Irisin mitigates diabetic cardiac damage and is associated with improved redox status and reduced p53/VCAM-1 mRNA...

Diabetic cardiomyopathy is driven by oxidative stress, impaired myocardial enzyme function, and inflammatory/apoptotic signaling. Irisin has emerged as a cardiometabolic regulator, but its integrated effects on cardiac redox status, enzyme activities, and injury biomarkers in diabetes remain incompletely understood.

Diabetes-like cardiometabolic injury was induced in male Wistar rats by fructose pre-treatment followed by low-dose streptozotocin (40 mg/kg, i.p.). Diabetic rats were treated with irisin (100 or 500 μg/kg/day, i.p.) or metformin (200 mg/kg/day, i.p.) for 21 days. Cardiac oxidative stress markers (MDA and GSH), antioxidant enzyme activities (SOD, CAT, GPx, and GST), ATPase activities (Na⁺/K⁺-ATPase, Ca²⁺/Mg²⁺-ATPase, and Mg²⁺-ATPase), phosphatase activities (ALP and ACP), and cardiac p53 and VCAM-1 mRNA expression were assessed. Serum injury biomarkers (CK-MB, cTnI, cTnT, and NT-proBNP) and histopathological changes were also evaluated.

Cardiac MDA was higher, and GSH was lower in diabetic rats (both p < 0.001) with marked reductions in SOD, CAT, GPx, and GST activities (p < 0.001). Diabetes also inhibited the activities of Na +/K + -ATPase, Ca 2+/Mg 2+ -ATPase, and Mg 2+ -ATPase (p < 0.001) and reduced ALP and ACP (p < 0.001). The mRNA levels of cardiac p53 and VCAM-1 were significantly elevated (p < 0.001), along with serum CK-MB, cTnI, cTnT, and NT-proBNP (p < 0.001). At 100 and 500 μg/kg, irisin significantly decreased MDA content and restored antioxidant enzymes, ATPases, phosphatases (all p < 0.001 vs diabetic control), and was associated with reduced p53 and VCAM-1 expression (p < 0.001); it also reduced CK-MB, troponins, and NT-proBNP levels (p < 0.001) more effectively at a higher tested dose (500 μg/kg). The histology results showed better myocardial architecture with irisin, similar to metformin.

Irisin produced marked improvement in biochemical and histological indices of diabetes-induced myocardial injury and was associated with improved redox balance, reduced p53 and VCAM-1 mRNA expression, and lower circulating cardiac injury biomarkers. These findings support a descriptive association between irisin treatment and attenuation of diabetes-related myocardial injury, while further protein-level and pathway-focused studies are needed to confirm the underlying mechanisms.