International Journal of Pharma and Bio Sciences
 
 
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ORIGINAL RESEARCH ARTICLE
Int J Pharm Bio Sci Volume 13 issue 2, April - June, Pages:22-29

Cellular and Biochemical Studies on Risperidone Induced Teratogenesis in Developing Chick Embryos

 

Dr. Pinakin Wagh , Saurabh Dey, Nistha Ananda, Navinya Gawali and Hritika Shinde
DOI: http://dx.doi.org/10.22376/Ijpbs.2022.13.2.b22-29
Abstract:

Risperidone is a second-generation antipsychotic drug that exhibits D2, 5-HT2A, α1, α2, and H1 receptor affinity. Patients suffering from Schizophrenia are prescribed with this drug. It is mostly used for controlling the overactivity of the central mesolimbic and mesocortical pathways of the patients. According to the studies conducted it has been found that Risperidone possesses teratogenic actions on various model organisms. Consumption of this antipsychotic drug is not only associated with behavioural changes but also with physical alterations. It increases the risk by elevating nitric oxide levels and activating macrophages which leads to apoptotic events in the viable cells. Furthermore, it has been established that Risperidone toxicity caused due to overdose induces neurological as well as cardiovascular defects. Risperidone has the ability to cross the placental barrier and reach the foetal bloodstream intuitively. In addition, Risperidone also gets distributed in the milk of a lactating mother leading to undesirable changes in the breastfed babies. Here in this study, we have shown that Gallus gallus domesticus embryos (HH 23-26) treated with a minimum dose of Risperidone (1000 ppm) altered the protein and enzyme biochemistry with respect to total protein content, alkaline phosphatase (ALP), and Acetylcholinesterase levels. Cell viability studies conducted using flowcytometry have indicated its possible role in the induction of apoptosis as well as necrosis in a developing chick embryo. The present study provides insight into the effects of Risperidone that it may possess on gestating and lactating women. The study also explains the teratogenic potential of Risperidone on target and non-target organisms.

Keywords: Acetylcholinesterase, Alkaline phosphatase (ALP), Antipsychotics, Apoptosis, Chick Embryogenesis, Flowcytometry, Necrosis, Risperidone
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REFERENCES 

