Glutathione metabolism in mice is enhanced more with hapten-induced allergic contact dermatitis than with irritant contact dermatitis

Abstract

Cutaneous inflammation induced by electrophilic compounds involves irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). Reduced glutathione (GSH) and related thiols have been postulated to play important roles in detoxification of electrophilic xenobiotics, protection of tissues against reactive oxygen species, and modulation of immunologic functions in normal and diseased subjects. The dynamic aspects of GSH metabolism, however, and its significance in patients with ICD and ACD remain to be clarified. The current study was carried out to elucidate the pathogenesis and possible involvement of GSH in both types of inflammation. Normal mice and mice sensitized with dinitrochlorobenzene (DNCB) were challenged by cutaneous administration of DNCB, and changes in GSH metabolism in skin and liver were determined. Kinetic analysis revealed that 24 h after challenge with DNCB, levels of hepatic glutathione and its secretion increased more markedly in the sensitized mice than in the unsensitized animals. Administration of buthionine-L-sulfoximine (BSO), a specific inhibitor of GSH synthesis, inhibited the increase in glutathione levels in the liver and the skin of both groups. Histologic examination revealed that cutaneous inflammation was enhanced by BSO more significantly in mice with ACD than with ICD. These results suggest that GSH might play an important role in the suppression of the immune reaction in mice with ACD.