Histological and Biochemical Changes Associated with Blocking of Serotonin Receptor doi.org/10.26538/tjnpr/v6i8.4
Main Article Content
Abstract
Schizophrenia is one of many psychotic disorders on a broad spectrum. The symptoms of psychosis resulting from schizophrenia and other spectrum disorders are treated with several medications, including aripiprazole, clozapine, risperidone, etc. However, these drugs are associated with adverse effects. This study was conducted to evaluate histological and biochemical changes linked to the blockage of serotonin receptors caused by risperidone and aripiprazole. Fifteen Sprague Dawley albino rats were divided into three groups of five rats each. Group 1 served as the control and received a placebo (normal saline), Group 2 received risperidone (20 mg/kg/day), and Group 3 was given aripiprazole (10 mg/kg/day). After three months of treatment, a biochemical analysis of liver enzymes was performed, followed by a histological examination. The results revealed that the architecture of the liver cells appeared normal in all three groups. However, when risperidone and aripiprazole treatment groups were compared to the control group, histology was slightly altered. The level of glutamic oxaloacetic transaminase (GOT) in the control group increased slightly from 70 to 75 U/L. GOT levels increased from 80 to 120 U/L and 130 to 140 U/L in the aripiprazole and risperidone groups, respectively. A similar observation was made for the levels of glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) compared to the control group. The findings of this study found the levels of the biochemical enzymes within safe limits with the administration of aripiprazole and risperidone. However, patients using these drugs should always have routine laboratory examinations for liver enzyme tests.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Barlati S, Deste G, Gregorelli M, Vita A. Autistic traits in a sample of adult patients with schizophrenia: prevalence and correlates. Psychol Med. 2019; 49(1):140-148.
Carruthers SP, Van Rheenen TE, Gurvich C, Sumner PJ, Rossell SL. Characterising the structure of cognitive heterogeneity in schizophrenia spectrum disorders. A systematic review and narrative synthesis. Neurosci Biobehav Rev. 2019; 107:252-278.
Lally J, Ajnakina O, Di Forti M, Trotta A, Demjaha A, Kolliakou A, Mondelli V, Marques TR, Pariante C, Dazzan P, Shergil SS. Two distinct patterns of treatment resistance: clinical predictors of treatment resistance in first-episode schizophrenia spectrum psychoses. Psychol Med. 2016; 46(15):3231-3240.
Lee D and Minko T. Nanotherapeutics for Nose-to-Brain Drug Delivery: An Approach to Bypass the Blood Brain Barrier. Pharmaceut. 2021; 13(12):1-47.
Rollini M and Schulz P. Atypical antipsychotics for elderly patients: to prescribe or to ban? Revue Medicale Suisse. 2008; 4(153):979-980.
Malhi GS, Bell E, Porter RJ. Serial quelling: The typical use of atypical antipsychotics? Aust N. Z. J Psych. 2019; 53(6):495-498.
Meltzer HY, Li Z, Kaneda Y, Ichikawa J. Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuro-Psychopharmacol Biol Psych. 2003; 27(7):1159-1172.
Zhu X, Hu J, Deng S, Qiu C, Shang D, Wen Y. Rhabdomyolysis and elevated liver enzymes after rapid correction of hyponatremia due to pneumonia and concurrent use of aripiprazole: A case report. Aust N. Z. J Psychiatry. 2018; 52(2):1-11.
Preda A, Shapiro BB. A safety evaluation of aripiprazole in the treatment of schizophrenia. Expert Opin. Drug Saf. 2020; 19(12):1529-1538.
Chopko TC and Lindsley CW. Classics in chemical neuroscience: risperidone. ACS Chem Neurosci. 2018; 9(7):1520-1529.
Sylvester E, Yi W, Han M, Deng C. Exercise intervention for preventing risperidone-induced dyslipidemia and glucose-metabolic disorders in female juvenile rats. Pharmacol Biochem Behav. 2020; 199:1-9.
