxidative stress and inflammation play a critical role in the etiopathogenesis of chronic tendinopathy. Melatonin is an endogenous molecule that exhibits antioxidant and anti-inflammatory activity. The aim of this study was to evaluate the biochemical and histopathological effects of exogenous melatonin administrations in supraspinatus overuse tendinopathy.
Methods: Fifty rats were divided into the following four groups: cage activity, melatonin treatment, corticosteriod therapy, and control. Melatonin (10 mg/kg, intraperitoneal; twice a day) and triamcinolone (0.3 mg/kg, subacromial; weekly) were administered to the treatment groups after the overuse period. Biochemical and histopathological evaluations were performed on serum samples and biopsies obtained from rats. Plasma inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were evaluated biochemically.
Results: The TAS, TOS, OSI, iNOS, and VEGF values were significantly lower than the pre-treatment levels in rats receiving exogenous melatonin treatment (3 or 6 weeks) (p<0.05). TOS, iNOS, VEGF, and OSI values after 3 weeks of triamcinolone administration, and TOS, VEGF, and OSI levels after 6 weeks of triamcinolone application, were significantly lower than the pre-treatment levels (p<0.05). 
Conclusions: Exogenous melatonin application in overuse tendinopathy reduces oxidative stress and inflammation. Melatonin might be an alternative potential molecule to corticosteroids in the treatment of chronic tendinopathy.
Keywords : Shoulder; Rotator cuff; Tendinopathy; Oxidative stress; Melatonin