Mahardian Rahmadi, M. Shofwan Haris, Anggraini Kusuma, Annisa Septiana Ahmad, Arina Dery Puspitasari, Dinda Monika Nusantara Ratri, Chrismawan Ardianto
Mahardian Rahmadi1*, M. Shofwan Haris2, Anggraini Kusuma1, Annisa Septiana Ahmad1, Arina Dery Puspitasari1, Dinda Monika Nusantara Ratri1, Chrismawan Ardianto1
1Department of Pharmacy Practice, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia.
2Post-graduate student, Master of Pharmacy, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.
Volume - 16,
Issue - 2,
Year - 2023
One factor that could contribute to the developing of gastric ulcer is stress. Fluvoxamine, an SSRI antidepressant showed protective effects to ulcers when administered before stress induction. In opposite, administration of fluvoxamine after stress induction delayed the mucosa healing. This study aimed to investigate the effects of pre-treatment and post-treatment of buspirone a 5-HT1A receptor partial agonist in the inhibition of gastric mucosal protection and healing by fluvoxamine in animals with stress-induced gastric ulcers. This study used ddY, male mice, weighed 25-30grams, which divided into two groups, pre-treatment and post-treatment groups. Each group consisted of subgroups that were administered low doses of buspirone (0.1mg/Kg and 0.3mg/Kg) and high doses of buspirone (10.0mg/Kg and 30.0mg/Kg). In the pre-treatment group, buspirone was administered intraperitoneally at 60 minutes before and continued with oral fluvoxamine 100mg/Kg administration at 30 minutes before stress induction. In the post-treatment group, buspirone was administered intraperitoneally followed fluvoxamine orally 30 minutes after stress induction done. The stress model used is water immersion restrain stress for 6 hours. In the pre-treatment group, the combination of high dose, but not low dose buspirone significantly inhibit the protection effects of fluvoxamine on stress-induced gastric ulcers. In addition, in the post-treatment group, the combination of low dose buspirone and fluvoxamine strengthen the delays of mucosal healing by fluvoxamine in mice with stress-induced gastric ulcers. Fluvoxamine protects and heals gastric mucosa from stress-induced gastric ulcer through the activation of 5HT1A receptor.
Cite this article:
Mahardian Rahmadi, M. Shofwan Haris, Anggraini Kusuma, Annisa Septiana Ahmad, Arina Dery Puspitasari, Dinda Monika Nusantara Ratri, Chrismawan Ardianto. Role of 5-HT1A Receptor on Fluvoxamine induced Gastrointestinal Mucosa Protection and Healing in Animal with Stress-Induced Gastric Ulcer. Research Journal of Pharmacy and Technology 2023; 16(2):709-4. doi: 10.52711/0974-360X.2023.00121
Mahardian Rahmadi, M. Shofwan Haris, Anggraini Kusuma, Annisa Septiana Ahmad, Arina Dery Puspitasari, Dinda Monika Nusantara Ratri, Chrismawan Ardianto. Role of 5-HT1A Receptor on Fluvoxamine induced Gastrointestinal Mucosa Protection and Healing in Animal with Stress-Induced Gastric Ulcer. Research Journal of Pharmacy and Technology 2023; 16(2):709-4. doi: 10.52711/0974-360X.2023.00121 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2023-16-2-40
1 Silva M.G. de Sousa F.F. Gastric ulcer etiology. Peptic Ulcer Disease. InTech, Croatia. 2011; 3-28.
2 Vyawahare NS. Kagathara VG. Katedeshmukh RG. Sharma PK. Mohod SM. Evaluation of Antiulcer Activity of Piper betel Leaves Extract in Rats. Research J. Pharmacology and Pharmacodynamics. 2010; 2(4): 278-282.
3 Muthusamy P. Suresh AJ. Balamurugan dG. Antiulcer Activity of Azima Tetracantha: A Biochemical Study. Research J. Pharm. and Tech. 2009; 2(2): 344-348.
