Inhibitory effects of polyphenol compounds on lipid peroxidation caused by antipsychotics (haloperidol and amisulpride) in human plasma in vitro

Abstract

Objective. Plant antioxidants protect cells against oxidative stress. Since oxidative stress observed in schizophrenia may be caused partially by the treatment of patients with various antipsychotics, the aim of the study was to assess whether there is a difference between a first-generation antipsychotic (FGA; haloperidol) and a second-generation antipsychotic (SGA; amisulpride (4-amino-N-[(1-ethylpyrrolidin-2-yl)methyl]-5-ethysufonyl-2-methoxy-benzamide)) action on peroxidation of plasma lipids, and to establish the effects of polyphenol compounds (resveratrol (3,4′,5-trihydroxystilbene) and quercetin (3,5,7,3′,4′- pentahydroxyflavone)) and the antipsychotics action on this process in vitro. Methods. Lipid peroxidation in human plasma was measured by the level of thiobarbituric acid reactive species (TBARS). The samples of plasma from healthy subjects were incubated with haloperidol or amisulpride in the presence of polyphenols: resveratrol and quercetin. Results. The two-way analysis variance (ANOVA II test) showed that the differences in TBARS levels were depended on the type of tested drugs (P=8.35×10⁻⁶). We observed a statistically increase of the level of biomarker of lipid peroxidation such as TBARS after 1 and 24 h incubation of plasma with haloperidol compared to the control samples (P<0.03, P<0.0002, respectively). Amisulpride, contrary to haloperidol (after 1 h) does not significantly influence the increase of plasma TBARS level in comparison with control samples. Amisulpride induced significantly decrease of plasma TBARS level after 24 h (P=0.03). We showed that in the presence of polyphenols: resveratrol and quercetin, lipid peroxidation in plasma samples treated with tested drugs was significantly decreased. After incubation (24 h) of plasma with haloperidol in the presence of resveratrol or quercetin we observed a significantly decreased the level of TBARS (P=3.9×10⁻⁴, P=2.1×10⁻³, respectively). Conclusion. Considering the data presented in this study, we showed that haloperidol, contrary to amisulpride caused a distinct increase of lipid peroxidation. Polyphenols reduced significantly lipid peroxidation caused by haloperidol.

• Schizophrenic disorders
• antipsychotic drugs
• oxidative stress
• polyphenol