Potential molecular targets on which methylene blue acts to promote its effects on cardiac electrophysiology, myocardial injury, and oxidative stress in spontaneously hypertensive rats submitted to cardiac ischemia and reperfusion.

purposeAlthough methylene blue (MB) has long been used to treat vasoplegic syndrome, its pharmacodynamics and cardiovascular effects remain unclear. Therefore, we decided to evaluate the potential molecular targets of MB through molecular docking and its cardioprotective and antioxidant actions.

methodsAdult male spontaneously hypertensive rats (SHR) were allocated into four groups: sham-operated; treated with vehicle and subjected to cardiac ischemia and reperfusion (CIR) (SS+CIR); treated with 2 mg/kg of MB before cardiac ischemia and reperfusion (MB+ISQ); and treated with 2 mg/kg of MB before cardiac reperfusion (ISQ+MB). The animals were monitored with electrocardiogram to assess the incidence of ventricular arrhythmias (VA), atrioventricular blocks (AVB), and lethality (LET). Blood samples and hearts were collected for histopathological analysis, serum creatine kinase MB dosage, and measurement of lipid hydroperoxide (LH) in myocardium serum creatine kinase MB.

resultsThe incidences of AVB and LET, serum CK-MB concentration, and myocardial injury increased in the MB+ISQ group, but not in the ISQ+MB group when compared with the SS+CIR group. LH concentration decreased in both MB-treated groups when compared with the SS+CIR group.

conclusionThese results indicate that MB produces a cardiotoxic effect only when administered before CIR, but not when administered before cardiac reperfusion.