Background: Oxidative stress contributes to hepatic ischaemia-reperfusion (IR) injury in a biphasic pattern. In addition to direct cytotoxic effects, oxidative stress also initiates the signal transduction processes that promote second-phase liver injury. The present study investigated the effects of the hydroxyl radical scavenger MCI-186 on the biphasic process of hepatic cold IR injury. Methods: After cold preservation for 16 h, rat livers were reperfused on an isolated liver perfusion system for 120 min with oxygenated Krebs-Henseleit bicarbonate buffer. Perfusate samples were obtained serially, and portal flow rates were also recorded. To determine whether MCI-186 affected cytokine levels that control the second-phase injury, levels of interleukin (IL) 10 and tumour necrosis factor (TNF) α were measured in the perfusate. Results: Addition of MCI-186 1 mg/l into the perfusate significantly improved portal flow (P < 0.050), hepatic enzyme release into the perfusate (P = 0.038), total bile production (P = 0.029) and malondialdehyde concentration (P = 0.038). Furthermore, treatment with MCI-186 led to a substantial increase in IL-10 release (P = 0.032). TNF-α levels were not affected. Conclusions: MCI-186, an agent ready for clinical use, appears to have direct and indirect protective effects against hepatic cold IR injury.
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