The influence of SARS-CoV-2 infection on expression of drug-metabolizing enzymes and transporters in a hACE2 murine model

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dc.contributor.authorDeshpande, Kiranen
dc.contributor.authorLange, Keith R.en
dc.contributor.authorStone, William B.en
dc.contributor.authorYohn, Christineen
dc.contributor.authorSchlesinger, Naomien
dc.contributor.authorKagan, Leoniden
dc.contributor.authorAuguste, Albert J.en
dc.contributor.authorFirestein, Bonnie L.en
dc.contributor.authorBrunetti, Luigien
dc.date.accessioned2023-06-22T13:12:42Zen
dc.date.available2023-06-22T13:12:42Zen
dc.date.issued2023-06en
dc.description.abstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting Coronavirus disease 2019 emerged in late 2019 and is responsible for significant morbidity and mortality worldwide. A hallmark of severe COVID-19 is exaggerated systemic inflammation, regarded as a "cytokine storm," which contributes to the damage of various organs, primarily the lungs. The inflammation associated with some viral illnesses is known to alter the expression of drug-metabolizing enzymes and transporters. These alterations can lead to modifications in drug exposure and the processing of various endogenous compounds. Here, we provide evidence to support changes in the mitochondrial ribonucleic acid expression of a subset of drug transporters (84 transporters) in the liver, kidneys, and lungs and metabolizing enzymes (84 enzymes) in the liver in a humanized angiotensin-converting enzyme 2 receptor mouse model. Specifically, three drug transporters (Abca3, Slc7a8, Tap1) and the pro-inflammatory cytokine IL-6 were upregulated in the lungs of SARS-CoV-2 infected mice. We also found significant downregulation of drug transporters responsible for the movement of xenobiotics in the liver and kidney. Additionally, expression of cytochrome P-450 2f2 which is known to metabolize some pulmonary toxicants, was significantly decreased in the liver of infected mice. The significance of these findings requires further exploration. Our results suggest that further research should emphasize altered drug disposition when investigating therapeutic compounds, whether re-purposed or new chemical entities, in other animal models and ultimately in individuals infected with SARS-CoV-2. Moreover, the influence and impact of these changes on the processing of endogenous compounds also require further investigation.en
dc.description.notesIDCareen
dc.description.sponsorshipIDCareen
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1002/prp2.1071en
dc.identifier.issn2052-1707en
dc.identifier.issue3en
dc.identifier.othere01071en
dc.identifier.pmid37133236en
dc.identifier.urihttp://hdl.handle.net/10919/115480en
dc.identifier.volume11en
dc.language.isoenen
dc.publisherWileyen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectCOVID-19en
dc.subjectdrug transportersen
dc.subjectdrug-metabolizing enzymesen
dc.subjecthACE2en
dc.subjectSARS-CoV-2en
dc.titleThe influence of SARS-CoV-2 infection on expression of drug-metabolizing enzymes and transporters in a hACE2 murine modelen
dc.title.serialPharmacology Research & Perspectivesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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