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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

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ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

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Research Article

Protection from Radiation-induced Damage in Rat’s Ileum and Colon by Combined Regimens of Melatonin and Metformin: A Histopathological Study

Author(s): Masoud Najafi , Mohsen Cheki*, Gholamreza Hassanzadeh, Peyman Amini, Dheyauldeen Shabeeb and Ahmed E. Musa

Volume 19, Issue 2, 2020

Page: [180 - 189] Pages: 10

DOI: 10.2174/1871523018666190718161928

Abstract

Background: Radiation-induced enteritis and proctitis are common side effects of abdominopelvic cancers among patients that undergo radiotherapy for prostate, colorectal or urinary cancers. Exposure of these tissues to high doses of radiation leads to damage to villous, inflammation, pain, ulcer and bleeding, which may cause malabsorption and gastrointestinal disorders. To date, several procedures such as pharmaceutical treatment have been proposed for protection and mitigation of gastrointestinal toxicity following radiotherapy.

Aims: In the current study, we aimed to investigate the possible radioprotection of ileum and colon in rats using a combination of melatonin and metformin.

Methods: In this experimental study, 30 male Wistar rats were randomly assigned to six groups: control, melatonin (100 mg/kg) treatment, melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment, radiation (10 Gy to whole body) group, radiation + melatonin (100 mg/kg) treatment, and radiation + melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment. After 3.5 days, rats were sacrificed and their ileum and colon tissues carefully removed. Histopathological evaluations were conducted on these tissue samples.

Results: Histological evaluations reported moderate to severe damages to ileum and colon following whole body irradiation. Melatonin administration was able to protect the ileum remarkably, while the combination of melatonin and metformin was less effective. Interestingly, for the colon, melatonin was less effective while its combination with metformin was able to protect against radiation toxicity completely.

Conclusion: For the ileum, melatonin was a more effective radioprotector compared to its combination with metformin. However, the combination of melatonin and metformin can be proposed as an ideal radioprotector for the colon.

Keywords: Colon, ileum, melatonin, metformin, radiation, radiation-induced enteritis.

