The Role of Dexmedetomidine in Hepatic Ischemia-Reperfusion Injury Via a Nitric Oxide-Dependent Mechanism in Rats

Background Dexmedetomidine is known to protect against ischemia-reperfusion (IR) in various organs; however, the mechanisms of dexmedetomidine in the liver remain unclear. We investigated whether dexmedetomidine preconditioning leads to hepatic protection and whether nitric oxide was associated with this protective mechanism by employing N-nitro- l -arginine methyl ester ( l -NAME), a nitrous oxide synthase inhibitor. Methods Experiment 1 included 24 rats in 4 groups: sham, IR, 30 μg/kg of dexmedetomidine, and 50 μg/kg of dexmedetomidine. Experiment 2 included 36 rats in 6 groups: IR, 50 μg/kg of dexmedetomidine, 10 mg/kg of l -NAME, 10 mg/kg of l -NAME + 50 μg/kg of dexmedetomidine, 30 of mg/kg l -NAME, and 30 mg/kg of l -NAME + 50 μg/kg of dexmedetomidine. All drugs were administered intraperitoneally. The levels of serum transaminases, malondialdehyde, superoxide dismutase, tumor necrosis factor-α, nuclear factor-κB, and c-Jun N-terminal kinase were measured 6 hours after hepatic surgery. Results Dexmedetomidine demonstrated a dose-dependent decrease in serum transaminase levels. The 50-μg/kg dexmedetomidine group showed a significant decrease in malondialdehyde levels (P = .002), increase in superoxide dismutase levels (P = .002), and a significantly lower level of phosphorylated tumor necrosis factor-α, nuclear factor-κB, and c-Jun N-terminal kinase (P = .002, respectively) compared with the IR injury group. These protective effects of dexmedetomidine were partially reversed by pretreatment with l -NAME (P l -NAME). Conclusion In hepatic IR injury, dexmedetomidine might protect the liver via antioxidative and anti-inflammatory responses, and nitric oxide production could play a role in these protective mechanisms.