Inhibition of NADPH oxidase

The existence of nitric oxide synthase (NOS) in phagocytes (see below) provides a different kind of stimulation and the inhibition of NADPH oxidase. It has been found [72] that the low physiological concentrations of peroxynitrite formed from NO and superoxide stimulated superoxide production by PMA-activated human PMNs through the ERK MAPK pathway, while higher peroxynitrite concentrations inhibited it. Moreover, NADPH oxidase was inhibited by lidocaine, a sodium-blocker, in OZ-activated neutrophils through the suppression of p47phox translocation [73]. 

Aspirin (acetylsalicylic acid) (Figure 29.21) is a widely applied drug for reducing ischemic cardiovascular events in patients with coronary artery disease, hypertension, or at cardiovascular risk. It is believed that the main protective function of aspirin is the inhibition of cyclooxygenase however, it has been recently proposed that aspirin may possess additional antioxidant activity [348]. It was found that long-term aspirin treatment of normotensive and hypertensive rats resulted in a decrease in vascular superoxide production by the inhibition of NADPH oxidase activity. 

Steffen Y, Schewe T, Sies H. 2007. (—)-Epicatechin elevates nitric oxide in endothelial cells via inhibition of NADPH oxidase. Biochem Biophys Res Commun 359 828-833. 

Wagner, A.H., Schroeter, M.R., and Hecker, M. 2001. 17b-Estradiol inhibition of NADPH oxidase expression in human endothelial cells. FASEB J. 15, 2121-2130. 

Qin, R, Simeone, M., and Patel, R. 2007. Inhibition of NADPH oxidase rednces myocardial oxidative stress and apoptosis and improves cardiac function in heart failure after myocardial infarction. 43, 271-81. 

More recently, the metabolism of the ubiquitous cell messenger, nitric oxide ( NO), has been identified as a major target for polyphenols. An interesting example is the inhibition of NADPH oxidase by 3 -0-methyl epicatechin (Steffen et al, 2008), which, by decreasing superoxide radical production, improves the bioactivity of NO in vivo. Also, it has been recently shown (Gago et al., 2007) that polyphenols from red wine are efficient catalyzers of nitrite reduction to NO in the gastric compartment and this constitutes a large source of "NO independent of its enzymatic synthesis from nitric oxide synthases. 

Obeso A, Gomez-Nino A, Gonzalez C. Inhibition of NADPH oxidase does not interfere with low PO2 transduction in chemoreceptor cells. Am J Physiol 1999 276 C593-C601. 

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