Radioprotective effect of olanzapine as an anti-psychotic drug against genotoxicity and apoptosis induced by ionizing radiation on human lymphocytes
- 23 Downloads
Olanzapine (OLA), is prescribed as an anti-psychotic medicine in schizophrenia patients. In this study, the protective effect of OLA against genotoxicity and apoptosis induced by ionizing radiation in human healthy lymphocytes was evaluated. At first, the antioxidant activities of OLA were assayed by two different methods as free radical scavenging with DPPH (2,2-diphenyl-1-picryl-hydrazyl) and ferric reducing power methods. In in vitro experiment, human blood samples were treated with OLA at various concentrations (0.25–20 μM) for 3 h and then were exposed to X-ray at a dose of 150 cGy. The genotoxicity was assessed in binucleated human lymphocytes with micronuclei assay. The apoptotic lymphocytes were assessed by flow cytometry in OLA treated and/or irradiated lymphocytes. OLA exhibited free radical scavenging and reducing power activities more than ascorbic acid. The results showed that the lymphocytes treated with OLA and later exposed to IR presented lower frequencies of micronuclei and apoptosis compared to the control sample which was irradiated and not treated to OLA. The maximum radioprotection was observed at 20 μM of OLA with 83% of efficacy. The present study suggested the protective role for OLA in protection radiation-induced genetic damage and apoptosis induced by ionizing irradiation in human normal cells.
KeywordsOlanzapine Ionizing radiation Genotoxicity Radioprotective Apoptosis
Funding was provided by Elite Researcher Grant Committee from the National Institute for Medical Research Development, Grant No. 963296, Tehran, Iran.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This study was approved by research and ethical committees of the Iranian National Institute for Medical Research and Development (ID#IR.NIMAD.REC.1396. 235).
Written informed consents were also obtained from healthy male volunteers. This study was performed only in vitro experiments on blood samples of healthy male volunteers.
- 6.Alizadeh F, Asghari M, Torabizadeh SA, Rahmanian N, Ghasemi A, Hosseinimehr SJ (2018) Radioprotective effect of sinapic acid against genotoxicity and apoptosis induced by ionizing radiation on human lymphocytes. Lett Drug Des Discov 15(11):1147–1154. https://doi.org/10.2174/1570180815666180219163626 CrossRefGoogle Scholar
- 7.Zal Z, Ghasemi A, Azizi S, Asgarian-Omran H, Montazeri A, Hosseinimehr SJ (2018) Radioprotective effect of cerium oxide nanoparticles against genotoxicity induced by ionizing radiation on human lymphocytes. Curr Radiopharm 11(2):109–115. https://doi.org/10.2174/1874471011666180528095203 CrossRefGoogle Scholar
- 14.Brinholi FF, Farias CC, Bonifacio KL, Higachi L, Casagrande R, Moreira EG, Barbosa DS (2016) Clozapine and olanzapine are better antioxidants than haloperidol, quetiapine, risperidone and ziprasidone in in vitro models. Biomed Pharmacother 81:411–415. https://doi.org/10.1016/j.biopha.2016.02.047 CrossRefGoogle Scholar
- 18.Hosseinimehr SJ, Izakmehri M, Ghasemi A (2015) In vitro protective effect of atorvastatin against ionizing radiation induced genotoxicity in human lymphocytes. Cell Mol Biol (Noisy-le-grand) 61(1):68–71Google Scholar
- 20.Cheki M, Shirazi A, Mahmoudzadeh A, Bazzaz JT, Hosseinimehr SJ (2016) The radioprotective effect of metformin against cytotoxicity and genotoxicity induced by ionizing radiation in cultured human blood lymphocytes. Mutat Res 809:24–32. https://doi.org/10.1016/j.mrgentox.2016.09.001 CrossRefGoogle Scholar
- 22.Macwan CP, Patel MA (2010) Antioxidant potential of dried root of Capparis zylanica linn. Int J Pharm Pharm Sci 30:58–60Google Scholar
- 24.Sharma D, Sandur SK, Rashmi R, Maurya DK, Suryavanshi S, Checker R, Krishnan S, Sainis KB (2010) Differential activation of NF-kappaB and nitric oxide in lymphocytes regulates in vitro and in vivo radiosensitivity. Mutat Res 703(2):149–157. https://doi.org/10.1016/j.mrgentox.2010.08.010 CrossRefGoogle Scholar
- 26.Castillo J, Benavente-Garcia O, Lorente J, Alcaraz M, Redondo A, Ortuno A, Del Rio JA (2000) 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 48(5):1738–1745. https://doi.org/10.1021/jf990665o CrossRefGoogle Scholar
- 28.Zhao QL, Ito H, Kondo T, Uehara T, Ikeda M, Abe H, Saitoh JI, Noguchi K, Suzuki M, Kurachi M (2019) Antipsychotic drugs scavenge radiation-induced hydroxyl radicals and intracellular ROS formation, and protect apoptosis in human lymphoma U937 cells. Free Radic Res. https://doi.org/10.1080/10715762.2019.1572889 Google Scholar
- 30.Rummel-Kluge C, Komossa K, Schwarz S, Hunger H, Schmid F, Lobos CA, Kissling W, Davis JM, Leucht S (2010) Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res 123(2–3):225–233. https://doi.org/10.1016/j.schres.2010.07.012 CrossRefGoogle Scholar
- 32.Zhang Y, Liu Y, Su Y, You Y, Ma Y, Yang G, Song Y, Liu X, Wang M, Zhang L, Kou C (2017) The metabolic side effects of 12 antipsychotic drugs used for the treatment of schizophrenia on glucose: a network meta-analysis. BMC Psychiatry 17(1):373. https://doi.org/10.1186/s12888-017-1539-0 CrossRefGoogle Scholar
- 33.Yood MU, DeLorenze G, Quesenberry CP Jr, Oliveria SA, Tsai AL, Willey VJ, McQuade R, Newcomer J, L’Italien G (2009) The incidence of diabetes in atypical antipsychotic users differs according to agent–results from a multisite epidemiologic study. Pharmacoepidemiol Drug Saf 18(9):791–799. https://doi.org/10.1002/pds.1781 CrossRefGoogle Scholar
- 38.Chiu L, Chow R, Popovic M, Navari RM, Shumway NM, Chiu N, Lam H, Milakovic M, Pasetka M, Vuong S, Chow E, DeAngelis C (2016) Efficacy of olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis. Support Care Cancer 24(5):2381–2392. https://doi.org/10.1007/s00520-016-3075-8 CrossRefGoogle Scholar