Brain antioxidant responses to acute iron and copper intoxications in rats

Abstract

Dose- and time-dependent antioxidant responses to Fe (0–60 mg kg⁻¹) and Cu overloads (0–30 mg kg⁻¹) in rat brains are described by the C₅₀ and the t_1/2, the brain metal concentration and the time for half maximal oxidative responses. Brain GSH and the GSH/GSSG ratio markedly decreased after Fe and Cu treatments (50–80%) with a t_1/2 of 9–10 h for GSH and of 4 h for GSH/GSSG for both metals. The GSH/GSSG ratio was the most sensitive indicator of brain oxidative stress. The decrease of GSH and the increase of in vivo chemiluminescence had similar time courses. The C₅₀ for brain chemiluminescence, GSH and hydrophilic and lipophilic antioxidants were in similar ranges (32–36 μg Fe g⁻¹ brain and 10–18 μg Cu g⁻¹ brain), which indicated a unique free-radical mediated process for each metal. The brain concentration of hydrophilic and lipophilic antioxidants decreased after Fe and Cu loads; hydrophilic antioxidants decreased by 46–68% with a t_1/2 of 10–11 h and lipophilic antioxidants decreased by 75–45% with a t_1/2 of 10–12 h. Cu,Zn-SOD and CAT activities and the protein expression were adaptively increased (100–90% after Fe and Cu loads), with a t_1/2 of 8–12 h. GPx-4 activity decreased after both metal loads by 73–27% with a t_1/2 of 8–4 h with decreased protein expression.