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  • Title: Ca2+ enhancement of hemolysis induced by the topical anesthetic oxethazaine in vitro.
    Author: Yasuno R, Oguma T, Masuda Y.
    Journal: Biol Pharm Bull; 1998 Dec; 21(12):1294-9. PubMed ID: 9881642.
    Abstract:
    Oxethazaine (OXZ), a potent topical anesthetic, was found to induce red blood cell (RBC) lysis in vitro, depending upon concentrations of OXZ, RBC and Ca2+. In a 2% RBC suspension, 100 microM OXZ caused almost complete hemolysis in the presence of 1.3 mM Ca2+ with only a minimal effect in its absence, while higher concentrations of OXZ (400 microM<) produced hemolysis without Ca2+. The hemolysis induced by OXZ plus Ca2+ was preceded by a rapid increase in 45Ca2+ uptake by RBCs, with both the hemolysis and Ca2+ uptake being inhibited by 1 mM CoCl2, NiCl2, and quinine. Together with the Ca2+ influx, rapid influx of Na+ and efflux of K+ occurred, and an increasing external K+/Na+ concentration ratio inhibited both hemolysis and Ca2+ influx. Morphologically, OXZ plus Ca2+ caused rapid transformation to spheroechinocytes, the formation of blebs and the pinching-off of blebs, whereas OXZ alone produced membrane invagination. SDS-PAGE analysis of the ghosts prepared from the RBCs treated with OXZ plus Ca2+ revealed derangement of cytoskeletal components. OXZ is a rare drug that exhibits a Ca2+ ionophore-like action, increasing the Ca2+ permeability of plasma membranes.
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