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Radioprotective effect of resveratrol for early and late ionizing radiation-induced damages on colon and rectum in rats

Yıl 2023, Cilt: 27 Sayı: 4, 1617 - 1625, 28.06.2025

Ayfer Beceren , Sezgin Aydemir , Beste Melek Atasoy Esin Ak , Feriha Ercan , Tarık Emre Şener Göksel Şener

Öz

Radiotherapy, which is routinely used to treat a wide range of oncological disorders, primarily affects the malignant tissue in the targeted area, but also have negative effects in the surrounding tissues. Pelvic radiotherapy causes early and late effects on the colon and rectum. Resveratrol (RVT) has been revealed to have a number of pharmacological effects in a variety of experimental models and clinical circumstances, therefore it has piqued the interest of scientists in recent years. In this study, we aimed to investigate the potential protective effects of resveratrol (RVT), a strong antioxidant, anti-inflammatory and anti-mutagenic agent, against toxicity of colonic and rectal tissues seen in the early and late stages after pelvic radiation. The treatment durations of the current study were designed as one week and ten weeks interval by following radiation exposure. Sprague Dawley rats were divided into 5 groups (8 animals/group) as the control, radiation-early effects (Rd-E), radiation-late effects (Rd-L), and RVT-treated Rd-E (Rd-E+RVT) and RVT-treated Rd-L (Rd-L+RVT) groups. İonizing radiation was performed to the pelvic area that covers colon and rectum in single fraction of 20 Gy in a linear accelerator using with 6 MV photon energy. RVT was orally administered (10 mg/kg/day) immediately following the radiation exposure and continued daily for 1 and 10 weeks for early and late groups, respectively. Pelvic radiation caused a significant decrease in glutathione level, while malondialdehyde levels, myeloperoxidase activity and 8-hydroxydeoxyguanosine were increased in both Rd-E and Rd-L groups in the colon and rectum tissues. Additionally, light microscopic evaluations (H&E staining) revealed degeneration of epithelium and inflammatory cell infiltration in the colonic and rectal tissues in radiation groups. RVT treatment reversed all conducted biochemical parameters and ameliorated histomorphological changes following early and late effects of pelvic radiation in tissues. In conclusion, resveratrol may be a candidate as a radioprotector for normal tissues during and after radiotherapy.

Anahtar Kelimeler

Resveratrol early and late effect of radiation pelvic radiation radioprotection oxidative stress 8-OHdG

