Cephalosporins Are Scavengers of Hypochlorous Acid

Biochem Pharmacol. 1995 May 11;49(9):1249-54. doi: 10.1016/0006-2952(95)00044-z.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Antioxidants / chemistry*
  • Carotenoids / chemistry
  • Cephalosporins / chemistry*
  • Glutathione / chemistry
  • Hypochlorous Acid / chemistry*
  • Microbial Sensitivity Tests
  • Oxidation-Reduction
  • beta Carotene

Substances

  • Antioxidants
  • Cephalosporins
  • beta Carotene
  • Carotenoids
  • Hypochlorous Acid
  • Glutathione