Romanian Society of Pharmaceutical Sciences

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EVALUATION OF DYSTROPHIN ROLE IN DUCHENNE MUSCULAR DYSTROPHY-RELATED GASTROENTERITIS FOCUSING ON OXIDATIVE STRESS MECHANISM

ALI TAGHIZADEHGHALEHJOUGHI 1, SIDIKA GENC 1, RAMAZAN CINAR 2, DAMLA GUL FINDIK 3, ESMANUR NIGDE 1, KUBRA KARABULUT 1, OZLEM TURELIK 3, ANCA OANA DOCEA 4*, ARISTIDIS TSATSAKIS 5,6,7

1 Şeyh Edebali University, Faculty of Medicine, Department of Medical Pharmacology, 11230 Bilecik, Turkey
2 Şeyh Edebali University, Faculty of Medicine, Department of Biophysics, 11230 Bilecik, Turkey
3 Şeyh Edebali University, Faculty of Medicine, Department of Pathology, 11230 Bilecik, Turkey
4 Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania
5 University of Crete, Faculty of Medicine, Department of Forensic Sciences and Toxicology, 71003 Heraklion, Greece
6 Universidad Ecotec, Km. 13.5 Samborondón, EC092302, Samborondón, Ecuador
7 Centre of Bioanalytical Research and Molecular Design, Sechenov First Moscow State Medical University, PC 119991 Moscow, Russian Federation

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Duchenne muscular dystrophy (DMD) is a muscle weakness disease characterised by dystrophin deficiency. Since dystrophin is found in all muscle types, it affects different organs, especially the digestive system. Our study aims to define the enteropathy associated with dystrophin deficiency at the levels of klotho, mTOR, apoptosis and cytokines. In our study, wild-type mice and D2-mdx mice were evaluated (n = 10). Elisa, RT-PCR, western blot (WB), histochemistry and immunohistochemistry (IHC) tests were performed on intestinal tissue. Enteropathy associated with dystrophin deficiency was seen in D2-mdx mice. Intestinal mucus, wall and villus thickness show a decrease in D2-mdx mice. Klotho, mTOR levels are highly suppressed, while IL-6, Caspase 3 and 8 levels show an increase. BAX and Bcl-2 levels in WB show increased oxidative stress in correlation with TOS, LDH and Galanin levels. Gastroenteritis in DMD is linked to the dystrophin complex. Dystrophin deficiency leads to decreased motility and increased oxidative stress levels. This results in changes in IL levels. The rise in inflammation has a surprising impact on Klotho and Galanin receptors. In this context, our study lays a foundation for future research to examine enteropathy related to dystrophin deficiency.