Inhibition of cytochrome P450 epoxygenase promotes endothelium-to-mesenchymal transition and exacerbates doxorubicin-induced cardiovascular toxicity
<h3>Background</h3><p dir="ltr">Doxorubicin (DOX) is a potent chemotherapy widely used in treating various neoplastic diseases. However, the clinical use of DOX is limited due to its potential toxic effect on the cardiovascular system. Thus, identifying the pathway involv...
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| مؤلفون آخرون: | , , , , , , |
| منشور في: |
2024
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| _version_ | 1864513541109710848 |
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| author | Hevna Dhulkifle (14724821) |
| author2 | Lubna Therachiyil (4246156) Maram H. Hasan (22047845) Tahseen S. Sayed (14724824) Shahd M. Younis (17380453) Hesham M. Korashy (1474849) Huseyin C. Yalcin (6695099) Zaid H. Maayah (9236533) |
| author2_role | author author author author author author author |
| author_facet | Hevna Dhulkifle (14724821) Lubna Therachiyil (4246156) Maram H. Hasan (22047845) Tahseen S. Sayed (14724824) Shahd M. Younis (17380453) Hesham M. Korashy (1474849) Huseyin C. Yalcin (6695099) Zaid H. Maayah (9236533) |
| author_role | author |
| dc.creator.none.fl_str_mv | Hevna Dhulkifle (14724821) Lubna Therachiyil (4246156) Maram H. Hasan (22047845) Tahseen S. Sayed (14724824) Shahd M. Younis (17380453) Hesham M. Korashy (1474849) Huseyin C. Yalcin (6695099) Zaid H. Maayah (9236533) |
| dc.date.none.fl_str_mv | 2024-07-27T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1007/s11033-024-09803-z |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Inhibition_of_cytochrome_P450_epoxygenase_promotes_endothelium-to-mesenchymal_transition_and_exacerbates_doxorubicin-induced_cardiovascular_toxicity/29900684 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Cardiovascular medicine and haematology Pharmacology and pharmaceutical sciences Doxorubicin Endothelial Mesenchymal Cytochrome p450 Epoxyeicosatrienoic acids |
| dc.title.none.fl_str_mv | Inhibition of cytochrome P450 epoxygenase promotes endothelium-to-mesenchymal transition and exacerbates doxorubicin-induced cardiovascular toxicity |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Background</h3><p dir="ltr">Doxorubicin (DOX) is a potent chemotherapy widely used in treating various neoplastic diseases. However, the clinical use of DOX is limited due to its potential toxic effect on the cardiovascular system. Thus, identifying the pathway involved in this toxicity may help minimize chemotherapy risk and improve cancer patients’ quality of life. Recent studies suggest that Endothelial-to-Mesenchymal transition (EndMT) and endothelial toxicity contribute to the pathogenesis of DOX-induced cardiovascular toxicity. However, the molecular mechanism is yet unknown. Given that arachidonic acid and associated cytochrome P450 (CYP) epoxygenase have been involved in endothelial and cardiovascular function, we aimed to examine the effect of suppressing CYP epoxygenases on DOX-induced EndMT and cardiovascular toxicity in vitro and in vivo.</p><h3>Methods and Results</h3><p dir="ltr">To test this, human endothelial cells were treated with DOX, with or without CYP epoxygenase inhibitor, MSPPOH. We also investigated the effect of MSPPOH on the cardiovascular system in our zebrafish model of DOX-induced cardiotoxicity. Our results showed that MSPPOH exacerbated DOX-induced EndMT, inflammation, oxidative stress, and apoptosis in our endothelial cells. Furthermore, we also show that MSPPOH increased cardiac edema, lowered vascular blood flow velocity, and worsened the expression of EndMT and cardiac injury markers in our zebrafish model of DOX-induced cardiotoxicity.</p><h3>Conclusion</h3><p dir="ltr">Our data indicate that a selective CYP epoxygenase inhibitor, MSPPOH, induces EndMT and endothelial toxicity to contribute to DOX-induced cardiovascular toxicity.</p><h2>Other Information</h2><p dir="ltr">Published in: Molecular Biology Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s11033-024-09803-z" target="_blank">https://dx.doi.org/10.1007/s11033-024-09803-z</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_8dc9427e8be4e6c8e22d46959247c18b |
