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: Haloperidol; Lipid peroxidation; Lithium; Oxidative stress; Toxicity.

Figure 1

The comparison of influence of lithium (prophylactic and therapeutic concentration), haloperidol and their combination on lipid peroxidation, expressed as TBARs levels, in human plasma (in vitro). The results are expressed in percentages of control and shown as mean ± SD.