Effect of benzoyl peroxide on antioxidant status, NF-kappaB activity and interleukin-1alpha gene expression in human keratinocytes.

Benzoyl peroxide (BP) is used as a topical treatment for acne. Besides its anti-bacterial activity, the exact molecular mechanisms underlying its mode of action are not fully understood. In the current study, the effects of BP on cell viability, antioxidant status and, IL-1 and IL-8 gene expression were investigated in HaCaT keratinocytes. Keratinocytes incubated for 24 h with BP exhibited a dose-dependent cytotoxicity at concentrations above 250 microM. Furthermore, in the presence of 300 microM BP about 50% of the cellular vitamin E was depleted within the first 30 min. The intracellular ratio of oxidized to reduced glutathione (GSSG/GSH) was increased significantly starting 6 h after BP treatments indicating that BP reacts rapidly with targets in the cell membrane and more slowly with those in the cytosol. NF-kappaB transactivation was not significantly affected by BP. However, BP treatment of HaCaT keratinocytes resulted in a dose-dependent increase in IL-1alpha gene expression whereas no changes in IL-8 mRNA levels were observed. These results demonstrate that BP induces an inflammatory reaction mediated by oxidative stress by a pathway independent of the redox-sensitive transcription factor NF-kappaB