An AMPK activator, Metformin, ameliorates aging-related oxidative hepatic injury induced by D-galactose via Irisin/ SIRT1 pathway, a possible role of PPAR-γ besides its antioxidant potency in rats. | ||||
| Bulletin of Egyptian Society for Physiological Sciences | ||||
| Volume 44, Issue 4, October 2024, Page 212-227 PDF (1.16 MB) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/besps.2024.303088.1170 | ||||
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| Authors | ||||
Marwa Hassan Muhammad   ; Heba S. Youssef; Mahmoud H Taha; Alaa H Eltalees; Reham Mohammed Ibrahim
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| Department of Physiology, Faculty of Medicine, Benha University, Benha, Egypt. | ||||
| Abstract | ||||
| Background: While many studies have investigated the metabolic and cellular effect of the AMPK activator anti-diabetic drug metformin, we have not come across a paper that deals with the molecular mechanism of its anti-aging impact via irisin hormone in a SIRT1/ PPAR-γ-dependent manner. Materials and Method: For this purpose, we conducted, besides the control group, an experimentally induced aging model through D-galactose and compared its solo effect versus the combined metformin and D-galactose administration. Furthermore, another group pretreated by Bisphenol-A-diglycidyl ether (BADGE), a selective PPAR-γ antagonist, was conducted. Results: Metformin blunted aging-associated hepatocellular changes in both structural and functional aspects as revealed by biochemical and histopathological evaluations. Also, it maintained glucose homeostasis. Such effects were accompanied by preserving redox homeostasis and boosting the level of Irisin and SIRT1 proteins. A mechanism that was, in part, dependent on PPAR-γ as evidenced after its blockade by BADGE. There was an observable negative correlation between serum irisin and ALT, HOMA-IR, and MDA while a positive correlation with total antioxidant capacity (TAC). Conclusion: The results came up with the geroprotective impact of metformin and its benefits could extend far beyond diabetes. It appears to be a promising anti-aging pill. It could retard aging-associated hepatic alterations and/or its bad consequences progression. | ||||
| Keywords | ||||
| Aging; Metformin; Oxidative stress; Irisin/SIRT1/PPAR-γ; BADGE | ||||
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