Yıl 2018, Cilt 7, Sayı 2, Sayfalar 196 - 206 2018-08-17

Assessment of Hepatotoxic Effects of Quetiapıne at Repeated Doses in Rats

SİNEM ILGIN [1] , DİLEK BURUKOĞLU [2] , MERVE BAYSAL [3] , ÖZLEM HİNİS [4] , ÖZLEM ATLI [5]

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Quetiapine is an atypical antipsychotic drug used for treatments of patients with schizophrenia. Although hepatotoxic effects related to quetiapine treatment were reported in a few studies, potential hepatotoxicity of this drug was not identified clearly. Therefore, it was aimed to evaluate possible hepatotoxic effects of quetiapine by oral administration of this drug at 10 and 20 mg/kg doses to rats for 30 days in our study. For this purpose, plasma aspartate aminotransferase, alanine aminotransferase, total bilirubin and direct bilirubin levels as markers of hepatotoxicity were determined and histopathological examination was performed in liver tissues. According to our results, serum aspartate aminotransferase and alanine aminotransferase levels were significantly increased in quetiapine-administered groups, whereas total and direct bilirubin levels were significantly increased in high dose group. Histopathological examination of liver tissue indicated that necrotic areas were observed in 10 mg/kg quetiapine-administered group whereas necrotic areas were present and sinusoidal dilatation was observed in 20 mg/kg quetiapine-administered group. According to these results, we concluded that quetiapine may induced hepatotoxic effects in rats, dose-dependently.

