Allopurinol reduces severity of delayed neurologic sequelae in experimental carbon monoxide toxicity in rats

• Allopurinol ameliorated cognitive deficits in rats after CO exposure.
• Allopurinol decreased TNF-α, ICAM-1 and HMGB1 protein in the cerebral cortex and hippocampus.
• Allopurinol reduced neuronal death in the cerebral cortex and hippocampus.
• Allopurinol prevented microglial activation in the cerebral hippocampus and corpus callosum.
• Allopurinol reduced demyelination in the corpus callosum and the hippocampus in rats after CO exposure.

Approximately half of those who survive severe carbon monoxide (CO) poisoning develop delayed neurologic sequelae. Growing evidence supports the crucial role of free radicals in delayed brain injury associated with CO toxicity. Xanthine oxidase (XO) has been reported to play a pivotal role in the generation of reactive oxygen species (ROS) in CO poisoning. A recent report indicates that allopurinol both attenuated oxidative stress and possessed anti-inflammatory properties in an animal model of acute liver failure. In this study, we aimed to explore the potential of allopurinol to reduce the severity of delayed neurologic sequelae. The rats were first exposed to 1000 ppm CO for 40 min and then to 3000 ppm CO for another 20 min. Following CO poisoning, the rats were injected with allopurinol (50 mg/kg, i.p.) six times. Results showed that allopurinol significantly reduced neuronal death and suppressed expression of pro-inflammatory factors, including tumor necrosis factor-α, intercellular adhesion molecule-1, ionized calcium-binding adapter molecule 1, and degraded myelin basic protein. Furthermore, behavioral studies revealed an improved performance in the Morris water maze test. Our findings indicated that allopurinol may have protective effects against delayed neurologic sequelae caused by CO toxicity.