Journal
DRUG DEVELOPMENT RESEARCH
Volume 82, Issue 7, Pages 980-989Publisher
WILEY
DOI: 10.1002/ddr.21800
Keywords
agranulocytosis; clozapine side effects; hyperglycemia; hyperlipidemia; Naringin; weight gain
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This study aimed to investigate the potential of naringin as an add-on benefits to alleviate the main side effects of clozapine in ketamine-induced psychosis in rats. Naringin was found to reduce adverse effects induced by clozapine treatment, improve total leukocyte count, lower serum cholesterol and triglycerides levels, prevent weight gain, and reduce serum glucose level. These findings suggest that naringin may have a beneficial role as an add-on therapy to clozapine in the treatment of schizophrenia.
Schizophrenia is one of the major neuropsychiatric disorders affecting people worldwide. Unfortunately, currently available antipsychotic medications possess several side effects. Among them, clozapine is one of the atypical antipsychotics prescribed in schizophrenia wing to its blocking effect on dopamine (D2) and serotonin (5-HT1c) receptors. However, it has been recently reserved for resistant schizophrenia due to its several side effects. The current research aimed at investigating potential naringin add-on benefit to cease the main side effects of clozapine in ketamine-induced psychosis in rats. In this study, schizophrenia was induced in rats via ketamine administration that could promote neuropathological patterns of schizophrenia. Afterwards, clozapine and naringin were administered to rats in order to improve such effects induced by ketamine. Clozapine administration promoted weight gain, hyperglycemia, dyslipidemia, and agranulocytosis. However, naringin was able to reduce such adverse effects when added to clozapine treatment. Naringin increased total leukocyte count preventing agranulocytosis either when administered alone or in combination with clozapine. In addition, via its metabolic activities, naringin treatment lowered serum total cholesterol and triglycerides levels. Moreover, naringin prevented weight gain when administered. Finally, naringin reduced serum glucose level preventing hyperglycemia associated with clozapine treatment. Collectively, these findings may suggest that naringin possesses a potential add-on benefit to clozapine in treatment of schizophrenia.
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