Drug Res (Stuttg) 2022; 72(06): 343-349
DOI: 10.1055/a-1830-8701
Original Article

Risperidone Toxicity on Human Blood Lymphocytes in Nano molar Concentrations

Bahareh Sadat Yousefsani
1   Research Institute for Islamic and Complementary Medicine, Iran University of Medical Sciences, Tehran, Iran
2   School of Persian Medicine, Iran University of Medical Sciences, Tehran, Iran
,
Ahmad Salimi
3   Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
,
Farnaz Imani
4   Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
Maral Ramezani
4   Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
,
Kobra Shirani
5   Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
,
Enayatollah Seydi
6   Department of Occupational Health and Safety Engineering, School of Health, Alborz University of Medical Sciences, Karaj, Iran
7   Research Center for Health, Safety and Environment, Alborz University of Medical Sciences, Karaj, Iran
,
Jalal Pourahmad
4   Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
› Author Affiliations

Abstract

Risperidone is an atypical antipsychotic drug used for the pharmacotherapy of psychiatric disorders. Some reports indicate that risperidone is toxic to various systems of the body, including the immune system. This study evaluated the toxicity effect of risperidone on human blood lymphocytes. To achieve this aim, lymphocytes were isolated using Ficoll paque plus. The results showed that risperidone (12, 24 and 48 nM) causes toxicity in human blood lymphocytes by increasing the level of intracellular reactive oxygen species (ROS), damage to lysosomal membrane, the collapse of the mitochondrial membrane potential (MMP), and increased extracellular oxidized glutathione (GSSG). Also, exposure of human blood lymphocytes to risperidone is associated with a decrease in intracellular glutathione (GSH) levels. Finally, it could be concluded that oxidative stress is one of the mechanisms of risperidone-induced toxicity in human blood lymphocytes.



