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

Abstract

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. 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. 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 < .01 for 20 and 30 mg/kg of l-NAME). 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.