The effects of therapeutic concentrations of ziprasidone on free thiols and thiobarbituric acid reactive substances levels in human plasma – in vitro studies
Anna Dietrich-Muszalska1,2, Justyna Kopka1, Bogdan Kontek3, Anna Kwiatkowska1
The first and second generation antipsychotics may induce opposing effects on redox. Establishing the effects of antipsychotics on oxidative stress biomarkers is very important in clinical respect, because these drugs are used for the treatment of mental disorders in which oxidative stress occurs. Effects of ziprasidone on redox processes are not sufficiently known as yet. The study was aimed at establishing the effects of ziprasidone in doses recommended for mechatreatment of acute episode of schizophrenia on human plasma free thiols and thiobarbituric acid-reactive substances (TBARS) in in vitro model. Material and methods: Blood for the study was collected from 10 healthy male volunteers (aged 24-26 years) for ACD solution. Active substance of ziprasidone was dissolved in 0.01% dimethyl sulfoxide to the final concentrations (139 ng/ml and 250 ng/ml) and incubated with plasma for 24 hours at 37°C. Control samples were performed for each experiment (without the drug). The free thiols level was measured using the Ellman method, whereas the levels of thiobarbituric acid-reactive substances by spectrophotometric method (acc. to Rice-Evans, 1991). The results were analysed using the paired Student t-test (StatSoft Inc., Statistica v. 6.0). Results: In relation to control samples, ziprasidone in concentrations 139 ng/ml and 250 ng/ml after 24 hours’ incubation with plasma caused a statistically insignificant increase in the free thiols level in plasma (p>0.05), whereas in concentration 250 ng/ml – an increase in TBARS concentration by 27.6% (p=3.9×10-4). Conclusions: Ziprasidone in concentrations corresponding to doses used for treatment of acute episode of schizophrenia does not induce any significant increase in the free thiols level in plasma, simultaneously significantly increasing plasma lipid peroxidation.