Perfluorocarbon-facilitated CNS oxygen toxicity in rats: reversal by edaravone.
Perfluorocarbon (PFC) has been hypothesized to potentially increase the risk of central nervous system oxygen toxicity (CNS-OT) under hyperbaric oxygen (HBO) conditions. However, little is known about the effects, mechanism and prevention of PFC-facilitated CNS-OT. A rat model of CNS-OT was used to evaluate the effects of intravenously-administered PFC emulsion. The electroencephalogram (EEG) was recorded during treatment with HBO(2) at 6.0 ATA in the presence and absence of PFC. Concentrations of malondialdehyde (MDA), nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) in the brain cortex and hippocampus were quantified. Changes in the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and NO synthase (NOS) in the brain cortex and hippocampus were also determined. Edaravone, a potent antioxidant, was used to prevent PFC-facilitated CNS-OT. The results showed that after PFC administration, the latency to first electrical discharge in EEG was significantly shortened; MDA, H(2)O(2), NO levels and NOS activity increased; and SOD, GPx and CAT activities decreased. Edaravone effectively protected against CNS-OT and the adverse effects of PFC. The results clearly demonstrate that PFC administered before HBO(2) would promote the occurrence of CNS-OT, and edaravone could serve as a promising chemoprophylactic agent to prevent CNS-OT.
Department of Diving Medicine, the Second Military Medical University, Shanghai 200433, P.R. China.
Shulin
S
Liu
Runping
R
Li
Xiaoxiao
X
Ni
Zhiyu
Z
Cai
Rongjia
R
Zhang
Xuejun
X
Sun
Raymond M
RM
Quock
Weigang
W
Xu
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D004357:Drug Synergism; D000077553:Edaravone; D004569:Electroencephalography; D005466:Fluorocarbons / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010100:Oxygen / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D005466:Fluorocarbons; D016166:Free Radical Scavengers; D009569:Nitric Oxide; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D000077553:Edaravone; D010100:Oxygen; D000983:Antipyrine