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Protective effect of Curcumin, the active principle of turmeric (Curcuma longa) in haloperidol-induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes in rat brain.

Centre with Potential for Excellence in Biomedical Sciences, Panjab University, Chandigarh, 160014, India.
Pharmacology Biochemistry and Behavior (Impact Factor: 2.82). 03/2008; 88(4):511-22. DOI: 10.1016/j.pbb.2007.10.009
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ABSTRACT Tardive dyskinesia (TD) is a motor disorder of the orofacial region resulting from chronic neuroleptic treatment. A high incidence and irreversibility of this hyperkinetic disorder has been considered a major clinical issue in the treatment of schizophrenia. The molecular mechanism related to the pathophysiology of tardive dyskinesia is not completely known. Various animal studies have demonstrated an enhanced oxidative stress and increased glutamatergic transmission as well as inhibition in the glutamate uptake after the chronic administration of haloperidol. The present study investigated the effect of curcumin, an antioxidant, in haloperidol-induced tardive dyskinesia by using different behavioural (orofacial dyskinetic movements, stereotypy, locomotor activity, % retention), biochemical (lipid peroxidation, reduced glutathione levels, antioxidant enzyme levels (SOD and catalase) and neurochemical (neurotransmitter levels) parameters. Chronic administration of haloperidol (1 mg/kg i.p. for 21 days) significantly increased vacuous chewing movements (VCM's), tongue protrusions, facial jerking in rats which was dose-dependently inhibited by curcumin. Chronic administration of haloperidol also resulted in increased dopamine receptor sensitivity as evident by increased locomotor activity and stereotypy and also decreased % retention time on elevated plus maze paradigm. Pretreatment with curcumin reversed these behavioral changes. Besides, haloperidol also induced oxidative damage in all major regions of brain which was attenuated by curcumin, especially in the subcortical region containing striatum. On chronic administration of haloperidol, there was a decrease in turnover of dopamine, serotonin and norepinephrine in both cortical and subcortical regions which was again dose-dependently reversed by treatment with curcumin. The findings of the present study suggested for the involvement of free radicals in the development of neuroleptic-induced tardive dyskinesia and point to curcumin as a possible therapeutic option to treat this hyperkinetic movement disorder.

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    • "Recent studies suggest neuroprotective properties of curcumin in prevention of neurodegenerative diseases (Cole et al., 2007; Kulkarni and Dhir, 2010). Curcumin exerts its neuroprotective effects by changing the level of brain neurotransmitters and inflammatory mediators (Bishoni et al., 2008; Wang et al., 2010). Experimental evidences have shown protective effects of curcumin in various animal models of epilepsy (Bharal et al., 2008; Du et al., 2009; Gupta et al., 2009; Jyoti et al., 2009). "
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    ABSTRACT: Objective: Curcumin is a major constituent of turmeric and has many biological functions such as anticancer and anti-inflammatory effects. The present study was conducted to investigate the effects of curcumin and diazepam in separate and combined treatments on penicillin-induced seizures in rats. Materials and Methods: In urethane-anesthetized rats, epileptiform activity was induced by intracortical (i.c.) administration of penicillin (200 IU, 1 µl), and frequency and amplitude of spike waves were analyzed using electrocorticographic recordings. Results: Intraperitoneal (i.p.) injections of curcumin at doses of 100 and 200 mg/kg, and intracerebroventricular (i.c.v.) injection of diazepam at a dose of 5 µg significantly (p<0.05) reduced both frequency and amplitude of spike waves. Co-administrations of curcumin (50 mg/kg, i.p.) with diazepam (5 µg, i.c.v) enhanced the antiepileptic effect of diazepam (5 µg, i.c.v). Conclusion: The results suggested that both curcumin and diazepam suppressed penicillin-induced epileptiform activity. A potentiation effect was observed between curcumin and diazepam in reducing penicillin-induced seizures.
    Avicenna Journal of Phytomedicine 02/2012; 2(4):196-205.