Kaynakça

  • [1] Abdallah NM, Noaman E, Eltahawy NA, Badawi AM, Kandil E, Mansour NA and Mohamed HE. Anticancer and radiosensitization efficacy of nanocomposite Withania somnifera extract in mice bearing tumor cells. Asian Pac J Cancer Prev. 2016;17(9):4367-4375.
  • [2] Shadad AK, Sullivan FJ, Martin JD, Egan LJ. Gastrointestinal radiation injury: symptoms, risk factors and mechanisms. World J Gastroenterol. 2013;19(2):185-198. https://doi.org/10.3748/wjg.v19.i2.185.
  • [3] Schmidt-Ullrich RK, Dent P, Grant S, Mikkelsen RB, Valerie K. Signal transduction and cellular radiation responses. Radiat Res. 2000;153(3):245-257. https://doi.org/10.1667/0033-7587(2000)153%5b0245:stacrr%5d2.0.co;2.
  • [4] Ertekin MV, Koçer I, Karslioğlu I, Taysi S, Gepdiremen A, Sezen O, Balci E, Bakan N. Effects of oral Ginkgo biloba supplementation on cataract formation and oxidative stress occurring in lenses of rats exposed to total cranium radiotherapy. Jpn J Ophthalmol. 2004;48(5):499-502. https://doi.org/10.1007/s10384-004-0101-z.
  • [5] Dainiak N, Tan BJ. Utility of biological membranes as indicators for radiation exposure: alterations in membrane structure and function over time. Stem Cells. 1995;13 Suppl 1:142-152.
  • [6] Hubenak JR, Zhang Q, Branch CD, Kronowitz SJ. Mechanisms of injury to normal tissue after radiotherapy: a review. Plast Reconstr Surg. 2014;133(1):49e-56e. https://doi.org/10.1097/01.prs.0000440818.23647.0b.
  • [7] Pervaiz S, Holme AL. Resveratrol: its biologic targets and functional activity. Antioxid Redox Signal. 2009;11(11):2851-2897. https://doi.org/10.1089/ars.2008.2412
  • [8] Siemann EH, Creasy LL. Concentration of the phytoalexin resveratrol in wine. Am J Eno Vitic. 1992;43:49-52.
  • [9] Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997;275(5297):218-220. https://doi.org/10.1126/science.275.5297.218.
  • [10] Della-Morte D, Dave KR, DeFazio RA, Bao YC, Raval AP, Perez-Pinzon MA. Resveratrol pretreatment protects rat brain from cerebral ischemic damage via a sirtuin 1-uncoupling protein 2 pathway. Neuroscience. 2009;159(3):993-1002. https://doi.org/10.1016/j.neuroscience.2009.01.017.
  • [11] Martinez J, Moreno JJ. Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. Biochem Pharmacol. 2000;59(7):865-870. https://doi.org/10.1016/s0006-2952(99)00380-9.
  • [12] Alturfan AA, Tozan-Beceren A, Sehirli AO, Demiralp E, Sener G, Omurtag GZ. Resveratrol ameliorates oxidative DNA damage and protects against acrylamide-induced oxidative stress in rats. Mol Biol Rep. 2012;39(4):4589-4596. https://doi.org/10.1007/s11033-011-1249-5.
  • [13] Brown KR, Rzucidlo E. Acute and chronic radiation injury [published correction appears in J Vasc Surg. 2012;55(2):627]. J Vasc Surg. 2011;53(1 Suppl):15S-21S. https://doi.org/10.1016/j.jvs.2010.06.175.
  • [14] Monti P, Wysocki J, van der Meeren A, Griffiths NM. The contribution of radiation induced injury to the gastrointestinal tract in the development of multi-organ dysfunction syndrome or failure. Br J Radiol Suppl. 2005;27:89-94. https://doi.org/10.1259/bjr/53186341.
  • [15] Ooi BS, Tjandra JJ, Green MD. Morbidities of adjuvant chemotherapy and radiotherapy for resectable rectal cancer: an overview. Dis Colon Rectum. 1999;42(3):403-418. https://doi.org/10.1007/BF02236362.
  • [16] International Agency for Research on Cancer (IARC). Ionizing radiation, part 1: X- and gamma (γ)-radiation, and neutrons in IARC monographs on the evaluation of carcinogenic risks to humans, volume 75. IARC, Lyon-France, 2000.
  • [17] Panés J, Granger DN. Neutrophils generate oxygen free radicals in rat mesenteric microcirculation after abdominal irradiation. Gastroenterology. 1996;111(4):981-989. https://doi.org/10.1016/s0016-5085(96)70065-3.
  • [18] Dizdaroglu M, Jaruga P. Mechanisms of free radical-induced damage to DNA. Free Radic Res. 2012;46(4):382-419. https://doi.org/10.3109/10715762.2011.653969.
  • [19] Aydemir S, Akgun SG, Beceren A, Yuksel M, Kumas M, Erdogan N, Sardas S, Omurtag GZ. Melatonin ameliorates oxidative DNA damage and protects against formaldehyde-induced oxidative stress in rats. Int J Clin Exp Med. 2017;10(4):6250-6261.
  • [20] Fenga C, Gangemi S, Teodoro M, Rapisarda V, Golokhvast K, Docea AO, Tsatsakis AM, Costa C. 8-Hydroxydeoxyguanosine as a biomarker of oxidative DNA damage in workers exposed to low-dose benzene. Toxicol Rep. 2017;31(4):291-295. https://doi.org/10.1016/j.toxrep.2017.05.008.
  • [21] Zhao W, Robbins ME. Inflammation and chronic oxidative stress in radiation-induced late normal tissue injury: therapeutic implications. Curr Med Chem. 2009;16(2):130-143. https://doi.org/10.2174/092986709787002790.
  • [22] Kaya H, Delibas N, Serteser M, Ulukaya E, Ozkaya O. The effect of melatonin on lipid peroxidation during radiotherapy in female rats. Strahlenther Onkol. 1999;175(6):285-288. https://doi.org/10.1007/BF02743581.
  • [23] Deniz M, Atasoy BM, Dane D, Can G, Erzik C, Çetinel Ş, Yeğen BÇ. Radiation-induced oxidative injury of the ileum and colon is alleviated by glucagon-like peptide-1 and -2. J Radiat Res Appl Sci. 2015;8(2):234-242. https://doi.org/10.1016/j.jrras.2015.01.010.
  • [24] Rubin P, Finkelstein J, Shapiro D. Molecular biology mechanisms in the radiation induction of pulmonary injury syndromes: interrelationship between the alveolar macrophage and the septal fibroblast. Int J Radiat Oncol Biol Phys. 1992;24(1):93-101. https://doi.org/10.1016/0360-3016(92)91027-k.
  • [25] Stanojković TP, Matić IZ, Petrović N, et al. Evaluation of cytokine expression and circulating immune cell subsets as potential parameters of acute radiation toxicity in prostate cancer patients. Sci Rep. 2020;10(1):19002. https://doi.org/10.1038/s41598-020-75812-0.
  • [26] Velioğlu-Oğünç A, Sehirli O, Toklu HZ, et al. Resveratrol protects against irradiation-induced hepatic and ileal damage via its anti-oxidative activity. Free Radic Res. 2009;43(11):1060-1071. https://doi.org/10.1080/10715760903171100.
  • [27] Panés J, Granger DN. Neutrophils generate oxygen free radicals in rat mesenteric microcirculation after abdominal irradiation. Gastroenterology. 1996;111(4):981-989. https://doi.org/10.1016/s0016-5085(96)70065-3.
  • [28] Casini AF, Ferrali M, Pompella A, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol. 1986;123(3):520-531.
  • [29] Aykaç G, Uysal M, Yalçin AS, Koçak-Toker N, Sivas A, Oz H. The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology. 1985;36(1):71-76. https://doi.org/10.1016/0300-483x(85)90008-3.
  • [30] Hillegass LM, Griswold DE, Brickson B, Albrightson-Winslow C. Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods. 1990;24(4):285-295. https://doi.org/10.1016/0160-5402(90)90013-b.
  • [31] Gué M, Bonbonne C, Fioramonti J, Moré J, Del Rio-Lachèze C, Coméra C, Buéno L. Stress-induced enhancement of colitis in rats: CRF and arginine vasopressin are not involved. Am J Physiol. 1997;272(1 Pt 1):G84-G91. https://doi.org/10.1152/ajpgi.1997.272.1.g84.

