AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Brain Science Advances Article
PDF (44.7 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article | Open Access

Assessment the effect of Dapoxetine and/or Acetaminophen in rats; neurochemicals and oxidative stress biomarkers evaluation

Gehan S. Georgy1, Ibrahim M. Ibrahim Laila2, Mohamed E. Amer3, Ebtehal Mohammad F.1( )
Pharmacology Department, Egyptian Drug Authority (EDA), Giza P.O. 29, Egypt.
Molecular Drug Evaluation Department, Egyptian Drug Authority (EDA), Giza P.O. 29, Egypt
Histology Department, Faculty of Medicine, Al-Azhar University, Damietta P.O. 11651, Egypt
Show Author Information

Abstract

Dapoxetine is a newer anti-depressant that is used for severe forms of depression via selective serotonin reuptake inhibition conduit. We aimed to evaluate the effect of different doses of dapoxetine lonely or with acetaminophen (AMP). Seven groups of albino rats were used where dapoxetine was administered orally at the doses of 3, 5, and 8 mg/kg body weight for a period of 14 days in groups 2, 4, and 6, respectively. AMP (67.5 mg/kg body weight) was co-administered with dapoxetine (3, 5, and 8 mg/kg body weight) for 14 days in groups 3, 5 and 7, respectively. Dapoxetine in mid and high dose plus AMP increased body weight and hematological parameters. Ambulation and rearing were declined with mid and high doses of dapoxetine+AMP, contrary to grooming. Struggling was decreased with high doses of dapoxetine+AMP. High dose of dapoxetine+AMP induced lowering of serotonin and dopamine as well as increasing of cholinesterase. Brain derived neurotrophic factor was decreased in all groups. Oxidative stress biomarkers were augmented with high dose of dapoxetine+AMP. High doses of dapoxetine and/or AMP induced loss of the Purkinje cell layer at cerebellum. The high dose of dapoxetine+AMP denotes behavioral, histopathological and neurochemical alterations, even though no serotonin syndrome occurs.

