@entity1499 ( @entity1500 ) is a @entity1501 antagonist used in high doses as an anti- @entity5 treatment and in low doses for the treatment of some @entity792 . @entity1500 use has been linked to oxidative imbalance, which may cause @entity137 that can be attenuated by antioxidant supplementation. Despite the oxidative effect of @entity1500 , the influence of antioxidant gene polymorphisms on @entity1500 @entity137 is not well studied. Therefore, we analyzed here whether a genetic imbalance of the @entity921 -dependent @entity224 dismutase ( @entity4723 ) gene could have some impact on the @entity1500 cytotoxic response. An in vitro study using @entity1 peripheral blood mononuclear cells (PBMCs) obtained from carriers with different @entity15789 - @entity4723 genotypes (AA, VV and AV) was carried out, and the effect on cell viability and proliferation was analyzed, as well as the effect on oxidative, inflammatory and apoptotic markers. AA-PBMCs that present higher @entity4723 efficiencies were more resistance to high @entity1500 doses (10 and 100   M) than were the VV and AV genotypes. Both lipoperoxidation and ROS levels increased significantly in PBMCs exposed to @entity1500 independent of @entity15789 - @entity4723 genotypes, whereas @entity101 was observed only in PBMCs from V allele carriers. The AA-PBMCs exposed to @entity1500 showed decreasing @entity4723 activity, but a concomitant up regulation of the @entity4723 gene was observed. A significant increase in @entity2041 peroxidase (GPX) levels was observed in all PBMCs exposed to @entity1500 . However, this effect was more intense in AA-PBMCs. @entity61320 levels were increased in cells exposed to @entity1500 , but the modulation of these genes, as well as that of the @entity589 and @entity588 genes involved in the apoptosis pathway, presented a modulation that was dependent on the @entity4723 genotype. @entity1500 at a concentration of 10   M also increased inflammatory cytokines ( @entity1356 , @entity650 , @entity310 and Igy) and decreased the level of @entity688 anti-inflammatory cytokine, independent of @entity4723 genetic background. The results suggest that potential pharmacogenetic effect on the cytotoxic response to @entity1500 due differential redox status of cells carriers different @entity4723 genotypes.

@entity1499 -Related Response on @entity1 Peripheral Blood Mononuclear Cells May Be Modulated by the XXXX - @entity4723 Gene Polymorphism.

@entity1501 :: ('MESH:D005492', 'Chemical') :: ['folic acid'] @entity1 :: ('9606', 'Species') :: ['human'] @entity15789 :: ('p|SUB|A|16|V', 'ProteinMutation') :: ['Ala16Val'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'multi-organ toxicities'] @entity589 :: ('581', 'Gene') :: ['Bax'] @entity921 :: ('MESH:D008345', 'Chemical') :: ['manganese'] @entity101 :: ('MESH:D006973', 'Disease') :: ['increased protein carbonylation'] @entity61320 :: ('841;836', 'Gene') :: ['Caspase-8 and -3'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity4723 :: ('6648', 'Gene') :: ['SOD2'] @entity588 :: ('596', 'Gene') :: ['Bcl-2'] @entity1356 :: ('3553', 'Gene') :: ['IL-1b'] @entity2041 :: ('MESH:D005978', 'Chemical') :: ['glutathione'] @entity310 :: ('7124', 'Gene') :: ['TNFa'] @entity650 :: ('3569', 'Gene') :: ['IL-6'] @entity688 :: ('3586', 'Gene') :: ['IL-10'] @entity1500 :: ('CHEBI:44185', 'Chemical') :: ['MTX'] @entity1499 :: ('MESH:D008727', 'Chemical') :: ['Methotrexate'] @entity224 :: ('MESH:D013481', 'Chemical') :: ['superoxide'] @entity792 :: ('MESH:D001327', 'Disease') :: ['autoimmune diseases']
@entity15789 :: (p|SUB|A|16|V,ProteinMutation) :: ['Ala16Val']
