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Investigation of the Genotoxic Effect of Fluoxetine Hydrochloride in Drosophila melanogaster

Yıl 2024, , 316 - 324, 01.04.2024

Selda Öz , Zeynep Nur Sarıkaya , Özüm Larçın , Rabia Sarıkaya

https://doi.org/10.18016/ksutarimdoga.vi.1310729

Öz

This study aimed to determine the potential genotoxic effect of fluoxetine hydrochloride (FLX-HCl), an antidepressant commonly used for treating depression, using Somatic Mutation and Recombination Test (SMART). Third-¬instar Drosophila melanogaster larvae transheterozygous for the mutations multiple wing hair (mwh) and flare (flr3) were chronically fed in a medium containing different concentrations of FLX-HCl (0.1, 0.5, 1, and 2 mg/mL) in the experimental group. Distilled water, 0.1 mM ethyl methane sulfonate (EMS), and 2% dimethyl sulfoxide (DMSO) were used in negative, positive, and solvent control groups, respectively. The survival percentages were calculated by determining the number of individuals surviving when the larvae completed their development in the experimental and control groups. In all application groups, the wings of 40 individuals with both normal and serrate wing phenotypes were examined under a microscope, and genetic changes were evaluated by counting the mutant clones in the wings. The data obtained show that 1 and 2 mg/mL concentrations of FLX-HCl caused toxic effects in D. melanogaster individuals. Additionally, FLX-HCl showed a negative genotoxic effect at 0.1 mg/mL concentration, insignificant at 0.5 mg/mL concentration, and positive at 1 and 2 mg/mL concentrations in terms of total mutation evaluation and clone induction frequency in D. melanogaster individuals.

Anahtar Kelimeler

Drosophila melanogaster Fluoxetine hydrochloride Genotoxicity Survival SMART

Kaynakça

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  • Allgayer, N., de Campos, R. A., Gonzalez, L. P. F., do Amaral Flores, M., Dihl, R. R., & Lehmann, M. (2019). Evaluation of mutagenic activity of platinum complexes in somatic cells of Drosophila melanogaster. Food and Chemical Toxicology, 133, 110782.
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  • Anet, A., Olakkaran, S., Purayil, A. K., & Puttaswamygowda, G. H. (2019). Bisphenol A induced oxidative stress mediated genotoxicity in Drosophila melanogaster. Journal of Hazardous Materials, 370, 42-53.
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Fluoksetin Hidroklorür’ün Genotoksik Etkisinin Drosophila melanogaster’de Araştırılması

Yıl 2024, , 316 - 324, 01.04.2024

Selda Öz , Zeynep Nur Sarıkaya , Özüm Larçın , Rabia Sarıkaya

https://doi.org/10.18016/ksutarimdoga.vi.1310729

Öz

Bu çalışmada depresyon tedavisinde yaygın olarak kullanılan bir antidepresan olan fluoksetin hidroklorürün (FLX-HCl) potansiyel genotoksik etkisinin Somatik Mutasyon ve Rekombinasyon Testi (SMART) kullanılarak belirlenmesi amaçlanmıştır. Deney grubunda çoklu kanat kılı (mwh) ve flare (flr3) mutasyonları için transheterozigot olan üçüncü dönem Drosophila melanogaster larvaları, farklı konsantrasyonlarda FLX-HCl (0.1, 0.5, 1 ve 2 mg/mL) içeren ortamda kronik olarak beslenmiştir. Distile su, 0.1 mM etil metan sülfonat (EMS) ve % 2 dimetil sülfoksit (DMSO) sırasıyla negatif, pozitif ve çözücü kontrol gruplarında kullanılmıştır. Deney ve kontrol gruplarında larvalar gelişimini tamamladığında hayatta kalan birey sayıları belirlenerek yaşama yüzdeleri hesaplanmıştır. Tüm uygulama gruplarında hem normal hem de serrat kanat fenotipine sahip 40 bireyin kanatları mikroskop altında incelenmiş ve kanatlardaki mutant klonlar sayılarak genetik değişimler değerlendirilmiştir. Elde edilen veriler, FLX-HCl'nin 1 ve 2 mg/mL konsantrasyonlarının D. melanogaster bireyleri üzerinde toksik etkiye neden olduğunu göstermiştir. Ayrıca FLX-HCl, D. melanogaster bireylerinde toplam mutasyon değerlendirmesi ve klon induksiyon frekansı bakımından 0.1 mg/mL konsantrasyonunda negatif, 0.5 mg/mL konsantrasyonunda önemsiz, 1 ve 2 mg/mL konsantrasyonlarında pozitif genotoksik etki göstermiştir.