Abdulqader SW, Faisal IM, Saeed MG, Merkhan MM. Fluvoxamine provide a gastro-protection against vitiated insult. Ind J For Med Toxicol. 2022; 16(1): 1046-1052.
Abdulqader SW, Faisal IM, Saeed MG, Merkhan MM. fluvoxamine suppressed oxidative stress associated with tissue erosion. Res J Pharm Technol. 2022; 15(2):819-824.
Huang XJ, Choi YK, Im HS, Yarimaga O, Yoon E, Kim HS. Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) detection techniques. Sensors. 2006; 6(7):756-782.
Kaplan MM. Alkaline phosphatase. Gastroenterology. 1972; 62(3):452-68.
Roth RA and Ganey PE. Animal models of idiosyncratic drug-induced liver injury: current status. Crit Rev Toxicol. 2011; 41(9):723-739.
Yuan X, Zhang P, Wang Y, Liu Y, Li X, Kumar BU, Hei G, Lv L, Huang XF, Fan X, Song X. Changes in metabolism and microbiota after 24-week risperidone treatment in drug naïve, normal weight patients with first episode schizophrenia. Schizophr Res. 2018; 201:299-306.
Goëb JL, Marco S, Duhamel A, Jardri R, Kechid G, Bordet R, Delion P, Thomas P. Metabolic side effects of risperidone in children and adolescents with early-onset schizophrenia. Prim Care Companion J Clin Psych. 2008; 10(6):486–487.
Zhang Y, Liu Y, Su Y, You Y, Ma Y, Yang G, Song Y, Liu X, Wang M, Zhang L, Kou C. The metabolic side effects of 12 antipsychotic drugs used for the treatment of schizophrenia on glucose: a network meta-analysis. BMC Psych. 2017; 17(1):1-9.
Nasrallah HA. Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol. Psychiatry. 2008; 13(1):27-35.
Koller D, Saiz‐Rodríguez M, Zubiaur P, Ochoa D, Almenara S, Román M, Romero‐Palacián D, de Miguel‐ Cáceres A, Martín S, Navares‐Gómez M, Mejía G. The effects of aripiprazole and olanzapine on pupillary light reflex and its relationship with pharmacogenetics in a randomized multiple‐dose trial. Br J Clin Pharmacol. 2020; 86(10):2051-2062.
Shah R, Subhan F, Sultan SM, Ali G. Short-term oral administration of risperidone induces pancreatic damage and hyperamylasemia in Sprague-dawley rats. Braz J Pharm Sci. 2019; 54 (4):1-7.
Hirose T, Uwahodo Y, Yamada S, Miwa T, Kikuchi T, Kitagawa H, Burris KD, Altar CA, Nabeshima T. Mechanism of action of aripiprazole predicts clinical efficacy and a favourable side-effect profile. J Psychopharmacol. 2004; 18(3):375-383.
Horton G, Maumi G, James K, Jainer AK, Somashekar B. Development of New Antipsychotics: Changing Trends. Int Med J. 2020; 27(4):433-437.
Koller D, Almenara S, Mejía G, Saiz-Rodríguez M, Zubiaur P, Román M, Ochoa D, Navares-Gómez M, Santos-Molina E, Pintos-Sánchez E, Abad-Santos F. Metabolic effects of aripiprazole and olanzapine multiple-dose treatment in a randomised crossover clinical trial in healthy volunteers: association with pharmacogenetics. Adv Ther. 2021; 38(2):1035-1054.
Soliman HM, Wagih HM, Algaidi SA, Hafiz AH. Histological evaluation of the role of atypical antipsychotic drugs in inducing non-alcoholic fatty liver disease in adult male albino rats (light and electron microscopic study). Folia Biol. 2013; 59(5):173.
