Impact of lithium alone or in combination with haloperidol on selected oxidative stress parameters in human plasma in vitro

Abstract

Objectives: Lithium may inhibit lipid peroxidation (LP) and protein oxidation, stimulate cell proliferation, increase neurogenesis, and delay cell death. Oxidative stress (OxS) is a state of imbalance between oxidative processes and antioxidant defenses, which may play an important role in the pathophysiology and disease course of bipolar disorder (BD). The aim of this study was to estimate the influence of lithium, administered alone or in combination with haloperidol, on selected OxS parameters in human plasma in vitro.

Methods: The OxS parameters evaluated were thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC). Plasma samples from healthy volunteers were incubated with drug concentrations used in psychiatry.

Results: Incubation of plasma with lithium or haloperidol alone did not produce statistically significant changes of TBARS levels in comparison with control samples. However, significantly higher TBARS levels were observed in samples incubated with haloperidol plus lithium compared to control, haloperidol, or lithium samples. The TAC value did not differ between samples.

Conclusions: Lithium does not influence OxS parameters in human plasma in vitro during short-term observation when applied at concentrations used in psychiatry. However, lithium increased the TBARS level in the samples when given in combination with haloperidol, which may be one of the mechanisms behind the neurotoxicity associated with combined lithium and haloperidol administration.

Keywords:

• Lithium
• Haloperidol
• Oxidative stress
• Lipid peroxidation
• Toxicity

Acknowledgments

The authors are thankful to the Head of Department of Pharmaceutical Biochemistry, Medical University of Lodz, Prof. Marek Mirowski for providing the facilities required to carry out the research work.

Disclaimer statements

Contributors None.

Funding Supported by grant 502-11-756 from the Medical University of Lodz, Poland, and by grant N402 456138 from the Polish Ministry of Science and Higher Education.

Conflict of interest There is no conflict of interest.

Ethics approval All subjects examined in the study signed an informed consent form for participation in the study in accordance with the protocol accepted by the Committee for Research on Human Subjects of the Medical University of Lodz (number RNN/13/08/KE).