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The Effects of Ziprasidone, Clozapine and Haloperidol on Lipid Peroxidation in Human Plasma (in vitro): Comparison

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Abstract

Oxidative injury in schizophrenia can be caused by the disease itself and probably by antipsychotics treatment. The aim of the study was to establish whether there is a difference between ziprasidone, clozapine and haloperidol effect on lipid peroxidation in human plasma, measured by the level of thiobarbituric acid reactive substances (TBARS). The samples of plasma from healthy subjects were incubated with the drugs (1 and 24 h) and compared with control samples. The levels of TBARS were measured spectrophotometrically, according to the Rice-Evans method. The multifactorial variance analysis ANOVA II test showed that the differences in TBARS levels significantly depended on the studied drugs (ziprasidone 40 ng/ml, haloperidol 4 ng/ml and clozapine 350 ng/ml) (F = 3.248 p = 0.047) and (ziprasidone 139 ng/ml, haloperidol 20 ng/ml and clozapine 420 ng/ml) (F = 2.248, p = 2.9 × 10−5). Statistically increased levels of TBARS after 24 h incubation of plasma with ziprasidone 139 ng/ml and haloperidol 20 ng/ml (p < 0.001, p < 0.05 respectively) in comparison with control samples were observed. Clozapine did not significantly (p > 0.05) increase TBARS level in plasma in comparison with control samples. The results obtained in the study showed that ziprasidone and haloperidol contrary to clozapine induced a significant increase in plasma lipid peroxidation.

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References

  1. Al-Chalabi BM, Thanoon IA, Ahmed FA (2009) Potential effect of olanzapine on total antioxidant status and lipid peroxidation in schizophrenic patients. Neuropsychobiology 59(1):8–11

    Article  PubMed  CAS  Google Scholar 

  2. Akyol O, Herken H, Uz E, Fadillioğlu E, Unal S, Söğüt S et al (2002) The indices of endogenous oxidative and antioxidative processes in plasma from schizophrenic patients. The possible role of oxidant/antioxidant imbalance. Prog Neuropsychopharmacol Biol Psychiatry 26:995–1005

    Article  PubMed  CAS  Google Scholar 

  3. Bartosz G (2003) Total antioxidant capacity. Adv Clin Chem 37:219–292

    Article  PubMed  CAS  Google Scholar 

  4. Cadet JL, Lohr JB (1987) Free radicals and the developmental pathobiology of schizophrenic burnout. Integr Psychiatry 5:40–48

    Google Scholar 

  5. Cadet JL, Perumal AS (1990) Chronic treatment with prolixin causes oxidative stress in rat brain. Biol Psychiatry 28:738–740

    Article  PubMed  CAS  Google Scholar 

  6. Cadet JL, Lohr JB, Jeste DV (1986) Free radicals and tardive dyskinesia. Trends Neurosci 9:107–108

    Article  CAS  Google Scholar 

  7. Dadheech G, Mishra S, Gautam S, Sharma P (2008) Evaluation of antioxidant deficit in schizophrenia. Indian J Psychiatry 50(1):16–20

    Article  PubMed  Google Scholar 

  8. Dakhale G, Khanzode S, Khanzode S, Saoji A, Khobragade L, Turankar A (2004) Oxidative damage and schizophrenia: the potential benefit by atypical antipsychotics. Neuropsychobiology 49(4):205–209

    Article  PubMed  Google Scholar 

  9. Dalla Libera A, Rigobello MP, Bindoli A (1996) Inhibitory action of neuroleptic drugs and serotonin on dopamine autooxidation and lipid peroxidation. Prog Neuropsychopharmacol Biol Psychiatry 19:291–298

    Article  Google Scholar 

  10. Dalla Libera A, Scutari G, Boscolo R, Rigobello MP, Bindoli A (1998) Antioxidant properties of clozapine and related neuroleptics. Free Radic Res 29(2):151–157

    Article  PubMed  CAS  Google Scholar 

  11. Dietrich-Muszalska A, Olas B, Rabe-Jablonska J (2005) Oxidative stress in blood platelets from schizophrenic patients. Platelets 16(7):386–391