Keywords

neurotransmittersacetaminophendapoxetineoxidative stress biomarkers

References

[1]
Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005, 352(11): 1112–1120. .
Crossref Google Scholar
[2]
Scotton WJ, Hill LJ, Williams AC, et al. Serotonin syndrome: pathophysiology, clinical features, management, and potential future directions. Int J Tryptophan Res 2019, 12: 1178646919873925. .
Crossref Google Scholar
[3]
Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J 2013, 13(4): 533–540.
Google Scholar
[4]
Beakley BD, Kaye AM, Kaye AD. Tramadol, pharmacology, side effects, and serotonin syndrome: a review. Pain Physician 2015, 18(4): 395–400.
Crossref Google Scholar
[5]
McCarty E, Dinsmore W. Dapoxetine: an evidence-based review of its effectiveness in treatment of premature ejaculation. Core Evid 2012, 7: 1–14. .
Crossref Google Scholar
[6]
McMahon CG. Dapoxetine: a new option in the medical management of premature ejaculation. Ther Adv Urol 2012, 4(5): 233–251. .
Crossref Google Scholar
[7]
Clément P, Bernabé J, Gengo P, et al. Supraspinal site of action for the inhibition of ejaculatory reflex by dapoxetine. Eur Urol 2007, 51(3): 825–832. .
Crossref Google Scholar
[8]
Kendirci M, Salem E, Hellstrom WJ. Dapoxetine, a novel selective serotonin transport inhibitor for the treatment of premature ejaculation. Ther Clin Risk Manag 2007, 3(2): 277–289. .
Crossref Google Scholar
[9]
Essawy, A. E., Alkhuriji, A. F., & Soffar, A. A. Paracetamol overdose induces physiological and pathological aberrations in rat brain. J App Pharm Sci 2017: 185-190. .
Crossref Google Scholar
[10]
Philippot G, Gordh T, Fredriksson A, et al. Adult neurobehavioral alterations in male and female mice following developmental exposure to paracetamol (acetaminophen): characterization of a critical period. J Appl Toxicol 2017, 37(10): 1174–1181. .
Crossref Google Scholar
[11]
Courad JP, Besse D, Delchambre C, et al. Acetaminophen distribution in the rat central nervous system. Life Sci 2001, 69(12): 1455–1464. .
Crossref Google Scholar
[12]
Blecharz-Klin K, Piechal A, Pyrzanowska J, et al. Paracetamol—the outcome on neurotransmission and spatial learning in rats. Behav Brain Res 2013, 253: 157–164. .
Crossref Google Scholar
[13]
Bauer AZ, Kriebel D, Herbert MR, et al. Prenatal paracetamol exposure and child neurodevelopment: a review. Horm Behav 2018, 101: 125–147. .
Crossref Google Scholar
[14]
Daya S, Anoopkumar-Dukie S. Acetaminophen inhibits liver trytophan-2, 3-dioxygenase activity with a concomitant rise in brain serotonin levels and a reduction in urinary 5-hydroxyindole acetic acid. Life Sci 2000, 67(3): 235–240. .
Crossref Google Scholar
[15]
Ratajczak PK, Kus K, Zaprutko T, et al. Antidepressant and anxiolytic efficacy of single, chronic and concomitant use of vortioxetine, dapoxetine and fluoxetine in prenatally stressed rats. Acta Neurobiol Exp 2019, 79(1): 13–24.
Crossref Google Scholar
[16]
Matić MM, Paunović MG, Milošević MD, et al. Hematoprotective effects and antioxidant properties of β-glucan and vitamin C against acetaminophen-induced toxicity: an experimental study in rats. Drug Chem Toxicol 2021, 44(3): 302–309. .
Crossref Google Scholar
[17]
Chen, J., Xu, Z. C., Xu, X. M., & Zhang, J. H. (ed.). Animal models of acute neurological injury. Springer, 2019.
Crossref
[18]
Sayed RH, Saad MA, El-Sahar AE. Dapoxetine attenuates testosterone-induced prostatic hyperplasia in rats by the regulation of inflammatory and apoptotic proteins. Toxicol Appl Pharmacol 2016, 311: 52–60. .
Crossref Google Scholar
[19]
ElMazoudy R, AbdelHameed N, ElMasry A. Paternal dapoxetine administration induced deterioration in reproductive performance, fetal outcome, sexual behavior and biochemistry of male rats. Int J Impot Res 2015, 27(6): 206–214. .
Crossref Google Scholar
[20]
Bancroft JD, Stevens A. The haematoxylin and eosin. Theory and practice of histological techniques. 4th ed. Ch 6. London, New York & Tokyo: Churchill Livingstone 1996. 4:99–112.
[21]
Goda AA, Naguib KM, Mohamed MM, et al. Astaxanthin and docosahexaenoic acid reverse the toxicity of the maxi-K (BK) channel antagonist mycotoxin penitrem A. Mar Drugs 2016, 14(11): 208. .
