Study of Tissue-Specific Reactive Oxygen Species Formation by Cell Membrane Microarrays for the Characterization of Bioactive Compounds
The production of reactive oxygen species (ROS) increases considerably in situations of cellular stress, inducing lipid peroxidation and multiple alterations in proteins and nucleic acids. However, sensitivity to oxidative damage varies between organs and tissues depending on the triggering process....
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
|
| Series: | Membranes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0375/11/12/943 |
| _version_ | 1797502568400683008 |
|---|---|
| author | Ane Elexpe Nerea Nieto Claudia Fernández-Cuétara Celtia Domínguez-Fernández Teresa Morera-Herreras María Torrecilla Cristina Miguélez Antonio Laso Eneko Ochoa María Bailen Azucena González-Coloma Iñigo Angulo-Barturen Egoitz Astigarraga Gabriel Barreda-Gómez |
| author_facet | Ane Elexpe Nerea Nieto Claudia Fernández-Cuétara Celtia Domínguez-Fernández Teresa Morera-Herreras María Torrecilla Cristina Miguélez Antonio Laso Eneko Ochoa María Bailen Azucena González-Coloma Iñigo Angulo-Barturen Egoitz Astigarraga Gabriel Barreda-Gómez |
| author_sort | Ane Elexpe |
| collection | DOAJ |
| description | The production of reactive oxygen species (ROS) increases considerably in situations of cellular stress, inducing lipid peroxidation and multiple alterations in proteins and nucleic acids. However, sensitivity to oxidative damage varies between organs and tissues depending on the triggering process. Certain drugs used in the treatment of diverse diseases such as malaria have side effects similar to those produced by oxidative damage, although no specific study has been conducted. For this purpose, cell membrane microarrays were developed and the superoxide production evoked by the mitochondrial activity was assayed in the presence of specific inhibitors: rotenone, antimycin A and azide. Once the protocol was set up on cell membrane isolated from rat brain areas, the effect of six antimalarial drugs (atovaquone, quinidine, doxycycline, mefloquine, artemisinin, and tafenoquine) and two essential oils (<i>Rosmarinus officinalis</i> and <i>Origanum majoricum</i>) were evaluated in multiple human samples. The basal activity was different depending on the type of tissue, the liver, jejunum and adrenal gland being the ones with the highest amount of superoxide. The antimalarial drugs studied showed specific behavior according to the type of human tissue analyzed, with atovaquone and quinidine producing the highest percentage of superoxide formation, and doxycycline the lowest. In conclusion, the analysis of superoxide production evaluated in cell membranes of a collection of human tissues allowed for the characterization of the safety profile of these antimalarial drugs against toxicity mediated by oxidative stress. |
| first_indexed | 2024-03-10T03:35:57Z |
| format | Article |
| id | doaj.art-32b7ea09859d4ca198c7221b751be429 |
| institution | Directory Open Access Journal |
| issn | 2077-0375 |
| language | English |
| last_indexed | 2024-03-10T03:35:57Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Membranes |
| spelling | doaj.art-32b7ea09859d4ca198c7221b751be4292023-11-23T09:30:15ZengMDPI AGMembranes2077-03752021-11-01111294310.3390/membranes11120943Study of Tissue-Specific Reactive Oxygen Species Formation by Cell Membrane Microarrays for the Characterization of Bioactive CompoundsAne Elexpe0Nerea Nieto1Claudia Fernández-Cuétara2Celtia Domínguez-Fernández3Teresa Morera-Herreras4María Torrecilla5Cristina Miguélez6Antonio Laso7Eneko Ochoa8María Bailen9Azucena González-Coloma10Iñigo Angulo-Barturen11Egoitz Astigarraga12Gabriel Barreda-Gómez13Research and Development Division, IMG Pharma Biotech, 48160 Derio, SpainResearch and Development Division, IMG Pharma Biotech, 48160 Derio, SpainDepartment of Preventive Medicine and Public Health and Microbiology, Faculty of Medicine, Autonomus University of Madrid UAM, 28029 Madrid, SpainResearch and Development Division, IMG Pharma Biotech, 48160 Derio, SpainDepartment of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, 48940 Leioa, SpainDepartment of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, 48940 Leioa, SpainDepartment of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, 48940 Leioa, SpainResearch and Development Division, AleoVitro, 48160 Derio, SpainResearch and Development Division, AleoVitro, 48160 Derio, SpainDepartment of Preventive Medicine and Public Health and Microbiology, Faculty of Medicine, Autonomus University of Madrid UAM, 28029 Madrid, SpainInstitute of Agricultural Sciences (ICA), Spanish Research Council (CSIC), 28006 Madrid, SpainThe Art of Discovery, 48160 Derio, SpainResearch and Development Division, IMG Pharma Biotech, 48160 Derio, SpainResearch and Development Division, IMG Pharma Biotech, 48160 Derio, SpainThe production of reactive oxygen species (ROS) increases considerably in situations of cellular stress, inducing lipid peroxidation and multiple alterations