Reference : The unexpected hidden face of the Cephalosporin Antibiotic Ceftazidime: From biological ...
Scientific congresses and symposiums : Unpublished conference
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/61821
The unexpected hidden face of the Cephalosporin Antibiotic Ceftazidime: From biological to chemical and physical activities against oxidant species produced by phagocytes
English
Mouithys-Mickalad, Ange mailto [Université de Liège - ULg > > Centre de l'oxygène : Recherche et développement (C.O.R.D.) >]
Deby-Dupont, Ginette [ > > ]
Mathy-Hartert, Marianne [Université de Liège - ULg > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.) >]
Lamy, Maurice mailto [Université de Liège - ULg > > Anesthésie et réanimation >]
Serteyn, Didier mailto [Université de Liège - ULg > Département clinique des animaux de compagnie et des équidés > Anesthésiologie gén. et pathologie chirurg. des grds animaux >]
Deby, Carol [ > > ]
3-Oct-2008
Yes
Yes
International
2nd World Conference on Magic Bullets - Ehrlich II
du 3 au 5 octobre 2008
German Association of Pharmaceutical Scientists & International Society of Anti-infective Pharmacology
Nuremberg (Nurnberg)
Germany
[en] Ceftazidime ; antioxidant ; reactive oxygen species (ROS) ; neutrophil (PMN) ; Myeloperoxidase (MPO)
[en] Background: Over several decades the use of antibiotics to treat infectious and bacterial diseases has been the main challenge. Ceftazidime (CAZ), belonging to the cephalosporin’s family, is known as empiric treatment for severe sepsis. Beside its antibiotic effect, CAZ has been shown to have other properties, making it unique. This study is aimed to investigate unexpected antioxidant properties of CAZ with special emphasis on the mechanism of action.
Methods: Four in vitro and ex-vivo experimental models were designed 1) Assay of proteinases inhibitory activity of α2-macroglobulin (α2M) in the presence of trypsine (1.4µg) with or without 10-3 M CAZ, in 0.1 M Tris-HCl at pH 8.1. 2) Assessment of MPO-induced toxicity on endothelial cells or oxidant activities of stimulated phagocytes (PMNs) using 160 µM ferricytochrome C. 3) Effect of CAZ on two models of anoxia/reoxygenation from adherent and suspension alveolar cells (A549, 106 to 1010 cells/ml) using oxymetry coupled to EPR-spin trapping technique. 4) Cell-free systems to investigate: lipoperoxidation of linoleate induced by γ-irradiation, Fe2+/ascorbate system or ferryl species; Quenching of hydroxyl radical (·OH) and singlet oxygen (1O2)-scavenging activity from Mallet’s (H2O2/NaOCl) and Fenton’ reactions.
Results: Ex-vivo assays show efficient protective effect of CAZ on plasmatic antiproteinases against oxidative stress; a dose-dependent inhibitory capacity on endothelial and A549 cells against MPO toxicity or excessive production of ROS during anoxia/reoxygenation. On cell-free systems, CAZ had unique 1O2–scavenging activity; and less effect on ferryl species. CAZ exerts its antioxidant effect by chelating activity.
Conclusions: Overall results indicate that: 1) CAZ protects endothelial cells against MPO toxicity but also A549 cells towards the effect of anoxia/reoxygenation; 2) CAZ protects α2M and 3) acts as efficient inhibitor of lipid peroxidation of linoleate and hydroxyl radical and as singlet oxygen-scavengers. Antioxidant properties of CAZ might be relevant in clinical situations where excessive activation of leukocytes is known and in anoxia/reoxygenation model cause an increased production of ROS.
Centre de l’Oxygène, Recherche et Développement - CORD
Université de Liège (Patrimoine, financement du voyage)
Researchers ; Professionals ; Others
http://hdl.handle.net/2268/61821

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