INTERNATIONAL IMMUNOPHARMACOLOGY, cilt.3, sa.5, ss.757-764, 2003 (SCI-Expanded)
We investigated the abilities of an ester-type local anesthetic tetracaine and an amide-type local anesthetic bupivacaine to inhibit reactive oxygen and/or nitrogen species generated by either human leukocytes or cell-free systems via luminol- and lucigenin-enhanced chemiluminescence (CL). Tetracaine (96 +/- 1%, n = 6, 1 mM) and bupivacame (97 +/- 0.4%, n = 5, 1 mM) significantly inhibited FMLP-induced-CL in leukocyte assay. In cell-free experiments, CL due to superoxide production was significantly inhibited by tetracaine (23 +/- 2%, n = 6) and bupivacaine (25 +/- 4%, n = 6) at 1 mM. Although bupivacaine was ineffective on H2O2-induced CL, tetracaine activated H2O2-induced luminol CL. Additionally, tetracaine inhibited FeSO4-induced CL (42 +/- 2%, n = 6, 1 mM). In hypochlorous acid (HOC)-induced CL assay, 70 +/- 10% (n = 5) and 57 +/- 4% (n = 15) inhibitions were observed by tetracaine and bupivacaine, respectively. Peroxynitrite-induced luminol (54 +/- 7%, n = 7, tetracaine, and 26 +/- 5%, n = 8, bupivacaine, at 1 mM) and lucigenin CL (58 +/- 3%, n = 6, tetracaine, and 22 +/- 14%, n = 9, bupivacaine, at I mM) were markedly inhibited. Tetracaine interacted with superoxide, hydroxyl radical, HOCl and peroxynitrite, while bupivacaine scavenged superoxide, HOCl and peroxynitrite. These direct scavenging properties of these drugs might be involved in the inhibition observed in leukocyte free radical release. In general, a decrease in CL-response was seen with higher concentrations (0.1 - 1 mM) of the local anesthetics, it is likely that tetracine and bupivacaine at therapeutic concentrations do not suppress leukocyte function in vivo. (C) 2003 Elsevier Science B.V. All rights reserved.