Dose- and Segment-Dependent Disturbance of Rat Gut by Ionizing Radiation: Impact of Tight Junction Proteins
The damaging effect of ionizing radiation (IR) exposure results in the disturbance of the gut natural barrier, followed by the development of severe gastrointestinal injury. However, the dose and application segment are known to determine the effects of IR. In this study, we demonstrated the dose- a...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/1753 |
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| author | Alexandra A. Livanova Arina A. Fedorova Alexander V. Zavirsky Igor I. Krivoi Alexander G. Markov |
| author_facet | Alexandra A. Livanova Arina A. Fedorova Alexander V. Zavirsky Igor I. Krivoi Alexander G. Markov |
| author_sort | Alexandra A. Livanova |
| collection | DOAJ |
| description | The damaging effect of ionizing radiation (IR) exposure results in the disturbance of the gut natural barrier, followed by the development of severe gastrointestinal injury. However, the dose and application segment are known to determine the effects of IR. In this study, we demonstrated the dose- and segment-specificity of tight junction (TJ) alteration in IR-induced gastrointestinal injury in rats. Male Wistar rats were subjected to a total-body X-ray irradiation at doses of 2 or 10 Gy. Isolated jejunum and colon segments were tested in an Ussing chamber 72 h after exposure. In the jejunum, 10-Gy IR dramatically altered transepithelial resistance, short-circuit current and permeability for sodium fluorescein. These changes were accompanied by severe disturbance of histological structure and total rearrangement of TJ content (increased content of claudin-1, -2, -3 and -4; multidirectional changes in tricellulin and occludin). In the colon of 10-Gy irradiated rats, lesions of barrier and transport functions were less pronounced, with only claudin-2 and -4 altered among TJ proteins. The 2-Gy IR did not change electrophysiological characteristics or permeability in the colon or jejunum, although slight alterations in jejunum histology were noted, emphasized with claudin-3 increase. Considering that TJ proteins are critical for maintaining epithelial barrier integrity, these findings may have implications for countermeasures in gastrointestinal acute radiation injury. |
| first_indexed | 2024-03-09T12:17:13Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:17:13Z |
| publishDate | 2023-01-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d8fd0f8861db432195798f7a9be9089a2023-11-30T22:45:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242175310.3390/ijms24021753Dose- and Segment-Dependent Disturbance of Rat Gut by Ionizing Radiation: Impact of Tight Junction ProteinsAlexandra A. Livanova0Arina A. Fedorova1Alexander V. Zavirsky2Igor I. Krivoi3Alexander G. Markov4Department of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaDepartment of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaDepartment of Military Toxicology and Radiation Defense, S. M. Kirov Military Medical Academy, 194044 St. Petersburg, RussiaDepartment of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaDepartment of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaThe damaging effect of ionizing radiation (IR) exposure results in the disturbance of the gut natural barrier, followed by the development of severe gastrointestinal injury. However, the dose and application segment are known to determine the effects of IR. In this study, we demonstrated the dose- and segment-specificity of tight junction (TJ) alteration in IR-induced gastrointestinal injury in rats. Male Wistar rats were subjected to a total-body X-ray irradiation at doses of 2 or 10 Gy. Isolated jejunum and colon segments were tested in an Ussing chamber 72 h after exposure. In the jejunum, 10-Gy IR dramatically altered transepithelial resistance, short-circuit current and permeability for sodium fluorescein. These changes were accompanied by severe disturbance of histological structure and total rearrangement of TJ content (increased content of claudin-1, -2, -3 and -4; multidirectional changes in tricellulin and occludin). In the colon of 10-Gy irradiated rats, lesions of barrier and transport functions were less pronounced, with only claudin-2 and -4 altered among TJ proteins. The 2-Gy IR did not change electrophysiological characteristics or permeability in the colon or jejunum, although slight alterations in jejunum histology were noted, emphasized with claudin-3 increase. Considering that TJ proteins are critical for maintaining epithelial barrier integrity, these findings may have implications for countermeasures in gastrointestinal acute radiation injury.https://www.mdpi.com/1422-0067/24/2/1753ionizing radiationintestinecolongut permeabilitytight junctionsclaudins |
| spellingShingle | Alexandra A. Livanova Arina A. Fedorova Alexander V. Zavirsky Igor I. Krivoi Alexander G. Markov Dose- and Segment-Dependent Disturbance of Rat Gut by Ionizing Radiation: Impact of Tight Junction Proteins International Journal of Molecular Sciences ionizing radiation intestine colon gut permeability tight junctions claudins |
| title | Dose- and Segment-Dependent Disturbance of Rat Gut by Ionizing Radiation: Impact of Tight Junction Proteins |
| title_full | Dose- and Segment-Dependent Disturbance of Rat Gut by Ionizing Radiation: Impact of Tight Junction Proteins |
| title_fullStr | Dose- and Segment-Dependent Disturbance of Rat Gut by Ionizing Radiation: Impact of Tight Junction Proteins |
| title_full_unstemmed | Dose- and Segment-Dependent Disturbance of Rat Gut by Ionizing Radiation: Impact of Tight Junction Proteins |
| title_short | Dose- and Segment-Dependent Disturbance of Rat Gut by Ionizing Radiation: Impact of Tight Junction Proteins |
| title_sort | dose and segment dependent disturbance of rat gut by ionizing radiation impact of tight junction proteins |
| topic | ionizing radiation intestine colon gut permeability tight junctions claudins |
| url | https://www.mdpi.com/1422-0067/24/2/1753 |
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