    Article  PubMed  CAS  Google Scholar 

  12. Dietrich-Muszalska A, Kontek B, Rabe-Jablonska J (2011) Quetiapine, olanzapine and haloperidol affect human plasma lipid peroxidation in vitro. Neuropsychobiology 63:197–201

    Article  PubMed  CAS  Google Scholar 

  13. Dietrich-Muszalska A, Olas B (2007) Isoprostanes as indicators of oxidative stress in schizophrenia. World J Biol Psychiatry 14:1–6

    Google Scholar 

  14. Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Möller HJ (2005) WFSBP Task Force on Treatment Guidelines for Schizophrenia. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 1: acute treatment of schizophrenia. World J Biol Psychiatry 6:132–191

    Article  PubMed  Google Scholar 

  15. Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Möller HJ (2006) WFSBP Task Force on Treatment Guidelines for Schizophrenia. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: long-term of schizophrenia. World J Biol Psychiatry 7:5–40

    Article  PubMed  Google Scholar 

  16. Fischer V, Haar JA, Greiner L, Lioyd RV, Mason RP (1991) Possible role of free radical formation in clozapine (clozaril)-induced agranulocytosis. Mol Pharmacol 40:846–853

    PubMed  CAS  Google Scholar 

  17. Gama CS, Salvador M, Andreazza AC, Kapczinski F, Belmonte-de-Abreu PS (2006) Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in schizophrenia: a study of patients treated with haloperidol or clozapine. Prog Neuropsychopharmacol Biol Psychiatry 30:512–515

    Article  PubMed  CAS  Google Scholar 

  18. Horrobin DF (1996) Schizophrenia as a membrane lipid disorder which is expressed throughout the body. Prostaglandins Leukot Essent Fatty Acids 55:3–7

    Article  PubMed  CAS  Google Scholar 

  19. Jeding I, Evans PJ, Akanmu D, Dexter D, Spencer JD, Arunoma OI et al (1995) Characterisation of the potential antioxidant and pro-oxidant actions of some neuroleptic drugs. Biochem Pharmacol 49:359–365

    Article  PubMed  CAS  Google Scholar 

  20. Khan MM, Evans DR, Gunna V, Scheffer RE, Parikh VV, Mahadik SP (2002) Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first-episode of psychosis and after years of treatment with antipsychotics. Schizophr Res 58(1):1–10

    Article  PubMed  Google Scholar 

  21. Khan NS, Das I (1997) Oxidative stress and superoxide dismutase in schizophrenia. Biochem Soc Trans 25:418

    Google Scholar 

  22. Kropp S, Kern V, Lange K, Degner D, Hajak G, Kornhuber J et al (2005) Oxidative stress during treatment with first- and second-generation antipsychotics. J Neuropsych 17:227–231

    Article  CAS  Google Scholar 

  23. Lohr JB, Kuczenski R, Bracha HS, Moir M, Jeste DV (1990) Increased indices of free radical activity in the cerebrospinal fluid of patients with tardive dyskinesia. Biol Psychiatry 28(6):535–539

    Article  PubMed  CAS  Google Scholar 

  24. Mahadik SP, Evans DR (2003) Is schizophrenia a metabolic brain disorder? Membrane phospholipid dysregulation and its therapeutic implications. Psychiatr Clin North Am 26(1):85–102

    Article  PubMed  Google Scholar 

  25. Miyamoto S, Duncan GE, Marx CE, Lieberman JA (2005) Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs. Mol Psychiatry 10(1):79–104

    Article  PubMed  CAS  Google Scholar 

  26. Möller HJ (2004) Novel antipsychotics in the long-term treatment of schizophrenia. World J Biol Psychiatry 5:9–19

    Article  PubMed  Google Scholar 

  27. Padurariu M, Ciobica A, Dobrin I, Stefanescu C (2010) Evaluation of antioxidant enzymes activities and lipid peroxidation in schizophrenic patients treated with typical and atypical antipsychotics. Neurosci Lett 479(3):317–320

