Effect of sodium butyrate on reactive oxygen species generation by human neutrophils

Background: Short-chain fatty acids enema has been shown to be effective in the treatment of ulcerative colitis (UC). However. the mechanisms that lea d to this response have not been well characterized. The aims of this study were to investigate the effect sodium butyrate has on reactive oxygen spec ies (ROS) generation by human neutrophils, which are responsible for mucosa l injury. Methods: Human neutrophils incubated with or without sodium butyr ate were stimulated with opsonized zymosan (OZ) or phorbol myristate acetat e (PMA). ROS generation was largely differentiated with flow cytometry assa ys of hydroethidine oxidation and dichlorofluorescein oxidation for superox ide anion and hydrogen peroxide respectively, and luminol-dependent chemilu minescence fur myeloperoxidase-mediated oxidants. Results: Sodium butyrate (up to 50 mM) did not alter hydroethidine oxidation upon stimulation of the OZ or PMA. However, sodium butyrate at a concentration of 25 mM elevated d ichlorofluorescein oxidation to 125 +/- 8% (P = 0.028) of control upon stim ulation of OZ and to 191 +/- 30% (P = 0.0016) upon stimulation of PMA. Cont rary to these results, sodium butyrate greatly inhibited chemiluminescence responses in a dose-dependent manner. The inhibition by 50 mM sodium butyra te was 61 +/- 6% upon OZ and 71 +/- 9% upon PMA, respectively. Conclusions: These data indicate that sodium butyrate up-regulates hydrogen peroxide ge neration but down-regulates generation of myeloperoxidase-mediated oxidants . the latter being more potent in killing microorganisms and in inducing ti ssue injury. A possible mechanism is suggested whereby sodium butyrate may inhibit myeloperoxidase activity and hence attenuate the destructive activi ties of neutrophils in UC.