Histological study on the effect of sildenafil citrate (Viagra) on cerebral hemisphere of adult and aged male Albino rats
Main Article Content
Keywords
Sildenafil, brain, vacuolation, morphological, tissue
Abstract
ABSTRACT
Objectives: Sildenafil(Viagra) is a known as perfect medications for treatment in patients agony from impotence and pulmonary arterial raised blood pressure, it cause numerous effects on the nervous system by “nitrogen monoxide-cyclic guanosine monophosphate pathway”. The current paper is designed to examine the histostructural variations that may happen in the brain of both adult and elderly male rats after long course duration of Sildenafil(Viagra) drug treatment. Material and Methods: Forty white albino male rats were bought from the veterinary animal house of Mosul University. Twenty of them were between the ages of 3-4 months ( adult ) while the others were between the ages of 22-24 months ( senile ). Grouр I ( 10 adult rats ) and grouр II ( 10 old age rats ) were given distilled water and regarded as control grouрs . Grouр III ( 10 adult rats ) and grouр IV ( 10 old age rats ) were treated with Viagra in a dosage of ten mg. kg. day orally for thirty days. Results: The histological sections from the control adult group showed normal architecture of the frontal lobe cerebral cortex with distinct multipolar neurons , many glial cells and prominent blood vessel while the cerebral cortex of adult rats from treated group showed gliosis with satellitosis (glial cells around neurons)vasogenic and cytogenetic edema with perineuronal vacuolation and vascular congestion., there was mild shrinkage of some neurons Conclusion: Long-lasting administration with sildenafil citrate (Viagra) triggered a noxious outcome on the brain tissues with morphological changes in cells in both adults and the elderly male rats alike, although its effect was greater in the elderly, but this is not attributed to the drug as much as it contributes to the aging process.
References
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2. Vonk MC, Vandecasteele E, van Dijk AP. Pulmonary hypertension in connective tissue diseases, new evidence and challenges. Eur J Clin Invest. 2021 Apr;51(4):e13453. doi: 10.1111/eci.13453. Epub 2020 Dec 5. PMID: 33216992; PMCID: PMC7988614.
3. Anand Ganapathy A, Hari Priya VM, Kumaran A. Medicinal plants as a potential source of phosphodiesterase-5 inhibitors: A review. J Ethnopharmacol. 2021 Mar 1;267:113536. doi: 10.1016/j.jep.2020.113536. Epub 2020 Nov 1. PMID: 33137431.
4. De Souza ILL, Ferreira EDS, Vasconcelos LHC, Cavalcante FA, da Silva BA. Erectile dysfunction: Key role of cavernous smooth muscle cells. Front Pharmacol. 2022 Jul 5;13:895044. doi: 10.3389/fphar.2022.895044. PMID: 35865945; PMCID: PMC9294450.
5. Cooper TJ, Cleland JGF, Guazzi M, Pellicori P, Ben Gal T, Amir O. Effects of sildenafil on symptoms and exercise capacity for heart failure with reduced ejection fraction and pulmonary hypertension (the SilHF study): A randomized placebo-controlled multicentre trial. Eur J Heart Fail. 2022 Jul;24(7):1239–48. doi: 10.1002/ejhf.2527. Epub 2022 Jun 6. PMID: 35596935; PMCID: PMC9544113.
6. Abdelhady, S. Chronic administration of sildenafil citrate (Viagra) on the frontal cortex of adult male rats: An ultrastructural study. Forensic Med Anat Res. 2020;8:38–44. doi: 10.4236/fmar.2020.82004
7. Kilicarslan B, Kilicarslan E, Kizmazoglu C, Aydin HE, Kaya I, Danyeli AE, Karabekir HS. Evaluation of the efficacy of sildenafil citrate following severe head trauma in an experimental rat model. Turk Neurosurg. 2020;30(4):501–6. doi: 10.5137/1019-5149.JTN.23864-18.3. PMID: 30829389.
8. Chen Z, Huang Y, Cao D, Qiu S, Chen B, Li J, Bao Y, Wei Q, Han P, Liu L. Function of sildenafil on diseases other than urogenital system: An umbrella review. Front Pharmacol. 2023 Feb 6;14:1033492. doi: 10.3389/fphar.2023.1033492. PMID: 36814496; PMCID: PMC9939646.
9. Simonca L, Tulloh R. Sildenafil in infants and children. Children (Basel). 2017 Jul 24;4(7):60. doi: 10.3390/children4070060. PMID: 28737730; PMCID: PMC5532552.
10. Erickson MA, Banks WA. Neuroimmune axes of the blood-brain barriers and blood-brain interfaces: Bases for physiological regulation, disease states, and pharmacological interventions. Pharmacol Rev. 2018 Apr;70(2):278–314. doi: 10.1124/pr.117.014647. PMID: 29496890; PMCID: PMC5833009.