Quetiapine, hepatotoxicity, hepatic biomarkers, oxidative stress
  • [1] Kaplowitz N. Drug-induced liver injury. Clin Infect Dis 2004; 38(2): S44-8.
  • [2] Grattagliano I, Bonfrate L, Diogo CV, Wang HH, Wang DQ, Portincasa P. Biochemical mechanisms in drug-induced liver injury: certainties and doubts. World J Gastroenterol 2009; 15(39): 4865-76.
  • [3] Russmann S, Kullak-Ublick GA, Grattagliano I. Current concepts of mechanisms in drug-induced hepatotoxicity. Curr Med Chem 2009; 16(23): 3041-3053.
  • [4] Vinken M, Maes M, Vanhaecke T, Rogiers V. Drug-induced liver injury: mechanisms, types and biomarkers. Curr Med Chem 2013; 20(24): 3011-21.
  • [5] van Tonder JJ, Steenkamp V, Gulumian M. Pre-Clinical Assessment of the Potential Intrinsic Hepatotoxicity of Candidate Drugs. New Insights into Toxicity and Drug Testing. Edited by Sivakumar Gowder, Publisher: InTech 2013.
  • [6] Chalasani NP, Hayashi PH, Bonkovsky HL, Navarro VJ, Lee WM, Fontana RJ. Practice Parameters Committee of the American College of Gastroenterology. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol 2014; 109(7): 950-66.
  • [7] Sanford M, Keating GM. Quetiapine: a review of its use in the management of bipolar depression. CNS Drugs 2012; 26(5): 435-460.
  • [8] Pringsheim T, Gardner DM. Dispensed prescriptions for quetiapine and other second-generation antipsychotics in Canada from 2005 to 2012: a descriptive study. CMAJ Open 2014; 2(4): E225-32.
  • [9] Lindsley CW. The Top Prescription Drugs of 2011 in the United States: Antipsychotics and Antidepressants Once Again Lead CNS Therapeutics, ACS Chem. Neurosci 2012; 3(8): 630-631.
  • [10] El Hajj I, Sharara AI, Rockey DC. Subfulminant liver failure associated with quetiapine. Eur. J. Gastroenterol. Hepatol 2004; 16: 1415−1418.
  • [11] Shpaner A, Li W, Ankoma-Sey V, Botero RC. Drug-induced liver injury: Hepatotoxicity of quetiapine revisited. Eur. J. Gastroenterol. Hepatol 2008; 20: 1106−1109.
  • [12] Al Mutairi F, Dwivedi G, Al Ameel T. Fulminant hepatic failure in association with quetiapine: a case report. J Med Case Rep 2012; 6: 418.
  • [13] Garver DL. Review of quetiapine side effects. J Clin Psychiatry 2000; 61(8): 31-35.
  • [14] Atasoy N, Erdogan A, Yalug I, Ozturk U, Konuk N, Atik L, Ustundag Y. A review of liver function tests during treatment with atypical antipsychotic drugs: a chart review study. Prog Neuro-Psychopharmacol Biol Psychiatry 2007; 31: 1255−1260.
  • [15] Naharci MI, Karadurmus N, Demir O, Bozoglu E, Ak M, Doruk H. Fatal hepatotoxicity in an elderly patient receiving low-dose quetiapine. Am J Psychiatry 2011; 168: 212−213.
  • [16] Guan HJ, Dai J, Zhu XZ. Atypical antipsychotic effects of quetiapine fumarate in animal models. Acta Pharmacol Sin 2000; 21(3): 205-10.
  • [17] Pisu C, Pira L, Pani L. Quetiapine anxiolytic-like effect in the Vogel conflict test is serotonin dependent. Behav Pharmacol 2010; 21(7): 649-53.
  • [18] Zhang XR, Zhang ZJ, Jenkins TA, Cheng WR, Reynolds GP. The dose-dependent effect of chronic administration of haloperidol, risperidone, and quetiapine on sexual behavior in the male rat. J Sex Med 2011; 8(12): 3345-53.
  • [19] IACUC Guidelines: Anesthesia. Published on Office of Animal Resources. Institutional Animal Care and Use Committee. 2017.
  • [20] Yang X, Schnackenberg LK, Shi Q, Salminen WF. Hepatic toxicity biomarkers. R. Gupta (Ed): Biomarkers in Toxicology. Elsevier Inc., 2014: page 241-259.
  • [21] Singh A, Bhat TK, Sharma OP. Clinical Biochemistry of Hepatotoxicity.J Clinic Toxicol 2011; 4: 1
  • [22] Aubrecht J, Schomaker SJ, Amacher DE. Emerging hepatotoxicity biomarkers and their potential to improve understanding and management of drug-induced liver injury. Genome Med 2013; 5(9): 85.
  • [23] U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER). Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation. 2009.
  • [24] Holt MP, Ju C. Mechanisms of drug-induced liver injury. AAPS J 2006; 8(1): E48-54.
  • [25] Kirchain WR, Allen RE. eChapter 17. Drug-Induced Liver Disease. DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014.
  • [26] Yuan L, Kaplowitz N. Mechanisms of Drug Induced Liver Injury Clin Liver Dis 2013; 17(4): 507–518.
  • [27] Stephens C, Andrade RJ, Lucena MI. Mechanisms of drug-induced liver injury. Curr Opin Allergy Clin Immunol 2014; 14(4): 286-92.
  • [28] Li X, Cameron MD. Potential role of a quetiapine metabolite in quetiapine-induced neutropenia and agranulocytosis. Chem Res Toxicol 2012; 25(5): 1004-11.
  • [29] Wang H, Xu H, Dyck LE, Li XM. Olanzapine and quetiapine protect PC12 cells from beta-amyloid peptide(25-35)-induced oxidative stress and the ensuing apoptosis. J Neurosci Res 2005; 81(4): 572-80.
  • [30] Xu H, Wang H, Zhuang L, Yan B, Yu Y, Wei Z, Zhang Y, Dyck LE, Richardson SJ, He J, Li X, Kong J, Li XM. Demonstration of an anti-oxidative stress mechanism of quetiapine: implications for the treatment of Alzheimer's disease. FEBS J 2008; 275(14): 3718-28.
  • [31] Padurariu M, Ciobica A, Dobrin I, Stefanescu C. Evaluation of antioxidant enzymes activities and lipid peroxidation in schizophrenic patients treated with typical and atypical antipsychotics. Neurosci Lett 2010; 479(3): 317-20.
  • [32] Dietrich-Muszalska A, Kontek B, Rabe-Jabłońska J. Quetiapine, olanzapine and haloperidol affect human plasma lipid peroxidation in vitro. Neuropsychobiology 2011; 63(4): 197-201.
  • [33] Luo G, Liu M, He J, Guo H, Xue M, Wang X, Li XM. Quetiapine attenuates recognition memory impairment and hippocampal oxidative stress in a transgenic mouse model of Alzheimer's disease. Neuroreport 2014; 25(9): 647-50.
  • [34] Han JH, Tian HZ, Lian YY, Yu Y, Lu CB, Li XM, Zhang RL, Xu H. Quetiapine mitigates the ethanol-induced oxidative stress in brain tissue, but not in the liver, of the rat. Neuropsychiatr Dis Treat 2015; 11: 1473-82.
  • [35] Xuan Y, Yan G, Wu R, Huang Q, Li X, Xu H. The cuprizone-induced changes in (1)H-MRS metabolites and oxidative parameters in C57BL/6 mouse brain: Effects of quetiapine. Neurochem Int 2015; 90: 185-92.
  • [36] Ignácio ZM, Réus GZ, Abelaira HM, de Moura AB, de Souza TG, Matos D, Goldim MP, Mathias K, Garbossa L, Petronilho F, Quevedo J. Acute and chronic treatment with quetiapine induces antidepressant-like behavior and exerts antioxidant effects in the rat brain. Metab Brain Dis 2017; 32(4): 1195-1208.
  • [37] Zitka O, Skalickova S, Gumulec J, Masarik M, Adam V, Hubalek J, Trnkova L, Kruseova J, Eckschlager T, Kizek R. Redox status expressed as GSH: GSSG ratio as a marker for oxidative stress in paediatric tumor patients. Oncol Lett 2012; 4(6): 1247-1253.
  • [38] Frijhoff J, Winyard PG, Zarkovic N, Davies SS, Stocker R, Cheng D, Knight AR, Taylor EL, Oettrich J, Ruskovska T, Gasparovic AC, Cuadrado A, Weber D, Poulsen HE, Grune T, Schmidt HH, Ghezzi P. Clinical Relevance of Biomarkers of Oxidative Stress. Antioxid Redox Signal 2015; 23(14): 1144-70.
  • [39] Birben E, Sahiner EM, Sackesen C, Erzurum S, Kalayci O. Oxidative Stress and Antioxidant Defense. World Allergy Organ J 2012; 5(1): 9–19.
  • [40] Rahal A, Kumar A, Singh V, Yadav B, Tiwari R, Chakraborty S, Dhama K. Oxidative Stress, Prooxidants, and Antioxidants: The Interplay Biomed Res Int 2014; 2014: 761264.
Birincil Dil en
Konular Fen
Dergi Bölümü Araştırma Makalesi
Yazarlar

