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

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-AcAc) was reported to have the characteristics of increasing blood oxygen partial pressure (ppO) 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-AcAc against DCS in a rat model. A single dose of BD-AcAc 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-AcAc compared with those treated with saline ( < 0.05). Although BD-AcAc failed to reduce bubble load ( > 0.05), it showed an obvious decreasing trend. BD-AcAc significantly increased blood ppO and ameliorated oxidative and inflammatory responses, represented by increased plasma malondialdehyde (MDA), IL-1, IL-6, and TNF-α and decreased glutathione thiol ( < 0.05) levels, whereas blood pH remained unchanged ( > 0.05). These results suggest that BD-AcAc exerted beneficial effects on DCS rats mainly related to increasing ppO and anti-inflammatory and antioxidant properties. Together with its capacity for delaying central nervous system (CNS) oxygen toxicity seizures, BD-AcAc might be an ideal drug candidate for DCS prevention and treatment. This is the first study exploring the effects of BD-AcAc on DCS prevention, and it was proven to be an efficient and simple method. The role of BD-AcAc in increasing ppO, anti-inflammatory and antioxidant properties was thought to be the critical mechanism in DCS prevention.