Alprostadil alleviates liver injury in septic rats via TLR4/NF-κB pathway.

Abstract

The aim of this study was to explore the role of alprostadil (Alp) in cecal ligation and puncture (CLP)-induced septic injury in rats and its possible mechanism of action. Wistar rats were randomly assigned into three groups, including: Sham group (no CLP was performed), CLP group (CLP was conducted) and Alp group (Alp was injected after CLP). Serum liver function markers, pathological changes in liver tissues, alterations in the level of oxidative stress, activity of the Toll-like receptor 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, and release of inflammatory factor tumor necrosis factor alpha (TNF-α) in the liver tissue homogenate were detected in each group. Compared with Sham group, the rats in CLP group had substantially elevated content of serum liver function markers, increased apoptotic liver cells, upregulated levels of oxidative stress, enhanced activity of the TLR4/NF-κB pathway, and increased release of TNF-α (p<0.05). Meanwhile, there were evident pathological changes under microscopic examination in CLP group compared with Sham group (p<0.05). In comparison with CLP group, Alp group exhibited significantly decreased concentrations of liver function markers, microscopic findings, such as decreased inflammatory cell infiltration in the interstitum, notably lowered proportion of apoptotic cells, decreased level of oxidative stress, weakened activity of the TLR4/NF-κB pathway and restrained release of TNF-α (p<0.05). Furthermore, normal morphology of liver cells was observed in Alp group compared with CLP group (p<0.05). Alp alleviates liver injury in septic rats by inhibiting the TLR4/NF-κB pathway.