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Clozapine is an atypical antipsychotic widely used for schizophrenia patients.Although it shows therapeutic efficacy for both positive and negative symptoms in patients,this drug is associated with adverse metabolic effects thus decreases its compliance in schizophrenia patients.In this study,we examined possible if any effects of the antimalarial agent artesunate in rats chronically exposed to clozapine with the aim to seeking effective avenues for improving the clozapine-associated side effects.The adult male Wistar rats were intraperitoneally given artesunate(ART,3 mg/kg),clozapine(CLZ,10 mg/kg),both of ART and CLZ at the same doses(ART+CLZ),or saline(SAL),once a day for 6 weeks during which period the rats were weighed every week.Twenty-four hours after the last injection the elevated plus maze,Y-maze,and social interaction tests were performed with rats to evaluate their anxiety level,spatial working memory and social interaction.The blood samples were taken under deep anaethesia for biochemical analyses to measure lipid and carbohydrate metabolism indexes.The livers of anesthetized rats were removed and processed for before histology staining.Behavioral tests showed no differences between any groups.No differences in weight gain,glucose and insulin levels were found between any two groups.Although glutamic-pyruvic transaminase activity did not change by artesunate,the plasma glutamic-oxalacetic transaminase activity significantly increased in the CLZ group compared to SAL,but this increase was not seen in the other two groups.Likewise,the triglycerides levels significantly increased in the CLZ group compared to the SAL group,but not in the other two groups.No difference was found in the total cholesterol levels.Histochemical staining showed hepatic steatosis in liver tissue of CLZ-treated rats,as evidenced by fatty vacuoles in some hepatocytes of them.But,the hepatic steatosis was not shown in the other groups.These results confirmed the adverse effects of clozapine on lipid metabolism and hepatocytes.More significantly,it for the first time demonstrated a protective effect of artesunate on the clozapine-induced hepatic steatosis and dyslipidemia in rats thus has specific relevance to the prevention of clozapine-induced adverse effects on lipid metabolism and hepatic function in schizophrenia patients.