Crossref Google Scholar
[22]
Georgy GS, Nassar NN, Mansour HA, et al. Cerebrolysin ameloriates cognitive deficits in type III diabetic rats. PLoS One 2013, 8(6): e64847. .
Crossref Google Scholar
[23]
Kaid F, Alabsi AM, Alafifi N, et al. Histological, biochemical, and hematological effects of goniothalamin on selective internal organs of male sprague-dawley rats. J Toxicol 2019, 2019: 6493286. .
Crossref Google Scholar
[24]
Valvassori, S. S., Varela, R. B., & Quevedo, J. Animal models of mood disorders: focus on bipolar disorder and depression. In Animal Models for The Study of Human Disease, 2017, 991-1001.
Crossref Google Scholar
[25]
Detke MJ, Rickels M, Lucki I. Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology 1995, 121(1): 66–72. .
Crossref Google Scholar
[26]
Trinder P. Determination of blood glucose using an oxidase-peroxidase system with a non-carcinogenic chromogen. J Clin Pathol 1969, 22(2): 158–161. .
Crossref Google Scholar
[27]
Vrablic AS, Albright CD, Craciunescu CN, et al. Altered mitochondrial function and overgeneration of reactive oxygen species precede the induction of apoptosis by 1-O-octadecyl-2-methyl-rac-glycero-3-phosphocholine in p53-defective hepatocytes. FASEB J 2001, 15(10): 1739–1744. .
Crossref Google Scholar
[28]
Smerjac SM, Bizzozero OA. Cytoskeletal protein carbonylation and degradation in experimental autoimmune encephalomyelitis. J Neurochem 2008, 105(3): 763–772. .
Crossref Google Scholar
[29]
Wang J, Mazza G. Inhibitory effects of anthocyanins and other phenolic compounds on nitric oxide production in LPS/IFN-gamma-activated RAW 264.7 macrophages. J Agric Food Chem 2002, 50(4): 850–857. .
Crossref Google Scholar
[30]
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979, 95(2): 351–358. .
Crossref Google Scholar
[31]
Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974, 249(22): 7130–7139.
Crossref Google Scholar
[32]
Bradley PP, Christensen RD, Rothstein G. Cellular and extracellular myeloperoxidase in pyogenic inflammation. Blood 1982, 60(3): 618–622.
Crossref Google Scholar
[33]
Kontur P, Dawson R, Monjan A. Manipulation of mobile phase parameters for the HPLC separation of endogenous monoamines in rat brain tissue. J Neurosci Methods 1984, 11(1): 5–18. .
Crossref Google Scholar
[34]
Thoenen H. The changing scene of neurotrophic factors. Trends Neurosci 1991, 14(5): 165–170. .
Crossref Google Scholar
[35]
Viswanathan G, Dan VM, Radhakrishnan N, et al. Protection of mouse brain from paracetamol-induced stress by Centella asiatica methanol extract. J Ethnopharmacol 2019, 236: 474–483. .
Crossref Google Scholar
[36]
Lalert L, Ji-Au W, Srikam S, et al. Alterations in synaptic plasticity and oxidative stress following long-term paracetamol treatment in rat brain. Neurotox Res 2020, 37(2): 455–468. .
Crossref Google Scholar
[37]
Bkhairia I, Dhibi S, Nasri R, et al. Bioactive properties: enhancement of hepatoprotective, antioxidant and DNA damage protective effects of golden grey mullet protein hydrolysates against paracetamol toxicity. RSC Adv 2018, 8(41): 23230–23240. .
Crossref Google Scholar
[38]
Andersson KE, Mulhall JP, Wyllie MG. Pharmacokinetic and pharmacodynamic features of dapoxetine, a novel drug for ‘on-demand’ treatment of premature ejaculation. BJU Int 2006, 97(2): 311–315. .
Crossref Google Scholar
[39]
Lam DD, Garfield AS, Marston OJ, et al. Brain serotonin system in the coordination of food intake and body weight. Pharmacol Biochem Behav 2010, 97(1): 84–91. .
Crossref Google Scholar
[40]
Deshmukh R, Franco K. Managing weight gain as a side effect of antidepressant therapy. Cleve Clin J Med 2003, 70(7): 614, 616, 618, passim. .
Crossref Google Scholar
[41]
Dikstein S, Zor U, Ruah D, et al. Stimulatory effect of paracetamol on chicken growth. Poult Sci 1966, 45(4): 744–746. .
Crossref Google Scholar
[42]
Hegazy A, Abd Al Hameed E, El-Wafaey D, et al. Effect of Paracetamol administration on the Rat kidney structure: a Morphological Study. Zagazig Univ Med J 2019..
Crossref Google Scholar
[43]