Anahtar Kelimeler

Drosophila melanogaster Fluoksetin hidroklorür Genotoksisite Hayatta Kalış SMART

Kaynakça

  • Al-Eitan, L.N., Alzoubi, K.H., Al-Smadi, L.I., & Khabour, O.F. (2020). Vitamin E protects against cisplatin-induced genotoxicity in human lymphocytes. Toxicology In Vitro, 62, 104672. https://doi.org/10.1016/j.tiv.2019.104672.
  • Allgayer, N., de Campos, R. A., Gonzalez, L. P. F., do Amaral Flores, M., Dihl, R. R., & Lehmann, M. (2019). Evaluation of mutagenic activity of platinum complexes in somatic cells of Drosophila melanogaster. Food and Chemical Toxicology, 133, 110782.
  • Al-Obaidi, I.A., & Al-Shawi, N.N. (2020). Assessment the Genotoxic Potential of Fluoxetine and Amitriptyline at Maximum Therapeutic Doses for Four-Week Treatment in Experimental Male Rats. Iraqi Journal of Pharmaceutical Science, 30 (1), 81-90.
  • Álvarez-González, I., Camacho-Cantera, S., Gómez-González, P., Barrón, M.J.R., Morales- González, J.A., Madrigal-Santillán, E.O., Paniagua-Perez, R., & Madrigal-Bujadar, E. (2021). Genotoxic and oxidative effect of duloxetine on mouse brain and liver tissues. Scientific Reports, 11(1), 6897. https://doi.org/10.1038/s41598-021-86366-0.
  • Anet, A., Olakkaran, S., Purayil, A. K., & Puttaswamygowda, G. H. (2019). Bisphenol A induced oxidative stress mediated genotoxicity in Drosophila melanogaster. Journal of Hazardous Materials, 370, 42-53.
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  • Jiménez, E., Pimentel, E., Cruces, M. P., & Amaya-Chavez, A. (2019). Relationship between viability and genotoxic effect of gamma rays delivered at different dose rates in somatic cells of Drosophila melanogaster. Journal of Toxicology and Environmental Health, Part A, 82(13), 741-751.
  • Karimi-Khouzani, O., Heidarian, E., & Amini, S.A. (2017). Anti-inflammatory and ameliorative effects of gallic acid on fluoxetine-induced oxidative stress and liver damage in rats. Pharmacological Reports, 69(4), 830-835. https://doi.org/10.1016/ j.pharep. 2017.03.011.
  • Kastenbaum, M.A., & Bowman, K.O. (1970). Tables for determining the statistical significance of mutation frequencies. Mutation Research, 9, 527-549.
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  • Khodeer, D.M., Mehanna, E.T., Abushouk, A.I., & Abdel-Daim, M.M. (2020). Protective effects of evening primrose oil against cyclophosphamide-induced biochemical, histopathological, and genotoxic alterations in mice. Pathogens, 9(2),98. https://doi.org/10.3390/pathogens 9020098.
  • Kumar, M., Cyriac, K.S., & Murulidhara, Y.L. (2020). Genotoxicity and its mechanism of antidepressant and antipsychotic drugs: A revıew. Journal of Advenced Scientific Research, 11(3), 79-83.
  • Lemos, N.G., Vicentini, V.E.P., & Mantovani, M.S. (2005). Avaliação do efeito genotóxico do Prozac (fluoxetina), sem e com adição de vitaminas A e C, através do teste do cometa em cultura de células CHO-K1. Semina: Ciências Biológicas e da Saúde, 26(2), 95-100.
  • Lindsley, D.L., & Zimm, G.G. (1992). The genome of D. melanogaster. San Diego (CA): Academic Press. 1133 p.
  • Majeed, Z.R., Ritter, K., Robinson, J., Blümicha, S.L.E., Brailoiu, E., & Cooper, R.L. (2015). New insights into the acute actions from a high dosage of fluoxetine on neuronal and cardiac function: Drosophila, crayfish and rodent models. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 176-177, 52-61. https://doi.org/10.1016/j.cbpc.2015.07. 010.
