Piroxicam-copper complexes: Inhibition of polymorphonuclear leukocyte migration toPseudomonas aeruginosa chemotactinsin vivo and superoxide dismutase-like activityin vitro

Abstract

Piroxicam-copper (Cu2+) complexes, formed spontaneously by mixing solutions of piroxicam and CuSO4 (1:1 Cu2+:piroxicam), inhibited the superoxide anion-catalyzed reduction of ferricytochrome C in a dose-related fashion. Addition of ethylenediaminetetraacetate to the mixture decreased in a dose-related manner the superoxide dismutase (SOD)-like activity of piroxicam-Cu2+. Piroxicam alone (10(-5) M, final concentration) did not display SOD-like activity but 10(-5) M Cu2+ exhibited significant activity, similar to that of piroxicam-Cu2+. Intraperitoneal treatment of mice with either 0.64 mg/kg piroxicam or its Cu2+ complexes (0.64 mg/kg piroxicam + 0.12 mg/kg Cu2+) was equally effective in diminishing both the migration of polymorphonuclear leukocytes (PMNL) to the airways and the content of myeloperoxidase activity in the lungs, induced by aerosol challenge with Pseudomonas aeruginosa peptide chemotactins. Therefore, piroxicam-Cu2+ complexes may provide both the anti-inflammatory activity of piroxicam plus the SOD-like activity of Cu2+.

Nutritional supplementation with copper in the rat. I. Effects on adjuvant arthritis development and on some in vivo- and ex vivo-markers of blood neutrophils

“…2) Different synthetic organic or biologically derived copper containing molecules, ceruloplasmin and yeast Cu(I)-thionein included, can decrease some rat or human neutrophil functions such as the chemotactic response [15,16], the superoxide anion generation [17][18][19][20] and the endothelial adhesion [19]. In contrast, the exposure of human polymorphonuclear leukocytes to Cu(II) chloride enhances the fMLP-induced cell migration [21].…”