  1. Grant S, Fitton A. Risperidone. Drugs. 1994 Aug;48(2):253–73.
  2. Dos Santos-Júnior A, Henriques TB, de Mello MP, Della Torre OH, Paes LA, Ferreira-Neto AP, et al. Pharmacogenetics of Risperidone and Cardiovascular Risk in Children and Adolescents. International Journal of Endocrinology. 2016;2016:1–10.
  3. Madaan V. Clinical utility of the risperidone formulations in the management of schizophrenia. Neuropsychiatric Disease and Treatment. 2011 Oct;611.
  4. Ostinelli EG, Hussein M, Ahmed U, Rehman F, Miramontes K, Adams CE. Risperidone for psychosis-induced aggression or agitation (rapid tranquillisation). Cochrane Database of Systematic Reviews. 2018 Apr 10;2018(4).
  5. Schotte A, Janssen PFM, Gommeren W, Luyten WHML, Van Gompel P, Lesage AS, et al. Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology. 1996 Mar;124(1–2):57–73.
  6. Risperidone in the treatment of schizophrenia. American Journal of Psychiatry. 1994 Jun;151(6):825–35.
  7. Corena-McLeod M. Comparative Pharmacology of Risperidone and Paliperidone. Drugs in R&D. 2015 May 6;15(2):163–74.
  8. Mathews M, Adetunji B, Mahmud J, et al. Long-acting Risperidone in the treatment of schizophrenia: An evidence-based approach. Psychiatry 2005. 2005;2(2):36–9.
  9. Urban A, Cuba?a W. Therapeutic drug monitoring of atypical antipsychotics. Psychiatria Polska. 2017 Dec 30;51(6):1059–77.
  10. Huang M-L, Peer AV, Woestenborghs R, De Coster R, Heykants J, Jansen AAI, et al. Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects. Clinical Pharmacology and Therapeutics. 1993;54(3):257–68.
  11. Kumar S. Risperidone implicated in the onset of tarspane dyskinesia in a young woman. Postgraduate Medical Journal. 2000 May 1;76(895):316–7.
  12. Acri AA, Henretig FM. Effects of risperidone in overdose. The American Journal of Emergency Medicine. 1998 Sep;16(5):498–501.
  13. Yu W, Zhu M, Fang H, Zhou J, Ye L, Bian W, et al. Risperidone Reverses the Downregulation of BDNF in Hippocampal Neurons and MK801-Induced Cognitive Impairment in Rats. Frontiers in Behavioral Neuroscience. 2019 Jul 23;13.
  14. Chen M-L, Chen C-H. Microarray Analysis of Differentially Expressed Genes in Rat Frontal Cortex Under Chronic Risperidone Treatment. Neuropsychopharmacology. 2004 Nov 10;30(2):268–77.
  15. Lian J, De Santis M, He M, Deng C. Risperidone-induced weight gain and reduced locomotor activity in juvenile female rats: The role of histaminergic and NPY pathways. Pharmacological Research. 2015 May;95–96:20–6.
  16. Bilgiç S, Korkmaz DT, Azirak S, Güvenç AN, Kocaman N, Özer MK. Risperidone-Induced Renal Damage and Metabolic Side Effects: The Protective Effect of Resveratrol. Oxidative Medicine and Cellular Longevity. 2017;2017:1–10.
  17. Idalencio R, Kalichak F, Rosa JGS, Oliveira TA de, Koakoski G, Gusso D, et al. Waterborne Risperidone Decreases Stress Response in Zebrafish. PLOS ONE. 2015 Oct 16;10(10):e0140800.
  18. Singh KP, Singh MK, Gautam S. Effect ofin uteroexposure to the atypical anti-psychotic risperidone on histopathological features of the rat placenta. International Journal of Experimental Pathology. 2016 Apr;97(2):125–32.
  19. Iqbal MM, Aneja A, Rahman A, et al. The potential risks of commonly prescribed antipsychotics: during pregnancy and lactation. Psychiatry (Edgmont) 2005;2(8):36–44.
  20. Determination of the injection deposition site in chicken embryos by a novel in ovo injection system [Internet]. EggInject. [cited 2022 Feb 24]. Available from: https://www.egginject.com/Egginject-R-Systems/Technical-data/Determination-of-the-injection-deposition-site-in-chicken-embryos-by-a-novel-in-ovo-injection-system
  21. N. J. Kruger, “The Bradford Method for Protein Quantitation,” in Protein Protocols Handbook, The, New Jersey: Humana Press, pp. 15–22.
  22. “Dead Cell Apoptosis Kit with Annexin V Alexa FluorTM 488 & Propidium Iodide (PI).” https://www.thermofisher.com/order/catalog/product/V13241#/V13241 (accessed Oct. 17, 2021).
  23. Farrelly LA, Dicker P, Wynne K, English J, Cagney G, Föcking M, et al. Adolescent Risperidone treatment alters protein expression associated with protein trafficking and cellular metabolism in the adult rat prefrontal cortex. PROTEOMICS. 2014 May 16;14(12):1574–8.
  24. Erdogan A, Karaman MG, Ozdemir E, Yurteri N, Tufan AE, Kurcer MA. Six Months of Treatment with Risperidone May Be Associated with Nonsignificant Abnormalities of Liver Function Tests in Children and Adolescents: A Longitudinal, Observational Study from Turkey. Journal of Child and Adolescent Psychopharmacology. 2010 Oct;20(5):407–13.
  25. Erdogan A, Atasoy N, Akkurt H, Ozturk D, Karaahmet E, Yalug I, et al. Risperidone and liver function tests in children and adolescents: A short term prospective study. European Psychiatry. 2008 Apr;23:S158.
  26. Erdogan A, Yurteri N, Tufan AE, Ankarali H, Demirci E. Liver function tests and one year risperidone treatment in children and adolescents. European Psychiatry. 2011 Mar;26(S2):280–280.
  27. Zheng L, Yang L, Zhao X, Long N, Li P, Wang Y. Effect of risperidone on proliferation and apoptosis of MC3T3-E1 cells. Brazilian Journal of Medical and Biological Research. 2019;52(3).
  28. Shirazi-Southall S. Effects of Typical and Atypical Antipsychotics and Receptor Selective Compounds on Acetylcholine Efflux in the Hippocampus of the Rat. Neuropsychopharmacology. 2002 May;26(5):583–94.
  29. Obara K, Fujii A, Arie C, Harada N, Yamaki F, Matsuo K, et al. Inhibition of Recombinant Human Acetylcholinesterase Activity by Antipsychotics. Pharmacology. 2019;104(1–2):43–50.
  30. Apoptosis in Embryonic Development [Internet]. The Embryo Project Encyclopedia. [cited 2021 Oct 21]. Available from: https://embryo.asu.edu/pages/apoptosis-embryonic-development
  31. Kerr JFR, Wyllie AH, Currie AR. Apoptosis: A Basic Biological Phenomenon with Wideranging Implications in Tissue Kinetics. British Journal of Cancer. 1972 Aug;26(4):239–57.
  32. Li P, Wang Y, Liu X, Zhou Z, Wang J, Zhou H, et al. Atypical antipsychotics induce human osteoblasts apoptosis via Wnt/β-catenin signaling. BMC Pharmacology and Toxicology. 2019 Feb 12;20(1).
  33. Chen M-L, Tsai T-C, Wang L-K, Lin Y-Y, Tsai Y-M, Lee M-C, et al. Risperidone modulates the cytokine and chemokine release of dendritic cells and induces TNF-α-directed cell apoptosis in neutrophils. International Immunopharmacology. 2012 Jan;12(1):197–204.
  34. Atolagbe A, Nkemjika S, Popoola O, Oladeji O, Kogan I, Saeed H, et al. Risperidone-Induced Neutropenia in a Schizophrenic Patient: A Case Report and Literature Review. Case Reports in Psychiatry. 2021 Aug 17;2021:1–3.
  35. Singh KP, Singh MKr, Singh M. Effects of prenatal exposure to antipsychotic risperidone on developmental neurotoxicity, apoptotic neurodegeneration and neurobehavioral sequelae in rat offspring. International Journal of Developmental Neuroscience. 2016 May 13;52(1):13–23.
  36. da Cruz Jung IE, Machado AK, da Cruz IBM, Barbisan F, Azzolin VF, Duarte T, et al. Haloperidol and Risperidone at high concentrations activate an in vitro inflammatory response of RAW 264.7 macrophage cells by induction of apoptosis and modification of cytokine levels. Psychopharmacology. 2015 Sep 21;233(9):1715–23.

 

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