Cephalosporins are scavengers of hypochlorous acid.
Potential scavenging properties of cephalosporins (i.e. cefamandole, cefotaxime and ceftriaxone) towards hypochlorous acid (HOCl) as well as the antibacterial activity of control and HOCl-reacted antibiotics were investigated. We found that these drugs, at therapeutically relevant concentrations, are indeed scavengers of HOCl, with ceftriaxone showing the highest anti-HOCl capacity. However, the efficiency of cephalosporins in protecting biological molecules is also related to the chemical identity of such molecules. Indeed, the polyenoic compound beta-carotene is much better protected that the thiol compound GSH against HOCl attack. Moreover, the drugs do not appear to form chloramine derivatives as a result of their reaction with HOCl, and they inhibit taurine-chloramine formation. After HOCl challenge, the antibacterial activity of cefamandole, cefotaxime and ceftriaxone (tested against the standard strain Escherichia coli ATCC 25922) is approx. 8-, 5- and 4-fold lower, respectively, than that of the HOCl-unreacted antibiotics. The depression of the antibacterial activity of cephalosporins appears inversely related to their HOCl scavenging capacity, suggesting that the drug antioxidant groups may protect the beta-lactam ring against HOCl attack. In conclusion, physiological biomolecules are protected by cephalosporins against HOCl-driven oxidative injury with varying efficiency, this antioxidant defence being a consequence of a direct drug scavenging capacity towards HOCl. The interaction of cephalosporins with HOCl, however, results in a depression of their antibacterial activity.
Lapenna
D
D
Istituto di Fisiopatologia Medica, Universita' degli Studi G. D'Annunzio, Facolta' di Medicina e Chirurgia, Chieti, Italy.
Cellini
L
L
De Gioia
S
S
Mezzetti
A
A
Ciofani
G
G
Festi
D
D
Cuccurullo
F
F
D000975:Antioxidants / Q000737:chemistry*; D002338:Carotenoids / Q000737:chemistry; D002511:Cephalosporins / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry; D006997:Hypochlorous Acid / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D010084:Oxidation-Reduction; D019207:beta Carotene
D000975:Antioxidants; D002511:Cephalosporins; D019207:beta Carotene; D002338:Carotenoids; D006997:Hypochlorous Acid; D005978:Glutathione