Dexmedetomidine Attenuates Orthotopic Liver Transplantation-Induced Acute Gut Injury via α(2)-Adrenergic Receptor-Dependent Suppression of Oxidative Stress

Patients with orthotopic liver transplantation (OLT) frequently develop acute gut injury (AGI), and dexmedetomidine (Dex) has been reported to exert a protective effect against AGI. We investigated whether Dex protects against AGI through antioxidative stress effects by the Nrf2/HO-1 antioxidative signaling pathway. Rats were randomly allocated into a sham group and six orthotopic autologous liver transplantation (OALT) groups receiving different doses of Dex together with/without α(2)-adrenergic receptor (AR) blockers. Intestinal tissues were collected to visualize the barrier damage and to measure the indexes of oxidative stress. For in vitro studies, rat intestinal recess epithelial cells (IEC-6) underwent hypoxia/reoxygenation (H/R), and the protective role of Dex was evaluated after α(2A)-AR siRNA silencing. OALT resulted in increased oxidative stress, significant intestinal injury, and barrier dysfunction. Dex attenuated OALT-induced oxidative stress and intestinal injury, which was abolished by the pretreatment with the nonspecific α(2A)-AR siRNA blocker atipamezole and the specific α(2A)-AR siRNA blocker BRL-44408, but not by the specific (2B/C)-AR siRNA blocker ARC239. Silencing of α(2A)-AR siRNA also attenuated the protective role of Dex on alleviating oxidative stress in IEC-6 cells subjected to H/R. Dex exerted its protective effects by activating Nrf2/HO-1 antioxidative signaling. Collectively, Dex attenuates OALT-induced AGI via α(2A)-AR-dependent suppression of oxidative stress, which might be a novel potential therapeutic target for OALT-induced AGI.