Copyright © 2004, European Society of Cardiology
Free radicals trigger TNF
-induced cardioprotection
aHatter Institute for Cardiology Research, Department of Medicine, University of Cape Town Medical School Observatory, 7925 Cape Town, South Africa
bLPPCE, Facultes de Medecine et Pharmacie, Dijon, France
* Corresponding author. Tel.: +27 21 406 63 58; fax: +27 21 447 87 89. Email address: Sandrine{at}capeheart.uct.ac.za
Objective: Tumor Necrosis Factor 
(TNF) induces programmed cell death and contributes to cardiac ischemia/reperfusion injury. Paradoxically, we have recently demonstrated that low doses of TNF can induce cardiac preconditioning (PC). We hypothesized that the production of free radicals participates in this cardioprotective program.
Methods: Control isolated rat hearts underwent 30 min regional ischemia and 120 min of reperfusion. A second group of hearts received a low dose of TNF (0.5 ng/ml) for 7 min followed by 10 min washout prior to I/R. In other groups, the antioxidant N-2-mercaptopropionyl glycine (MPG) (1 mM) was given for 15 min prior to I/R alone or during TNF perfusion. Infarct size was determined at the end of the reperfusion period. Ventricular catalase and superoxide dismutase activities were assessed as an index of oxidative stress and free radical production was directly measured by the oxidation of 1-hydroxy-3-carboxy-pyrrolidine (CP-H) to paramagnetic 3-carboxy-proxyl (CP.) using electron spin resonance spectroscopy.
Results: TNF reduced the infarct/area at risk (I/AAR) ratio (7.2 ± 1.7% vs. 36.5 ± 1.7% for controls, p<0.05). MPG reduced the cardioprotective effect of TNF (I/AAR ratio: 20.5 ± 3.3%, p<0.05). TNF-perfusion increased catalase activity in the ventricles (15.8 ± 1.2 I.U./mg for controls vs. 19.9 ± 1.1 I.U/mg for TNF, p<0.05). Proof of formation of free radicals was increased CP formation in the coronary effluent during TNF infusion (24.2 ± 4.5 for TNF vs. 11.9 ± 1.5 arbitrary units for controls, p<0.05), with decreased CP after addition of MPG.
Conclusions: Our data provide firm evidence for a production and role of free radicals in TNF-induced cardioprotection.
KEYWORDS Cytokines; Ischemia; Oxygen radicals; Preconditioning; Reperfusion
Time for primary review 30 days
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