Publication History

Received: 23 February 2022

Accepted: 19 April 2022

Article published online:
23 May 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Chaplin DD. Overview of the immune response. Journal of Allergy and Clinical Immunology 2010; 125: S3-S23
  • 2 Raju S, Kavimani S, Rao UMV. et al. Immunotoxicants, Immunotoxicity and Immunotoxicity testing: An outline of in-vitro alternatives. Journal of Current Pharma Research 2011; 1: 341
  • 3 Shirani K, Zanjani BR, Mahmoudi M. et al. Immunotoxicity of aflatoxin M1: as a potent suppressor of innate and acquired immune systems in a subacute study. Journal of the Science of Food and Agriculture 2018; 98: 5884-92.
  • 4 Ray S, Mukherjee S, Bhunia NS. et al. Immunotoxicological threats of pollutants in aquatic invertebrates. Emerging Pollutants in the Environment-Current and Further Implications InTech, Croatia 2015; 149-165
  • 5 Thompson PA, Khatami M, Baglole CJ. et al. Environmental immune disruptors, inflammation and cancer risk. Carcinogenesis 2015; 36: S232-S253
  • 6 Chopko TC, Lindsley CW. Classics in chemical neuroscience: risperidone. ACS chemical neuroscience 2018; 9: 1520-1529
  • 7 Oshikoya KA, Carroll R, Aka I. et al. Adverse Events Associated with Risperidone Use in Pediatric Patients: A Retrospective Biobank Study. Drugs-real world outcomes 2019; 6: 59-71
  • 8 May M, Beauchemin M, Vary C. et al. The antipsychotic medication, risperidone, causes global immunosuppression in healthy mice. PloS one 2019; 14: e0218937-e0218937
  • 9 Motyl KJ, Beauchemin M, Barlow D. et al. A novel role for dopamine signaling in the pathogenesis of bone loss from the atypical antipsychotic drug risperidone in female mice. Bone 2017; 103: 168-176
  • 10 Bilgiç S, Korkmaz DT, Azirak S. et al. Risperidone-induced renal damage and metabolic side effects: the protective effect of resveratrol. Oxidative medicine and cellular longevity 2017; 2017: 8709521
  • 11 Eftekhari A, Ahmadian E, Azarmi Y. et al. In vitro/vivo studies towards mechanisms of risperidone-induced oxidative stress and the protective role of coenzyme Q10 and N-acetylcysteine. Toxicology mechanisms and methods 2016; 26: 520-528
  • 12 Görmüş G, Ilgın S, Baysal M. et al. Risperidone induced reproductive toxicity in male rats targeting leydig cells and hypothalamic-pituitary-gonadal axis by inducing oxidative stress. Andrologia 2021; 53: e13813
  • 13 Chan K, Truong D, Shangari N. et al. Drug-induced mitochondrial toxicity. Expert Opin Drug Metab Toxicol 2005; 1: 655-669
  • 14 Modica-Napolitano JS, Lagace CJ, Brennan WA. et al. Differential effects of typical and atypical neuroleptics on mitochondrial functionin vitro. Archives of pharmacal research 2003; 26: 951-959
  • 15 Bock FJ, Tait SW. Mitochondria as multifaceted regulators of cell death. Nature reviews Molecular cell biology 2020; 21: 85-100
  • 16 Hasnat M, Yuan Z, Ullah A. et al. Mitochondria-dependent apoptosis in triptolide-induced hepatotoxicity is associated with the Drp1 activation. Toxicology mechanisms and methods 2020; 30: 124-33.
  • 17 Hernansanz-Agustín P, Enríquez JA. Generation of reactive oxygen species by mitochondria. Antioxidants 2021; 10: 415
  • 18 Bøyum A. Isolation of lymphocytes, granulocytes and macrophages. Scandinavian journal of immunology 1976; 5: 9-15
  • 19 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55-63
  • 20 Halliwell B, Whiteman M. Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?. British journal of pharmacology 2004; 142: 231-255
  • 21 Salimi A, Vaghar-Moussavi M, Seydi E. et al. Toxicity of methyl tertiary-butyl ether on human blood lymphocytes. Environmental Science and Pollution Research 2016; 23: 8556-8564
  • 22 Baracca A, Sgarbi G, Solaini G. et al. Rhodamine 123 as a probe of mitochondrial membrane potential: evaluation of proton flux through F0 during ATP synthesis. Biochimica et Biophysica Acta (BBA) – Bioenergetics 2003; 1606: 137-146
  • 23 Salimi A, Pirhadi R, Jamali Z. et al. Mitochondrial and lysosomal protective agents ameliorate cytotoxicity and oxidative stress induced by cyclophosphamide and methotrexate in human blood lymphocytes. Human & experimental toxicology 2019; 38: 1266-1274
  • 24 Görmüş G, Ilgın S, Baysal M. et al. Risperidone induced reproductive toxicity in male rats targeting leydig cells and hypothalamic-pituitary-gonadal axis by inducing oxidative stress. Andrologia 2021; 53: e13813
  • 25 Hissin PJ, Hilf R. A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 1976; 74: 214-226
  • 26 Kiani A, Yousefsani BS, Doroudian P. et al. The mechanism of hepatotoxic effects of sodium nitrite on isolated rat hepatocytes. Toxicology and Environmental Health Sciences 2017; 9: 244-250
  • 27 Ananth J, Parameswaran S, Gunatilake S. Side effects of atypical antipsychotic drugs. Current pharmaceutical design 2004; 10: 2219-2229
  • 28 May M, Beauchemin M, Vary C. et al. The antipsychotic medication, risperidone, causes global immunosuppression in healthy mice. PLoS One 2019; 14: e0218937
  • 29 Alvarez-Herrera S, Escamilla R, Medina-Contreras O. et al. Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics. Frontiers in endocrinology 2020; 11: 195
  • 30 Pourahmad J, Salimi A. Isolated Human Peripheral Blood Mononuclear Cell (PBMC), a Cost Effective Tool for Predicting Immunosuppressive Effects of Drugs and Xenobiotics. Iran J Pharm Res 2015; 14: 979–980
  • 31 Scialò F, Fernández-Ayala DJ, Sanz A. Role of Mitochondrial Reverse Electron Transport in ROS Signaling: Potential Roles in Health and Disease. Front Physiol 2017; 8: 428
  • 32 Simpson DSA, Oliver PL. ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease. Antioxidants (Basel) 2020; 9: 743
  • 33 Umeno A, Biju V, Yoshida Y. In vivo ROS production and use of oxidative stress-derived biomarkers to detect the onset of diseases such as Alzheimer’s disease, Parkinson’s disease, and diabetes. Free Radic Res 2017; 51: 413-427
  • 34 Bhatti JS, Bhatti GK, Reddy PH. Mitochondrial dysfunction and oxidative stress in metabolic disorders – A step towards mitochondria based therapeutic strategies. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2017; 1863: 1066-1077
  • 35 Casademont J, Garrabou G, Miró O. et al. Neuroleptic treatment effect on mitochondrial electron transport chain: peripheral blood mononuclear cells analysis in psychotic patients. J Clin Psychopharmacol 2007; 27: 284-288
  • 36 Martins MR, Petronilho FC, Gomes KM. et al. Antipsychotic-induced oxidative stress in Rat Brain. Neurotoxicity Research 2008; 13: 63-69
  • 37 Cikánková T, Fišar Z, Bakhouche Y. et al. In vitro effects of antipsychotics on mitochondrial respiration. Naunyn Schmiedebergs Arch Pharmacol 2019; 392: 1209-1223
  • 38 Zdolsek JM, Svensson I. Effect of reactive oxygen species on lysosomal membrane integrity. Virchows Archiv B 1993; 64: 401