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Cardiovascular & Hematological Agents in Medicinal Chemistry

Editor-in-Chief

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

Research Article

Radioprotective Effect of Pioglitazone Against Genotoxicity Induced by Ionizing Radiation in Healthy Human Lymphocytes

Author(s): Roya Kazemi and Seyed J. Hosseinimehr*

Volume 19, Issue 1, 2021

Published on: 24 May, 2020

Page: [72 - 75] Pages: 4

DOI: 10.2174/1871525718666200525005231

Price: $65

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Abstract

Objective: Pioglitazone (PG) is used to control high blood sugar in patients with type 2 diabetes mellitus. PG acts as a peroxisome proliferator-activated receptor γ agonist. In addition to the insulin-sensitizing effect, PG possesses anti-inflammatory effect. In this study, the protective effect of PG was evaluated against DNA damage induced by ionizing radiation in healthy human lymphocytes.

Methods: The microtubes containing human whole blood were treated with PG at various concentrations (1-50 μM) for three hours. Then, the blood samples were irradiated with X-ray. Lymphocytes were cultured for determining the frequency of micronuclei as a genotoxicity biomarker in binucleated lymphocytes.

Results: The mean percentage of micronuclei was significantly increased in human lymphocytes when exposed to IR, while it was decreased in lymphocytes pre-treated with PG. The maximum reduction in the frequency of micronuclei in irradiated lymphocytes was observed at 5 μM of PG treatment (48% decrease).

Conclusion: The anti-inflammatory property suggested the mechanism action of PG for protecting human lymphocytes against genotoxicity induced by ionizing radiation.

Keywords: Anti-inflammatory, DNA damage, micronucleus test, pioglitazone, radiation biology, radioprotective.

