Putative effect of melatonin on cardiomyocyte senescence in mice with type 1 diabetes mellitus

Rahbarghazi, Reza and Farhoudi, Mohammad and Rahmani‑Youshanlouei, Hamed and Hassanpour, Mehdi and Rahbarghazi, Afshin and Rezaie, Jafar and Ahmadi, Mahdi (2022) Putative effect of melatonin on cardiomyocyte senescence in mice with type 1 diabetes mellitus. Journal of Diabetes & Metabolic Disorders.

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Abstract

To date, many investigators have tried to clarify the molecular mechanism of cardiovascular injuries after T1D. In present study, we evaluated the possible effects of melatonin on the levels of aging-related factors in the heart tissue of streptozotocin-induced diabetic mice. Methods 40 male mice were enrolled in this study and randomly allocated into 4 groups (n = 10) as follows: Control group (C), Control group + melatonin (CM), Diabetic group (D), Diabetic + melatonin (DM) group. Single Streptozotocin (50 mg/ kbW) was applied for the induction of T1D. 3 mg/kg melatonin was injected intraperitoneally twice a week for consequent four weeks. After the completion of this period, the animals were sacrificed and their heart tissue was obtained for histologi- cal examination (IHC analysis of vWF and α-SMA cells), aging and inflammation-related gene analysis. Result Hematoxylin and Eosin staining indicated cardiomyocyte toxicity in T1D mice. IHC analysis of vascular tissue showed the detachment of vWF and α-SMA cells and disintegration into the vascular lumen. Additionally, real-time PCR assay showed the up-regulation of β-galactosidase and suppression of SOX2, Klotho, and Telomerase genes in T1D mice compared to the control group (p < 0.05). We noted that melatonin administration can revert these condition and closed near- to-control levels. Along with these conditions, the levels of IL-1β were also decreased after melatonin treatment. Conclusions In general, one can hypothesize that modulation of different effectors associated with aging is beneficial to alleviate cardiac injuries under hypergylcemic condition. Melatonin can exert its therapeutic effects, in part, through anti- aging capacity

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