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:: Volume 19, Issue 4 (12-2017) ::
J Gorgan Univ Med Sci 2017, 19(4): 15-20 Back to browse issues page
Alterations in tissue and hepatic enzymes in male rats born to mothers treated with haloperidol
Najmeh Ghafori1 , Behdokht Jamshidnezhad1 , Mehrdad Shariati * 2
1- M.Sc in Cell and Developmental Biology, Department of Biology, Kazerun Branch, Islamic Azad University, Kazerun, Iran
2- Associate Professor, Department of Biology, Kazerun Branch, Islamic Azad University, Kazerun, Iran , mehrdadshariati@hotmail.com
Abstract:   (13065 Views)
Background and Objective: Liver is an important organ with specific function in relation to drug metabolism. Haloperidol is a drug for the treatment of schizophrenia, mania in bipolar disorder and dizziness. This study was performed to determine the changes in tissue and hepatic enzymes in male rats born to mothers treated with haloperidol.
Methods: In this experimental study, 25 adult female Wistar rats were allocated into 5 groups. The control group, the sham group and experimental groups 1, 2, 3. Dams in experimental groups 1, 2, 3 in the pregnancy period were received 12.5, 25 ,50 mg/kg /bw of haloperidol for 21 days orally, respectively. The control groups were sham and three experimental, first, second and third experimental groups. Mothers of mice received 12.5, 25 and 50 mg/kg of haloperidol during the pregnancy as 21 days of gavage. At the end of pregnancy and 22 days of infant, all infants were weighed. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and aspartate transaminase (AST), albumin and total protein were measured by autoanalysis and liver tissues were stained using hepatoxylin-eosin method.
Results: The mean concentration of albumin and total protein in the second and third experimental groups significantly reduced in compare to control group (P<0.05). The mean concentration of AST in the second and third experimental groups significantly increased in comparsion with control group (P<0.05). The mean concentration of ALT and ALP in all experimental groups was significantly higher than the control group (P<0.05). The mean of liver indices in all experimental groups was not significant in comparison with the control group. In the tissue samples of the experimental groups, necrosis was observed with increasing dosage.
Conclusion: Haloperidol has been shown to increase liver enzymes and liver necrosis and increase liver necrosis in a dose-proportional manner.
Keywords: Liver, Haloperidol, Liver Enzymes, Necrosis, Rat
Full-Text [PDF 286 kb] [English Abstract]   (15554 Downloads) |   |   Abstract (HTML)  (944 Views)  
Type of Study: Original Articles | Subject: Physiology - Pharmacology
References
1. Ståhle L, Ungerstedt U. Effects of neuroleptic drugs on the inhibition of exploratory behaviour induced by a low dose of apomorphine: implications for the identity of dopamine receptors. Pharmacol Biochem Behav. 1986 Aug; 25(2): 473-80.
2. Bowles TM, Levin GM. Aripiprazole: a new atypical antipsychotic drug. Ann Pharmacother. 2003 May; 37(5): 687-94. doi:10.1345/aph.1C297
3. Jensen RJ. Effects of antipsychotic drugs haloperidol and clozapine on visual responses of retinal Ganglion cells in a rat model of retinitis pigmentosa. J Ocul Pharmacol Ther. 2016 Dec; 32(10): 685-90. doi:10.1089/jop.2016.0102
4. Waddington JL, Gamble SJ. Spontaneous activity and apomorphine stereotypy during and after withdrawal from 3 1/2 months continuous administration of haloperidol: some methodological issues. Psychopharmacology (Berl). 1980; 71(1): 75-7.
5. He K, Cai L, Shi Q, Liu H, Woolf TF. Inhibition of MDR3 activity in human hepatocytes by drugs associated with liver injury. Chem Res Toxicol. 2015 Oct; 28(10): 1987-90. doi:10.1021/acs.chemrestox.5b00201
6. Van Putten T, Marder SR, Mintz J, Poland RE. Haloperidol plasma levels and clinical response: a therapeutic window relationship. Am J Psychiatry. 1992 Apr; 149(4): 500-5.
7. Shinoda Y, Tagashira H, Bhuiyan MS, Hasegawa H, Kanai H, Fukunaga K. Haloperidol aggravates transverse aortic constriction-induced heart failure via mitochondrial dysfunction. J Pharmacol Sci. 2016 Jul; 131(3): 172-83. doi:10.1016/j.jphs.2016.05.012
8. 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 Dec; 8(12): 3345-53. doi:10.1111/j.1743-6109.2010.01740.x
9. Halici Z, Dursun H, Keles ON, Odaci E, Suleyman H, Aydin N, et al. Effect of chronic treatment of haloperidol on the rat liver: a stereological and histopathological study. Naunyn Schmiedebergs Arch Pharmacol. 2009 Mar; 379(3): 253-61. doi:10.1007/s00210-008-0362-z
10. Meganathan M, Madhana Gopal K, Sasikala P, Mohan J, Gowdhaman N, Balamurugan K, et al. Evaluation of hepatoprotective effect of omega 3-Fatty acid against paracetamol induced liver injury in albino rats. Global Journal of Pharmacology. 2011; 5(1): 50-53.
