INVESTİGATİON OF ZONULA OCCLUDENS-1 PROTEİN LEVEL İN RECTUM TİSSUE AFTER RADİOTHERAPY
DOI:
https://doi.org/10.29121/granthaalayah.v8.i10.2020.1619Keywords:
Radiotherapy, Acute Side Effect, Tight Junction, Zonula Occludens, RectumAbstract [English]
The transmembrane protein zonula occludens of rectal tissue has function to prevents the spread of bacterial toxins into the intestinal mucosa and to systemic circulation. But radiotherapy causes ablation of crypt cell proliferation, mitotic catastrophe, and apoptosis leading to gastrointestinal mucositis. We investigated the acute radiation effect on gastrointestinal mucosa of rectum tissue thickness with immunohistochemistry method for zonula occludens-1 (ZO-1) protein in animal model.
A total of 24 healthy Swiss Albino mice were divided into 4 groups, and except control group the groups of 1–3 was exposed to 500 cGy total body irradiation. All rectum tissue samples were taken from the groups of control, 24 h, 72 h, and 168 h after irradiation and stained with hematoxylin and eosin for histochemical examination, and for immunohistochemical staining with anti ZO-1 polyclonal antibody.
We observed edema especially in the groups 2 and 3 but not in group 1. Immunohistochemical examination of staining of rectum tissue samples for ZO-1 showed poor staining for control group (1.48 ± 0.06) and group 1 (1.38 ± 0.09) and group 2 (1.50 ± 0.01) but the group 3 (2.12 ± 0.04) samples showed moderate ZO-1 immunostaining. It was found that the amount and thickness of ZO-1 expression increased in the late period for more than 24 hours. The comparison of the values of ZO-1 between the group 3 which is the group in the late period after radiation exposure and control group or group 1 or group 2, showed statistically significant differences (p <0.001).
It was concluded that ZO-1 protein may have a role in the side effects of radiation injury, and the understanding of cellular and molecular activity will help us to develop pharmacological modulators to mitigate or treat the injury.
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References
Lomax M, Folkes L, O'neill P: Biological consequences of radiation-induced DNA damage: relevance to radiotherapy. Clinical oncology 2013, 25(10):578-585. DOI: https://doi.org/10.1016/j.clon.2013.06.007
Stone HB, Coleman CN, Anscher MS, McBride WH: Effects of radiation on normal tissue: consequences and mechanisms. The lancet oncology 2003, 4(9):529-536. DOI: https://doi.org/10.1016/S1470-2045(03)01191-4
i Garau MM, Calduch AL, López EC: Radiobiology of the acute radiation syndrome. Reports of Practical Oncology & Radiotherapy 2011, 16(4):123-130. DOI: https://doi.org/10.1016/j.rpor.2011.06.001
Damman CJ, Surawicz CM: The gut microbiota: a microbial arsenal protecting us from infectious and radiation-induced diarrhea. Gastroenterology 2009, 136(2):722-724. DOI: https://doi.org/10.1053/j.gastro.2008.12.020
Dubois A, Walker RI: Prospects for management of gastrointestinal injury associated with the acute radiation syndrome. Gastroenterology 1988, 95(2):500-507. DOI: https://doi.org/10.1016/0016-5085(88)90512-4
Harb AH, Fadel CA, Sharara AI: Radiation enteritis. Current gastroenterology reports 2014, 16(5):383. DOI: https://doi.org/10.1007/s11894-014-0383-3
Wang A, Ling Z, Yang Z, Kiela PR, Wang T, Wang C, Cao L, Geng F, Shen M, Ran X: Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: a pilot study. PloS one 2015, 10(5):e0126312. DOI: https://doi.org/10.1371/journal.pone.0126312
Suzuki F, Loucas BD, Ito I, Asai A, Suzuki S, Kobayashi M: Survival of Mice with Gastrointestinal Acute Radiation Syndrome through Control of Bacterial Translocation. The Journal of Immunology 2018:ji1701515. DOI: https://doi.org/10.4049/jimmunol.1701515
DeCosse J, Rhodes R, Wentz W, Reagan J, Dworken H, Holden W: The natural history and management of radiation induced injury of the gastrointestinal tract. Annals of surgery 1969, 170(3):369. DOI: https://doi.org/10.1097/00000658-196909010-00006
Guzman-Stein G, Bonsack M, Liberty J, Delaney J: Abdominal radiation causes bacterial translocation. Journal of Surgical Research 1989, 46(2):104-107. DOI: https://doi.org/10.1016/0022-4804(89)90211-4
Somosy Z, Horvath G, Telbisz A, Rez G, Palfia Z: Morphological aspects of ionizing radiation response of small intestine. Micron 2002, 33(2):167-178. DOI: https://doi.org/10.1016/S0968-4328(01)00013-0
Potten CS: Radiation, the ideal cytotoxic agent for studying the cell biology of tissues such as the small intestine. Radiation research 2004, 161(2):123-136. DOI: https://doi.org/10.1667/RR3104
Crawford PA, Gordon JI: Microbial regulation of intestinal radiosensitivity. Proceedings of the National Academy of Sciences 2005, 102(37):13254-13259. DOI: https://doi.org/10.1073/pnas.0504830102
Turner JR: Intestinal mucosal barrier function in health and disease. Nature reviews immunology 2009, 9(11):799. DOI: https://doi.org/10.1038/nri2653
Salim SaY, Söderholm JD: Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflammatory bowel diseases 2010, 17(1):362-381. DOI: https://doi.org/10.1002/ibd.21403
Anderson JM, Van Itallie CM: Physiology and function of the tight junction. Cold Spring Harbor perspectives in biology 2009, 1(2): a002584. DOI: https://doi.org/10.1101/cshperspect.a002584
Groschwitz KR, Hogan SP: Intestinal barrier function: molecular regulation and disease pathogenesis. Journal of allergy and clinical immunology 2009, 124(1):3-20. DOI: https://doi.org/10.1016/j.jaci.2009.05.038
Shukla PK, Gangwar R, Manda B, Meena AS, Yadav N, Szabo E, Balogh A, Lee SC, Tigyi G, Rao R: Rapid disruption of intestinal epithelial tight junction and barrier dysfunction by ionizing radiation in mouse colon in vivo: protection by N-acetyl-l-cysteine. American Journal of Physiology-Gastrointestinal and Liver Physiology 2016, 310(9): G705-G715. DOI: https://doi.org/10.1152/ajpgi.00314.2015
Erkanlı Şentürk G, Ersoy Canillioĝlu Y, Umay C, Demiralp‐Eksioglu E, Ercan F: Distribution of Zonula Occludens‐1 and Occludin and alterations of testicular morphology after in utero radiation and postnatal hyperthermia in rats. International journal of experimental pathology 2012, 93(6):438-449. DOI: https://doi.org/10.1111/j.1365-2613.2012.00844.x
Garg S, Zheng J, Wang J, Authier S, Pouliot M, Hauer-Jensen M: Segmental differences in radiation-induced alterations of tight junction-related proteins in non-human primate jejunum, ileum and colon. Radiation research 2015, 185(1):50-59. DOI: https://doi.org/10.1667/RR14157.1
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