The protective effects of 1,3-butanediol acetoacetate diester on decompression sickness in rats.

Abstract

Inert gas bubbles are widely accepted as the causative factor of decompression sickness (DCS), resulting in gas embolism and systemic inflammatory responses. The anticonvulsive ketone ester 1,3-butanediol acetoacetate diester (BD-AcAc2) was reported to have the characteristics of increasing blood oxygen partial pressure (ppO2) and anti-inflammation and was thought to have the potential to reduce bubble formation and alleviate the pathological process of DCS. This study aims to investigate the potential protection of BD-AcAc2 against DCS in a rat model. A single dose of BD-AcAc2 was administered orally to adult male rats (5 g/kg body wt), followed by pharmacokinetic analysis or simulated air dives. After decompression, signs of DCS were monitored, and blood was sampled for biochemical measurements. Blood ketosis peaked at 2 h and lasted for more than 4 h. The incidence of DCS was decreased and postponed significantly in rats treated with BD-AcAc2 compared with those treated with saline (P < 0.05). Although BD-AcAc2 failed to reduce bubble load (P > 0.05), it showed an obvious decreasing trend. BD-AcAc2 significantly increased blood ppO2 and ameliorated oxidative and inflammatory responses, represented by increased plasma malondialdehyde (MDA), IL-1, IL-6, and TNF-α and decreased glutathione thiol (P < 0.05) levels, whereas blood pH remained unchanged (P > 0.05). These results suggest that BD-AcAc2 exerted beneficial effects on DCS rats mainly related to increasing ppO2 and anti-inflammatory and antioxidant properties. Together with its capacity for delaying central nervous system (CNS) oxygen toxicity seizures, BD-AcAc2 might be an ideal drug candidate for DCS prevention and treatment.NEW & NOTEWORTHY This is the first study exploring the effects of BD-AcAc2 on DCS prevention, and it was proven to be an efficient and simple method. The role of BD-AcAc2 in increasing ppO2, anti-inflammatory and antioxidant properties was thought to be the critical mechanism in DCS prevention.