Araştırma Makalesi


DOI :10.26650/IstanbulJPharm.2019.0081   IUP :10.26650/IstanbulJPharm.2019.0081    Tam Metin (PDF)

Evaluation of the hepatotoxic potential of citalopram in rats

Sinem Ilgın SerinFulya DağaşanDilek Burukoğlu DönmezMerve BaysalÖzlem Atlı Eklioğlu

Background and Aims: Citalopram is a selective serotonin reuptake inhibitor with a high potency which is occasionally prescribed and used to treat major depression associated with mood disorders as a first-line drug. According to the results of previous studies, evidence of hepatotoxicity related to citalopram treatment were limited and conflicting. Therefore, we aimed to evaluate the hepatotoxicity potential of sub-chronic citalopram administration. Methods: Citalopram was administered to female rats orally in 5 and 10 mg/kg for 30 days. After the exposure period, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and direct bilirubin levels as biomarkers of hepatotoxicity were measured and histopathological examination of liver tissues was performed. Additionally, GSH levels of liver tissues were determined. Results: The risk of hepatotoxicity related to citalopram was shown by significant increases of serum hepatic biomarkers, AST, ALT, and total bilirubin in citalopram-administered groups. According to the histopathological findings, hepatocellular necrosis, hepatic nuclear asymmetry, and disarrangement of hepatic cord cells (hepatocytes) were prominent in the 10 mg/kg citalopram-administered group. On the other hand, there was no significant difference among the groups in terms of GSH levels. Conclusion: The results suggested that the administration of citalopram might cause hepatotoxic effects, depending on the dose.


