Abstract 3315: Antioxidant N-acetyl Cysteine Extinguish Cigarette Smoke Induced Myocardial Infarction by Inhibiting Inflammation and Oxidative Stress in a Rat Model
Background: We studied the efficacy of antioxidant N-acetyl cysteine (NAC) to reverse the cigarette smoke exposure induced progression of Myocardial infarction (MI).
Methods: MI in rats was created by ligation of left anterior descending artery, sham rats were without ligation. Sham (6) and MI (7) rats were either tobacco naïve or exposed to tobacco with four cigarettes per day for six weeks with or without treatment with antioxidant N-acetyl cysteine (10 mg/kg/day). Cardiac function was monitored by echocardiography, histological changes by mason trichrome staining and molecular changes of pro-inflammatory cytokines, tissue repair molecules and markers of oxidative stress was studied by real time PCR.
Results: The results demonstrate a NAC treatment significantly reduced tobacco exposed induced infarct size (Figures A, B, C⇓) and %fractional shortening (Figure D⇓). A significantly increased LVESD was observed in tobacco exposed sham, compared to tobacco naïve sham (4.92±0.41 vs 3.45±0.33, p<0.05), tobacco exposed MI compared to tobacco naïve MI (8.24±0.3 vs 6.1±0.49 p<0.01). These positive effects of NAC were accompanied by decreased intracardiac mRNA expression of IL-6 (p=0.001); TNF-α (p=0.001); IFN-γ (p=0.001); MMP-2 (p=0.001); SDF-1 (p=0.001); p22phox (p=0.001); Nrf2 (p=0.001), Keap-1 (p=0.001), TGF-beta (p=0.001) and PARP (p=0.001). In contrast mRNA expression increased significantly for antioxidants; SOD (p=0.001) and TXN (p=0.0001). The treatment of tobacco exposed MI rats with NAC resulted in significantly increased levels of glutathione (7±0.12 vs 10±0.18, p=<0.001), the levels were almost identical to the tobacco naïve sham rats.
Discussion: The results from this study uniquely demonstrate that N-acetyl cysteine (NAC) reverses vascular dysfunction, histological changes and inhibits inflammation by normalizing serum glutathione levels and increased expression of anti-oxidants superoxide dismutase and Thioredoxin in cardiac tissues. These results advocate the use of dietary supplement anti-oxidants for habitual smokers to prevent and reverse cardiovascular adverse effects of tobacco usage in the absence of successful achievement of cessation of smoking,