Mitochondrial Impact of Organophosphate Pesticide-Induced Cardiotoxicity: An In Silico and In Vitro Study

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dc.authoridKARAKUŞ, Fuat/0000-0002-5260-3650
dc.contributor.authorKarakus, Fuat
dc.contributor.authorArzuk, Ege
dc.contributor.authorErguc, Ali
dc.date.accessioned2024-08-31T07:47:34Z
dc.date.available2024-08-31T07:47:34Z
dc.date.issued2024
dc.departmentEge Üniversitesien_US
dc.description.abstractOrganophosphate 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.identifier.doi10.1177/10915818241261624
dc.identifier.issn1091-5818
dc.identifier.issn1092-874X
dc.identifier.pmid38897602en_US
dc.identifier.scopus2-s2.0-85196513983en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.urihttps://doi.org/10.1177/10915818241261624
dc.identifier.urihttps://hdl.handle.net/11454/104474
dc.identifier.wosWOS:001250803100001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSage Publications Incen_US
dc.relation.ispartofInternational Journal of Toxicologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmz20240831_Uen_US
dc.subjectCardiotoxicityen_US
dc.subjectCatalaseen_US
dc.subjectMethyl Parathionen_US
dc.subjectMitotoxicityen_US
dc.subjectOrganophosphate Pesticidesen_US
dc.subjectPhorateen_US
dc.subjectSuperoxide Dismutaseen_US
dc.titleMitochondrial Impact of Organophosphate Pesticide-Induced Cardiotoxicity: An In Silico and In Vitro Studyen_US
dc.typeArticleen_US

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