Background and Aims Fetal (FA) and perinatal asphyxia (PA) are major causes of neonatal morbidity and death worldwide. Although most studies are focused on the brain, FA and PA are known to be associated with multi-organ disease. Therefore, as part of the systemic impact, we aimed to investigate the hepatic inflammatory response after asphyxia.
Methods A clinical relevant rat model was used, inducing global asphyctic insults to reflect the human pathophysiology. At different time points (acute and chronic) after FA and PA, we assessed hepatic inflammation, ceramide signaling and hepatocellular damage. Additionally, we assessed whether the combination of both insults (preconditioning) would have any protective effect on the liver.
Results FA induced significant changes in inflammatory cytokines and ceramide metabolism genes with increased interleukin (IL)-1b mRNA at 6h, increased mRNA levels of IL-6, LAG1 homolog ceramide synthase 1 and ceramide transporters at 24h and finally, increased acid sphingomyelinase and sphingomyelin synthase 1 mRNA at 96h. Also PA induced an inflammatory response, with increased IL-6 and IL-10 levels 2h after birth. The combination of FA and PA (preconditioning) attenuated the inflammatory response, reflecting comparable IL-6 and IL-10 levels as control animals. 8 months after birth, no significant differences between groups were observed in hepatic mRNA levels for all cytokines and ceramide enzymes. Nevertheless, markers for hepatocellular damage, AST and ALP, showed increased levels when animals experienced FA and PA.
Conclusions FA and PA induce acute changes in hepatic cytokine and ceramide levels which may lead to hepatocellular damage in later life.