Anti-inflammatory actions of benzoyl peroxide: effects on the generation of reactive oxygen species by leucocytes and the activity of protein kinase C and calmodulin.
For many years, benzoyl peroxide has been used as a topical treatment for acne. Although the drug has been shown to interfere with a variety of pathways, believed to be of importance in the aetiopathogenesis of acne, its mechanism of action is thought to be principally antibacterial. Recent circumstantial evidence suggests that protein kinase C might serve as an additional pharmacological target of benzoyl peroxide. In the present study, we investigated the effects of benzoyl peroxide on the release of reactive oxygen species, regulated by protein kinase C and calmodulin, from human neutrophils, a potentially important step in acne inflammation. Micromolar drug concentrations were found to inhibit the release of reactive oxygen species, but there was marked drug-induced cytotoxicity in neutrophils. However, when tested in cell-free assays, benzoyl peroxide displayed marginal inhibition of protein kinase C, but failed to antagonize calmodulin. Further investigations on its mechanism of action revealed non-specific interference with nucleotide binding sites. Therefore, the data presented here indicate that, in contrast with our previous findings with tetracycline derivatives, the clinical anti-inflammatory activity of benzoyl peroxide is unlikely to be mediated by protein kinase C or calmodulin. The differential interaction of drugs with protein kinase C and calmodulin might help to explain their different clinical usefulness in various degrees of acne severity.
Hegemann
L
L
Department of Dermatology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Toso
S M
SM
Kitay
K
K
Webster
G F
GF
D000152:Acne Vulgaris / Q000188:drug therapy / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001585:Benzoyl Peroxide / Q000494:pharmacology* / Q000627:therapeutic use; D002147:Calmodulin / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002147:Calmodulin; D017382:Reactive Oxygen Species; D011493:Protein Kinase C; D001585:Benzoyl Peroxide