PDF Görünüm

Referanslar

  • • Ahmadian, E., Eftekhari, A., Fard, J. K., Babaei, H., Nayebi, A. M., Mohammadnejad, D., & Eghbal, M. A. (2017). In vitro and in vivo evaluation of the mechanisms of citalopram-induced hepatotoxicity. Archives of Pharmacal Research, 40(11), 1296–1313. google scholar
  • • Alempijevic, T., Zec, S., & Milosavljevic, T. (2017). Drug-induced liver injury: Do we know everything? World Journal of Hepatology, 9(10), 491–502. google scholar
  • • Anderson, I. M., & Edwards, J. G. (2001). Guidelines for choice of selective serotonin reuptake inhibitor in depressive illness. Advances in Psychiatric Treatment, 7, 170–180. google scholar
  • • Babai, S., Auclert, L., & Le-Louët, H. (2018). Safety data and withdrawal of hepatotoxic drugs. Therapie. [Epub ahead of print] https://doi.org/10.1016/j.therap.2018.02.004 google scholar
  • • Bech, P., Tanghøj, P., Andersen, H. F., & Overø, K. (2002). Citalopram dose-response revisited using an alternative psychometric approach to evaluate clinical effects of four fixed citalopram doses compared to placebo in patients with major depression. Psychopharmacology (Berl), 163(1), 20–25. google scholar
  • • Campion, S., Aubrecht, J., Boekelheide, K., Brewster, D. W., Vaidya, V. S., Anderson, L., Burt, D., Dere, E., Hwang, K., Pacheco, S., Saikumar, J., Schomaker, S., Sigman, M., & Goodsaid, F. (2013). The current status of biomarkers for predicting toxicity. Expert Opinion on Drug Metabolism & Toxicology, 9(11), 1391–408. google scholar
  • • Chen, M., Suzuki, A., Borlak, J., Andrade, R. J., & Lucena, M. I. (2015). Drug-induced liver injury: Interactions between drug properties and host factors. Journal of Hepatology, 63(2), 503–514. google scholar
  • • Church, R. J., & Watkins, P. B. (2017). The transformation in biomarker detection and management of drug-induced liver injury. Liver International, 37(11), 1582–1590. google scholar
  • • Dufour, D. R., Lott, J. A., Nolte, F. S., Gretch, D. R., Koff, R. S., & Seeff, L. B. (2000). Diagnosis and monitoring of hepatic injury. II. Recommendations for use of laboratory tests in screening, diagnosis, and monitoring. Clinical Chemistry, 46(12), 2050–2068. google scholar
  • • Ferguson, J. M. (2001). SSRI Antidepressant Medications: Adverse Effects and Tolerability. Primary Care Companion to the Journal of Clinical Psychiatry, 3(1), 22–27. google scholar
  • • Flores-Serrano, A., Vila-Luna, M., Álvarez-Cervera, F., Heredia- López, F., Góngora-Alfaro, J., & Pineda, J. C. (2013). Clinical doses of citalopram or reboxetine differentially modulate passive and active behaviors of female Wistar rats with high or low immobility time in the forced swimming test. Pharmacology Biochemistry & Behavior, 110, 89–97. google scholar
  • • Fredricson-Overo, K., & Svendsen, O. (1978). Hepatotoxicity of citalopram in rats and first-pass metabolism. Archives of Toxicology, 1, 177–180. google scholar
  • • Friedrich, M. E., Akimova, E., Huf, W., Konstantinidis, A., Papageorgiou, K., Winkler, D., Toto, S., Greil, W., Grohmann, R., & Kasper, S. (2016). Drug-Induced Liver Injury during Antidepressant Treatment: Results of AMSP, a Drug Surveillance Program. International Journal of Neuropsychopharmacology, 19(4). google scholar
  • • Gessel, L., & Alcorn, J. (2016). When Good Medications Go Bad, Don’t DILI Dally. Digestive Diseases and Sciences, 61(6), 1491–1494. google scholar
  • • Gowda, S., Desai, P. B., Hull, V. V., Math, A. A., Vernekar, S. N., & Kulkarni, S. S. (2009). A review on laboratory liver function tests. Pan African Medical Journal, 3, 17. google scholar
  • • Gwaltney-Brant, S. M. (2016). Nutraceuticals in Hepatic Diseases. In R.C. Gupta (Eds.), Nutraceuticals: Efficacy, Safety and Toxicity (pp. 7-99). London, UK: Academic Press. google scholar
  • • Herrlin, K., Yasui-Furukori, N., Tybring, G., Widén, J., Gustafsson, L. L., & Bertilsson, L. (2003). Metabolism of citalopram enantiomers in CYP2C19/CYP2D6 phenotyped panel of healthy Swedes. British Journal of Clinical Pharmacology, 56(4), 415–421. google scholar
  • • Hunfeld, N. G. M., ten Berge, R. L., LeBrun, P. P. H., Smith, S. J., & Melief, P. H. G. J. (2010). Hepatotoxicity related to citalopram intake: a case report. International Journal of Risk & Safety in Medicine, 22, 1–5. google scholar
  • • Institutional Animal Care and Use Committee (IACUC) (2017). Anesthesia (Guideline). Retrieved from https://animal.research. uiowa.edu/iacuc-guidelines-anesthesia google scholar
  • • Jaeschke, H., Gores, G.J., Cederbaum, A. I., Hinson, J. A., Pessayre, D., & Lemasters J.J. (2002). Mechanisms of hepatotoxicity. Toxicological Sciences, 65(2), 166–176. google scholar
  • • Karlsson, L., Carlsson, B., Hiemke, C., Ahlner, J., Bengtsson, F., Schmitt, U., & Kugelberg, F. C. (2013). Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment. European Neuropsychopharmacology, 23(11), 1636–1644. google scholar
  • • Kim, E., & Nam, H. (2017). Prediction models for drug-induced hepatotoxicity by using weighted molecular fingerprints. BMC Bioinformatics, 18(7), 227. google scholar
  • • Kullak-Ublick, G. A., Andrade, R. J., Merz, M., End, P., Benesic, A., Gerbes, A. L., & Aithal, G. P. (2017). Drug-induced liver injury: recent advances in diagnosis and risk assessment. Gut, 66(6), 1154–1164. google scholar
  • • Lassila, T., Mattila, S., Turpeinen, M., & Tolonen, A. (2015). Glutathione trapping of reactive drug metabolites produced by biomimetic metalloporphyrin catalysts. Rapid Communications in Mass Spectrometry, 29(6), 521–532. google scholar
