Antioxidant effects of rice bran oil mitigate repeated haloperidol-induced tardive dyskinesia in male rats

Abstract

Tardive dyskinesia (TD) is associated with the use of antipsychotic drugs such as D2 antagonist haloperidol (HP). The chronic use of HP is involved in the causation of free radicals and/or oxidative stress. In view of the nootropic, anti-anxiety, anti-inflammatory-like effects of rice bran oil (RBO) in a variety of investigations, we assessed the protective properties of RBO on HP-induced TD and neurochemical alteration. Rats treated with HP orally at a dose of 0.2 mg/kg/day for a period of 5 weeks developed VCMs which increased progressively as the treatment continued for 5 weeks. Co-administration of RBO by oral tubes at a dose of 0.4 ml/day prevented the induction of HP-induced VCMs. Repeated administration of HP increases the turnover of dopamine metabolism in the striatum. Conversely animals treated with HP + RBO decrease the metabolism of DA than water + HP treated animals. Striatal, malondieldehyde (MDA), hydrogen peroxide (HO) and antioxidant enzyme superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were also determined. It is suggested that beneficial role of RBO in attenuation of HP-induced TD. The results therefore recommended that supplementation of RBO may be useful in the HP-induced TD. The findings have also potential implication in the treatment of schizophrenia and motor disorders.

Biochemical Pathways Triggered by Antipsychotics in Human Oligodendrocytes: Potential of Discovering New Treatment Targets

“…However, the exact pathophysiology of how this drug induces these side effects is not totally clear (Perera et al, 2011). Oxidative stress constitutes a potential pathogenic mechanism that may contribute to movement disturbances, especially to tardive dyskinesia (Perera et al, 2011; Wu et al, 2014; Samad and Haleem, 2017). Recent studies have shown that the repeated administration of haloperidol is able to induce tardive dyskinesia in rats (Samad and Haleem, 2017).…”

“…Oxidative stress constitutes a potential pathogenic mechanism that may contribute to movement disturbances, especially to tardive dyskinesia (Perera et al, 2011; Wu et al, 2014; Samad and Haleem, 2017). Recent studies have shown that the repeated administration of haloperidol is able to induce tardive dyskinesia in rats (Samad and Haleem, 2017). Another study using plasma and the enzyme manganese superoxide dismutase (MnSOD) as a biomarker of patients with schizophrenia analyzed the relationship of oxidative stress and tardive dyskinesia.…”

Functional Profiling and Future Research Direction of Rice Bran Oil in Bangladesh

“…It was also observed that treatment of activated microglia with RBE further enhanced the gene expression of the microglial M2 marker IL-10 and reduced the expression of pro-inflammatory M1 markers (TNF-α, IL-1β) . Specific protective properties of RBO were observed in the postsynaptic receptor (D2) antagonist haloperidol-induced Tardive dyskinesia, which has potential implications in the treatment of schizophrenia and motor disorders 76) . Nevertheless, the exact mechanism of the whole RBO s activity in cognitive development remains to be discovered.…”

Antioxidant Properties of Second-Generation Antipsychotics: Focus on Microglia

“…The severe adverse effects due to haloperidol treatment, resulting in DA receptors blockade and neurotoxicity, have been associated to increased ROS production [96,97]. Its metabolite, haloperidol pyridiniumion, is highly toxic and increases oxidative stress inducing plasma membrane damages, explaining, at least in part, the pathogenesis of haloperidol-induced parkinsonism symptoms [98,99].…”