AIM: To investigate the influence of trimetazidine, which is known to be an 
antioxidant and modulator of metabolism, on cardiac function and the development 
of diabetic cardiomyopathy in db/db mouse.
METHODS: Trimetazidine was administered to db/db mice for eight weeks. Cardiac 
function was measured by inserting a Millar catheter into the left ventricle, 
and oxidative stress and AMP-activated protein kinase (AMPK) activity in the 
myocardium were evaluated.
RESULTS: Untreated db/db mice exhibited a significant decrease in cardiac 
function compared to normal C57 mice. Oxidative stress and lipid deposition were 
markedly increased in the myocardium, concomitant with inactivation of AMPK and 
increased expression of peroxisome proliferator-activated receptor coactivator-1 
alpha (PGC-1 alpha). Trimetazidine significantly improved systolic and diastolic 
function in hearts of db/db mice and led to reduced production of reactive 
oxygen species and deposition of fatty acid in cardiomyocytes. Trimetazidine 
also caused AMPK activation and reduced PGC-1 alpha expression in the hearts of 
db/db mice.
CONCLUSION: The data suggest that trimetazidine significantly improves cardiac 
function in db/db mice by attenuating lipotoxicity and improving the oxidation 
status of the heart. Activation of AMPK and decreased expression of PGC-1 alpha 
were involved in this process. Furthermore, our study suggests that 
trimetazidine suppresses the development of diabetic cardiomyopathy, which 
warrants further clinical investigation.