Cytokines modulate oxidative stress in ischemia reperfusion‐induced heart injury in rats: Role of gp91phox and its homologues, Nox1 and Nox4

Abstract

Oxidative stress plays a major role in myocardial ischemia reperfusion (MI/R) injury and contributes to the pathogenesis of cardiovascular disease. Hypothesis: Cytokines modulate NADPH oxidase subunits, gp91phox, Nox1 and Nox4 in MI/R. Methods Rats underwent 30 min of coronary artery occlusion and 1 or 4h of reperfusion. Pentoxifylline (PTX), a phosphodiesterase inhibitor was used @ 20 mg/kg to block cytokine production. Results MI/R caused a significant increase in circulating and myocardial tissue levels of cytokines (IL-1β and TNF-α). MI/R also increased the production of superoxide after 1h and upregulated the protein and mRNA expression of gp91phox and its homologues Nox1 and Nox4 after 4h of reperfusion. The activities of the antioxidant enzymes CuZnSOD and glutathione peroxidase were elevated, while that of catalase was unaffected. Pretreatment with PTX reduced reperfusion-induced Nox homologues, cytokines and oxidative markers. Conclusions 1) MI/R increases both myocardial and circulating cytokine levels. 2) MI/R induces the production of superoxide via gp91phox, Nox1 and Nox4 3) MI/R-induced oxidative stress may be in part, mediated through cytokines.