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.
Keywords: BD-AcAc2; anti-inflammation; antioxidation; bubble formation; decompression sickness.