DOI: 10.20350/digitalcsic/13925
title: Dataset related to article: Aripiprazole cytotoxicity coincides with activation of the unfolded protein response in human hepatic cells

description: Folder 1. Aripiprazole at Low Micromolar Concentration Induces ER Stress. This folder contains four folders Folder 1a These jpg files show the analysis by immunoblotting for phosphorylated IRE1, total IRE1, total PERK of cell extracts. Folder 1b. These pzt files show the relative quantification of phosphorylated IRE1 after 24 hours of treatment. Statistical significance is indicated by **P &lt; 0.01; ***P &lt; 0.001 Folder 1c. These 2 jpg files represent a time course of an cell extract vs control (4, 8, 12 and 24 h of IRE1 phosphorylation after Ari treatment. Folder 1d. The jpg files represent analysis of the extract cells after a treatment with Olanzapine.
description: Folder 2. Aripiprazole promotes immobilization of calcium to the cytoplasm. The pzt file show the levels of intracellular calcium, the changes on it after the treatment with aripiprazole Statistical significance is indicated by *P &lt; 0.05 of at least five independent measurements by ANOVA.
description: Folder 3. IRE1 contributes more than PERK to Ari-induced cytotoxicity. Representative dot plots of forward vs. side scattering properties and percentage of PI-positive cells after treatment with ari are shown in the .pzt files of folders 3a and 3b. The data for the percentage of PI-positive cells shown in the files were obtained by measure with flow cytometry, after overnight treatment with DMSO, Ari (30 µM), and Ari with Z-VAD-FMK (25 µM) Statistical significance is indicated by *P &lt; 0.05; **P &lt; 0.01 by ANOVA for Z-VAD-FMK treatment and for the KO cells by paired Student’s t test.
description: Folder 4 N-acetyl cysteine (NAC), BAPTA-AM, and EGTA do not protect from Aripiprazole-induced cell death. The .pzt files shown the data obtained by the treatment overnight of the cells HepG2 with DMSO and 30 µM of Ari in the absence or presence of NAC, BAPTA-AM, or EGTA. Percentage of PI-positive cells, as measured by flow cytometry after treatment, is shown. Data of three independent experiments ± S.D. is shown.
description: Folder 5. GSH ethyl ester protects from Aripiprazole-induced cell death. The .pzt file shown the data obtained by the treatment overnight of the cells with DMSO and 30 µM of Ari in the absence or presence of GSH ethyl ester. Percentage of PI-positive cells, as measured by flow cytometry after treatment, is shown.
description: Folder 6. Aripiprazole induces ER stress, and accumulation of lipids and calcium mobilization form the ER in primary mouse hepatocytes These folder contains several subfolders with the data for the panels A to H of the article
description: Demographics and pharmacokinectics data of the study. This folder contains five docs file with those data 1. Demographic characteristics of the volunteers from the studies
description: Aripiprazole treatment in schizophrenic patients was previously associated with lower or normalized prolactin levels. Genetic variants in cytochrome P450 (CYP) (CYP2D6), dopamine receptor (DRD2, DRD3) and serotonin receptor (HTR2A, HTR2C) genes were previously associated with antipsychotic-induced hyperprolactinaemia. Our aim was to evaluate whether aripiprazole affects prolactin secretion and its relationship with pharmacogenetics. Thirty-one healthy volunteers receiving a 10-mg single oral dose of aripiprazole were genotyped for 12 polymorphisms in CYP2D6, DRD2, DRD3, HTR2A and HTR2C genes by qPCR. Aripiprazole and dehydro-aripiprazole plasma concentrations were measured by HPLC-MS/MS. Prolactin concentrations of the 31 volunteers taking aripiprazole and 12 volunteers receiving ibuprofen were determined by ELISA. Prolactin concentrations after ibuprofen intake were considered as control, since it is known to cause no effect. Prolactin concentrations were slightly higher in the aripiprazole group compared to the ibuprofen group. All prolactin pharmacokinetic parameters were higher in females than in males. CYP2D6 poor and intermediate metabolizers had notably higher prolactin Cmax and AUC0-12 than normal and ultrarapid metabolizers. The DRD3 rs6280 polymorphism affected prolactin levels: volunteers carrying Ser/Ser genotype had significantly lower prolactin levels than volunteers carrying the Gly allele. Furthermore, HTR2C rs3813929 C/C homozygotes had significantly lower prolactin levels than T allele carriers. Nevertheless, aripiprazole did increase prolactin levels compared to ibuprofen.