Neuroprotective Effects of AEOL10150 in a Rat Organophosphate Model. (20th December 2017)

• Record Type: Journal Article
• Authors: Liang, Li-Ping; Pearson-Smith, Jennifer N; Huang, Jie; McElroy, Pallavi; Day, Brian J; Patel, Manisha
• Is Part Of: Toxicological sciences. Volume 162:Number 2(2018)
• Page Start: 611
• Page End: 621
• Publication Date: 2017-12-20
• Subjects: seizures -- antioxidant -- oxidative stress -- neuroinflammation -- diisopropylflurorphoshate -- pharmacokinetic analysis; Toxicology -- Periodicals; Toxicology -- Periodicals; Toxicology; Periodicals; 615.9
• DOI: 10.1093/toxsci/kfx283
• Languages: English
• ISSNs: 1096-6080

Abstract

Abstract: Prolonged seizure activity or status epilepticus (SE) is one of the most critical manifestations of organophosphate exposure. Previous studies in our laboratory have demonstrated that oxidative stress is a critical mediator of SE-induced neuronal injury. The goal of this study was to determine if diisopropylflurorphoshate (DFP) exposure in rats resulted in oxidative stress and whether scavenging reactive oxygen species attenuated DFP-induced neurotoxicity. DFP treatment increased indices of oxidative stress in a time- and region- dependent manner. Neuronal loss measured by Fluoro-Jade B staining was significantly increased in the hippocampus, piriform cortex and amygdala following DFP. Similarly, levels of the proinflammatory cytokines, particularly TNF-α, IL-6, and KC/GRO were significantly increased in the piriform cortex and in the hippocampus following DFP treatment. The catalytic antioxidant AEOL10150, when treatment was initiated 5 min after DFP-induced SE, significantly attenuated indices of oxidative stress, neuroinflammation and neuronal damage. This study suggests that catalytic antioxidant treatment may be useful as a novel therapy to attenuate secondary neuronal injury following organophosphate exposure.