5-Aminolevulinic acid combined with ferrous iron ameliorates myocardial ischemia/reperfusion injury by increasing heme oxygenase-1.

Background: 5-Aminolevulinic acid (5-ALA) is a naturally occurring metabolic precursor of heme, and 5-ALA combined with ferrous iron can induce heme oxygenase-1 (HO-1) in various cells. In this study, we investigated the cardioprotective effect of 5-ALA after myocardial ischemia/reperfusion (I/R) injury using a murine model.

Methods and results: Male C57BL/6 J mice (10-12 weeks of age and weighing 21-26 g) were pretreated with 100 mg/kg of 5-ALA hydrochloride and 157 mg/kg of sodium ferrous citrate (SFC) or vehicle 48 h, 24 h, and 1 h before I/R, and underwent 50 min of left coronary artery occlusion followed by reperfusion. Infarct area (IA) and area at risk (AAR) were determined by Evans blue and triphenyltetrazolium chloride double staining after reocclusion. Pre-administration with 5-ALA/SFC significantly reduced IA/AAR compared with placebo (34.0% vs. 51.7%, respectively; p = 0.001). Real-time PCR assay after reperfusion showed that mRNA expressions of TNF-α, IL-1β, and BNP were significantly lower, and that of HO-1 was significantly higher in the 5-ALA/SFC group than in the vehicle group in ischemic sites. An inhibition experiment revealed that zinc protoporphyrin IX, an inhibitor of HO-1, inhibited the cardioprotective effects of 5-ALA/SFC.

Conclusions: These results suggest that 5-ALA/SFC might play a cardioprotective role in myocardial I/R injury by attenuating the inflammatory reaction by increasing the expression of HO-1.