Yıl 2023, Cilt: 27 Sayı: 4, 1617 - 1625, 28.06.2025

Ayfer Beceren , Sezgin Aydemir , Beste Melek Atasoy Esin Ak , Feriha Ercan , Tarık Emre Şener Göksel Şener

Öz

Kaynakça

  • [1] Abdallah NM, Noaman E, Eltahawy NA, Badawi AM, Kandil E, Mansour NA and Mohamed HE. Anticancer and radiosensitization efficacy of nanocomposite Withania somnifera extract in mice bearing tumor cells. Asian Pac J Cancer Prev. 2016;17(9):4367-4375.
  • [2] Shadad AK, Sullivan FJ, Martin JD, Egan LJ. Gastrointestinal radiation injury: symptoms, risk factors and mechanisms. World J Gastroenterol. 2013;19(2):185-198. https://doi.org/10.3748/wjg.v19.i2.185.
  • [3] Schmidt-Ullrich RK, Dent P, Grant S, Mikkelsen RB, Valerie K. Signal transduction and cellular radiation responses. Radiat Res. 2000;153(3):245-257. https://doi.org/10.1667/0033-7587(2000)153%5b0245:stacrr%5d2.0.co;2.
  • [4] Ertekin MV, Koçer I, Karslioğlu I, Taysi S, Gepdiremen A, Sezen O, Balci E, Bakan N. Effects of oral Ginkgo biloba supplementation on cataract formation and oxidative stress occurring in lenses of rats exposed to total cranium radiotherapy. Jpn J Ophthalmol. 2004;48(5):499-502. https://doi.org/10.1007/s10384-004-0101-z.
  • [5] Dainiak N, Tan BJ. Utility of biological membranes as indicators for radiation exposure: alterations in membrane structure and function over time. Stem Cells. 1995;13 Suppl 1:142-152.
  • [6] Hubenak JR, Zhang Q, Branch CD, Kronowitz SJ. Mechanisms of injury to normal tissue after radiotherapy: a review. Plast Reconstr Surg. 2014;133(1):49e-56e. https://doi.org/10.1097/01.prs.0000440818.23647.0b.
  • [7] Pervaiz S, Holme AL. Resveratrol: its biologic targets and functional activity. Antioxid Redox Signal. 2009;11(11):2851-2897. https://doi.org/10.1089/ars.2008.2412
  • [8] Siemann EH, Creasy LL. Concentration of the phytoalexin resveratrol in wine. Am J Eno Vitic. 1992;43:49-52.
  • [9] Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997;275(5297):218-220. https://doi.org/10.1126/science.275.5297.218.
  • [10] Della-Morte D, Dave KR, DeFazio RA, Bao YC, Raval AP, Perez-Pinzon MA. Resveratrol pretreatment protects rat brain from cerebral ischemic damage via a sirtuin 1-uncoupling protein 2 pathway. Neuroscience. 2009;159(3):993-1002. https://doi.org/10.1016/j.neuroscience.2009.01.017.
  • [11] Martinez J, Moreno JJ. Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. Biochem Pharmacol. 2000;59(7):865-870. https://doi.org/10.1016/s0006-2952(99)00380-9.
  • [12] Alturfan AA, Tozan-Beceren A, Sehirli AO, Demiralp E, Sener G, Omurtag GZ. Resveratrol ameliorates oxidative DNA damage and protects against acrylamide-induced oxidative stress in rats. Mol Biol Rep. 2012;39(4):4589-4596. https://doi.org/10.1007/s11033-011-1249-5.
  • [13] Brown KR, Rzucidlo E. Acute and chronic radiation injury [published correction appears in J Vasc Surg. 2012;55(2):627]. J Vasc Surg. 2011;53(1 Suppl):15S-21S. https://doi.org/10.1016/j.jvs.2010.06.175.
  • [14] Monti P, Wysocki J, van der Meeren A, Griffiths NM. The contribution of radiation induced injury to the gastrointestinal tract in the development of multi-organ dysfunction syndrome or failure. Br J Radiol Suppl. 2005;27:89-94. https://doi.org/10.1259/bjr/53186341.
  • [15] Ooi BS, Tjandra JJ, Green MD. Morbidities of adjuvant chemotherapy and radiotherapy for resectable rectal cancer: an overview. Dis Colon Rectum. 1999;42(3):403-418. https://doi.org/10.1007/BF02236362.
  • [16] International Agency for Research on Cancer (IARC). Ionizing radiation, part 1: X- and gamma (γ)-radiation, and neutrons in IARC monographs on the evaluation of carcinogenic risks to humans, volume 75. IARC, Lyon-France, 2000.
