Cytogenetic Effects of Valproic Acid and Ziprasidone in Human Lymphocyte Cultures

Abstract

Background/Aims: Valproic acid or valproate (VA) is an anticonvulsant and mood-stabilizing drug primarily used in the treatment of epilepsy and bipolar disorder. Ziprasidone (ZPN) is an atypical antipsychotic drug used mainly for the treatment of schizophrenia. Methods: This study is a part of our investigation on the cytogenetic effects of psychotropic drugs. Lymphocytes of peripheral blood cultures from 3 healthy donors treated with VA, ZPN and combinations of these (at concentrations equivalent to the oral doses) were used for the estimation of sister chromatid exchanges (SCEs) and the proliferation rate index (PRI). As a biomarker of genotoxicity, we used SCEs, one of the most sensitive methods reflecting DNA damage and/or subsequent DNA repair, and as a marker of cytostaticity we estimated the PRI. Results: All treated lymphocyte cultures showed a statistically significant increase in SCE frequency and a significant decrease in PRI values (p < 0.001). The combined effect of the drugs induced similar or more intense results, without reaching levels indicating synergistic action. Conclusion: This in vitro study investigated the cytogenetic activity of monotherapy vs. combined chronic drug exposure, and could form a catalyst for further investigations aiming to develop more efficacious therapy with decreased cytogenetic damage.

Oxidative stress in bipolar and schizophrenia patients

“…Atypical antipsychotics such as olanzapine, risperidon and quetiapine did not induce genotoxicity in human whole blood cultures (Togar et al, 2012) and prevented DNA fragmentation (Qing et al, 2003). Contrary to these studies, there are studies in literature reporting that perphenazine (Gil-ad et al, 2001) valproic acid and ziprasidone (Karapidaki et al, 2011) and aripiprazole (Picada et al, 2011) leads to DNA damage. It is argued that typical antipsychotics are more toxic than atypical ones (Gil-ad et al, 2001;Parikh et al, 2002).…”

Effect of saffron (Crocus sativusL.) on sodium valporate induced cytogenetic and testicular alterations in albino rats

“…?2 months. Karapidaki et al [25] found a statistically significant increase in sister chromatid exchanges frequency and a significant decrease in the proliferation rate index in lymphocytes of peripheral blood cultures from 3 healthy donors given VPA and ziprasidone. Witczak et al [4] showed that the anti-epileptic drugs, VPA and carbamazepine analogues, given to epileptic women in mono- and poly-therapy during pregnancy evoked potentially clastogenic and genotoxic effects in cord-blood lymphocytes.…”

Typical versus atypical antipsychotics: Genotoxicity and cytostaticity testing

“…There is evidence that antipsychotics exhibit genotoxic and carcinogenic or cytostatic effects [18,19]. In a previous study of our group, we examined the genotoxic and cytotoxic effect of Valproic Acid and Ziprasidone [20]. In the current study we decided to use Levomepromazine (LVZ) and Perphenazine (PRZ) as typical antipsychotics and Amisulpride (AMD) and Sulpiride (SPD) as atypical ones.…”