Abstract 21202: 5-Aminolevulinic Acid Combined With Sodium Ferrous Citrate Ameliorates Post Cardiac Ischemia/Reperfusion Injury via Regulating Inflammatory Cytokines

Abstract

Post ischemia/reperfusion injury (I/R) reduces beneficial effect of restoration of coronary flow in the setting of acute myocardial infarction. Heme oxygenase-1 (HO-1) is inducible enzyme, and plays a crucial role in reaction against for oxidative stress, inflammatory, and apoptosis. Previous studies reported that HO-1 could reduce the infarct size after ischemia/reperfusion injury (I/R). 5-aminolevulinic acid (5-ALA) is known to be a naturally occurring metabolic precursor of heme, and 5-ALA combined with ferrous iron can induce HO-1 in various cells. In this study, we investigate the protective effect of 5-ALA pretreatment after I/R using mice model. Male C57/BL 6J mice (8-12 weeks of age and weighing 21-26 g) were pretreated with 100 mg/kg 5-ALA/HCL and 157 mg/kg sodium ferrous citrate or placebo 48, 24, 1 h before I/R, and underwent 50 minutes of left coronary artery occlusion followed by 24 h reperfusion. Infarct area (IA), area at risk (AAR), and area of left ventricle (LV) were determined by 5% Evans blue and 1% triphenyltetrazolium chloride (TTC) double staining after 24h reperfusion (Figure [A]). Pretreatment of 5-ALA group significantly reduced IA/AAR compared to the placebo group (34.0% [28.1 - 37.6%] VS 51.7% [45.8 - 54.0%], p= 0.001, n=6, Figure [B and C]). Real time PCR assay after 24h reperfusion showed that expression of mRNA of TNF-α (p=0.040), IL-1β(p=0.024), MMP-9 (p=0.011) and BNP (p=0.046) were significantly lower in 5-ALA group than that in placebo group. These findings suggested that 5-ALA pretreatment regulated inflammatory reaction after I/R. The beneficial effect of 5-ALA could be related with HO-1 induction. In conclusion, pretreatment of 5-ALA combined with ferrous iron could play a protective role after I/R by attenuating inflammatory reaction.