  • • Lassila, T., Rousu, T., Mattila, S., Chesné, C., Pelkonen, O., Turpeinen, M., & Tolonen, A. (2015). Formation of GSH-trapped reactive metabolites in human liver microsomes, S9 fraction, HepaRG-cells, and human hepatocytes. Journal of Pharmaceutical and Biomedical Analysis, 115, 345–351. google scholar
  • • Locher, C., Koechlin, H., Zion, S. R., Werner, C., Pine, D. S., Kirsch, I., Kessler, R. C., & Kossowsky, J. (2017). Efficacy and Safety of Selective Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, and Placebo for Common Psychiatric Disorders Among Children and Adolescents: A Systematic Review and Meta-analysis. JAMA Psychiatry, 74(10), 1011–1020. google scholar
  • • López-Torres, E., Lucena, M. I., Seoane, J., Verge, C., & Andrade, R. J. (2004). Hepatotoxicity related to citalopram (letter). American Journal of Psychiatry, 161(5), 923–924. google scholar
  • • Neumann, H., Csepregi, A., Evert, M., & Malfertheiner, P. (2008). Drug-induced liver disease related to citalopram (letter). Journal of Clinical Psychopharmacology, 28(2), 254–255. google scholar
  • • Ortega-Alonso, A., Stephens, C., Lucena, M. I., & Andrade, R. J. (2016). Case Characterization, Clinical Features and Risk Factors in Drug-Induced Liver Injury. International Journal of Molecular Sciences, 17(5). google scholar
  • • Raschi, E., & De Ponti, F. (2015). Drug- and herb-induced liver injury: Progress, current challenges and emerging signals of postmarketing risk. World Journal of Hepatology, 7(13), 1761–1771. google scholar
  • • Robles-Díaz, M., Medina-Caliz, I., Stephens, C., Andrade, R. J., & Lucena, M. I. (2016). Biomarkers in DILI: One More Step Forward. Frontiers in Pharmacology, 7, 267. google scholar
  • • Sanchez, C., Reines, E. H., & Montgomery, S. A. (2014). A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike? International Clinical Psychopharmacology, 29(4), 185–196. google scholar
  • • Sangkuhl, K., Klein, T. E., & Altman, R. B. (2011). PharmGKB summary: citalopram pharmacokinetics pathway. Pharmacogenetics and Genomics, 21(11), 769–772. google scholar
  • • Sekar, S., Verhoye, M., Van Audekerke, J., Vanhoutte, G., Lowe, A. S., Blamire, A. M., Steckler, T., Van der Linden, A., & Shoaib, M. (2011). Neuroadaptive responses to citalopram in rats using pharmacological magnetic resonance imaging. Psychopharmacology, 213(2-3), 521–531. google scholar
  • • Sharbaf-Shoar, N., & Padhy, R. K. (Updated 20 January 2020). Citalopram. In: StatPearls [Internet]. Retrieved from https://www.ncbi. nlm.nih.gov/books/NBK482222/ google scholar
  • • Singh, A., Bhat, T. K., & Sharma, O. P. (2011). Clinical Biochemistry of Hepatotoxicity. Journal of Clinical Toxicology, S:4. google scholar
  • • Solomons, K., Gooch, S., & Wong, A. (2005). Toxicity with selective serotonin reuptake inhibitors (letter). American Journal of Psychiatry, 162(6), 1225. google scholar
  • • Sturgill, M. G., & Lambert, G. H. (1997). Xenobiotic-induced hepatotoxicity: mechanisms of liver injury and methods of monitoring hepatic function. Clinical Chemistry, 43(8 Pt 2), 1512–1526. google scholar
  • • The National Institute for Health and Care Excellence (NICE) Pathways. (Updated 1 January, 2019). Depression in children and young people: identification and management. Retrieved from • https://www.nice.org.uk/guidance/ng134/documents/draftguideline google scholar
  • • The National Institute for Health and Care Excellence (NICE) Pathways. (Updated 10 September, 2020). Antidepressant treatment in adults. Retrieved from • https://pathways.nice.org.uk/pathways/depression/antidepressant- treatment-in-adults google scholar
  • • U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). (July 2005). Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. Retrieved from https://www.fda.gov/regulatoryinformation/ search-fda-guidance-documents/estimatingmaximum- safe-starting-dose-initial-clinical-trials-therapeutics- adult-healthy-volunteers google scholar
  • • Vega-Rivera, N. M., Gallardo-Tenorio, A., Fernández-Guasti, A., & Estrada-Camarena, E. (2016). The Post-Ovariectomy Interval Affects the Antidepressant-Like Action of Citalopram Combined with Ethynyl-Estradiol in the Forced Swim Test in Middle Aged Rats. Pharmaceuticals (Basel), 9(2). google scholar
  • • Vermoesen, K., Massie, A., Smolders, I., & Clinckers, R. (2012). The antidepressants citalopram and reboxetine reduce seizure frequency in rats with chronic epilepsy. Epilepsia, 53(5), 870–878. google scholar
  • • Voican, C. S., Corruble, E., Naveau, S., & Perlemuter, G. (2014). Antidepressant- induced liver injury: a review for clinicians. American Journal of Psychiatry, 171(4), 404–415. google scholar
  • • Whittington, C. J., Kendall, T., Fonagy, P., Cottrell, D., Cotgrove, A., & Boddington, E. (2004). Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet, 363(9418), 1341–1345. google scholar
  • • Wiese, B. (2011). Geriatric Depression: The Use of Antidepressants in The Elderly. British Columbia Medical Journal, 53(47), 341– 347. google scholar
  • • Zhang, J., Dennis, K. A., Darling, R. D., Alzghoul, L., Paul, I. A., Simpson, K. L., & Lin, R. C. (2013). Neonatal citalopram exposure decreases serotonergic fiber density in the olfactory bulb of male but not female adult rats. Frontiers in Cellular Neuroscience, 7, 67. google scholar

