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Bassenge, Eberhard, Olaf Sommer, Michael Schwemmer, and Rolf Bunger. Antioxidant pyruvate inhibits cardiac formation of reactive oxygen species through changes in redox state. Am J Physiol Heart Circ Physiol 279: H2431-H2438, 2000.--Myocardial ischemia-reperfusion is associated with bursts of reactive oxygen species (ROS) such as superoxide radicals ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII]). Membrane-associated NADH oxidase (NADHox) activity is a hypothetical source of [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII], implying the NADH concentration-to-[NAD.sup.+] concentration ratio ([NADH]/[[NAD.sup.+]]) as a determinant of ROS. To test this hypothesis, cardiac NADHox and ROS formation were measured as influenced by pyruvate or L-lactate. Pre- and post-ischemic Langendorff guinea pig hearts were perfused at different pyruvate/L-lactate concentrations to alter cytosolic [NADH]/[[NAD.sup.+]]. NADHox and ROS were measured with the use of lucigenin chemiluminescence and electron spin resonance, respectively. In myocardial homogenates, pyruvate (0.05, 0.5 mM) and the NADHox blocker hydralazine markedly inhibited NADHox (16 [+ or -] 2%, 58 [+ or -] 9%). In postischemic hearts, pyruvate (0.1-5.0 mM) dose dependently inhibited ROS up to 80%. However, L-lactate (1.0-15.0 mM) stimulated both basal and postischemic ROS severalfold. Furthermore, L-lactate-induced basal ROS was dose dependently inhibited by pyruvate (0.1-5.0 mM) and not the xanthine oxidase inhibitor oxypurinol. Pyruvate did not inhibit ROS from xanthine oxidase. The data suggest a substantial influence of cytosolic NADH on cardiac [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] formation that can be inhibited by submillimolar pyruvate. Thus cytotoxicities due to cardiac ischemia-reperfusion ROS may be alleviated by redox reactants such as pyruvate. reduced nicotinamide adenine dinucleotide oxidase; heart; ischemia-reperfusion

Both adenosine and interleukin-6 (IL-6) have been implicated in the pathophysiology of, e.g., epileptic seizures, traumatic brain injury, and affective disorders. Stimulation of adenosine A2B receptors on astrocytes in vitro leads to the increased synthesis and secretion of IL-6. We investigated whether or not activation of adenosine receptors evokes an increase of IL-6 release also in vivo. 5′- N-ethylcarboxamidoadenosine, a non-specific adenosine-agonist or vehicle was administered into the striatum of freely moving mice by reverse microdialysis. A statistical significant increase of the IL-6 concentration in the perfusate was detected already 60 min after 5′- N-ethylcarboxamidoadenosine administration. IL-6 increased progressively and reached a maximum after 240 min. This effect appears to be mediated through adenosine A2B receptors since it was counteracted by the specific A2B receptor antagonist MRS1706 but not by the specific A1 receptor antagonist DPCPX. We conclude that adenosine via activation of A2B receptors evokes IL-6 release also in vivo. [ABSTRACT FROM AUTHOR]