The Effects of Colchicum Dispert and Bone Marrow-Derived Mesenchymal Stem Cell Therapy on Skeletal Muscle Injury in a Rat Aortic Ischemia–Reperfusion Model

Author:

Orhan Atilla1ORCID,Çiçek Ömer Faruk1ORCID,Öztürk Bahadır2,Akbayrak Hakan1,Ünlükal Nejat3ORCID,Vatansev Hakan4ORCID,Solmaz Merve3,Büyükateş Mustafa1,Aniç Seda3,Ovalı Fadime5,Almaghrebi Eissa2ORCID,Akat Fatma2ORCID,Vatansev Hüsamettin2

Affiliation:

1. Department of Cardiovascular Surgery, Medical Faculty, Selçuk University, Konya 42250, Turkey

2. Department of Biochemistry, Medical Faculty, Selçuk University, Konya 42250, Turkey

3. Department of Histology, Medical Faculty, Selçuk University, Konya 42250, Turkey

4. Department of Food Processing, Meram Vocational School, Necmettin Erbakan University, Konya 42092, Turkey

5. Department of Medical Biochemistry, Institute of Health Sciences, Selçuk University, Konya 42250, Turkey

Abstract

Background: Abdominal aortic aneurysms and peripheral artery disease pose significant health risks, ranking third after heart attacks and cerebral strokes. Surgical interventions often involve temporary aortic clamping, leading to ischemia–reperfusion injury and tissue damage. Colchicine and mesenchymal stem cells have shown promise, individually, in mitigating ischemia–reperfusion injury, but their combined effects remain understudied. Methods: This study utilized 42 male Wistar rats, divided into six groups: Control, Sham, Ischemia–Reperfusion, Colchicine, Mesenchymal stem cell, and Mix (colchicine and mesenchymal stem cell). The ischemia–reperfusion model involved clamping the abdominal aorta for 60 min, followed by 120 min of reperfusion. Colchicine and mesenchymal stem cell treatments were administered as pre- and post-ischemia interventions, respectively. Mesenchymal stem cells were cultured, characterized by flow cytometry, and verified for specific surface antigens. Blood and tissue samples were analyzed for oxidative stress markers, nitric oxide metabolites, and apoptosis using TUNEL. Results: There were significant differences between the groups in terms of the serum total antioxidant capacity (p < 0.001) and inflammation markers (ischemia-modified albumin, p = 0.020). The combined therapy group (Mix) exhibited the lowest inflammation levels. Arginine levels also showed significant variation (p = 0.028), confirming the ischemia–reperfusion injury model. In muscle tissues, the total antioxidant capacity (p = 0.022), symmetric dimethylarginine, and citrulline levels (p < 0.05) indicated nitric oxide metabolism. Apoptosis was notably high in the ischemia–reperfusion injury group as anticipated. It appeared to be reduced by colchicine, mesenchymal stem cells, and their combination, with the most significant decrease observed in the Mix group (p < 0.001). Conclusions: This study highlights the potential of using combined colchicine and mesenchymal stem cell therapy to reduce muscle damage caused by ischemia–reperfusion injury. Further research is needed to understand the underlying mechanisms and confirm the clinical significance of this approach in treating extremity ischemia–reperfusion injuries.

Funder

Scientific Research Projects Coordinator’s Office

Publisher

MDPI AG

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