title: Edaravone attenuates brain damage in rats after acute CO poisoning through inhibiting apoptosis and oxidative stress.
abstract: Acute carbon monoxide (CO) poisoning is the most common cause of death from poisoning all over the world and may result in neuropathologic and neurophysiologic changes. Acute brain damage and delayed encephalopathy are the most serious complication, yet their pathogenesis is poorly understood. The present study aimed to evaluate the neuroprotective effects of Edaravone against apoptosis and oxidative stress after acute CO poisoning. The rat model of CO poisoning was established in a hyperbaric oxygen chamber by exposed to CO. Ultrastructure changes were observed by transmission electron microscopy (TEM). TUNEL stain was used to assess apoptosis. Immunohistochemistry and immunofluorescence double stain were used to evaluate the expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2) protein and their relationship. By dynamically monitored the carboxyhemoglobin (HbCO) level in blood, we successfully established rat model of severe CO poisoning. Ultrastructure changes, including chromatin condensation, cytoplasm dissolution, vacuoles formation, nucleus membrane and cell organelles decomposition, could be observed after CO poisoning. Edaravone could improve the ultrastructure damage. CO poisoning could induce apoptosis. Apoptotic cells were widely distributed in cortex, striatum and hippocampus. Edaravone treatment attenuated neuronal apoptosis as compared with the poisoning group (P < 0.01). Basal expressions of HO-1 and Nrf-2 proteins were found in normal brain tissue. CO poisoning could activate HO-1/Nrf-2 pathway, start oxidative stress response. After the administration of Edaravone, the expression of HO-1 and Nrf-2 significantly increased (P < 0.01). These findings suggest that Edaravone may inhibit apoptosis, activate the Keapl-Nrf/ARE pathway, and thus improve the ultrastructure damage and neurophysiologic changes following acute CO poisoning.
authors.affiliation: Emergency Centre, Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University Medical College, Yantai Shandong, 264000, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Emergency Centre, Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University Medical College, Yantai Shandong, 264000, People's Republic of China.
authors.forename: Ming Jun
authors.initials: MJ
authors.lastname: Bi
authors.affiliation: Department of Clinical Medicine, Qingdao University Medical College, Qingdao Shandong, 266003, People's Republic of China.
authors.forename: Wei Kang
authors.initials: WK
authors.lastname: Bi
authors.affiliation: Emergency Centre, Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University Medical College, Yantai Shandong, 264000, People's Republic of China.
authors.forename: Hai
authors.initials: H
authors.lastname: Kang
authors.affiliation: Emergency Centre, Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University Medical College, Yantai Shandong, 264000, People's Republic of China.
authors.forename: Le Jing
authors.initials: le J
authors.lastname: Yan
authors.affiliation: Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University Medical College, Qingdao Shandong, 266003, People's Republic of China.
authors.forename: Yun-Liang
authors.initials: YL
authors.lastname: Guo
mesh_terms: D000208:Acute Disease; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001927:Brain Diseases / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D002249:Carbon Monoxide Poisoning / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D000077553:Edaravone; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D051547:Heme Oxygenase-1; D000077553:Edaravone; D000983:Antipyrine
keywords: CO poisoning; HO-1; Nrf-2; apoptosis; edaravone; oxidative stress response; ultrastructure changes