Acetaminophen and oxidant‐induced osteopontin in the myocardium

Abstract

Acetaminophen (APAP) exhibits cardioprotective, antioxidant effects in the injured mammalian myocardium. A number of mechanisms mediate ischemia/reperfusion‐induced myocardial injury, the most prevalent involving oxidative stress. The oxidant scavenging properties of APAP appear to terminate many signal transduction cascades which would normally become activated by injury‐generated reactive oxygen species (ROS). ROS target substrates of cell metabolism, growth, chemotaxis, survival, and death. One such substrate is the cytokine osteopontin (OPN), a phosphoglycoprotein found in body fluids and extracellular matrix of mineralized tissues. Its expression is minimal in normal adult cardiomyocytes and fibroblasts, but increases during pathological events including tissue remodeling. A recent study found that in OPN‐deficient mice the myocardial angiogenic response and post‐infarct tissue remodeling were reduced relative to wild type. These observations prompted us to hypothesize that APAP will reduce oxidant‐induced OPN expression in dogs. Respiratory, metabolic, and hemodynamic variables were measured in anesthetized, open‐chest dogs after administration of H2O2, in the presence or absence of 15mg/kg APAP. Femoral plasma was analyzed for OPN levels using western blot and ELISA. Preliminary results suggest APAP‐treated dogs express lower OPN levels than vehicle‐treated dogs.