Lipid peroxidation is one of the major outcomes of free radical-mediated injury to tissue in vivo, including the central nervous system (CNS). The aim of this study was to examine whether malathion, a commonly used organophosphorus (OP), might induce oxidative stress in cerebrospinal fluid, blood serum and brain structures in male Wistar rats. Malathion was administered intraperitoneally in the doses of 25, 50, 100 and 150 mg/kg for 28 days. Oxidative damage was determined by measuring the thiobarbituric acid reactive species (TBARS) content, as an index of lipid peroxidation. TBARS concentration in the cerebrospinal fluid (CSF) and brain structures were increased, but a decrease in TBARS concentration in serum was observed. The results of the present study suggest the usefulness of TBARS measurement as a good biomarker in the estimation of malathion-induced oxidative stress affecting CSF and brain structures.
Recently, a fixed combination of the atypical antipsychotic olanzapine and the serotonin selective reuptake inhibitor (SSRI) fluoxetine has been approved in the US for the treatment of bipolar I depression. In this work, we evaluated the effect of acute and chronic administration of fluoxetine, olanzapine and the combination of fluoxetine/olanzapine on creatine kinase (CK) activity in the brain of rats. For acute treatment, adult male Wistar rats received one single injection of olanzapine (3 or 6 mg/kg) and/or fluoxetine (12.5 or 25mg/kg). For chronic treatment, adult male Wistar rats received daily injections of olanzapine (3 or 6 mg/kg) and/or fluoxetine (12.5 or 25mg/kg) for 28 days. In the present study we observed that acute administration of OLZ inhibited CK activity in cerebellum and prefrontal cortex. The acute administration of FLX inhibited creatine kinase in cerebellum, prefrontal cortex, hippocampus, striatum and cerebral cortex. In the chronic treatment, when the animals were killed 2h after the last injection a decrease in creatine kinase activity after FLX administration, alone or in combination with OLZ, in cerebellum, prefrontal cortex, hippocampus, striatum and cerebral cortex of rats occurred. However, when the animals were killed 24h after the last injection, we found no alterations in the enzyme. Although it is difficult to extrapolate our findings to the human condition, the inhibition of creatine kinase activity by these drugs may be associated to the occurrence of some side effects of OLZ and FLX.
A growing body of evidence has indicated that energy metabolism impairment may be involved in pathophysiology of some neuropsychiatric disorders. In this study, we evaluated the effect of acute and chronic administration of fluoxetine, olanzapine and the combination of fluoxetine/olanzapine on citrate synthase activity in brain of rats. For acute treatment, Wistar rats received one single injection of olanzapine (3 or 6mg/kg) and/or fluoxetine (12.5 or 25mg/kg). For chronic treatment, rats received daily injections of olanzapine (3 or 6mg/kg) and/or fluoxetine (12.5 or 25mg/kg) for 28 days. In the present study we observed that acute administration of olanzapine inhibited citrate synthase activity in cerebellum and prefrontal cortex. The acute administration of olanzapine increased citrate synthase activity in prefrontal cortex, hippocampus and striatum and fluoxetine increased citrate synthase activity in striatum. Olanzapine 3mg/kg and fluoxetine 12.5mg/kg in combination increased citrate synthase activity in prefrontal cortex, hippocampus and striatum. In the chronic treatment we did not observed any effect on citrate synthase activity. Our results showed that olanzapine and fluoxetine increased citrate synthase activity after acute, but not chronic treatment.
Quevedo J. Olanzapine plus fluoxetine treatment alters mitochondrial respiratory chain activity in the rat brain.Background: Evidence is emerging for the role of dysfunctional mitochondria in pathophysiology and treatment of mood disorders. In this study, we evaluated the effects of acute and chronic administration of fluoxetine (FLX), olanzapine (OLZ) and the combination of FLX/OLZ on mitochondrial respiratory chain activity in the rat brain. Methods: For acute treatment, Wistar rats received one single injection of OLZ (3 or 6 mg/kg) and/or FLX (12 or 25 mg/kg) and for chronic treatment, rats received daily injections of OLZ (3 or 6 mg/kg) and/or FLX (12 or 25 mg/kg) for 28 days and we evaluated the activity of mitochondrial respiratory chain complexes I, II, II-III and IV in prefrontal cortex, hippocampus and striatum. Results: Our results showed that both acute and chronic treatments with FLX and OLZ alone or in combination altered respiratory chain complexes activity in the rat brain, but in combination we observed larger alterations. Conclusions: Finally, these findings further support the hypothesis that metabolism energy could be involved in the treatment with antipsychotics and antidepressants in combination to mood disorders. Significant outcomes• Effects of FLX and OLZ alone or in combination on mitochondrial respiratory chain. • Acute and chronic treatment of FLX and OLZ alone or in combination altered respiratory chain complexes activity. • In combination, FLX and OLZ caused larger alterations. Limitations• The results did not follow a pattern. Sometimes FLX and/or OLZ increased and sometimes decreased the activity of the complexes.
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