Pretreatment effect of adenosine on activation of NF—κB and level of TNF—α during myocardial ischemia and reperfusion in rats

Ithasbeenshownthatischemiaandreperfusion(I/R)increasecytokinelevelsincludingTNF α ,IL 1,IL 6 ,IL 8,IF γ ,andintercellularadhesionmolecule 1(ICAM 1)inthemyocardium .1TNF αandIL 6arethoughttobeimportantintheprogressionofmyocardialdysfunction .2 AdenosineinhibitsmyocardialTNF αproductionin postischenmicrat ,reduceshumanmyocardialinjuryafterI/R ,3anddecreasesLipopolysaccharide (LPS )inducedcardiacandmacrophageTNF a production .4 However ,themolecularmechanismsofadenosineinthedown …

Pretreatment effect of adenosine on activation of NF-κB and level of TNF-α during myocardial ischemia and reperfusion in rats

OBJECTIVE: To study the pretreatment effect of adenosine on NF-kappaB nuclear activity in ischemia/reperfusion myocardium in rats. METHODS: Eighteen healthy male S-D rats were randomly divided into three groups. Group I was the control group. The other two groups were subjected to 30 minutes of ischemia, followed by 2 hours of reperfusion. In group III, adenosine was given 40 microg.kg(-1).min(-1) 30 minutes before coronary artery occlusion. The NF-kappaB in nuclear was extracted and measured with western blot analysis. TNF-alpha levels in myocardium were measured with enzyme-linked immunosorbent assay (ELISA) system. All the data were recorded with mean +/- SEM, differences at the 95% confidence level were considered significant. RESULTS: NF-kappaB activity in the nucleus significantly increased after ischemia/reperfusion and TNF-alpha levels changed. Adenosine significantly inhibited NF-kappaB activity in nucleus, and concomitantly decreased the level of TNF-alpha in myocardium. CONCLUSIONS: Adenosine modulation of NF-kappaB activation may be the cellular molecular mechanism of decreasing of TNF-alpha. The cardioprotective action of adenosine may be involved in the differential modulation of NF-kappaB activation during myocardial ischemia/reperfusion.