Pineda E, Shin D, Sankar R, et al. Comorbidity between epilepsy and depression: experimental evidence for the involvement of serotonergic, glucocorticoid, and neuroinflammatory mechanisms. Epilepsia 2010, 51(Suppl 3): 110–114. .
Crossref Google Scholar
[44]
Srikiatkhachorn A, Tarasub N, Govitrapong P. Acetaminophen-induced antinociception via central 5-HT(2A) receptors. Neurochem Int 1999, 34(6): 491–498. .
Crossref Google Scholar
[45]
Sandrini M, Romualdi P, Vitale G, et al. The effect of a paracetamol and morphine combination on dynorphin A levels in the rat brain. Biochem Pharmacol 2001, 61(11): 1409–1416. .
Crossref Google Scholar
[46]
Sandrini M, Vitale G, Ruggieri V, et al. Effect of acute and repeated administration of paracetamol on opioidergic and serotonergic systems in rats. Inflamm Res 2007, 56(4): 139–142. .
Crossref Google Scholar
[47]
Ohashi N, Kohno T. Analgesic effect of acetaminophen: a review of known and novel mechanisms of action. Front Pharmacol 2020, 11: 580289. .
Crossref Google Scholar
[48]
Blecharz-Klin K, Joniec-Maciejak I, Piechal A, et al. Paracetamol impairs the profile of amino acids in the rat brain. Environ Toxicol Pharmacol 2014, 37(1): 95–102. .
Crossref Google Scholar
[49]
Blecharz-Klin K, Wawer A, Jawna-Zboińska K, et al. Early paracetamol exposure decreases brain-derived neurotrophic factor (BDNF) in striatum and affects social behaviour and exploration in rats. Pharmacol Biochem Behav 2018, 168: 25–32. .
Crossref Google Scholar
[50]
Rigobello C, Klein RM, Debiasi JD, et al. Perinatal exposure to paracetamol: dose and sex-dependent effects in behaviour and brain’s oxidative stress markers in progeny. Behav Brain Res 2021, 408: 113294. .
Crossref Google Scholar
[51]
Kandis S, Ates M, Kizildag S, et al. Acetaminophen (paracetamol) affects empathy-like behavior in rats: dose-response relationship. Pharmacol Biochem Behav 2018, 175: 146–151. .
Crossref Google Scholar
[52]
Kaizer RR, Corrêa MC, Spanevello RM, et al. Acetylcholinesterase activation and enhanced lipid peroxidation after long-term exposure to low levels of aluminum on different mouse brain regions. J Inorg Biochem 2005, 99(9): 1865–1870. .
Crossref Google Scholar
[53]
Am M, El-Hanbuli HM. Deterioration of brain cell function induced by dapoxetine administration in male rats. Int J Clin Pharmacol Toxicol 2018: 284–289. .
Crossref Google Scholar
[54]
Wankhar W, Srinivasan S, Sundareswaran L, et al. Role of Scoparia dulcis linn on noise-induced nitric oxide synthase (NOS) expression and neurotransmitter assessment on motor function in Wistar albino rats. Biomed Pharmacother 2017, 86: 475–481. .
Crossref Google Scholar
[55]
Ashafaq M, Hussain S, Alshahrani S, et al. Role of cinnamon oil against acetaminophen overdose induced neurological aberrations through brain stress and cytokine upregulation in rat brain. Drug Chem Toxicol 2022, 45(2): 633–640. .
Crossref Google Scholar
[56]
Jaeschke H, Bajt ML. Intracellular signaling mechanisms of acetaminophen-induced liver cell death. Toxicol Sci 2006, 89(1): 31–41. .
Crossref Google Scholar
[57]
Moyer AM, Fridley BL, Jenkins GD, et al. Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci 2011, 120(1): 33–41. .
Crossref Google Scholar
[58]
Mohammed ET, Safwat GM. Assessment of the ameliorative role of selenium nanoparticles on the oxidative stress of acetaminophen in some tissues of male albino rats. Beni Suef Univ J Basic Appl Sci 2013, 2(2): 80–85. .
Crossref Google Scholar
Brain Science Advances
Volume 10 Issue 1,
March 2024
Pages 56-70
DOI: 10.26599/BSA.2023.9050027
Cite this article:
Georgy GS, Ibrahim Laila IM, Amer ME, et al. Assessment the effect of Dapoxetine and/or Acetaminophen in rats; neurochemicals and oxidative stress biomarkers evaluation. Brain Science Advances, 2024, 10(1): 56-70. https://doi.org/10.26599/BSA.2023.9050027

195

Views

16

Downloads

0

Crossref

Altmetrics
Received: 07 July 2023
Revised: 19 October 2023
Accepted: 01 November 2023
Published: 05 March 2024
© The authors 2023.

This article is published with open access at journals.sagepub.com/home/BSA

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
Return