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[1]
Arnold, M.; Sierra, M.S.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global patterns and trends in colorectal cancer incidence and mortality. Gut, 2017, 66(4), 683-691.
[http://dx.doi.org/10.1136/gutjnl-2015-310912] [PMID: 26818619]
[2]
Czito, B.G.; Meyer, J.J.; Willett, C.G. Overview of gastrointestinal toxicity of radiation therapy; Uptodate, 2017.
[3]
Peach, M.S.; Showalter, T.N.; Ohri, N. Systematic review of the relationship between acute and late gastrointestinal toxicity after radiotherapy for prostate cancer. Prostate Cancer, 2015, 2015 624736
[http://dx.doi.org/10.1155/2015/624736]
[4]
Gestaut, M.M.; Swanson, G.P. Long term clinical toxicity of radiation therapy in prostate cancer patients with Inflammatory Bowel Disease. Rep. Pract. Oncol. Radiother., 2016, 22(1), 77-82.
[5]
Stansborough, R.L.; Bateman, E.H.; Al-Dasooqi, N.; Bowen, J.M.; Keefe, D.M.K.; Yeoh, A.S.J.; Logan, R.M.; Yeoh, E.E.K.; Stringer, A.M.; Gibson, R.J. Fractionated abdominal irradiation induces intestinal microvascular changes in an in vivo model of radiotherapy-induced gut toxicity. Support. Care Cancer, 2017, 25(6), 1973-1983.
[http://dx.doi.org/10.1007/s00520-017-3601-3] [PMID: 28175996]
[6]
Azzam, E.I.; Jay-Gerin, J-P.; Pain, D. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Lett., 2012, 327(1-2), 48-60.
[http://dx.doi.org/10.1016/j.canlet.2011.12.012] [PMID: 22182453]
[7]
Akbulut, A.; Sadic, M.; Yumusak, N.; Aydinbelge, F.; Koca, G.; Korkmaz, M. The effects of zinc in the gastrointestinal system as a radioprotective agent. Int. J. Radiation Res., 2018, 16(3), 333-339.
[8]
Deniz, M.; Atasoy, B.M.; Dane, F.; Can, G.; Erzik, C.; Çetinel, Ş.; Yeğen, B.Ç. Radiation-induced oxidative injury of the ileum and colon is alleviated by glucagon-like peptide-1 and-2. J. Radiation Res. Appl. Sci., 2015, 8(2), 234-242.
[http://dx.doi.org/10.1016/j.jrras.2015.01.010]
[9]
Pişkin, Ö.; Aydın, B.G.; Baş, Y.; Karakaya, K.; Can, M.; Elmas, Ö.; Büyükuysal, M.Ç. Protective effects of quercetin on intestinal damage caused by ionizing radiation. Med. Bull. Haseki, 2018, 56(1), 14-21.
[10]
Akpolat, M.; Kanter, M.; Uzal, M.C. Protective effects of curcumin against gamma radiation-induced ileal mucosal damage. Arch. Toxicol., 2009, 83(6), 609-617.
[http://dx.doi.org/10.1007/s00204-008-0352-4] [PMID: 18754102]
[11]
Haghi-Aminjan, H.; Asghari, M.H.; Farhood, B.; Rahimifard, M.; Hashemi Goradel, N.; Abdollahi, M. The role of melatonin on chemotherapy-induced reproductive toxicity. J. Pharm. Pharmacol., 2018, 70(3), 291-306.
[http://dx.doi.org/10.1111/jphp.12855] [PMID: 29168173]
[12]
Haghi-Aminjan, H.; Farhood, B.; Rahimifard, M.; Didari, T.; Baeeri, M.; Hassani, S.; Hosseini, R.; Abdollahi, M. The protective role of melatonin in chemotherapy-induced nephrotoxicity: a systematic review of non-clinical studies. Expert Opin. Drug Metab. Toxicol., 2018, 14(9), 937-950.
[http://dx.doi.org/10.1080/17425255.2018.1513492] [PMID: 30118646]
[13]
Mortezaee, K.; Shabeeb, D.; Musa, A.E.; Najafi, M.; Farhood, B. Metformin as a radiation modifier; implications to normal tissue protection and tumor sensitization. Curr. Clin. Pharmacol., 2019, 14(1), 41-53.
[http://dx.doi.org/10.2174/1574884713666181025141559] [PMID: 30360725]
[14]
Ashabi, G.; Khalaj, L.; Khodagholi, F.; Goudarzvand, M.; Sarkaki, A. Pre-treatment with metformin activates Nrf2 antioxidant pathways and inhibits inflammatory responses through induction of AMPK after transient global cerebral ischemia. Metab. Brain Dis., 2015, 30(3), 747-754.
[http://dx.doi.org/10.1007/s11011-014-9632-2] [PMID: 25413451]
[15]
Sanli, T.; Steinberg, G.R.; Singh, G.; Tsakiridis, T. AMP-activated protein kinase (AMPK) beyond metabolism: a novel genomic stress sensor participating in the DNA damage response pathway. Cancer Biol. Ther., 2014, 15(2), 156-169.
[http://dx.doi.org/10.4161/cbt.26726] [PMID: 24100703]
[16]
MacPherson, B.R.; Pfeiffer, C.J. Experimental production of diffuse colitis in rats. Digestion, 1978, 17(2), 135-150.
[http://dx.doi.org/10.1159/000198104] [PMID: 627326]
[17]
Madani, Z.S.; Azarakhsh, S.; Shakib, P.A.; Karimi, M. Histopathological changes in dental pulp of rats following radiotherapy. Dent Res J (Isfahan), 2017, 14(1), 19-24.
[http://dx.doi.org/10.4103/1735-3327.201139] [PMID: 28348613]
[18]
Guney, Y.; Hicsonmez, A.; Uluoglu, C.; Guney, H.Z.; Ozel Turkcu, U.; Take, G.; Yucel, B.; Caglar, G.; Bilgihan, A.; Erdogan, D.; Nalca Andrieu, M.; Kurtman, C.; Zengil, H. Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine. Braz. J. Med. Biol. Res., 2007, 40(10), 1305-1314.
[http://dx.doi.org/10.1590/S0100-879X2006005000156] [PMID: 17713655]
[19]
Dogan Turacli, I.; Candar, T.; Yuksel, E.B.; Kalay, S.; Oguz, A.K.; Demirtas, S. Potential effects of metformin in DNA BER system based on oxidative status in type 2 diabetes. Biochimie, 2018, 154, 62-68.
[http://dx.doi.org/10.1016/j.biochi.2018.08.002] [PMID: 30098371]
[20]
Asghari, A.; Akbari, G.; Meghdadi, A.; Mortazavi, P. Effects of melatonin and metformin co-administration on testicular ischemia/reperfusion injury in rats. J. Pediatr. Urol., 2016, 12(6), 410.e411-410.e417.
[21]
Cheki, M.; Shirazi, A.; Mahmoudzadeh, A.; Bazzaz, J.T.; Hosseinimehr, S.J. The radioprotective effect of metformin against cytotoxicity and genotoxicity induced by ionizing radiation in cultured human blood lymphocytes. Mutat. Res., 2016, 809, 24-32.
[http://dx.doi.org/10.1016/j.mrgentox.2016.09.001] [PMID: 27692296]
[22]
Azmoonfar, R.; Amini, P.; Saffar, H.; Rezapoor, S.; Motevaseli, E.; Cheki, M.; Yahyapour, R.; Farhood, B.; Nouruzi, F.; Khodamoradi, E.; Shabeeb, D.; Eleojo Musa, A.; Najafi, M. Metformin protects against radiation-induced pneumonitis and fibrosis and attenuates upregulation of dual oxidase genes expression. Adv. Pharm. Bull., 2018, 8(4), 697-704.
[http://dx.doi.org/10.15171/apb.2018.078] [PMID: 30607342]
[23]
Yahyapour, R.; Amini, P.; Saffar, H.; Rezapoor, S.; Motevaseli, E.; Cheki, M.; Farhood, B.; Nouruzi, F.; Shabeeb, D.; Musa, A.E; Najafi, M. Metformin protects against radiation-induced heart injury and attenuates the up-regulation of dual oxidase genes following rat’s chest irradiation. Int. J. Mol. Cellular. Med., 2018, 7(3), 193-202.
[http://dx.doi.org/10.22088/IJMCM.BUMS.7.3.193]

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