AIM To observe the protective effect of 4-cresol on diabetic hearts following ischemia/reperfusion (I/R) and to explore the possible molecular mechanisms.
METHODS Forty-six male SD rats were randomly divided into normal control (CON) group and diabetes mellitus (DM) group. The DM rat model was induced by high-fat diet combined with a low-dose intraperitoneal injection of streptozotocin. Diabetic rats were randomly subdivided into three groups: Sham-operated DM rats (DM+Sham), DM+MI/R, and DM+MI/R+4-cresol (5.5 mmol/L 4-cresol, 0.15 µL/h). The MI/R model was established by coronary artery ligation. After 30 min of ischemia, the myocardium was reperfused for 3 h.
RESULTS 4-cresol significantly attenuated myocardial injury in diabetes as evidenced by decreased infarct size, serum CK and LDH activities and cell apoptosis. Moreover, 4-cresol increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased malonaldehyde (MDA) in I/R hearts (P<0.05, P<0.01). Additionally, 4-cresol supplementation markedly inhibited dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A) expression and decreased the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) (P<0.05, P<0.01).
CONCLUSION 4-cresol effectively inhibits Dyrk1A expression, reduces oxidative stress and cardiomyocyte apoptosis and eventually alleviates MI/R injury in diabetic hearts.
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