11. Hussein RRS, Soliman RH, Abdelhaleem Ali AM, Tawfeik MH, Abdelrahim MEA. Effect of antiepileptic drugs on liver enzymes. Beni-Suef University Journal of Basic and Applied Sciences. 2013; 2(1): 14-19. https://doi.org/10.1016/j.bjbas.2013.09.002
12. Harper HA, Redwel UM, Mayes PA. Review of physiological chemistry. 17th ed. California: Long Medical Publication. 2009; p: 7.
13. Kaplowitz N. Drug-induced liver disorders: implications for drug development and regulation. Drug Saf. 2001;24(7):483-90.
14. Bogin JF. Animal Anatomy and physiology. 2nd ed. Virginia: Reston Publishing. 2009; pp: 154-56.
15. Devlin JW, Roberts RJ, Fong JJ, Skrobik Y, Riker RR, Hill NS, et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med. 2010 Feb; 38(2): 419-27. doi:10.1097/CCM.0b013e3181b9e302
16. Baratta JL, Ngo A, Lopez B, Kasabwalla N, Longmuir KJ, Robertson RT. Cellular organization of normal mouse liver: a histological, quantitative immunocytochemical, and fine structural analysis. Histochem Cell Biol. 2009 Jun; 131(6): 713-26. doi:10.1007/s00418-009-0577-1
17. Raeder MB, Fernø J, Vik-Mo AO, Steen VM. SREBP activation by antipsychotic- and antidepressant-drugs in cultured human liver cells: relevance for metabolic side-effects? Mol Cell Biochem. 2006 Sep; 289(1-2): 167-73. doi:10.1007/s11010-006-9160-4
18. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 1995 Jul; 269(5223): 540-43.
19. Holt MP, Cynthia JU. Mechanisms of drug-induced liver injury. AAPS J. 2006; 8(1): E48-E54. doi:10.1208/aapsj080106
20. Manceaux P, Constant E, Zdanowicz N, Jacques D, Reynaert C. Management of marked liver enzyme increase during olanzapine treatment: a case report and review of the literature. Psychiatr Danub. 2011 Sep; 23 Suppl 1: S15-7.
21. Berk P, Korenblat K. Approach to the patient with jaundice or abnormall liver tests. In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. Philadelphia: Sunders Company. 2011; p: 149.
22. Billiard M, Blood DC, Radostits OM. Veterinary medicine. 7th ed. London: Baillier and Tindal. 2009; pp: 228-98.
23. Gill M, Sanyal SN, Sareen ML. Interaction of H2-receptor antagonists, cimetidine and ranitidine with microsomal drug metabolizing and other systems in liver. Indian J Exp Biol. 1991 Sep; 29(9): 852-56.
24. Murray RK, Granner DK, Mayes PA, Rodwell VW. Harpers Biochemestry. 23rd ed. California: Appleton and Lange. 2010; pp: 145-251, 345-51.
25. Lauressergues E, Bert E, Duriez P, Hum D, Majd Z, Staels B, Cussac D. Does endoplasmic reticulum stress participate in APD-induced hepatic metabolic dysregulation? Neuropharmacology. 2012 Feb; 62(2): 784-96. doi:10.1016/j.neuropharm.2011.08.048
26. Mesure G, Bayle F, Vanelle JM, Olié JP, Lôo H. [Cytolytic hepatitis during treatment with phenothiazines: apropos of a case]. Encephale. 1996 Sep-Oct; 22(5): 388-90. [Article in French]
27. Arana GW, Hyman SE, Rosen Baum JF. Hand book of psychiatric drug therapy. 4th ed. Philadelphia: Lippincott Williams & Wilkins. 2010. pp: 1-20.
28. Giboney PT. Mildly elevated liver transaminase levels in the asymptomatic patient. Am Fam Physician. 2005 Mar; 71(6): 1105-10.
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Ghafori N, Jamshidnezhad B, Shariati M. Alterations in tissue and hepatic enzymes in male rats born to mothers treated with haloperidol . J Gorgan Univ Med Sci 2017; 19 (4) :15-20
URL: http://goums.ac.ir/journal/article-1-3220-en.html


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Volume 19, Issue 4 (12-2017) Back to browse issues page
مجله دانشگاه علوم پزشکی گرگان Journal of Gorgan University of Medical Sciences
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