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    • "Sumanont et al. (2007) showed that treatment with manganese complexes of curcumin and diacetyl curcumin inhibited kainic acid induced oxidative stress suggesting protective effect of curcumin in neuronal damage. Curcumin treatment was able to reverse neuroleptic-induced tardive dyskinesia in rats (Bishnoi et al., 2008). Antioxidant and iron binding properties of curcumin and other spice ingredients were linked with the prevention and treatment of Alzheimer's disease (Dairam et al., 2008). "
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    ABSTRACT: Our recent studies have shown that curcumin protects arsenic induced neurotoxicity by modulating oxidative stress, neurotransmitter levels and dopaminergic system in rats. As chronic exposure to arsenic has been associated with cognitive deficits in humans, the present study has been carried out to implore the neuroprotective potential of curcumin in arsenic induced cholinergic dysfunctions in rats. Rats treated with arsenic (sodium arsenite, 20mg/kg body weight, p.o., 28 days) exhibited a significant decrease in the learning activity, assessed by passive avoidance response associated with decreased binding of (3)H-QNB, known to label muscarinic-cholinergic receptors in hippocampus (54%) and frontal cortex (27%) as compared to controls. Decrease in the activity of acetylcholinesterase in hippocampus (46%) and frontal cortex (33%), staining of Nissl body, immunoreactivity of choline acetyltransferase (ChAT) and expression of ChAT protein in hippocampal region was also observed in arsenic treated rats as compared to controls. Simultaneous treatment with arsenic and curcumin (100mg/kg body weight, p.o., 28 days) increased learning and memory performance associated with increased binding of (3)H-QNB in hippocampus (54%), frontal cortex (25%) and activity of acetylcholinesterase in hippocampus (41%) and frontal cortex (29%) as compared to arsenic treated rats. Increase in the expression of ChAT protein, immunoreactivity of ChAT and staining of Nissl body in hippocampal region was also observed in rats simultaneously treated with arsenic and curcumin as compared to those treated with arsenic alone. The results of the present study suggest that curcumin significantly modulates arsenic induced cholinergic dysfunctions in brain and also exhibits neuroprotective efficacy of curcumin.
    NeuroToxicology 08/2011; 32(6):760-8. DOI:10.1016/j.neuro.2011.07.004 · 3.05 Impact Factor
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    • "The loss of GSH and the formation of protein glutathione mixed disulfide (PrSSG) in the brain results in various membrane dysfunctions, such as inhibition on Na + K + -ATPase activity (Reed, 1990), which is essential for cellular excitability and is very susceptible to free radical reaction and lipid peroxidation because it is embedded in a cell membrane and requires phospholipids for the maintenance of its activity (Cooper and Winter, 1980; Furui et al., 1990; Ildan et al., 1996). There are several reports about the modulatory effect of curcumin on lipid peroxidation and antioxidant enzymes following injuries like hypoxia/ischemia, and CNS injuries (Bishnoi et al., 2008; Dohare et al., 2008; Ishrat et al., 2009; Ataie et al., 2010). In agreement with these findings, we also found that curcumin significantly reduced the TBARS level along with the increased activity of antioxidant enzymes in the striatum portion following 6-OHDA induction. "
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    ABSTRACT: Curcumin, the active principle of turmeric used in Indian curry is known for its antitumor, antioxidant, antiarthritic, anti-ischemic and anti-inflammatory properties and might inhibit the accumulation of destructive beta-amyloid in the brains of Alzheimer's disease patients. A Parkinsonian model in rats was developed by giving 6-hydroxydopamine (10 μg/2 μl in 0.1% ascorbic acid–saline) in the right striatum. After 3 weeks of lesioning, the behavior activities (rotarod, narrow beam test, grip test and contra-lateral rotations) were increased in a lesioned group as compared to a sham group and these activities were protected significantly with the pretreatment of curcumin. A significant protection on lipid peroxidation, glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, tyrosine hydroxylase and D 2 receptor binding was observed in the striatum of lesioned group animals pretreated with 80 mg/kg body weight of curcumin for 21 days as compared to lesion group animals. No significant alterations on behavior and biochemical parameters were observed in sham group animals and the animals of sham group pretreated with curcumin. This study indicates that curcumin, which is an important ingredient of diet in India and also used in various systems of indigenous medicine, is helpful in preventing Parkinsonism and has therapeutic potential in combating this devastating neurologic disorder.
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