Olanzapine administration may induce inflammatory reactions with nitric oxide triggered lipid abnormality

초록

Chronic treatment with new atypical antipsychotic drug, olanzapine (OLZ) in schizophrenia patients is associated with the incidence of the adverse effects like hypertriglyceridemia, weight gain and obesity-induced diabetes. Nitric oxide (NO) overproduced by inducible NO synthase in the inflammatory reaction may trigger these lipid abnormalities. We hypothesized that OLZ-induced adverse effects might be accompanied by a low-grade systemic inflammatory reaction. The serum levels of major inflammatory markers like NO and prostaglandin E2 (PGE2) and lipid markers were determined in animal models treated with OLZ. OLZ administered to mice increased the average body weight compared to controls, whereas an iNOS selective inhibitor aminoguanidine (AG) prevented the OLZ-induced increase in body weight (p=0.043). In addition, in the OLZ-treated group, the serum levels of triglyceride (TG), glucose, NO, and PGE2 were significantly increased, whereas AG prevented these increases significantly. In particular, the serum NOx (nitrate+nitrite) concentration was positively correlated with TG values (p=0.0003, r2=0.6443). Furthermore, food intake after OLZ-treatment showed significant increase, but this increasewas prevented in a group co-treated with AG. Thus, we suggested that the atypical antipsychotic drug OLZ may induce the inflammatory reaction together with systemic increases in NO and PGE2 concentration, and the overproduced NO may trigger lipid abnormalities and hyperglycemic effect.