4 Bardou M. Quenot JP. Barkun A. Stress-related mucosal disease in the critically ill patient. Nat. Rev. Gastroenterol. Hepatol. 2015; 12(2): 98–107. doi.org/10.1038/nrgastro.2014.235.
5 Rahmadi M. Nurhan AD. Pratiwi ED. Prameswari DA. Panggono SM. Nisak K. Khotib J. The effect of various high-fat diet on liver histology in the development of NAFLD models in mice. J. Basic Clin. Physiol. Pharmacol. 2021; 32(4), 547-553. doi.org/10.1515/jbcpp-2020-0426
6 Elsaed WM. Alahmadi A. M. Al-Ahmadi BT. Taha JA. Tarabishi RM. Gastroprotective and antioxidant effects of fluvoxamine on stress-induced peptic ulcer in rats. J. Taibah Univ. Med. Sci. 2018; 13(5): 422–431. doi.org/10.1016/J.JTUMED.2018.04.010.
7 Johnson DB. Gorle A. Paleti SK., Javvadi A. Anti-Gastric Ulcer Studies on Certain Siddha Drugs. Research J. Pharmacology and Pharmacodynamics. 2011; 3(3): 123-128.
8 Bhagat V. Symbak NB. Husain R. Mat KC. The role of selective serotonin reuptake inhibitors and cognitive behavioral therapy in preventing relapse of Major Depressive Disorder. Research J. Pharm. and Tech 2019; 12(8): 3818-3824.
9 Rahmadi M. Su’aida N. Yustisari P. Dewaandika WA. Hanaratri EO. Andarsari MR. Aryani T. Gastroprotective effect of fluvoxamine and ondansetron on stress-induced gastric ulcers in mice. J. Basic Clin. Physiol. Pharmacol. 2021; 32(4): 485-490. https://doi.org/10.1515/jbcpp-2020-0424.
10 Muthukumaran P. Pattabiraman K. Anti-Ulcer Effects of Ipomoea aquatica forsk Leaves against Gastric Ulcers in Rats. Research J. Pharmacognosy and Phytochemistry 2010; 2(6): 468-471
11 De Ponti F. Pharmacology of serotonin: what a clinician should know. Gut. 2004; 53(10): 1520–1535. doi.org/10.1136/GUT.2003.035568.
12 Browning KN. Role of central vagal 5-HT3 receptors in gastrointestinal physiology and pathophysiology. Frontiers in Neuroscience. 2015; 9:413. doi.org/10.3389/FNINS.2015.00413.
13 Boeckxstaens GE. Tytgat GN. Wajs E. Van Nueten L. De Ridder F. Meulemans A. Tack J. The influence of the novel 5‐HT1A agonist R137696 on the proximal stomach function in healthy volunteers. Neurogastroenterology & Motility, 2006; 18(10): 919-926. doi.org/10.1111/J.1365-2982.2006.00812.X.
14 Manimekalai P. Maheshwari P. Velmurugan R. Gurumoorthy M. Kumar S.H. Vijayakumar G. Gastro Protective effect of Standardized Ethanolic leaf extract of Indigofera tinctoriao on experimental Gastric Ulcers in Rats. Research J. Pharm. and Tech. 2018; 11(2):527-531.
15 Sullivan RM. Henke PG. Ray A. The effects of buspirone, a selective anxiolytic, on stress ulcer formation in rats. Pharmacology Biochemistry and Behavior. 1988; 31(2): 317–319. doi.org/10.1016/0091-3057(88)90352-8.
16 Mathure D. Madan JR. Ranpise HA. Awasthi R. Dua K., Gujar KN. Formulation and Evaluation of Nano structured lipid carriers for intranasal delivery of Buspirone hydrochloride. Research J. Pharm. and Tech. 2021; 14(2):585-593.
17 Guo S. Gao Q. Jiao Q. Hao W. Gao X. Cao JM. (2012). Gastric mucosal damage in water immersion stress: mechanism and prevention with GHRP-6. World journal of gastroenterology. 2012; 18(24):3145. doi.org/10.3748/WJG.V18.I24.3145.
