Hongjie Yi1, Shichong Yu2, Yanan Zhang1, Runping Li1, Dazhi Zhang1, Dazhi Zhang1, Weigang Xu1,3. 1. Department of Diving and Hyperbaric Medicine, Naval Medical University, Shanghai, P R China. 2. Department of Organic Chemistry, Naval Medical University, Shanghai. 3. Corresponding author: Department of Diving and Hyperbaric Medicine, Naval Medical University, Shanghai 200433, China, wg_hsu@163.com.
Abstract
BACKGROUND: Recent studies indicated that ketone ester R,S-1,3-butanediol acetoacetate diester (BD-AcAc2) may be effective in preventing central nervous system oxygen toxicity (CNS-OT) and concomitant acute lung injury, a serious medical problem to be faced when breathing hyperbaric oxygen (HBO). This study aimed to further investigate the protective effects of BD-AcAc2 against CNS-OT and concomitant acute lung injury (ALI) in mice. METHODS: Mice were treated with BD-AcAc2 in peanut oil vehicle (2.5, 5.0 or 10.0 g·kg⁻² body weight) by gavage 20 minutes before 600 kPa HBO exposure. Control mice received the vehicle only. Seizure latency was recorded. Malondialdehyde content in brain and lung tissues, total protein level in bronchoalveolar lavage fluid (BLF) and lung water content were measured 60 minutes after the hyperbaric exposure. Histopathology of lung tissue was undertaken. RESULTS: Compared with the vehicle alone, BD-AcAc2 prolonged seizure latency in a dose-dependent manner (P < 0.01). The HBO-induced increase in brain malondialdehyde, BLF protein and lung water were significantly reduced by BD-AcAc2 (P < 0.01). CONCLUSION: Oral administration of the ketone ester BD-AcAc2 significantly protected against CNS-OT and concomitant ALI. Alleviation of oxidative stress may be one underlying mechanism providing this effect. Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.
BACKGROUND: Recent studies indicated that ketone ester R,S-1,3-butanediol acetoacetate diester (BD-AcAc2) may be effective in preventing central nervous system oxygentoxicity (CNS-OT) and concomitant acute lung injury, a serious medical problem to be faced when breathing hyperbaric oxygen (HBO). This study aimed to further investigate the protective effects of BD-AcAc2 against CNS-OT and concomitant acute lung injury (ALI) in mice. METHODS:Mice were treated with BD-AcAc2 in peanut oil vehicle (2.5, 5.0 or 10.0 g·kg⁻² body weight) by gavage 20 minutes before 600 kPa HBO exposure. Control mice received the vehicle only. Seizure latency was recorded. Malondialdehyde content in brain and lung tissues, total protein level in bronchoalveolar lavage fluid (BLF) and lung water content were measured 60 minutes after the hyperbaric exposure. Histopathology of lung tissue was undertaken. RESULTS: Compared with the vehicle alone, BD-AcAc2 prolonged seizure latency in a dose-dependent manner (P < 0.01). The HBO-induced increase in brain malondialdehyde, BLF protein and lung water were significantly reduced by BD-AcAc2 (P < 0.01). CONCLUSION: Oral administration of the ketone ester BD-AcAc2 significantly protected against CNS-OT and concomitant ALI. Alleviation of oxidative stress may be one underlying mechanism providing this effect. Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.
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