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

Abstract

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.

Keywords: Diabetic cardiomyopathy; 5-Methoxytryptophan; Cardiac remodeling; Echocardiography; N-terminal pro-B-type natriuretic peptide; Experimental model

Core Tip: Diabetic cardiomyopathy (DCM) is characterized by progressive myocardial remodeling and a lack of therapies that specifically target the underlying inflammatory and fibrotic processes. This study evaluated the effects of 5-methoxytryptophan (5-MTP) in a rat model of DCM. Treatment with 5-MTP significantly reduced N-terminal pro-B-type natriuretic peptide levels and attenuated early structural remodeling but did not improve systolic or diastolic cardiac function. These findings suggest that 5-MTP may influence early myocardial remodeling; however, additional studies are needed to determine whether optimized dosing, longer treatment durations, or other treatment strategies can produce sustained structural and functional benefits.