11. Miura, G., Baba, T., Hashimoto, R., Yamamoto S. Long-term follow-up of retinal morphology and physiology after 2000 mg sildenafil overdose as a means of attempted suicide: A case report. BMC Ophthalmol. 2022;22:216. doi: 10.1186/s12886-022-02426-7
12. Eltony SA, Abdelhameed SY. Effect of chronic administration of sildenafil citrate (Viagra) on the histology of the retina and optic nerve of adult male rat. Tissue Cell. 2017 Apr;49(2 Pt B):323–35. doi: 10.1016/j.tice.2017.01.006. Epub 2017 Feb 5. PMID: 28237322.
13. Pauls MM, Moynihan B, Barrick TR, Kruuse C, Madigan JB, Hainsworth AH, Isaacs JD. The effect of phosphodiesterase-5 inhibitors on cerebral blood flow in humans: A systematic review. J Cereb Blood Flow Metab. 2018 Feb;38(2):189–203. doi: 10.1177/0271678X17747177. Epub 2017 Dec 19. PMID: 29256324; PMCID: PMC5951021.
14. Socala K, Nieoczym D, Pieróg M, Szuster-Ciesielska A, Wyska E, Wlaź P. Antidepressant-like activity of sildenafil following acute and subchronic treatment in the forced swim test in mice: Effects of restraint stress and monoamine depletion. Metab Brain Dis. 2016 Oct;31(5):1095–104. doi: 10.1007/s11011-016-9852-8. Epub 2016 Jun 10. PMID: 27283174; PMCID: PMC5031750
15. Becker M, Pinhasov A, Ornoy A. Animal models of depression: What can they teach us about the human disease? Diagnostics (Basel). 2021 Jan 14;11(1):123. doi: 10.3390/diagnostics11010123. PMID: 33466814; PMCID: PMC7830961.
16. Michael L. Seibenhener 1 and Michael C. Wooten. Use of the open field maze to measure locomotor and anxiety-like behavior in mice. J Vis Exp. 2015;(96):52434. doi: 10.3791/52434.
17. Socala K, Nieoczym D, Wyska E, Wlaź P. Effect of sildenafil on the activity of some antidepressant drugs and electroconvulsive shock treatment in the forced swim test in mice. Naunyn Schmiedebergs Arch Pharmacol. 2017 Apr;390(4):339–49. doi: 10.1007/s00210-016-1334-3. Epub 2016 Dec 24. PMID: 28013355; PMCID: PMC5346141
18. Demirci D, Mutlu O, Akar F, Komsuoglu Celikyurt I, Ulak G. Sildenafil enhances locomotor activity in young mice and exerts anxiogenic effects in both young and aged mice. Med Sci Monit Basic Res. 2014 Feb 5;20:15-21. doi: 10.12659/MSMBR.890280. PMID: 24500039; PMCID: PMC3936918.
19. Tar M, Draganaski A, Friedman J, Davies K. 47 synergy between sildenafil and topically delivered nitric-oxide in eliciting an erectile response in a rat model of radical prostatectomy. J Sex Med. 2022 April;19(1):S24–5. doi: 10.1016/j.jsxm.2022.01.058
20. Dadomo H, Ponzi D, Nicolini Y, Vignali A, Ablondi F, Ceresini G, Maggio M, Palanza P, Govoni P, Volpi R, Parmigiani S. Behavioral and hormonal effects of prolonged Sildenafil treatment in a mouse model of chronic social stress. Behav Brain Res. 2020 Aug 17;392:112707. doi: 10.1016/j.bbr.2020.112707. Epub 2020 May 24. PMID: 32461132.
21. Irina L, Anna G, Dmitry A, Natalia N. Hyperactivity and abnormal exploratory activity developing in CD-1 male mice under chronic experience of aggression and social defeats. J Behav Brain Sci. October 2015;5(11):12 p. doi: 10.4236/jbbs.2015.511046
22. Zuloaga DG, Heck AL, De Guzman RM, Handa RJ. Roles for androgens in mediating the sex differences of neuroendocrine and behavioral stress responses. Biol Sex Differ. 2020 Jul 29;11(1):44. doi: 10.1186/s13293-020-00319-2. PMID: 32727567; PMCID: PMC7388454.
23. Shalbafan M, Orooji M, Kamalzadeh L. Psychosis beas a rare side effect of sildenafil: A case report. J Med Case Rep. 2022;16:120. doi: 10.1186/s13256-022-03334-6
24. Andersson KE. PDE5 inhibitors - Pharmacology and clinical applications 20 years after sildenafil discovery. Br J Pharmacol. 2018 Jul;175(13):2554–65. doi: 10.1111/bph.14205. Epub 2018 Apr 25. PMID: 29667180; PMCID: PMC6003652.
25. Chakroborty S, Kim J, Schneider C, West AR, Stutzmann GE. Nitric oxide signaling is recruited as a compensatory mechanism for sustaining synaptic plasticity in Alzheimer’s disease mice. J Neurosci. 2015;35(17):6893–902. doi: 10.1523/JNEUROSCI.4002-14.2015.