  • Mishra, M., & Panda, M. (2021). Reactive oxygen species: the root cause of nanoparticle-induced toxicity in Drosophila melanogaster. Free Radical Research, 55(8), 919-935.
  • Mondal, S., Saha, I., Das, S., Ganguly, A., Das, D., & Tripathi, S.K. (2013). A new logical insight and putative mechanism behind fluoxetine-induced amenorrhea, hyperprolactinemia and galactorrhea in a case series. Therapeutic Advances in Psychopharmacology, 3(6), 322-334. https://doi.org/ 10.1177/2045125313490305.
  • Nagpal, I., & Abraham, S.K. (2019). Coffee mitigates cyclophosphamide-induced genotoxic damage in Drosophila melanogaster germ cells. Drug and Chemical Toxicology, 42(5), 502-508.
  • Neckameyer, W. S., Coleman, C. M., Eadie, S., & Goodwin, S. F. (2007). Compartmentalization of neuronal and peripheral serotonin synthesis in Drosophila melanogaster. Genes, Brain and Behavior, 6(8), 756-769.
  • Oakes, K.D., Coors, A., Escher, B.I., Fenner, K., Garric, J., Gust, M., Knacker, T., Küster, A., Kussatz, C., Metcalfe, C.D., Monteiro, S., Moon, T.W., Mennigen, J.A, Parrott, J., Péry, A.R.R., Ramil, M., Roennefahrt, I., Tarazona, J.V., Sánchez- Argüello, P., Ternes, T.A., Trudeau, V.L., Boucard, T., Van Der Kraak, G., & Servos, M.R. (2010). Environmental risk assessment for the serotonin re-uptake inhibitor fluoxetine: Case study using the European risk assessment framework. Integrated Environmental Assessment and Management, 6 (S1), 524-539. https://doi.org/10.1002/ieam. 77.
  • Ofoegbu, P.U., Lourenço, J., Mendo, S., Soares, A.M., & Pestana, J.L. (2019). Effects of low concentrations of psychiatric drugs (carbamazepine and fluoxetine) on the freshwater planarian, Schmidtea mediterranea. Chemosphere, 217, 542-549. https://doi.org/10.1016/ j.chemosphere.2018.10.198.
  • Orozco-Hernández, J.M., Gómez-Oliván, L.M., Elizalde Velázquez, G.A., Rosales Pérez, K.E., Cardoso Vera, J.D., Heredia García, G., Islas Flores, H., Garcia Medina, S., & Galar Martinez, M. (2022). Fluoxetine-induced neurotoxicity at environmentally relevant concentrations in adult zebrafish Danio rerio. Neurotoxicology, 90, 121-129. https://doi.org/10.1016/j.neuro. 2022.03.007.
  • Panwar, R., Sivakumar, M., Menon, V., & Vairappan, B. (2020). Changes in the levels of comet parameters before and after fluoxetine therapy in major depression patients. Anatomy & Cell Biology, 53(2), 194-200. https://doi.org/10.5115/acb.19.217.
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  • Power, B. M., Pinder, M., Hackett, L. P., & Ilett, K. F. (1995). Fatal serotonin syndrome following a combined overdose of moclobemide, clomipramine and fluoxetine. Anaesthesia and Intensive Care, 23(4), 499-502.
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  • Rossi, A., Barraco, A., & Donda, P. (2004). Fluoxetine: a review on evidence based medicine. Annals of General Hospital Psychiatry, 3(2),1-8. https://doi.org/10.1186/1475-2832-3-2.
  • Sallee, F. R., DeVane, C. L., & Ferrell, R. E. (2000). Fluoxetine-related death in a child with cytochrome P-4502D6 genetic deficiency. Journal of Child and Adolescent Psychopharmacology,10(1), 27–34.
