Pentoxifylline-supplemented resuscitation attenuates both early and late mediators of hepatic inflammation after hemorrhagic shock

摘要

Objective. After hemorrhage, resuscitation with racemic Ringer's lactate (RL) results in hepatic injury and an increase in pro-inflammatory mediator synthesis. The aim of this study was to determine the effect of resuscitation including pentoxifylline (PTX) on mediators of hepatic inflammation after hypovolemic shock. Material and methods. Male Sprague-Dawley rats underwent 1 h of hypotension followed by resuscitation with RL or RL+PTX (25 mg/kg). Liver sections were scored for injury histologically. Nitric oxide and pro-inflammatory cytokines were measured using an enzyme-linked immunosorbent assay. Inducible nitric oxide synthase (iNOS) and high mobility group box 1 (HMGB1) content were evaluated by means of Western blotting. Results. In the presence of PTX, histologic hepatic injury was markedly less than with RL resuscitation (p < 0.05). Furthermore, the addition of PTX to RL significantly attenuated the hepatic concentrations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, iNOS, NO and HMGB1 (p < 0.05). Conclusion. PTX-supplemented resuscitation effectively attenuates RL-induced hepatic injury after hemorrhagic shock through downregulation of both early and late mediators of inflammation.