{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:26:56Z","timestamp":1790011616598,"version":"4.0.1"},"reference-count":51,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020","award":["721236-TREATMENT"],"award-info":[{"award-number":["721236-TREATMENT"]}]},{"name":"European Union\u2019s Horizon 2020","award":["P3-0019"],"award-info":[{"award-number":["P3-0019"]}]},{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency","doi-asserted-by":"publisher","award":["721236-TREATMENT"],"award-info":[{"award-number":["721236-TREATMENT"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency","doi-asserted-by":"publisher","award":["P3-0019"],"award-info":[{"award-number":["P3-0019"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sthe Word Federation of Scientists","award":["721236-TREATMENT"],"award-info":[{"award-number":["721236-TREATMENT"]}]},{"name":"Sthe Word Federation of Scientists","award":["P3-0019"],"award-info":[{"award-number":["P3-0019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Antipsychotics used to treat schizophrenia can cause drug-induced liver injury (DILI), according to the Roussel Uclaf Causality Assessment Method. The role of oxidative stress in triggering injury in these DILI cases is unknown. We repeatedly administrated two second-generation antipsychotics, aripiprazole and olanzapine, at laboratory alert levels to study underlying mechanisms in stress prevention upon acute oxidative stress. The drugs were administered continuously for up to 8 weeks. For this, hepatoma Fao cells, which are suitable for metabolic studies, were used, as the primary hepatocytes survive in the culture only for about 1 week. Four stress responses\u2014the oxidative stress response, the DNA damage response and the unfolded protein responses in the endoplasmic reticulum and mitochondria\u2014were examined in H2O2-treated cells by antioxidant enzyme activity measurements, gene expression and protein quantification. Oxidant conditions increased the activity of antioxidant enzymes and upregulated genes and proteins associated with oxidative stress response in aripiprazole-treated cells. While the genes associated with DNA damage response, Gadd45 and p21, were upregulated in both aripiprazole- and olanzapine-treated cells, only aripiprazole treatment was associated with upregulation in response to even more H2O2, which also coincided with better survival. Endoplasmic reticulum stress-induced Chop was also upregulated; however, neither endoplasmic reticulum nor mitochondrial unfolded protein response was activated. We conclude that only aripiprazole, but not olanzapine, protects liver cells against oxidative stress. This finding could be relevant for schizophrenia patients with high-oxidative-stress-risk lifestyles and needs to be validated in vivo.<\/jats:p>","DOI":"10.3390\/ijms23158292","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T21:11:05Z","timestamp":1658956265000},"page":"8292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Antipsychotic Drug Aripiprazole Protects Liver Cells from Oxidative Stress"],"prefix":"10.3390","volume":"23","author":[{"given":"Barbara","family":"Kramar","sequence":"first","affiliation":[{"name":"University of Ljubljana, Faculty of Medicine, Institute of Pathophysiology, Zaloska 4, SI-1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinkara","family":"Pirc Marolt","sequence":"additional","affiliation":[{"name":"University of Ljubljana, Faculty of Medicine, Institute of Pathophysiology, Zaloska 4, SI-1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2796-1453","authenticated-orcid":false,"given":"Maria","family":"Monsalve","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas Alberto Sols (CSIC-UAM), Arturo Duperier, 4, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4031-7267","authenticated-orcid":false,"given":"Du\u0161an","family":"\u0160uput","sequence":"additional","affiliation":[{"name":"University of Ljubljana, Faculty of Medicine, Institute of Pathophysiology, Zaloska 4, SI-1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6948-7238","authenticated-orcid":false,"given":"Irina","family":"Milisav","sequence":"additional","affiliation":[{"name":"University of Ljubljana, Faculty of Medicine, Institute of Pathophysiology, Zaloska 4, SI-1000 Ljubljana, Slovenia"},{"name":"University of Ljubljana, Faculty of Health Sciences, Laboratory of Oxidative Stress Research, Zdravstvena pot 5, SI-1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s00204-020-02963-4","article-title":"Antidepressants- and antipsychotics-induced hepatotoxicity","volume":"95","author":"Dordevic","year":"2021","journal-title":"Arch. 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