18 García-Bueno B. Madrigal JL. Pérez-Nievas BG. Leza JC. Stress mediators regulate brain prostaglandin synthesis and peroxisome proliferator-activated receptor-γ activation after stress in rats. Endocrinology. 2008; 149(4):1969-1978. doi.org/10.1210/EN.2007-0482.
19 Holmes A. Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease. Neuroscience & Biobehavioral Reviews. 2008; 32(7):1293-1314. doi.org/10.1016/J.NEUBIOREV.2008.03.006.
20 Vidya B. Bin SN. Rohayah H. Che MK. The role of selective serotonin reuptake inhibitors and cognitive behavioral therapy in preventing relapse of Major Depressive Disorder. Research Journal of Pharmacy and Technology. 2019; 12(8):3818-24. doi.org/10.5958/0974-360X.2019.00654.1
21 Hannon J. Hoyer D. Molecular biology of 5-HT receptors. Behavioural brain research. 2008; 195(1):198-213. doi.org/10.1016/J.BBR.2008.03.020.
22 Gershon MD. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Current opinion in endocrinology, diabetes, and obesity. 2013; 20(1):14. doi.org/10.1097/MED.0B013E32835BC703.
23 Shirode DS. Powar P. Jain BB. Agarwa A. Antiulcer effect of Blumealacera against Gastric ulcers in rats. Research Journal of Pharmacy and Technology. 2020;13(7): 3340-2.
24 Andrade C. Sandarsh S. Chethan KB. Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. The Journal of clinical psychiatry. 2010; 71(12):0-0. doi.org/10.4088/JCP.09R05786BLU.
25 Dursun H. Bilici M. Albayrak F. Ozturk C. Saglam MB. Alp HH. Suleyman H. Antiulcer activity of fluvoxamine in rats and its effect on oxidant and antioxidant parameters in stomach tissue. BMC gastroenterology. 2009; 9(1):1-10. doi.org/10.1186/1471-230X-9-36.
26 Khotib J. Rahmadi M. Ardianto C. Nisak K. Oktavia R. Ratnasari A. Dinintia Y. Shinta DW. Suharjono Aryani T. Selective serotonin reuptake inhibitor fluvoxamine ameliorates stress-and NSAID-induced peptic ulcer possibly by involving Hsp70. J. Basic Clin. Physiol. Pharmacol. 2019; 30(2):195-203. doi.org/10.1515/JBCPP-2018-0067.
27 Konturek PC. Brzozowski T. Duda A. Kwiecien S. Löber S. Dembinski A. Hahn EG. Konturek, SJ. Epidermal growth factor and prostaglandin E2 accelerate mucosal recovery from stress-induced gastric lesions via inhibition of apoptosis. Journal of Physiology-Paris. 2001; 95(1-6):361-367. doi.org/10.1016/S0928-4257(01)00049-3.
28 Yuan Y. Tsoi K. Hunt RH. Selective serotonin reuptake inhibitors and risk of upper GI bleeding: confusion or confounding?. The American journal of medicine. 2006; 119(9):719-727. doi.org/10.1016/J.AMJMED.2005.11.006.
29 Yuet WC. Derasari D. Sivoravong J. Mason D. Jann M. Selective serotonin reuptake inhibitor use and risk of gastrointestinal and intracranial bleeding. Journal of Osteopathic Medicine. 2019; 119(2):102-111. doi.org/10.7556/JAOA.2019.016.
30 Tack J. Piessevaux H. Coulie B. Fischler B. De Gucht V. Janssens J. A placebo-controlled trial of buspirone, a fundus-relaxing drug, in functional dyspepsia: Effect on symptoms and gastric sensory and motor function. Gastroenterology. 1999; 116(4):A325-A325.
31 Farré AJ. Colombo M. Alvarez I. Glavin GB. Some novel 5-hydroxytryptamine1A (5-HT1A) receptor agonists reduce gastric acid and pepsin secretion, reduce experimental gastric mucosal injury and enhance gastric mucus in rats. Journal of Pharmacology and Experimental Therapeutics. 1995; 272(2):832-837.