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Mitochondrial Impact of Organophosphate Pesticide-Induced Cardiotoxicity: an in Silico and in Vitro Study

dc.authorid Karakus, Fuat/0000-0002-5260-3650
dc.authorscopusid 57201195704
dc.authorscopusid 57188622134
dc.authorscopusid 57201072236
dc.authorwosid Arzuk, Ege/Aav-5181-2021
dc.authorwosid Karakuş, Fuat/O-2627-2019
dc.authorwosid Ergüç, Ali/Aab-7521-2020
dc.contributor.author Karakus, Fuat
dc.contributor.author Arzuk, Ege
dc.contributor.author Erguc, Ali
dc.date.accessioned 2025-05-10T17:23:18Z
dc.date.available 2025-05-10T17:23:18Z
dc.date.issued 2024
dc.department T.C. Van Yüzüncü Yıl Üniversitesi en_US
dc.department-temp [Karakus, Fuat] Van Yuzuncu Yil Univ, Fac Pharm, Dept Pharmaceut Toxicol, Van, Turkiye; [Arzuk, Ege] Ege Univ, Fac Pharm, Dept Pharmaceut Toxicol, Izmir, Turkiye; [Erguc, Ali] Izmir Katip Celebi Univ, Fac Pharm, Dept Pharmaceut Toxicol, Izmir, Turkiye en_US
dc.description Karakus, Fuat/0000-0002-5260-3650 en_US
dc.description.abstract Organophosphate pesticides are widely used; however, their use is limited due to neurotoxicity and, to a lesser extent, cardiotoxicity in humans. Given the high energy demands of cardiac muscle, which is characterized by a dense population of mitochondria, any damage to these organelles can exacerbate cardiotoxicity. This study aims to elucidate whether the cardiotoxic effects of organophosphate pesticides originate from mitochondrial dysfunction. To investigate this, in silico toxicogenomic analyses were performed using various tools, such as the Comparative Toxicogenomic Database, GeneMANIA, STRING, and Cytoscape. Results revealed that 11 out of the 13 WHO-recommended Class Ia organophosphate pesticides target genes associated with cardiotoxicity. Notably, three of these genes were mitochondrial, with catalase (CAT) being the common differentially expressed gene among parathion, methyl parathion, and phorate. Furthermore, protein-protein interaction analysis indicated a strong association between CAT and superoxide dismutase 2, mitochondrial (SOD2). Subsequently, isolated heart mitochondria were utilized to assess CAT and superoxide dismutase (SOD) activities in vitro. The findings demonstrated that at a concentration of 7.5 ng/mu L, both methyl parathion and phorate significantly decreased CAT activity by approximately 35%. Moreover, phorate reduced total SOD and SOD2 activities by 17% and 19%, respectively, at the same concentration. In contrast, none of the three organophosphate pesticides induced the opening of the mitochondrial permeability transition pore. These results suggest that the reduction in CAT and SOD2 activities, critical antioxidant enzymes, leads to the accumulation of reactive oxygen species within mitochondria, ultimately resulting in mitochondrial damage. This mechanism likely underlies the observed cardiotoxicity induced by these organophosphate pesticides. en_US
dc.description.woscitationindex Science Citation Index Expanded
dc.identifier.doi 10.1177/10915818241261624
dc.identifier.endpage 471 en_US
dc.identifier.issn 1091-5818
dc.identifier.issn 1092-874X
dc.identifier.issue 5 en_US
dc.identifier.pmid 38897602
dc.identifier.scopus 2-s2.0-85196513983
dc.identifier.scopusquality Q3
dc.identifier.startpage 464 en_US
dc.identifier.uri https://doi.org/10.1177/10915818241261624
dc.identifier.uri https://hdl.handle.net/20.500.14720/10842
dc.identifier.volume 43 en_US
dc.identifier.wos WOS:001250803100001
dc.identifier.wosquality Q3
dc.language.iso en en_US
dc.publisher Sage Publications inc en_US
dc.relation.publicationcategory Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı en_US
dc.rights info:eu-repo/semantics/closedAccess en_US
dc.subject Cardiotoxicity en_US
dc.subject Catalase en_US
dc.subject Methyl Parathion en_US
dc.subject Mitotoxicity en_US
dc.subject Organophosphate Pesticides en_US
dc.subject Phorate en_US
dc.subject Superoxide Dismutase en_US
dc.title Mitochondrial Impact of Organophosphate Pesticide-Induced Cardiotoxicity: an in Silico and in Vitro Study en_US
dc.type Article en_US

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