Effects of Tacrolimus on Antioxidant Status and Oxidative Stress in Glioma Cells

Abstract

Objectives. After organ transplantation, some patients suf fer from mild neurologic symptoms, ranging from tremor to severe complications, including seizures and encepha- lopathy. Among the immunosuppressants, tacrolimus can cause neurologic side ef fects. However, the mechanisms of encephalopathy by tacrolimus are not fully understood. We measured the antioxidant status, hydrogen peroxide level, and malondialdehyde level in glioma cells after tacrolimus treatment. Methods. The production of hydrogen peroxide was determined by the modified xylenol orange method. The amount of malondialdehyde was measured by the thiobarbituric acid assay, which is based on malondialdehyde reaction with thiobarbituric acid to give a red species absorbing at 535 nm. Total antioxidant status (TAS) was measured using TAS kits (NX2332). Results. Tacrolimus resulted in dose- and time-dependent increases in the production of hydrogen peroxide by glioma cells. The antioxidant status decreased in the glioma cells after tacrolimus treatment. Malondialdehyde level was unchanged in the glioma cells after tacrolimus treatment. Conclusions. Increased production of reactive oxygen species and decreased antioxidant status by tacrolimus in glioma cells may contribute to neurologic side ef fects.