26. Kiaie N, Gorabi AM, Reiner Ž, Jamialahmadi T, Ruscica M, Sahebkar A. Effects of statins on renin-angiotensin system. J Cardiovasc Dev Dis. 2021 Jul 9;8(7):80. doi: 10.3390/jcdd8070080. PMID: 34357323; PMCID: PMC8305238.
27. Yuste JE, Tarragon E, Campuzano CM, Ros-Bernal F. Implications of glial nitric oxide in neurodegenerative diseases. Front Cell Neurosci. 2015 Aug 17;9:322. doi: 10.3389/fncel.2015.00322. PMID: 26347610; PMCID: PMC4538301.
28. Hafez MH, El-Kazaz SE. The impact of phosphodiesterase-5 inhibitor (sildenafil citrate) on some hippocampal neurotransmitters, oxidative stress status, minerals, and anxiety-like behavior in rats. J Adv Vet Anim Res. 2020 Apr 24;7(2):281–9. doi: 10.5455/javar.2020.g419. PMID: 32607359; PMCID: PMC7320816.
29. Ozdegirmenci O, Kucukozkant, Akdag E, Topal T, Haberal A, Kayir H. Effects of sildenafil citrate and tadalafil on ischemia/reperfusion injury in fetal rat brain. J Matern Fetal Neonatal Med. 2011;24(2):317–23. doi: 10.3109/14767058.2010.492061
30. Sikandaner HE, Park SY, Kim MJ, Park SN, Yang DW. Neuroprotective effects of sildenafil citrate against oxidative stress and memory dysfunction in mice exposed to noise stress. Behav Brain Res. 2017;319:37–47. doi: 10.1016/j.bbr.2016.10.046
31. Abdelhady SEE. Chronic administration of sildenafil citrate (Viagra) on the frontal cortex of adult male rats: An ultrastructural study. Forensic Med Anat Res. 2020;8(2):38–44. doi: 10.4236/fmar.2020.82004.
32. Ausó E, Gómez-Vicente V, Esquiva G. Visual side effects linked to sildenafil consumption: An update. Biomedicines. 2021 Mar 12;9(3):291. doi: 10.3390/biomedicines9030291. PMID: 33809319; PMCID: PMC7998971.
33. Hor M, Baradeiya AM, Qasim H, Nasr M, Mohammad A. Non-arteritic anterior ischemic optic neuropathy associated with the use of phosphodiesterase type 5 inhibitors: A literature review. Cureus. 2022 Aug 3;14(8):e27642. doi: 10.7759/cureus.27642. PMID: 36072219; PMCID: PMC9437418.
34. Murat G, Hakan C, Fatma G, Goncagul T, Unal B, Nur UB. Intracranial hemorrhage associated with sildenafil use: A very rare complication. Int J Neurol Neurother. 2020;7(1). doi: 10.23937/2378-3001/1410099.
35. Pomeranz, Howard & Smith, Kyle & Hart, William & Egan, Robert. (2002). Sildenafil-associated nonarteritic anterior ischemic optic neuropathy. Ophthalmology. 109. 584-7. doi: 10.1016/S0161-6420(01)00976-9.
36. Rickmann A., Macek M.A., Szurman P., Boden K. Acute monocular loss of vision: Differential diagnostic considerations apart from the internistic etiological clarification. Ophthalmologe. 2018;115:676–679. doi: 10.1007/s00347-017-0555-2.
37. Kim S, Choi S, Nah S, Han S. Multiple Cerebral infarctions and rhabdomyolysis after sildenafil citrate (Viagra®) intoxication: A case report. J Emerg Med. 2023 Mar 22:S0736-4679(23)00055-0. doi: 10.1016/j.jemermed.2023.02.007. Epub ahead of print. PMID: 37032204.
38. Ala M, Mohammad Jafari R, Dehpour AR. Sildenafil beyond erectile dysfunction and pulmonary arterial hypertension: Thinking about new indications. Fundam Clin Pharmacol. 2021 Apr;35(2):235–59. doi: 10.1111/fcp.12633. Epub 2020 Dec 2. PMID: 33226665.
39. Zinni M, Pansiot J, Léger PL, El Kamouh M, Baud O. Sildenafil-mediated neuroprotection from adult to neonatal brain injury: Evidence, mechanisms, and future translation. Cells. 2021 Oct 15;10(10):2766. doi: 10.3390/cells10102766. PMID: 34685745; PMCID: PMC8534574.
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Jan 14, 2024
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Histological study on the effect of sildenafil citrate (Viagra) on cerebral hemisphere of adult and aged male Albino rats. Iraqi Natl J Med [Internet]. 2024 Jan. 14 [cited 2025 Jan. 22];6(1):12-20. Available from: https://iqnjm.com/index.php/homepage/article/view/143
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