“Study on the effects of Naringin and Clozapine combination in an experimental model of Schizophrenia in rats“

Abstract

Schizophrenia is a chronic, disabling and one of the major neurological illnesses affecting nearly 1% of the global population. Currently available antipsychotic medications possess several side effects. The current research aimed at investigating potential therapeutic add-on benefit to enhance the effect and cease the side effects of clozapine anti-schizophrenic. In this study, naringin was given to Wistar rats at a dose of 100 mg/kg orally, alone or in combination with clozapine 5 mg/kg i.p. To induce schizophrenia, ketamine was administered at a dose of 25 mg/kg i.p. for 14 consecutive days. Ketamine induced positive, negative and cognitive schizophrenia symptoms together with neurotransmitters’ imbalance. In addition, ketamine administration caused significant glutathione depletion, lipid peroxidation and reduction in catalase activity. Naringin and/or clozapine treatment significantly attenuated ketamine-induced schizophrenic symptoms and oxidative injury. Additionally, ketamine provoked apoptosis via increasing Bax/Bcl2 expression, caspase-3 activity, and cytochrome-c and Akt protein expression while naringin/clozapine treatment significantly inhibited this apoptotic effect. Moreover, naringin activated the neurodevelopmental wnt/β-catenin signaling pathway evidenced by increasing pGSK-3β and reducing pβ-catenin protein expression. Furthermore, naringin was able to reduce main clozapine side effects including agranulocytosis, dyslipidemia, weight gain and hyperglycemia when added to clozapine treatment. Collectively, these findings may suggest that naringin possesses a potential therapeutic add-on effect against ketamine-induced schizophrenia.