Neuroprotective Effects of AEOL10150 in a Rat Organophosphate Model.

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.

• Authors: Li-Ping Liang, Jennifer N Pearson-Smith, Jie Huang, Pallavi McElroy, Brian J Day, Manisha Patel
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 162 Issue 2 Pg. 611-621 (04 01 2018) ISSN: 1096-0929 [Electronic] United States
• PMID: 29272548 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• AEOL 10150
• Antioxidants
• Metalloporphyrins
• Neuroprotective Agents
• Isoflurophate

Topics

• Animals
• Antioxidants (therapeutic use)
• Disease Models, Animal
• Isoflurophate (toxicity)
• Male
• Metalloporphyrins (therapeutic use)
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (therapeutic use)
• Neurotoxicity Syndromes (metabolism, pathology, prevention & control)
• Oxidative Stress (drug effects)
• Rats, Sprague-Dawley