Irisin mitigates diabetic cardiomyopathy in rats: targeting HMGB1/TLR4/NF-kB signaling pathway | ||||
| Medicine Updates | ||||
| Articles in Press, Accepted Manuscript, Available Online from 07 April 2025 PDF (1.15 MB) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/muj.2025.371855.1221 | ||||
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| Authors | ||||
Shorouk E. M. Elmorshdy1; Suzan A Khodir   2; Noha Abd El-aziz3; Mena Mahfouz4; Heba Ashraf Elmalky5; Sara A Khedr6; Mai A Nasser7; sarah Mohamed mowafy8; Menna Allah I El Menyawi9; Mohammed Hamza Kabil10; Asmaa I Bayomi11; Reem M Emam1
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| 1Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt | ||||
| 2Medical Physiology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt. | ||||
| 3Anatomy and Embryology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt | ||||
| 4Pathology Department, Faculty of Medicine, Mansoura University, Egypt. | ||||
| 5Endocrinology unit, Internal Medicine Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt | ||||
| 6Clinical Pharmacology Department, Faculty of Medicine, Ain Shams university, Egypt. | ||||
| 7Medical Biochemistry and Molecular Biology Department Faculty of Medicine, Mansoura University, Mansoura, Egypt | ||||
| 8Anatomy and Embryology Department, Faculty of Medicine, Portsaid University Egypt | ||||
| 9Medical Physiology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt. | ||||
| 10Cardiology Department, Faculty of Medicine, Suez University, Egypt. | ||||
| 11Zoology department, Faculty of Science, Menoufia University. | ||||
| Abstract | ||||
| Background: Cardiac inflammation, oxidative stress, and myocardial metabolic disruption are among the pathologic abnormalities that can result from diabetic cardiomyopathy (DCM), an independent diabetic cardiac disease. A new myokine called irisin has preventive properties against heart conditions. Objective: to demonstrate the potential underlying processes and cardiovascular protective impact of Irisin in diabetic cardiomyopathy. Material and methods: DCM, DCM+Irisin, and control (10/group) were the three groups into which thirty male albino rats were divided. After eight weeks, assessments of the following were made: LVW/ tibial length, serum glucose, serum insulin, HOMA-IR index, serum glycosylated Hb A1c, serum cholesterol, serum triglyceride, serum cTnI, serum LDH, serum CK-MB, cardiac MDA, cardiac SOD, cardiac TNF-α, cardiac IL-6, cardiac IL-10, cardiac HMGB1 gene expression, cardiac TLR4 gene expression and cardiac NF-kB gene expression. Furthermore, histological and immunohistochemical examinations of the heart and aorta were carried out. Results: The measured LVW/ tibial length, serum glucose, serum Insulin, HOMA-IR index, serum glycosylated Hb A1c, serum cholesterol, serum triglyceride, serum cTnI, serum LDH, serum CK-MB, cardiac MDA, cardiac TNF-α, cardiac IL-6, cardiac gene expression of HMGB1, TLR4 and NF-kB, were all markedly raised in DCM group compared to control, while the DCM group's cardiac SOD, and cardiac IL-10 were substantially lower than those of the control. Additionally there was dramatically downregulated cardiac and aortic NF-kB immunoreaction of DCM group compared to control. Irisin significantly mitigated diabetic cardiomyopathy induced changes. Conclusion: Irisin protects against DCM by downregulating the cardiac HMGB1/TLR4/NF-kB signaling pathway and displaying lipid-lowering, anti-inflammatory and antioxidant impacts. | ||||
| Keywords | ||||
| Diabetic Cardiomyopathy; Irisin; HMGB1; TLR4; NF-kB | ||||
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