Graphical Abstract
[1]
Hosseinimehr, S.J. Trends in the development of radioprotective agents. Drug Discov. Today, 2007, 12(19-20), 794-805.
[http://dx.doi.org/10.1016/j.drudis.2007.07.017] [PMID: 17933679]
[2]
Salehifar, E.; Hosseinimehr, S.J. The use of cyclooxygenase-2 inhibitors for improvement of efficacy of radiotherapy in cancers. Drug Discov. Today, 2016, 21(4), 654-662.
[http://dx.doi.org/10.1016/j.drudis.2016.02.019] [PMID: 26955911]
[3]
Devchand, P.R.; Liu, T.; Altman, R.B.; FitzGerald, G.A.; Schadt, E.E. The pioglitazone trek via human PPAR gamma: From discovery to a medicine at the FDA and beyond. Front. Pharmacol., 2018, 9, 1093.
[http://dx.doi.org/10.3389/fphar.2018.01093] [PMID: 30337873]
[4]
Marion-Letellier, R.; Savoye, G.; Ghosh, S. Fatty acids, eicosanoids and PPAR gamma. Eur. J. Pharmacol., 2016, 785, 44-49.
[http://dx.doi.org/10.1016/j.ejphar.2015.11.004] [PMID: 26632493]
[5]
Janani, C.; Ranjitha Kumari, B.D. PPAR gamma gene--a review. Diabetes Metab. Syndr., 2015, 9(1), 46-50.
[http://dx.doi.org/10.1016/j.dsx.2014.09.015] [PMID: 25450819]
[6]
Cippitelli, A.; Domi, E.; Ubaldi, M.; Douglas, J.C.; Li, H.W.; Demopulos, G.; Gaitanaris, G.; Roberto, M.; Drew, P.D.; Kane, C.J.M.; Ciccocioppo, R. Protection against alcohol-induced neuronal and cognitive damage by the PPARγ receptor agonist pioglitazone. Brain Behav. Immun., 2017, 64, 320-329.
[http://dx.doi.org/10.1016/j.bbi.2017.02.001] [PMID: 28167117]
[7]
Hong, S.W.; Lee, J.; Cho, J.H.; Kwon, H.; Park, S.E.; Rhee, E.J.; Park, C.Y.; Oh, K.W.; Park, S.W.; Lee, W.Y. pioglitazone attenuates palmitate-induced inflammation and endoplasmic reticulum stress in pancreatic β-cells. Endocrinol. Metab., 2018, 33(1), 105-113.
[http://dx.doi.org/10.3803/EnM.2018.33.1.105] [PMID: 29589392]
[8]
Gao, M.; Jiang, Y.; Xiao, X.; Peng, Y.; Xiao, X.; Yang, M. Protective effect of pioglitazone on sepsis-induced intestinal injury in a rodent model. J. Surg. Res., 2015, 195(2), 550-558.
[http://dx.doi.org/10.1016/j.jss.2015.02.007] [PMID: 25772146]
[9]
Kandeel, S.; Balaha, M. The possible protective effect of simvastatin and pioglitazone separately and in combination on bleomycin-induced changes in mice thin skin. Tissue Cell, 2015, 47(2), 159-170.
[http://dx.doi.org/10.1016/j.tice.2015.01.003] [PMID: 25712322]
[10]
Charkhpour, M.; Ghavimi, H.; Ghanbarzadeh, S.; Yousefi, B.; Khorrami, A.; Mesgari, M.; Hassanzadeh, K. Protective effect of pioglitazone on morphine-induced neuroinflammation in the rat lumbar spinal cord. J. Biomed. Sci., 2015, 22, 82.
[http://dx.doi.org/10.1186/s12929-015-0187-2] [PMID: 26394827]
[11]
Refaie, M.M.M.; El-Hussieny, M. Protective effect of pioglitazone on ovarian ischemia reperfusion injury of female rats via modulation of peroxisome proliferator activated receptor gamma and heme-oxygenase 1. Int. Immunopharmacol., 2018, 62, 7-14.
[http://dx.doi.org/10.1016/j.intimp.2018.06.037] [PMID: 29966944]
[12]
Wittayalertpanya, S.; Chompootaweep, S.; Thaworn, N. The pharmacokinetics of pioglitazone in Thai healthy subjects. J. Med. Assoc. Thai., 2006, 89(12), 2116-2122.
[PMID: 17214065]
[13]
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.
[http://dx.doi.org/10.4103/1735-5362.199051] [PMID: 28255318]
[14]
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.
[http://dx.doi.org/10.3857/roj.2015.33.3.256] [PMID: 26484310]
[15]
Asemi, S.; Ghaemi, A.; Hosseinimehr, S.J. Febuxostat mitigates genotoxicity induced by ionizing radiation in human normal lymphocytes. Erciyes Med. J., 2019, 41(1), 99-101.
[http://dx.doi.org/10.14744/etd.2019.35762]
[16]
Rojo de la Vega, M.; Krajisnik, A.; Zhang, D.D.; Wondrak, G.T. Targeting NRF2 for improved skin barrier function and photoprotection: Focus on the achiote-derived apocarotenoid bixin. Nutrients, 2017, 9(12)E1371
[http://dx.doi.org/10.3390/nu9121371] [PMID: 29258247]
[17]
Li, Y.; Xia, T.; Li, R.; Tse, G.; Liu, T.; Li, G. Renal-protective effects of the peroxisome proliferator-activated receptor-γ agonist pioglitazone in ob/ob Mice. Med. Sci. Monit., 2019, 25, 1582-1589.
[http://dx.doi.org/10.12659/MSM.913461] [PMID: 30820023]
[18]
Meng, X.; Sun, X.; Zhang, Y.; Shi, H.; Deng, W.; Liu, Y.; Wang, G.; Fang, P.; Yang, S. PPARγ agonist PGZ attenuates OVA-induced airway inflammation and airway remodeling via RGS4 signaling in mouse model. Inflammation, 2018, 41(6), 2079-2089.
[http://dx.doi.org/10.1007/s10753-018-0851-2] [PMID: 30022363]
[19]
Zhang, H.B.; Zhang, Y.; Chen, C.; Li, Y.Q.; Ma, C.; Wang, Z.J. Pioglitazone inhibits advanced glycation end product-induced matrix metalloproteinases and apoptosis by suppressing the activation of MAPK and NF-κB. Apoptosis, 2016, 21(10), 1082-1093.
[http://dx.doi.org/10.1007/s10495-016-1280-z] [PMID: 27515513]
[20]
Pordanjani, S.M.; Hosseinimehr, S.J. The role of NF-kB inhibitors in cell response to radiation. Curr. Med. Chem., 2016, 23(34), 3951-3963.
[http://dx.doi.org/10.2174/0929867323666160824162718 ] [PMID: 27554808]

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