Dexmedetomidine attenuates oxidative/nitrative stress in lung tissues of septic mice partly via activating heme oxygenase-1.

Excessive reactive oxygen/nitrogen species are considered to be one of the primary events that cause lung injury during sepsis. The present study aimed to determine whether dexmedetomidine (Dex) exhibits antioxidative and antinitrative effects on sepsis-induced lung injury and its effect on heme oxygenase-1 (HO-1) activation. The cecal ligation and puncture (CLP) mouse model was used, where male C57BL/6J mice were randomized into groups: Sham, CLP, Dex and Dex + zinc protoporphyrin (ZnPP). Following CLP or sham operation, intraperitoneal injections of 40 µg/kg Dex or saline were administered in the Dex + ZnPP group, intraperitoneal injections of ZnPP (40 mg/kg) were administered 1 h prior to the CLP operation. Subsequently, histopathological examination of the lungs and measurement of HO-1 activity in the lung, as well as oxidative and nitrative stress were determined 24 h following CLP. Dex significantly decreased the levels of oxidative and nitrative stress, as demonstrated by the decreased levels of malondialdehyde and nitrotyrosine, and the protein expression of inducible nitric oxide synthase, as well as increased superoxide dismutase in lung tissues. Also Dex inhibited the elevation of serum interleukin-6 and tumor necrosis factor-α and increased lung HO-1 activity. Furthermore, the effects of Dex were partially reverted by the HO-1 inhibitor ZnPP. In conclusion, Dex inhibited oxidative/nitrative stress in sepsis and attenuated sepsis-induced acute lung injury partially by increasing HO-1 activity.