THE ANTIPSYCHOTIC ZIPRASIDONE HAS CITO-GENOTOXIC AND PRO-INFLAMMATORY EFFECTS INFLUENCED BY VAL16ALA-SOD2 GENEPOLYMORPHISM

Objectives: In immune cells, especially macrophages some oxidant molecules present a key role on inflammatory response trigger by pathogens and non-pathogens substances. For this reason, basal genetic superoxide-hydrogen peroxide (S-HP) imbalance as caused by Val16Ala-SOD2 single nucleotide polymorphism (SNP) could has some influence on side effects induced by pharmacological drugs. This could be de case of Ziprasidone (ZIP), a second-generation antipsychotic (SGA) used to treat some psychiatric and neurodegenerative diseases that seems to act on oxidative-inflammatory metabolism. To test this hypothesis, an in vitro study using human peripheral blood mononuclear cells (PBMCs) carrying different Val16Ala-SOD2 genotypes was performed. In standardized 72h cell cultures, the effect of ZIP exposure at plasmatic therapeutic concentration in oxidative (including level of DNA oxidation quantified by 8-deoxiguanosine) and inflammatory markers were analysed. Results showed that AA-PBMCs that have basal higher HP levels presented cito-genotoxic effect when ZIP-exposed, whereas VV-PBMCs presented higher levels of proinflammatory cytokines. The whole of results indicated some pharmacogenomic action of Val16Ala-SOD2 SNP despite in vitro methodological constrains. A