Atıflar

Biçimlendirilmiş bir atıfı kopyalayıp yapıştırın veya seçtiğiniz biçimde dışa aktarmak için seçeneklerden birini kullanın


DIŞA AKTAR



APA

Serin, S.I., Dağaşan, F., Burukoğlu Dönmez, D., Baysal, M., & Atlı Eklioğlu, Ö. (2020). Evaluation of the hepatotoxic potential of citalopram in rats. İstanbul Journal of Pharmacy, 50(3), 188-194. https://doi.org/10.26650/IstanbulJPharm.2019.0081


AMA

Serin S I, Dağaşan F, Burukoğlu Dönmez D, Baysal M, Atlı Eklioğlu Ö. Evaluation of the hepatotoxic potential of citalopram in rats. İstanbul Journal of Pharmacy. 2020;50(3):188-194. https://doi.org/10.26650/IstanbulJPharm.2019.0081


ABNT

Serin, S.I.; Dağaşan, F.; Burukoğlu Dönmez, D.; Baysal, M.; Atlı Eklioğlu, Ö. Evaluation of the hepatotoxic potential of citalopram in rats. İstanbul Journal of Pharmacy, [Publisher Location], v. 50, n. 3, p. 188-194, 2020.


Chicago: Author-Date Style

Serin, Sinem Ilgın, and Fulya Dağaşan and Dilek Burukoğlu Dönmez and Merve Baysal and Özlem Atlı Eklioğlu. 2020. “Evaluation of the hepatotoxic potential of citalopram in rats.” İstanbul Journal of Pharmacy 50, no. 3: 188-194. https://doi.org/10.26650/IstanbulJPharm.2019.0081


Chicago: Humanities Style

Serin, Sinem Ilgın, and Fulya Dağaşan and Dilek Burukoğlu Dönmez and Merve Baysal and Özlem Atlı Eklioğlu. Evaluation of the hepatotoxic potential of citalopram in rats.” İstanbul Journal of Pharmacy 50, no. 3 (Apr. 2024): 188-194. https://doi.org/10.26650/IstanbulJPharm.2019.0081


Harvard: Australian Style

Serin, SI & Dağaşan, F & Burukoğlu Dönmez, D & Baysal, M & Atlı Eklioğlu, Ö 2020, 'Evaluation of the hepatotoxic potential of citalopram in rats', İstanbul Journal of Pharmacy, vol. 50, no. 3, pp. 188-194, viewed 23 Apr. 2024, https://doi.org/10.26650/IstanbulJPharm.2019.0081


Harvard: Author-Date Style

Serin, S.I. and Dağaşan, F. and Burukoğlu Dönmez, D. and Baysal, M. and Atlı Eklioğlu, Ö. (2020) ‘Evaluation of the hepatotoxic potential of citalopram in rats’, İstanbul Journal of Pharmacy, 50(3), pp. 188-194. https://doi.org/10.26650/IstanbulJPharm.2019.0081 (23 Apr. 2024).


MLA

Serin, Sinem Ilgın, and Fulya Dağaşan and Dilek Burukoğlu Dönmez and Merve Baysal and Özlem Atlı Eklioğlu. Evaluation of the hepatotoxic potential of citalopram in rats.” İstanbul Journal of Pharmacy, vol. 50, no. 3, 2020, pp. 188-194. [Database Container], https://doi.org/10.26650/IstanbulJPharm.2019.0081


Vancouver

Serin SI, Dağaşan F, Burukoğlu Dönmez D, Baysal M, Atlı Eklioğlu Ö. Evaluation of the hepatotoxic potential of citalopram in rats. İstanbul Journal of Pharmacy [Internet]. 23 Apr. 2024 [cited 23 Apr. 2024];50(3):188-194. Available from: https://doi.org/10.26650/IstanbulJPharm.2019.0081 doi: 10.26650/IstanbulJPharm.2019.0081


ISNAD

Serin, SinemIlgın - Dağaşan, Fulya - Burukoğlu Dönmez, Dilek - Baysal, Merve - Atlı Eklioğlu, Özlem. Evaluation of the hepatotoxic potential of citalopram in rats”. İstanbul Journal of Pharmacy 50/3 (Apr. 2024): 188-194. https://doi.org/10.26650/IstanbulJPharm.2019.0081



ZAMAN ÇİZELGESİ


Gönderim14.01.2020
Kabul26.06.2020
Çevrimiçi Yayınlanma31.12.2020

LİSANS


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


PAYLAŞ




İstanbul Üniversitesi Yayınları, uluslararası yayıncılık standartları ve etiğine uygun olarak, yüksek kalitede bilimsel dergi ve kitapların yayınlanmasıyla giderek artan bilimsel bilginin yayılmasına katkıda bulunmayı amaçlamaktadır. İstanbul Üniversitesi Yayınları açık erişimli, ticari olmayan, bilimsel yayıncılığı takip etmektedir.