in proteins and nucleic acids. However, sensitivity to oxidative damage varies between organs and tissues depending on the triggering process. Certain drugs used in the treatment of diverse diseases such as malaria have side effects similar to those produced by oxidative damage, although no specific study has been conducted. For this purpose, cell membrane microarrays were developed and the superoxide production evoked by the mitochondrial activity was assayed in the presence of specific inhibitors: rotenone, antimycin A and azide. Once the protocol was set up on cell membrane isolated from rat brain areas, the effect of six antimalarial drugs (atovaquone, quinidine, doxycycline, mefloquine, artemisinin, and tafenoquine) and two essential oils (<i>Rosmarinus officinalis</i> and <i>Origanum majoricum</i>) were evaluated in multiple human samples. The basal activity was different depending on the type of tissue, the liver, jejunum and adrenal gland being the ones with the highest amount of superoxide. The antimalarial drugs studied showed specific behavior according to the type of human tissue analyzed, with atovaquone and quinidine producing the highest percentage of superoxide formation, and doxycycline the lowest. In conclusion, the analysis of superoxide production evaluated in cell membranes of a collection of human tissues allowed for the characterization of the safety profile of these antimalarial drugs against toxicity mediated by oxidative stress.https://www.mdpi.com/2077-0375/11/12/943microarrayinhibitorsantimalarialsuperoxide production |
| spellingShingle | Ane Elexpe Nerea Nieto Claudia Fernández-Cuétara Celtia Domínguez-Fernández Teresa Morera-Herreras María Torrecilla Cristina Miguélez Antonio Laso Eneko Ochoa María Bailen Azucena González-Coloma Iñigo Angulo-Barturen Egoitz Astigarraga Gabriel Barreda-Gómez Study of Tissue-Specific Reactive Oxygen Species Formation by Cell Membrane Microarrays for the Characterization of Bioactive Compounds Membranes microarray inhibitors antimalarial superoxide production |
| title | Study of Tissue-Specific Reactive Oxygen Species Formation by Cell Membrane Microarrays for the Characterization of Bioactive Compounds |
| title_full | Study of Tissue-Specific Reactive Oxygen Species Formation by Cell Membrane Microarrays for the Characterization of Bioactive Compounds |
| title_fullStr | Study of Tissue-Specific Reactive Oxygen Species Formation by Cell Membrane Microarrays for the Characterization of Bioactive Compounds |
| title_full_unstemmed | Study of Tissue-Specific Reactive Oxygen Species Formation by Cell Membrane Microarrays for the Characterization of Bioactive Compounds |
| title_short | Study of Tissue-Specific Reactive Oxygen Species Formation by Cell Membrane Microarrays for the Characterization of Bioactive Compounds |
| title_sort | study of tissue specific reactive oxygen species formation by cell membrane microarrays for the characterization of bioactive compounds |
| topic | microarray inhibitors antimalarial superoxide production |
| url | https://www.mdpi.com/2077-0375/11/12/943 |
| work_keys_str_mv | AT aneelexpe studyoftissuespecificreactiveoxygenspeciesformationbycellmembranemicroarraysforthecharacterizationofbioactivecompounds AT nereanieto studyoftissuespecificreactiveoxygenspeciesformationbycellmembranemicroarraysforthecharacterizationofbioactivecompounds AT claudiafernandezcuetara studyoftissuespecificreactiveoxygenspeciesformationbycellmembranemicroarraysforthecharacterizationofbioactivecompounds AT celtiadominguezfernandez studyoftissuespecificreactiveoxygenspeciesformationbycellmembranemicroarraysforthecharacterizationofbioactivecompounds AT teresamoreraherreras studyoftissuespecificreactiveoxygenspeciesformationbycellmembranemicroarraysforthecharacterizationofbioactivecompounds AT mariatorrecilla studyoftissuespecificreactiveoxygenspeciesformationbycellmembranemicroarraysforthecharacterizationofbioactivecompounds AT cristinamiguelez studyoftissuespecificreactiveoxygenspeciesformationbycellmembranemicroarraysforthecharacterizationofbioactivecompounds AT antoniolaso studyoftissuespecificreactiveoxygenspeciesformationbycellmembranemicroarraysforthecharacterizationofbioactivecompounds AT enekoochoa studyoftissuespecificreactiveoxygenspeciesformationbycellmembranemicroarraysforthecharacterizationofbioactivecompounds AT mariabailen studyoftissuespecificreactiveoxygenspeciesformationbycellmembranemicroarraysforthecharacterizationofbioactivecompounds AT azucenagonzalezcoloma studyoftissuespecificreactiveoxygenspeciesformationbycellmembranemicroarraysforthecharacterizationofbioactivecompounds AT inigoangulobarturen studyoftissuespecificreactiveoxygenspeciesformationbycellmembranemicroarraysforthecharacterizationofbioactivecompounds AT egoitzastigarraga studyoftissuespecificreactiveoxygenspeciesformationbycellmembranemicroarraysforthecharacterizationofbioactivecompounds AT gabrielbarredagomez studyoftissuespecificreactiveoxygenspeciesformationbycellmembranemicroarraysforthecharacterizationofbioactivecompounds |