Background: Bilirubin encephalopathy, the most serious complication of hyperbilirubinemia during the neonatal period, with high mortality and morbidity, often causes irreversible neurological damage. Currently, caspase-1, a member of the cysteinyl aspartate-specific protease caspase family, is regarded as a key mediator of inflammatory processes, attracting widespread attention. The purpose of this study was to investigate whether caspase-1 is involved in bilirubin-induced neuronal injury.
Methods: VX-765, a highly potent and selective inhibitor of caspase-1, was used to investigate the effects of unconjugated bilirubin (UCB) on rat cortical neurons, including cell viability, morphological changes in the cell membrane, and nuclear factor-kappa B (NF-κB) activation.
Results: Neurons treated with UCB showed increased caspase-1 activity without the secretion of interleukin (IL)-1β and IL-18, and caspase-1 was significantly inhibited by pretreatment with VX-765. The cell viability of the VX-765-pretreated neurons was improved, and cell membrane rupture was prevented, as detected by lactate dehydrogenase release and ethidium bromide uptake. Moreover, NF-κB activation by UCB exposure, was attenuated by VX-765 pretreatment.
Conclusion: Bilirubin-induced neuronal injury involves the activation of caspase-1 and NF-κB, leading to membrane leakage, independently of IL-1β and IL-18.