Oxidant-Scavenging Activities of Beta-Lactam Agents
; ; et al
in European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology (1998), 17(1), 43-6
The relative antioxidant effect of ampicillin, ceftazidime, ceftriaxone, and cefuroxime on oxygen-reactive species was examined in vitro using stimulated human polymorphonuclear neutrophils. There was no ... [more ▼]
The relative antioxidant effect of ampicillin, ceftazidime, ceftriaxone, and cefuroxime on oxygen-reactive species was examined in vitro using stimulated human polymorphonuclear neutrophils. There was no evidence that any of the beta-lactam agents tested had an effect on superoxide or H2O2 generation. In contrast, all of the beta-lactam agents prevented hypochlorous acid (HOCI) chlorination of 1,1-dimethyl-4-chloro-3,5-cyclo-hexanedione in a cell-free system at concentrations of < 10 microg/ml. Furthermore, all antibiotics provided dose-dependent protection against HOCI cytotoxicity to 16HBE140 bronchial epithelial cells. Taken together, these data indicate a possible therapeutic role for beta-lactam agents in protecting host tissues from HOCI-induced oxidative damage. [less ▲]Detailed reference viewed: 16 (1 ULg)
The antibiotic ceftazidime is a singlet oxygen quencher as demonstrated by ultra-weak chemiluminescence and by inhibition of AAP consumption.
Deby, Ginette ; ; Mouithys-Mickalad, Ange et al
in Biochimica et Biophysica Acta (1998), 1379(1), 61-8
We demonstrated that the cephalosporin antibiotic ceftazidime (CAZ) deactivated singlet oxygen (1O2). We then studied the mechanisms of the CAZ effects on the ultra weak chemiluminescence (uwCL ... [more ▼]
We demonstrated that the cephalosporin antibiotic ceftazidime (CAZ) deactivated singlet oxygen (1O2). We then studied the mechanisms of the CAZ effects on the ultra weak chemiluminescence (uwCL) associated with the energy decay of 1O2 generated by the Mallet reaction (H2O2 + HOCl --> HCl + H2O + 1O2), and on the anthracene-9,10-dipropionic acid (AAP) consumption by 1O2 generated by irradiation of Rose Bengal (RB). The uwCL generated by the Mallet reaction was amplified (6.2 times) by CAZ. The use of red and blue filters, which absorb radiation below 610 nm and between 470 and 700 nm respectively, demonstrated that CAZ increased the uwCL by a radiation emission at wavelengths shorter than the 633 and 704 nm wavelength emissions of 1O2. CAZ was excited by scavenging the energy excess of 1O2, which so returned to its fundamental state, while CAZ deactivated with light emission between 430-480 nm. CAZ also inhibited in a dose-dependent manner the consumption of AAP by 1O2 generated by the irradiation of RB. The protection of AAP by 5 x 10(-3) M CAZ was equivalent to that of 10(-3) M histidine and 3 X 10(-6) M sodium azide. This process of 1O2 deactivation will be useful in diseases characterized by an excessive PMN activation with a release of activated oxygen species. [less ▲]Detailed reference viewed: 105 (18 ULg)
Cytotoxicity towards human endothelial cells, induced by neutrophil myeloperoxidase: protection by ceftazidime.
Mathy, Marianne ; Deby, Ginette ; et al
in Mediators of Inflammation (1995), 4(6), 437-43
We investigated the effects of the antibiotic ceftazidime (CAZ) on the cytolytic action of the neutrophil myeloperoxidase-hydrogen peroxide-chloride anion system (MPO/H(2)O(2)/Cl(-)). In this system ... [more ▼]
We investigated the effects of the antibiotic ceftazidime (CAZ) on the cytolytic action of the neutrophil myeloperoxidase-hydrogen peroxide-chloride anion system (MPO/H(2)O(2)/Cl(-)). In this system, myeloperoxidase catalyses the conversion of H(2)O(2) and CI(-) to the cytotoxic agent HOCl. Stimulated neutrophils can release MPO into the extracellular environment and then may cause tissue injury through direct endothelial cells lysis. We showed that human umbilical vein endothelial cells (HUVEC) were capable of taking up active MPO. In presence of H(2)O(2) (10(-4) M), this uptake was accompanied by cell lysis. The cytolysis was estimated by the release of (51)Cr from HUVEC and expressed as an index of cytotoxicity (IC). Dose dependent protection was obtained for CAZ concentrations ranging from 10(-5) to 10(-3) M;this can be attributed to inactivation of HOCl by the drug. This protection is comparable to that obtained with methionine and histidine, both of which are known to neutralize HOCl. This protection by CAZ could also be attributed to inactivation of H(2)O(2), but when cytolysis was achieved with H(2)O(2) or O(2) (-) generating enzymatic systems, no protection by CAZ was observed. Moreover, the peroxidation activity of MPO (action on H(2)O(2)) was not affected by CAZ, while CAZ prevented the chlorination activity of MPO (chlorination of monochlorodimedon). So, we concluded that CAZ acts via HOCl inactivation. These antioxidant properties of CAZ may be clinically useful in pathological situations where excessive activation of neutrophils occurs, such as in sepsis. [less ▲]Detailed reference viewed: 39 (5 ULg)