Effects of 5-methoxytryptophan on cardiac structure and functions in a rat model of diabetic cardiomyopathy

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BACKGROUND Diabetic cardiomyopathy (DCM) is characterized by ventricular remodeling and cardiac dysfunction, with limited therapies targeting the underlying myocardial remodeling process. AIM To investigate the effects of 5-methoxytryptophan (5-MTP) on cardiac structure and function in a rat model of DCM. METHODS Forty-eight Sprague-Dawley rats with DCM induced by a high-fat, high-fructose diet and streptozotocin (25 mg/kg) were randomized to a control group or 5-MTP treatment groups (25 mg/kg, 50 mg/kg, or 100 mg/kg). Animals were evaluated after 8 days, 16 days, or 32 days of treatment. Cardiac structure and systolic and diastolic functions were assessed by echocardiography, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured and compared among groups. RESULTS 5-MTP significantly reduced NT-proBNP levels after 16 days and 32 days of treatment (vs controls; P = 0.029 and P < 0.05, respectively) but not after 8 days. At day 8, 5-MTP significantly reduced left ventricular end-diastolic diameter (LVEDD; P = 0.026) and left ventricular end-systolic diameter (LVESD; P = 0.044). Significant reductions in LVEDD and LVESD from baseline were observed in the 25 mg/kg and 50 mg/kg treatment groups. Preservation of interventricular septal thickness in diastole and left ventricular posterior wall thickness in diastole was observed during the early treatment phase. However, these structural effects were not maintained after 16 days or 32 days of treatment. No significant improvements in systolic or diastolic function were observed in any treatment group. CONCLUSION 5-MTP reduced NT-proBNP levels and attenuated early structural remodeling in this rat model of DCM, although these structural effects were not sustained nor accompanied by improvements in cardiac function. Additional studies are needed to determine whether alternative dosing strategies or longer treatment durations can produce durable structural and functional benefit.

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