Protective Effects of 5-MTP in a Rat Model of Diabetic Cardiomyopathy Through Anti-Inflammatory, Anti-Apoptotic, and...

Diabetic cardiomyopathy (DCM) is characterized by myocardial inflammation, apoptosis, and fibrosis that contribute to ventricular remodeling and dysfunction. We investigated the effects of 5-methoxytryptophan (5-MTP) on histopathological and molecular markers of myocardial remodeling in a rat model of DCM.

Forty-eight Sprague-Dawley rats with DCM induced by a high-fat high-fructose diet and low-dose streptozotocin (25 mg/kg) were randomized to control or 5-MTP treatment (25, 50, or 100 mg/kg) and evaluated after 8, 16, and 32 days. Histopathological assessment using hematoxylin-eosin and Masson's trichrome staining, along with immunohistochemical analysis of inflammatory, apoptotic, and fibrotic markers, was performed.

Myocardial inflammatory histopathological scores did not differ significantly among groups. Myocardial fibrosis assessed by Masson's trichrome staining was significantly reduced at day 16 (p = 0.020), with all 5-MTP doses demonstrating lower fibrosis scores than DCM controls. Collagen I expression did not differ significantly. Caspase-3 expression was significantly reduced in all treatment groups at day 16 (p = 0.029), with persistent reduction at day 32 only in the 100 mg/kg group (p = 0.004). Early molecular modulation was observed through reduced TGF-β expression at day 8 in the 25 mg/kg and 50 mg/kg groups, followed by reduced SMAD3 expression at day 16 in the 25 mg/kg and 100 mg/kg groups. At day 16, AKT expression increased in the 25 mg/kg group, while cytoplasmic NF-κB expression decreased in the 25 mg/kg and 100 mg/kg groups.

5-MTP demonstrated time-dependent changes in molecular and histopathological markers associated with myocardial remodeling in experimental DCM.