Ketamine superinduces heme oxygenase-1(HO-1) in murine peritoneal macrophages after exposure to endotoxin (LPS)

Ketamine is a sympathomimetic anesthetic agent that has been recognized for its protective role in endotoxic shock and in LPS-induced lung injury. Antioxidant enzymes have been shown to provide protection against the deleterious effects of LPS. Here we chose to examine whether one such antioxidant enzyme and stress response gene heme oxygenase-1 (HO-1) may play a role in the ketamine-induced protective effect against LPS. Murine peritoneal macrophages (RAW 264.7 cells) were exposed to LPS (1 μg/ml) in the presence or absence of ketamine and the steady state levels of HO-1 mRNA were determined by Northern blot analysis. LPS treatment induced HO-1 mRNA levels in RAW 264.7 cells in a time and dose dependent manner. When cells were pretreated with ketamine (10 μg/ml) for 1 h prior to exposure to LPS (1 μg/ml), we observed that ketamine caused a superinduction of HO-1 mRNA. Ketamine alone also induced HO-1 mRNA levels in RAW 264.7 cells. Our data suggest that the stress response gene HO-1 may play a role in ketamine-induced protection against LPS.