    Article  PubMed  CAS  Google Scholar 

  28. Pai BN, Janakiramaiah N, Gangadhar BN, Ravindranath V (1994) Depletion of glutathione and enhanced lipid peroxidation in the CSF of acute psychotics following haloperidol administration. Biol Psychiatry 36:489–491

    Article  PubMed  CAS  Google Scholar 

  29. Pall HS, Williams AC, Blake DR, Lunec J (1987) Evidence of enhanced lipid peroxidation in the cerebrospinal fluid of patients taking phenothiazines. Lancet 2:596–599

    Article  PubMed  CAS  Google Scholar 

  30. Parikh V, Khan MM, Mahadik SP (2003) Differential effects of antipsychotics on expression of antioxidant enzymes and membrane lipid peroxidation in rat brain. J Psychiatr Res 37:43–51

    Article  PubMed  Google Scholar 

  31. Peet M, Laugharne J, Rangarajan N, Reynolds GP (1993) Tardive dyskinesia, lipid peroxidation, and sustained amelioration with vitamin E treatment. Int Clin Psychophamacol 8:151–153

    Article  CAS  Google Scholar 

  32. Pillai A, Parikh V, Terry AV Jr, Mahadik SP (2007) Long-term antipsychotic treatments and crossover studies in rats: differential effects of typical and atypical agents on the expression of antioxidant enzymes and membrane lipid peroxidation in rat brain. J Psychiatr Res 41(5):372–386

    Article  PubMed  Google Scholar 

  33. Rice-Evans CA (1994) Formation of free radicals and mechanisms of action in normal biochemical processes and pathological states. In: Rice-Evans CA, Burdone RH (eds) Free radical damage and its control. Elsevier, Amsterdam, pp 131–153

  34. Sagara Y (1998) Induction of reactive oxygen species in neurones by haloperidol. J Neurochem 71(3):1002–1012

    Article  PubMed  CAS  Google Scholar 

  35. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E et al (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:22–33

    PubMed  Google Scholar 

  36. Shivakumar BR, Ravindranath V (1993) Oxidative stress and thiol modification induced by chronic administration of haloperidol. J Pharmacol Exp Ther 265(3):1137–1141

    PubMed  CAS  Google Scholar 

  37. Tsai G, Goff DC, Chang RW, Flood J, Baer L, Coyle JT (1998) Markers of glutamatergic neurotransmission and oxidative stress associated with tardive dyskinesia. Am J Psychiatry 155:1207–1213

    PubMed  CAS  Google Scholar 

  38. Yao JK, Keshavan MS (2011) Antioxidants, redox signaling, and pathophysiology in schizophrenia: an integrative view. Antioxid Redox Signal 15(7):2011–2035

    Article  PubMed  CAS  Google Scholar 

  39. Yao JK, Reddy RD, van Kammen DP (2001) Oxidative damage and schizophrenia: an overview of the evidence and its therapeutic implications. CNS Drugs 15(4):287–310

    Article  PubMed  CAS  Google Scholar 

  40. Zhang XY, Tan YL, Cao LY, Wu GY, Xu Q, Shen Y et al (2006) Antioxidant enzymes and lipid peroxidation in different forms of schizophrenia treated with typical and atypical antipsychotics. Schizophr Res 81(2–3):291–300

    Article  PubMed  Google Scholar 

  41. Zhang M, Zhao Z, He L, Wan C (2010) A meta-analysis of oxidative stress markers in schizophrenia. Sci China Life Sci 53(1):112–124

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Supported by grants: 502-03-1-155-02/502-14-109 and 502-03/1-155-02/502-14-106 from Medical University of Lodz, Poland.

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Correspondence to Anna Dietrich-Muszalska.

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Dietrich-Muszalska, A., Kopka, J. & Kwiatkowska, A. The Effects of Ziprasidone, Clozapine and Haloperidol on Lipid Peroxidation in Human Plasma (in vitro): Comparison. Neurochem Res 38, 1490–1495 (2013). https://doi.org/10.1007/s11064-013-1050-z

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  • DOI: https://doi.org/10.1007/s11064-013-1050-z

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