Jiang T, Zhang Y, Bai M, Li P, Wang W, Chen M, Ma Z, Zeng S, Zhou H, Jiang H. Up-regulation of hepatic fatty acid transporters and inhibition/down-regulation of hepatic OCTN2 contribute to olanzapine-induced liver steatosis. Toxicol Lett. 2019; 316:183-93.
Todorović N, Tomanović N, Gass P, Filipović D. Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats. Eur J Pharm Sci. 2016; 81:94-102.
Elbakary RH. Histological study of the effects of olanzapine on the liver of adult male albino rat with and without Vitamin C. Egy J Hist. 2017; 40(1):1-11.
Chen CH, Shyue SK, Hsu CP, Lee TS. Atypical antipsychotic drug olanzapine deregulates hepatic lipid metabolism and aortic inflammation and aggravates atherosclerosis. Cell Physiol Biochem. 2018; 50(4):1216- 1229.
Mahmoud GS and El-Deek HE. Melatonin modulates inflammatory mediators and improves olanzapine-induced hepatic steatosis in rat model of schizophrenia. Int J Physiol Pathophysiol Pharmacol. 2019; 11(3):64–75.
Jiang T, Zhang Y, Bai M, Li P, Wang W, Chen M, Ma Z, Zeng S, Zhou H, Jiang H. Up-regulation of hepatic fatty acid transporters and inhibition/down-regulation of hepatic OCTN2 contribute to olanzapine-induced liver steatosis. Toxicol Lett. 2019; 316:183-193.
Liu XM, Zhao XM, Deng C, Zeng YP, Hu CH. Simvastatin improves olanzapine-induced dyslipidemia in rats through inhibiting hepatic mTOR signaling pathway. Acta Pharmacol Sin. 2019; 40(8):1049-1057.
Lauressergues E, Martin F, Helleboid A, Bouchaert E, Cussac D, Bordet R, Hum D, Luc G, Majd Z, Staels B, Duriez P. Overweight induced by chronic risperidone exposure is correlated with overexpression of the SREBP- 1c and FAS genes in mouse liver. Naunyn Schmiedebergs Arch Pharmacol. 2011; 383(4):423-436.
McNamara RK, Magrisso IJ, Hofacer R, Jandacek R, Rider T, Tso P, Benoit SC. Omega-3 fatty acid deficiency augments risperidone-induced hepatic steatosis in rats: positive association with stearoyl-CoA desaturase. Pharmacol Res. 2012; 66(4):283-291.
Coccurello R, Caprioli A, Ghirardi O, Conti R, Ciani B, Daniele S, Bartolomucci A, Moles A. Chronic administration of olanzapine induces metabolic and food intake alterations: a mouse model of the atypical antipsychotic-associated adverse effects. Psychopharmacol. 2006; 186(4):561-571.
Auger F, Martin F, Pétrault O, Samaillie J, Hennebelle T, Trabelsi MS, Bailleul F, Staels B, Bordet R, Duriez P. Risperidone-induced metabolic dysfunction is attenuated by Curcuma longa extract administration in mice. Metab Brain Dis. 2018; 33(1):63-77.
Eftekhari A, Ahmadian E, Azarmi Y, Parvizpur A, Hamishehkar H, Eghbal MA. In vitro/vivo studies towards mechanisms of risperidone-induced oxidative stress and the protective role of coenzyme Q10 and N-acetylcysteine. Toxicol Mech Methods. 2016; 26(7):520-528.
Azirak S, Bilgic S, Korkmaz DT, Guvenc AN, Kocaman N, Ozer MK. The protective effect of resveratrol against risperidone-induced liver damage through an action on FAS gene expression. Gen Physiol Biophys. 2019; 38:215-225.
Ilgin S, Burukoglu D, Baysal M, Hinis O, Atli O. Assessment of Hepatotoxic Effects of Quetiapıne at Repeated Doses in Rats. Anadolu Uni J Sci Tech C-Life Sci Biotech. 2018; 7(2):196-206.