title: Allopurinol reduces severity of delayed neurologic sequelae in experimental carbon monoxide toxicity in rats.
abstract: 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.
authors.affiliation: Department of Emergency Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China. Electronic address: edoctor@medmail.com.cn.
authors.forename: Guangtao
authors.initials: G
authors.lastname: Dong
authors.affiliation: Department of Neurology, The Affiliated Hospital of Weifang Medical University, Weifang, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ren
authors.affiliation: Department of Emergency Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
authors.forename: Xiujie
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China. Electronic address: fenghonglin@aliyun.com.
authors.forename: Honglin
authors.initials: H
authors.lastname: Feng
mesh_terms: D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002249:Carbon Monoxide Poisoning / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D016923:Cell Death / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D000493:Allopurinol
keywords: Allopurinol; Carbon monoxide poisoning; Delayed neurologic sequelae; Inflammation; Myelin basic protein