  • [17] Panés J, Granger DN. Neutrophils generate oxygen free radicals in rat mesenteric microcirculation after abdominal irradiation. Gastroenterology. 1996;111(4):981-989. https://doi.org/10.1016/s0016-5085(96)70065-3.
  • [18] Dizdaroglu M, Jaruga P. Mechanisms of free radical-induced damage to DNA. Free Radic Res. 2012;46(4):382-419. https://doi.org/10.3109/10715762.2011.653969.
  • [19] Aydemir S, Akgun SG, Beceren A, Yuksel M, Kumas M, Erdogan N, Sardas S, Omurtag GZ. Melatonin ameliorates oxidative DNA damage and protects against formaldehyde-induced oxidative stress in rats. Int J Clin Exp Med. 2017;10(4):6250-6261.
  • [20] Fenga C, Gangemi S, Teodoro M, Rapisarda V, Golokhvast K, Docea AO, Tsatsakis AM, Costa C. 8-Hydroxydeoxyguanosine as a biomarker of oxidative DNA damage in workers exposed to low-dose benzene. Toxicol Rep. 2017;31(4):291-295. https://doi.org/10.1016/j.toxrep.2017.05.008.
  • [21] Zhao W, Robbins ME. Inflammation and chronic oxidative stress in radiation-induced late normal tissue injury: therapeutic implications. Curr Med Chem. 2009;16(2):130-143. https://doi.org/10.2174/092986709787002790.
  • [22] Kaya H, Delibas N, Serteser M, Ulukaya E, Ozkaya O. The effect of melatonin on lipid peroxidation during radiotherapy in female rats. Strahlenther Onkol. 1999;175(6):285-288. https://doi.org/10.1007/BF02743581.
  • [23] Deniz M, Atasoy BM, Dane D, Can G, Erzik C, Çetinel Ş, Yeğen BÇ. Radiation-induced oxidative injury of the ileum and colon is alleviated by glucagon-like peptide-1 and -2. J Radiat Res Appl Sci. 2015;8(2):234-242. https://doi.org/10.1016/j.jrras.2015.01.010.
  • [24] Rubin P, Finkelstein J, Shapiro D. Molecular biology mechanisms in the radiation induction of pulmonary injury syndromes: interrelationship between the alveolar macrophage and the septal fibroblast. Int J Radiat Oncol Biol Phys. 1992;24(1):93-101. https://doi.org/10.1016/0360-3016(92)91027-k.
  • [25] Stanojković TP, Matić IZ, Petrović N, et al. Evaluation of cytokine expression and circulating immune cell subsets as potential parameters of acute radiation toxicity in prostate cancer patients. Sci Rep. 2020;10(1):19002. https://doi.org/10.1038/s41598-020-75812-0.
  • [26] Velioğlu-Oğünç A, Sehirli O, Toklu HZ, et al. Resveratrol protects against irradiation-induced hepatic and ileal damage via its anti-oxidative activity. Free Radic Res. 2009;43(11):1060-1071. https://doi.org/10.1080/10715760903171100.
  • [27] Panés J, Granger DN. Neutrophils generate oxygen free radicals in rat mesenteric microcirculation after abdominal irradiation. Gastroenterology. 1996;111(4):981-989. https://doi.org/10.1016/s0016-5085(96)70065-3.
  • [28] Casini AF, Ferrali M, Pompella A, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol. 1986;123(3):520-531.
  • [29] Aykaç G, Uysal M, Yalçin AS, Koçak-Toker N, Sivas A, Oz H. The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology. 1985;36(1):71-76. https://doi.org/10.1016/0300-483x(85)90008-3.
  • [30] Hillegass LM, Griswold DE, Brickson B, Albrightson-Winslow C. Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods. 1990;24(4):285-295. https://doi.org/10.1016/0160-5402(90)90013-b.
  • [31] Gué M, Bonbonne C, Fioramonti J, Moré J, Del Rio-Lachèze C, Coméra C, Buéno L. Stress-induced enhancement of colitis in rats: CRF and arginine vasopressin are not involved. Am J Physiol. 1997;272(1 Pt 1):G84-G91. https://doi.org/10.1152/ajpgi.1997.272.1.g84.
Toplam 31 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Farmasotik Toksikoloji
Bölüm Articles
Yazarlar

