Glutathione cycle in diquat neurotoxicity: Assessed by intrastriatal pre-treatment with glutathione reductase

Abstract

Diquat (DQ) neurotoxicity mechanisms are unknown, although, it's systemic toxicity is mediated by free radical reactions. The role of glutathione cycle was assessed by glutathione reductase (GR) applied in the pre-treatment of DQ poisoning. Wistar rats were used and tested compounds were administered intrastriatally (i.s.) in one single dose. Total glutathione (tGSH), glutathione disulfide (GSSG) and glutathione peroxidase (GPx) were measured in the vulnerable brain regions (VBRs) (striatum, hippocampus and cortex), at 30 minutes, 24 hours and 7 days post treatment. Results from the intact and the sham operated groups were not statistically different. Rapid spatial spreading of oxidative stress was confirmed in the examined VBRs. Mortality (30-40%, within 24hrs) and signs of lethargy were observed in the DQ group. Activity of GPx activity was elevated and GSSG/GSH was higher in the examined VBRs during the experiment, compared to the controls. The i.s. pre-treatment with GR achieved neuroprotective role against DQ induced neurotoxicity, based on animal survival, absence of lethargy and decreased GPx activity and GSSG/GSH in the examined VBRs during the experiment, compared to the DQ group. Our results confirmed that oxidation of GSH was the reason for the reduced antioxidative defense against DQ neurotoxicity. [Projekat Ministarstva nauke Republike Srbije, br. III41018]

Keywords

• diquat
• glutathione
• glutathione disulfide
• glutathione peroxidase
• glutathione reductase
• neurotoxicity