| identifier_str_mv | 10.1007/s11033-024-09803-z |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/29900684 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Inhibition of cytochrome P450 epoxygenase promotes endothelium-to-mesenchymal transition and exacerbates doxorubicin-induced cardiovascular toxicityHevna Dhulkifle (14724821)Lubna Therachiyil (4246156)Maram H. Hasan (22047845)Tahseen S. Sayed (14724824)Shahd M. Younis (17380453)Hesham M. Korashy (1474849)Huseyin C. Yalcin (6695099)Zaid H. Maayah (9236533)Biomedical and clinical sciencesCardiovascular medicine and haematologyPharmacology and pharmaceutical sciencesDoxorubicinEndothelialMesenchymalCytochrome p450Epoxyeicosatrienoic acids<h3>Background</h3><p dir="ltr">Doxorubicin (DOX) is a potent chemotherapy widely used in treating various neoplastic diseases. However, the clinical use of DOX is limited due to its potential toxic effect on the cardiovascular system. Thus, identifying the pathway involved in this toxicity may help minimize chemotherapy risk and improve cancer patients’ quality of life. Recent studies suggest that Endothelial-to-Mesenchymal transition (EndMT) and endothelial toxicity contribute to the pathogenesis of DOX-induced cardiovascular toxicity. However, the molecular mechanism is yet unknown. Given that arachidonic acid and associated cytochrome P450 (CYP) epoxygenase have been involved in endothelial and cardiovascular function, we aimed to examine the effect of suppressing CYP epoxygenases on DOX-induced EndMT and cardiovascular toxicity in vitro and in vivo.</p><h3>Methods and Results</h3><p dir="ltr">To test this, human endothelial cells were treated with DOX, with or without CYP epoxygenase inhibitor, MSPPOH. We also investigated the effect of MSPPOH on the cardiovascular system in our zebrafish model of DOX-induced cardiotoxicity. Our results showed that MSPPOH exacerbated DOX-induced EndMT, inflammation, oxidative stress, and apoptosis in our endothelial cells. Furthermore, we also show that MSPPOH increased cardiac edema, lowered vascular blood flow velocity, and worsened the expression of EndMT and cardiac injury markers in our zebrafish model of DOX-induced cardiotoxicity.</p><h3>Conclusion</h3><p dir="ltr">Our data indicate that a selective CYP epoxygenase inhibitor, MSPPOH, induces EndMT and endothelial toxicity to contribute to DOX-induced cardiovascular toxicity.</p><h2>Other Information</h2><p dir="ltr">Published in: Molecular Biology Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s11033-024-09803-z" target="_blank">https://dx.doi.org/10.1007/s11033-024-09803-z</a></p>2024-07-27T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s11033-024-09803-zhttps://figshare.com/articles/journal_contribution/Inhibition_of_cytochrome_P450_epoxygenase_promotes_endothelium-to-mesenchymal_transition_and_exacerbates_doxorubicin-induced_cardiovascular_toxicity/29900684CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/299006842024-07-27T09:00:00Z |
| spellingShingle | Inhibition of cytochrome P450 epoxygenase promotes endothelium-to-mesenchymal transition and exacerbates doxorubicin-induced cardiovascular toxicity Hevna Dhulkifle (14724821) Biomedical and clinical sciences Cardiovascular medicine and haematology Pharmacology and pharmaceutical sciences Doxorubicin Endothelial Mesenchymal Cytochrome p450 Epoxyeicosatrienoic acids |
| status_str | publishedVersion |
| title | Inhibition of cytochrome P450 epoxygenase promotes endothelium-to-mesenchymal transition and exacerbates doxorubicin-induced cardiovascular toxicity |
| title_full | Inhibition of cytochrome P450 epoxygenase promotes endothelium-to-mesenchymal transition and exacerbates doxorubicin-induced cardiovascular toxicity |
| title_fullStr | Inhibition of cytochrome P450 epoxygenase promotes endothelium-to-mesenchymal transition and exacerbates doxorubicin-induced cardiovascular toxicity |
| title_full_unstemmed | Inhibition of cytochrome P450 epoxygenase promotes endothelium-to-mesenchymal transition and exacerbates doxorubicin-induced cardiovascular toxicity |
| title_short | Inhibition of cytochrome P450 epoxygenase promotes endothelium-to-mesenchymal transition and exacerbates doxorubicin-induced cardiovascular toxicity |
| title_sort | Inhibition of cytochrome P450 epoxygenase promotes endothelium-to-mesenchymal transition and exacerbates doxorubicin-induced cardiovascular toxicity |
| topic | Biomedical and clinical sciences Cardiovascular medicine and haematology Pharmacology and pharmaceutical sciences Doxorubicin Endothelial Mesenchymal Cytochrome p450 Epoxyeicosatrienoic acids |