  • Schultz, M.M., Painter, M.M., Bartell, S.E., Logue, A., Furlong, E.T., Werner, S.L., & Schoenfuss, H.L. (2011). Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows. Aquatic Toxicology, 104(1-2), 38-47. https://doi.org/10.1016/j.aquatox.2011.03.011.
  • Shorey, S., Ng, E. D., & Wong, C. H. (2022). Global prevalence of depression and elevated depressive symptoms among adolescents: A systematic review and meta‐analysis. British Journal of Clinical Psychology, 61(2), 287-305.
  • Silva, B., Goles, N. I., Varas, R., & Campusano, J. M. (2014). Serotonin receptors expressed in Drosophila mushroom bodies differentially modulate larval locomotion. PloS one, 9(2), e89641.
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  • Teixeira da Silva, T., Braga Martins, J., Do Socorro de Brito Lopes, M., de Almeida, P. M., Silva Sá, J.L., & Alline Martins, F. (2021). Modulating effect of DL-kavain on the mutagenicity and carcinogenicity induced by doxorubicin in Drosophila melanogaster. Journal of Toxicology and Environmental Health, Part A, 84(19), 769-782.
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  • Uysal, H., & Celik, H. (2023). ‘Skualen’ Triterpeninin Somatik Mutasyonlar Üzerine Etkisinin Drosophila melanogaster’de In vivo Kanat Benek Testi ile Araştırılması. KSÜ Tarım ve Doğa Dergisi, 26(3), 477-486.
  • Véras, J. H., do Vale, C. R., da Silva Lima, D. C., Dos Anjos, M. M., Bernardes, A., de Moraes Filho, A. V., e Silva C.R., de Oliveira G.R., Pérez., C.N., & Chen-Chen, L. (2022). Modulating effect of a hydroxychalcone and a novel coumarin–chalcone hybrid against mitomycin-induced genotoxicity in somatic cells of Drosophila melanogaster. Drug and Chemical Toxicology, 45(2), 775-784.
  • Vijitkul, P., Kongsema, M., Toommakorn, T., & Bullangpoti, V. (2022). Investigation of genotoxicity, mutagenicity, and cytotoxicity in erythrocytes of Nile tilapia (Oreochromis niloticus) after fluoxetine exposure. Toxicology Reports, 9, 588-596. https://doi.org/10.1016/j. toxrep. 2022.03.031.
  • Wu, M. L., & Deng, J. F. (2011). Fatal serotonin toxicity caused by moclobemide and fluoxetine overdose. Chang Gung Medical Journal, 34(6), 644-649.
  • Yuzbasioglu, D., Avuloglu Yilmaz, E., & Unal, F. (2016). Antidepresan İlaçlar ve Genotoksisite. TÜBAV Bilim, 9(1), 17-28.
  • Zlatković, J., Todorović, N., Tomanović, N., Bošković, M., Djordjević, S., Lazarević-Pašti, T., Bernardi, R.E., Djurdjević, A., & Filipović, D. (2014). Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: a histopathological study. European Journal of Pharmaceutical Science, 59, 20-30. https://doi.org/10.1016/j.ejps. 2014.04.010.
Toplam 67 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Hayvan Bilimi (Diğer)
Bölüm ARAŞTIRMA MAKALESİ (Research Article)
Yazarlar

Selda Öz 0000-0003-1883-3441

Zeynep Nur Sarıkaya 0009-0003-9343-8887

Özüm Larçın 0009-0000-3232-9140

Rabia Sarıkaya 0000-0001-9247-8973

Erken Görünüm Tarihi 21 Ocak 2024
Yayımlanma Tarihi 1 Nisan 2024
Gönderilme Tarihi 7 Haziran 2023
Kabul Tarihi 27 Eylül 2023
Yayımlandığı Sayı Yıl 2024

Kaynak Göster

APA Öz, S., Sarıkaya, Z. N., Larçın, Ö., Sarıkaya, R. (2024). Investigation of the Genotoxic Effect of Fluoxetine Hydrochloride in Drosophila melanogaster. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 27(2), 316-324. https://doi.org/10.18016/ksutarimdoga.vi.1310729

21082



2022-JIF = 0.500

2022-JCI = 0.170

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