Ayfer Beceren 0000-0002-6770-6089

Sezgin Aydemir

Beste Melek Atasoy

Esin Ak 0000-0002-3467-7808

Feriha Ercan 0000-0003-2339-5669

Tarık Emre Şener 0000-0003-0085-7680

Göksel Şener

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 4

Kaynak Göster

APA Beceren, A., Aydemir, S., Atasoy, B. M., Ak, E., vd. (2025). Radioprotective effect of resveratrol for early and late ionizing radiation-induced damages on colon and rectum in rats. Journal of Research in Pharmacy, 27(4), 1617-1625.
AMA Beceren A, Aydemir S, Atasoy BM, Ak E, Ercan F, Şener TE, Şener G. Radioprotective effect of resveratrol for early and late ionizing radiation-induced damages on colon and rectum in rats. J. Res. Pharm. Temmuz 2025;27(4):1617-1625.
Chicago Beceren, Ayfer, Sezgin Aydemir, Beste Melek Atasoy, Esin Ak, Feriha Ercan, Tarık Emre Şener, ve Göksel Şener. “Radioprotective Effect of Resveratrol for Early and Late Ionizing Radiation-Induced Damages on Colon and Rectum in Rats”. Journal of Research in Pharmacy 27, sy. 4 (Temmuz 2025): 1617-25.
EndNote Beceren A, Aydemir S, Atasoy BM, Ak E, Ercan F, Şener TE, Şener G (01 Temmuz 2025) Radioprotective effect of resveratrol for early and late ionizing radiation-induced damages on colon and rectum in rats. Journal of Research in Pharmacy 27 4 1617–1625.
IEEE A. Beceren, S. Aydemir, B. M. Atasoy, E. Ak, F. Ercan, T. E. Şener, ve G. Şener, “Radioprotective effect of resveratrol for early and late ionizing radiation-induced damages on colon and rectum in rats”, J. Res. Pharm., c. 27, sy. 4, ss. 1617–1625, 2025.
ISNAD Beceren, Ayfer vd. “Radioprotective Effect of Resveratrol for Early and Late Ionizing Radiation-Induced Damages on Colon and Rectum in Rats”. Journal of Research in Pharmacy 27/4 (Temmuz 2025), 1617-1625.
JAMA Beceren A, Aydemir S, Atasoy BM, Ak E, Ercan F, Şener TE, Şener G. Radioprotective effect of resveratrol for early and late ionizing radiation-induced damages on colon and rectum in rats. J. Res. Pharm. 2025;27:1617–1625.
MLA Beceren, Ayfer vd. “Radioprotective Effect of Resveratrol for Early and Late Ionizing Radiation-Induced Damages on Colon and Rectum in Rats”. Journal of Research in Pharmacy, c. 27, sy. 4, 2025, ss. 1617-25.
Vancouver Beceren A, Aydemir S, Atasoy BM, Ak E, Ercan F, Şener TE, Şener G. Radioprotective effect of resveratrol for early and late ionizing radiation-induced damages on colon and rectum in rats. J. Res. Pharm. 2025;27(4):1617-25.