Login Register Cart 0
Generic placeholder image

Cardiovascular & Hematological Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5257
ISSN (Online): 1875-6182

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Radioprotective Effect of Gliclazide as an Anti-Hyperglycemic Agent Against Genotoxicity Induced by Ionizing Radiation on Human Lymphocytes

Author(s): Maysa Pouri, Zahra Shaghaghi, Arash Ghasemi and Seyed Jalal Hosseinimehr*

Volume 17, Issue 1, 2019

Page: [40 - 46] Pages: 7

DOI: 10.2174/1871525717666190524092918

Abstract

Objectives: Gliclazide (GL) is widely used to reduce hyperglycemia in diabetic patients. The aim of this study was to investigate the protective effect of GL against chromosome damage induced by ionizing radiation in human blood lymphocytes.

Methods: In this experimental study, peripheral blood samples were collected from human volunteers and treated with GL at various concentrations (5, 25, 50 or 100 μM) for three hours. Then samples were irradiated to X-ray (1.5 Gy). Blood samples were cultured with mitogenic stimulation. The frequencies of micronuclei in cytokinesis-blocked binucleated lymphocytes were determined in the different samples. The antioxidant activities of GL were assayed by two different methods as 1,1- diphenyl-2-picryl hydrazyl radical (DPPH) free radical scavenging and reducing antioxidant power assays.

Results: GL significantly reduced the percentage of micronuclei in lymphocytes which were irradiated. The maximum radioprotection in the reduction of percentage of micronuclei in lymphocytes was observed at 100 μM of GL with 52% efficacy. GL exhibited excellent free radical scavenging activity and reducing power at concentration dependent activities. The IC50 values of GL were lower than ascorbic acid. Higher potencies were observed in the antioxidant activities for GL than ascorbic acid in both methods.

Conclusion: This data exhibits that GL is a powerful radioprotective agent that could protect healthy cells against the chromosome damage induced by ionizing radiation through antioxidant activity. The radioprotective effect is new indication of GL for patient's protection against side effect induced by ionizing radiation.

Keywords: Genotoxicity, gliclazide, ionizing radiation, radioprotective, reactive oxygen species, DNA.

