Neurotoxicity Research

, Volume 20, Issue 3, pp 215–225 | Cite as

Protective Effect of Curcumin and its Combination with Piperine (Bioavailability Enhancer) Against Haloperidol-Associated Neurotoxicity: Cellular and Neurochemical Evidence

  • Mahendra Bishnoi
  • Kanwaljit Chopra
  • Lu Rongzhu
  • Shrinivas K. Kulkarni
Article

Abstract

Long-term treatment with haloperidol is associated with a number of extrapyramidal side effects, particularly the irregular movements of chorionic type. This limitation presents a marked therapeutic challenge. The present study investigates the molecular etiology of haloperidol neurotoxicity and the role of curcumin, a well-known anti-oxidant, in ameliorating these adverse effects. The redox status of haloperidol-treated brains along with NO, TNF-α, NF-kappaB p65 subunit, caspase-3, and monoamine neurotransmitters were measured in the striatum of rat brain. Chronic treatment with haloperidol (5 mg/kg, i.p., 21 days) produced orofacial dyskinetic movements which were coupled with marked increase in oxidative stress parameters, TNF-α, caspase-3 activity in cytoplasmic lysate and active p65 sub unit of NF-kappaB in nuclear lysates of the striatum. Neurochemically, chronic administration of haloperidol resulted in a significant decrease in the levels of norepinephrine, dopamine, and serotonin. The prototype atypical anti-psychotic, clozapine (10 mg/kg, i.p., 21 days) produced mild oxidative stress but did not alter any other parameters. Interestingly, co-administration of curcumin (25 and 50 mg/kg, i.p., 21 days) dose-dependently prevented all the behavioral, cellular, and neurochemical changes associated with the chronic administration of haloperidol. Curcumin per se (50 mg/kg) did not show any side effects. Co-administration of piperine significantly enhanced the effect of curcumin (25 mg/kg) but not of curcumin (50 mg/kg). Collectively, the data indicated the potential of curcumin as an adjunct to haloperidol treatment and provided initial clues to the underlying molecular mechanisms in haloperidol neurotoxicity. This study also provides a rationale for the combination of piperine and curcumin.

Keywords

Apoptosis Caspase-3 Curcumin Haloperidol NF-kappaB Tardive dyskinesia 

Notes

Acknowledgments

The study was supported by the UGC grant under Centre with Potential for Excellence in Biomedical Sciences (CPEBS).

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Mahendra Bishnoi
    • 4
    • 1
  • Kanwaljit Chopra
    • 2
  • Lu Rongzhu
    • 3
  • Shrinivas K. Kulkarni
    • 1
    • 2
  1. 1.Centre with Potential for Excellence in Biomedical Sciences (CPEBS)Panjab UniversityChandigarhIndia
  2. 2.Pharmacology DivisionUniversity Institute of Pharmaceutical Sciences, Panjab UniversityChandigarhIndia
  3. 3.Department of Preventive MedicineSchool of Medical Sciences and Laboratory Medicine, Jiangsu UniversityZhenjiangChina
  4. 4.Department of PharmacologySouthern Illinois University-School of MedicineSpringfieldUSA

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