Yazar: SİNEM ILGIN
Ülke: Turkey


Yazar: DİLEK BURUKOĞLU
Ülke: Turkey


Yazar: MERVE BAYSAL
Ülke: Turkey


Yazar: ÖZLEM HİNİS
Ülke: Turkey


Yazar: ÖZLEM ATLI

Bibtex @araştırma makalesi { aubtdc349864, journal = {Anadolu Üniversitesi Bilim ve Teknoloji Dergisi - C Yaşam Bilimleri Ve Biyoteknoloji}, issn = {2146-0264}, eissn = {2146-0213}, address = {Eskişehir Teknik Üniversitesi}, year = {2018}, volume = {7}, pages = {196 - 206}, doi = {10.18036/aubtdc.349864}, title = {Assessment of Hepatotoxic Effects of Quetiapıne at Repeated Doses in Rats}, key = {cite}, author = {HİNİS, ÖZLEM and ATLI, ÖZLEM and ILGIN, SİNEM and BAYSAL, MERVE and BURUKOĞLU, DİLEK} }
APA ILGIN, S , BURUKOĞLU, D , BAYSAL, M , HİNİS, Ö , ATLI, Ö . (2018). Assessment of Hepatotoxic Effects of Quetiapıne at Repeated Doses in Rats. Anadolu Üniversitesi Bilim ve Teknoloji Dergisi - C Yaşam Bilimleri Ve Biyoteknoloji, 7 (2), 196-206. DOI: 10.18036/aubtdc.349864
MLA ILGIN, S , BURUKOĞLU, D , BAYSAL, M , HİNİS, Ö , ATLI, Ö . "Assessment of Hepatotoxic Effects of Quetiapıne at Repeated Doses in Rats". Anadolu Üniversitesi Bilim ve Teknoloji Dergisi - C Yaşam Bilimleri Ve Biyoteknoloji 7 (2018): 196-206 <http://dergipark.gov.tr/aubtdc/issue/36940/349864>
Chicago ILGIN, S , BURUKOĞLU, D , BAYSAL, M , HİNİS, Ö , ATLI, Ö . "Assessment of Hepatotoxic Effects of Quetiapıne at Repeated Doses in Rats". Anadolu Üniversitesi Bilim ve Teknoloji Dergisi - C Yaşam Bilimleri Ve Biyoteknoloji 7 (2018): 196-206
RIS TY - JOUR T1 - Assessment of Hepatotoxic Effects of Quetiapıne at Repeated Doses in Rats AU - SİNEM ILGIN , DİLEK BURUKOĞLU , MERVE BAYSAL , ÖZLEM HİNİS , ÖZLEM ATLI Y1 - 2018 PY - 2018 N1 - doi: 10.18036/aubtdc.349864 DO - 10.18036/aubtdc.349864 T2 - Anadolu Üniversitesi Bilim ve Teknoloji Dergisi - C Yaşam Bilimleri Ve Biyoteknoloji JF - Journal JO - JOR SP - 196 EP - 206 VL - 7 IS - 2 SN - 2146-0264-2146-0213 M3 - doi: 10.18036/aubtdc.349864 UR - http://dx.doi.org/10.18036/aubtdc.349864 Y2 - 2018 ER -
EndNote %0 Anadolu Üniversitesi Bilim ve Teknoloji Dergisi - C Yaşam Bilimleri Ve Biyoteknoloji Assessment of Hepatotoxic Effects of Quetiapıne at Repeated Doses in Rats %A SİNEM ILGIN , DİLEK BURUKOĞLU , MERVE BAYSAL , ÖZLEM HİNİS , ÖZLEM ATLI %T Assessment of Hepatotoxic Effects of Quetiapıne at Repeated Doses in Rats %D 2018 %J Anadolu Üniversitesi Bilim ve Teknoloji Dergisi - C Yaşam Bilimleri Ve Biyoteknoloji %P 2146-0264-2146-0213 %V 7 %N 2 %R doi: 10.18036/aubtdc.349864 %U 10.18036/aubtdc.349864
ISNAD ILGIN, SİNEM , BURUKOĞLU, DİLEK , BAYSAL, MERVE , HİNİS, ÖZLEM , ATLI, ÖZLEM . "Assessment of Hepatotoxic Effects of Quetiapıne at Repeated Doses in Rats". Anadolu Üniversitesi Bilim ve Teknoloji Dergisi - C Yaşam Bilimleri Ve Biyoteknoloji 7 / 2 (Ağustos 2018): 196-206. http://dx.doi.org/10.18036/aubtdc.349864