올란자핀에 의한 급성염증반응

초록

Rationale: Chronic treatment with new atypical antipsychotic drug, olanzapine (OLZ) in schizophrenia patients are associated with the incidence of the adverse effects like hypertriglyceridemia, weight gain as well as obesity-induced diabetes. In healthy individuals, body mass index (BMI) and lipid abnormalities in overweight or obesity are strongly correlated with high concentrations of serum nitric oxide (NO), which plays an important role in inflammation. Furthermore, a positive association between BMI and C-reactive protein (CRP), a sensitive marker for systemic inflammation has been reported in healthy adults. Objectives: The goal of this study is to determine not only the serum levels of inflammatory markers like NO, CRP and prostaglandin E2 (PGE2), but also lipid level changes in animal models treated with OLZ. Methods: ICR male mice were used. Control (CON) and OLZ (n=8/cage) were administered for 27 d in the drinking water. In the isolated serum samples at the end of this experiment, concentrations of lipid markers [total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and TG] and inflammatory mediators [NO, PGE2 and CRP] were determined. These values were statistically evaluated by using Prism (Ver. 3.1) softwares. Results: In the OLZ-treated group, the serum levels of a typical lipid marker, TG and the products by inflammatory reactions like NO, PGE2 and CRP were significantly increased. In particular, the serum NOx (nitrate + nitrite) concentration was positively correlated with TG values (p=0.0003, r2 = 0.6443). Conclusions: We suggest that second-generation antipsychotic drug, OLZ may induce an inflammatory reactions together with systemic increase of NO and PGE2 concentrations, which released by iNOS and COX-2 overexpression, respectively.