« Previous Next »
Graphical Abstract

[1]
Hosseinimehr, S.J. Flavonoids and genomic instability induced by ionizing radiation. Drug Discov. Today, 2010, 15(21-22), 907-918.
[2]
Sage, E.; Shikazono, N. Radiation-induced clustered DNA lesions: Repair and mutagenesis. Free Radic. Biol. Med., 2017, 107, 125-135.
[3]
Smith, T.A.; Kirkpatrick, D.R.; Smith, S.; Smith, T.K.; Pearson, T.; Kailasam, A.; Herrmann, K.Z.; Schubert, J.; Agrawal, D.K. Radioprotective agents to prevent cellular damage due to ionizing radiation. J. Transl. Med., 2017, 15(1), 232.
[4]
Hosseinimehr, S.J. Trends in the development of radioprotective agents. Drug Discov. Today, 2007, 12(19-20), 794-805.
[5]
Hosseinimehr, S.J.; Mahmoudzadeh, A.; Ahmadi, A.; Ashrafi, S.A.; Shafaghati, N.; Hedayati, N. The radioprotective effect of Zataria multiflora against genotoxicity induced by γ irradiation in human blood lymphocytes. Cancer Biother. Radiopharm., 2011, 26(3), 325-329.
[6]
Hosseinimehr, S.J.; Izakmehri, M.; Ghasemi, A. In vitro protective effect of atorvastatin against ionizing radiation induced genotoxicity in human lymphocytes. Cell. Mol. Biol., 2015, 61(1), 68-71.
[7]
Hosseinimehr, S.J.; Nobakht, R.; Ghasemi, A.; Pourfallah, T.A. Radioprotective effect of mefenamic acid against radiation-induced genotoxicity in human lymphocytes. Radiat. Oncol. J., 2015, 33(3), 256-260.
[8]
Hosseinimehr, S.J.; Fathi, M.; Ghasemi, A.; Shiadeh, S.N.; Pourfallah, T.A. Celecoxib mitigates genotoxicity induced by ionizing radiation in human blood lymphocytes. Res. Pharm. Sci., 2017, 12(1), 82-87.
[9]
Hosseinimehr, S.J.; Ahmadi, A.; Beiki, D.; Habibi, E.; Mahmoudzadeh, A. Protective effects of hesperidin against genotoxicity induced by (99m)Tc-MIBI in human cultured lymphocyte cells. Nucl. Med. Biol., 2009, 36(7), 863-867.
[10]
Hosseinimehr, S.J. Natural Product as potential radioprotective agents. J. Mazand. Univ. Med. Sci., 2007, 17(61), 175-189.
[11]
Landman, G.W.; De Bock, G.H.; Van Hateren, K.J.; Van Dijk, P.R.; Groenier, K.H.; Gans, R.O.; Houweling, S.T.; Bilo, H.J.; Kleefstra, N. Safety and efficacy of gliclazide as treatment for type 2 diabetes: A systematic review and meta-analysis of randomized trials. PLoS One, 2014, 9(2)e82880
[12]
O’Brien, R.C.; Luo, M.; Balazs, N.; Mercuri, J. In vitro and in vivo antioxidant properties of gliclazide. J. Diabetes Complications, 2000, 14(4), 201-206.
[13]
Sena, C.M.; Louro, T.; Matafome, P.; Nunes, E.; Monteiro, P.; Seiça, R. Antioxidant and vascular effects of gliclazide in type 2 diabetic rats fed high-fat diet. Physiol. Res., 2009, 58(2), 203-209.
[14]
Drzewoski, J.; Zurawska-Klis, M. Effect of gliclazide modified release on adiponectin, interleukin-6, and tumor necrosis factor-alpha plasma levels in individuals with type 2 diabetes mellitus. Curr. Med. Res. Opin., 2006, 22(10), 1921-1926.
[15]
Rastkhah, E.; Zakeri, F.; Ghoranneviss, M.; Rajabpour, M.R.; Farshidpour, M.R.; Mianji, F.; Bayat, M. The cytokinesis-blocked micronucleus assay: Dose-response calibration curve, background frequency in the population and dose estimation. Radiat. Environ. Biophys., 2016, 55(1), 41-51.
[16]
Rossnerova, A.; Spatova, M.; Schunck, C.; Sram, R.J. Automated scoring of lymphocyte micronuclei by the meta systems metafer image cytometry system and its application in studies of human mutagen sensitivity and biodosimetry of genotoxin exposure. Mutagenesis, 2011, 26(1), 169-175.
[17]
Fenech, M. The in vitro micronucleus technique. Mutat. Res., 2000, 455(1-2), 81-95.
[18]
Hosseinimehr, S.J.; Azadbakht, M.; Mousavi, S.M.; Mahmoudzadeh, A.; Akhlaghpoor, S. Radioprotective effects of hawthorn fruit extract against gamma irradiation in mouse bone marrow cells. J. Radiat. Res. (Tokyo), 2007, 48(1), 63-68.
[19]
Macwan, C.P.; Patel, M.A. Antioxidant potential of dried root of Capparis zylanica linn. Int. J. Pharm. Pharm. Sci., 2010, 30, 58-60.
[20]
Pinkawa, M.; Brzozowska, K.; Kriehuber, R.; Eble, M.J.; Schmitz, S. Prediction of radiation-induced toxicity by in vitro radiosensitivity of lymphocytes in prostate cancer patients. Future Oncol., 2016, 12(5), 617-624.
[21]
Sharma, D.; Sandur, S.K.; Rashmi, R.; Maurya, D.K.; Suryavanshi, S.; Checker, R.; Krishnan, S.; Sainis, K.B. Differential activation of NF-κB and nitric oxide in lymphocytes regulates in vitro and in vivo radiosensitivity. Mutat. Res., 2010, 703(2), 149-157.
[22]
Weiss, J.F.; Landauer, M.R. Radioprotection by antioxidants. Ann. N. Y. Acad. Sci., 2000, 899, 44-60.
[23]
Castillo, J.; Benavente-García, O.; Lorente, J.; Alcaraz, M.; Redondo, A.; Ortuño, A.; Del Rio, J.A. Antioxidant activity and radioprotective effects against chromosomal damage induced in vivo by X-rays of flavan-3-ols (Procyanidins) from grape seeds (Vitis vinifera): Comparative study versus other phenolic and organic compounds. J. Agric. Food Chem., 2000, 48(5), 1738-1745.
[24]
Vladimir-Knežević, S.; Blažeković, B.; Štefan, M.B.; Alegro, A.; Koszegi, T.; Petrik, J. Antioxidant activities and polyphenolic contents of three selected Micromeria species from Croatia. Molecules, 2011, 16(2), 1454-1470.
[25]
Sliwinska, A.; Rogalska, A.; Szwed, M.; Kasznicki, J.; Jozwiak, Z.; Drzewoski, J. Gliclazide may have an antiapoptotic effect related to its antioxidant properties in human normal and cancer cells. Mol. Biol. Rep., 2012, 39(5), 5253-5267.
[26]
Alp, H.; Varol, S.; Celik, M.M.; Altas, M.; Evliyaoglu, O.; Tokgoz, O.; Tanrıverdi, M.H.; Uzar, E. Protective effects of beta glucan and gliclazide on brain tissue and sciatic nerve of diabetic rats induced by streptozosin. Exp. Diabetes Res., 2012, 2012230342
[27]
Memişoǧullari, R.; Türkeli, M.; Bakan, E.; Akçay, F. Effect of metformin or gliclazide on lipid peroxidation and antioxidant levels in patients with diabetes mellitus. Turk. J. Med. Sci., 2008, 38(6), 545-548.
[28]
Chan, S.P.; Colagiuri, S. Systematic review and meta-analysis of the efficacy and hypoglycemic safety of gliclazide versus other insulinotropic agents. Diabetes Res. Clin. Pract., 2015, 110(1), 75-81.
[29]
Sarkar, A.; Tiwari, A.; Bhasin, P.; Mitra, M. Pharmacological and pharmaceutical profile of gliclazide: A review. J. Appl. Pharm. Sci., 2011, 1(9), 11-19.

Rights & Permissions Print Cite
Article Metrics
35
5
1
1
© 2024 Bentham Science Publishers | Privacy Policy