Differences in antioxidant enzyme activity in adverse drug reactions

Abstract

Rationale In adverse drug reactions with an immunological basis (ADRIB) innate systems can also be activated, amplifying the specific response and making it more severe and long-lasting. Reactive oxygen species (ROS) are involved in inflammatory processes including allergic diseases. We studied differences in the in vivo antioxidant enzyme activities in patients with immediate, accelerated and delayed reactions to drugs. Methods Determinations of enzymatic activity of catalase, copper-zinc superoxide dismutase (Cu, Zn-SOD) and cellular glutathione peroxidase (cGPX), and oxidative damage (TBARS and carbonyl content) were undertaken in peripheral blood mononuclear cells using spectrophotometry. Results We evaluated 38 patients with ADRIB: 12 immediate, 8 accelerated and 18 delayed. Catalase and Cu, Zn-SOD activity were increased in patients with immediate and delayed reactions versus controls (p=0.011 and p=0.004 for catalase and p=0.002 and p=0.001 for Cu, Zn-SOD). However cGPX showed a significant decrease compared to controls in immediate, accelerated and delayed reactions (p=0.035, p=0.002 and p=0.002). The oxidative damage was significantly increased in TBARS and in carbonyl in all types of reaction. Conclusions An oxidative damage in ADRIB exists. Although there is a significant increase in catalase and superoxide dismutase in immediate and delayed reactions, the important decrease in all three groups of glutathione peroxidase seems to be related with the oxidative damage observed. Whether this is a primary drug effect in a subset of individuals or a consequence of the reaction is at present unknown.