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The effect of the antipsychotic, clozapine, on monocyte mitochondria function and cytokine production
Author(s) -
Heart Dylan Lee,
Contreras-Shan Veronica,
Walss-Bass Consuelo
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.833.12
Subject(s) - clozapine , proinflammatory cytokine , pharmacology , cytokine , mitochondrion , endocrinology , chemistry , medicine , antipsychotic , biochemistry , schizophrenia (object oriented programming) , inflammation , psychiatry
This project studied the effects of the atypical antipsychotic, clozapine, on monocyte mitochondria and the production of proinflammatory cytokines. Cultured monocytes were treated with different doses of clozapine (0, 25, 50 and 75 uM) and effects on viability, mitochondria morphology, membrane potential, ATP and cytokine secretion were assessed. With increasing doses of clozapine, mitochondria appear spotty and speckled, an indication of fission. Western blots demonstrate an increase in both profusion (OPA1) and profission (DLP1) proteins; OPA1 increased significantly with increasing clozapine relative to the control. As clozapine increased, the membrane potential increased and was significantly different (p < 0.05) from the control at all doses. An ATP luminescence assay showed ATP levels decreased significantly (p < 0.005) at all clozapine doses relative to the control. Increased clozapine caused increased cytokine production. Cytokines that were significantly altered (p < 0.05) with clozapine treatment included GMCSF, IL‐1b, IL‐10, IL‐13, and MCP1. Therefore, increasing doses of the antipsychotic clozapine negatively affects mitochondria function and causes the production of proinflammatory cytokines. Supported by SURF to DLH from the URO at St. Mary's University