DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20204098

“We are antidepressant also”: aspirin and diclofenac sodium

Meera Sumanth, Prajwala R. Khapale

Abstract


Background: Many studies have indicated that inflammation and depression are associated with each other. Present study was taken up to prove antidepressant effect of aspirin and diclofenac sodium.

Methods: The present study was divided into 6 phases with 5 groups of animals N=10. In study 1, C57Bl mice were used and in remaining 4 studies swiss albino mice. Amitriptyline was standard drug used. For each study first group of animals was treated with a saline solution 1ml P.O., and second group of animals injected with 0.1 ml of 2% formalin. In group 3, 4, 5 animals depression was produced by stressors and treated with aspirin 14mg/kg P.O., diclofenac sod. 10 mg/kg P.O. and amitriptyline 10 mg/kg P.O., respectively. Antidepressant activity of aspirin and diclofenac sodium was determined by using forced swim test, tail suspension test, elevated plus maze test and light dark box test. Inflammatory mediators (IL-6, TNF-α) and central neurotransmitters (5-HT, NE, Ach) were estimated.

Results: In light dark box test, latency of first crossing, time spent in dark area were decreased and no. of crossing increased significantly in the aspirin, diclofenac sod. treated animals. In forced swim test, the immobility time was decreased. Swiss albino mice treated with aspirin, diclofenac sod. showed decreased concentration of IL-6 and TNF-α and increased concentration of serotonin, nor epinephrine and acetylcholine. In elevated plus maze test, no. of open arm, closed arm entries, time spent in open arm increased and time spent in closed arm decreased. In tail suspension test immobility time was decreased.

Conclusions: Aspirin and diclofenac sodium has antidepressant activity.


Keywords


Depression, Aspirin, Diclofenac sodium, Amitriptyline, Cytokines, Central neurotransmitters

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References


Schimelpfening N. The Chemistry of Depression. Verywell mind. 2020 Feb 4 [cited on 2020 Mar 4]. Available at: https://www.verywellmind.com. Accessed on 20 June 2020.

Cagliostro D. Depression: Persistent Sadness and Loss of Interest in Life. PSYCOM. [Cited on 2020 Mar 4]. Available at: https://www.psycom.com. Accessed on 23 June 2020.

Mohan H. Textbook of Pathology. 6th rev. ed., Jaypee Brothers Medical publishers Ltd New Delhi, 2010;130-73.

Libby P. Inflammatory mechanisms: the molecular basis of inflammation and disease. Nutr Rev. 2007;65(12):140-6.

Abdulkhaleq LA, Assi MA, Abdullah R, Zamri-Saad M, Taufiq-Yap YH, Hezmee MN. The crucial roles of inflammatory mediators in inflammation: A review. Vet world. 2018;11(5):627-35.

Barnes TC, Anderson ME, Moots RJ. The many faces of interleukin-6: the role of IL-6 in inflammation, vasculopathy, and fibrosis in systemic sclerosis. Int. J Rheumatol. 2011;1:1-5.

Scaccia A. Seotonin: What You Need to Know. Healthline. 18 May 2017. Available at: https://www.healthline.com. Accessed on 05 March 2020.

Dunn A J. Effects of cytokines and infections on brain neurochemistry. Clin Neurosci Res. 2006;6 (1-2):52-68.

Sedger LM, McDermott MF. TNF and TNF-receptors: From mediators of cell death and inflammation to therapeutic giants–past, present and future. Cytokine Growth FR. 2014;25(4):453-72.

Felger JC, Lotrich FE. Inflammatory Cytokines in Depression: Neurobiological Mechanism and Therapeutic Implications. Neuroscience. 2013;246: 199-229.

Morris T, Stables M, Hobbs A, Souza P de, Colville-Nash P, Warner T, et al. Effects of Low Dose Aspirin on Acute Inflammatory Responses in humans. J Immunol. 2019;183:2089-96.

Lahoti A, Kalra BS, TekurU. Evaluation of the analgesic and anti-Inflammatory activity of fixed dose combination: Non-Steroidal –Inflammatory drugs in experimental animals. Ind. J. Dental Res. 2014;25(5):551-4.

Gupta G, Jia Jia T, Yee Woon L, Kumar Chellappan D, Candasamy M, Dua K. Pharmacological evaluation of antidepressant-like effect of genistein and its combination with amitriptyline: an acute and chronic study. Adv Pharmacol Sci. 2015;2015:1-6.

Madhuri AS, Mohanvelu R, Ramabhimaiah S. Evaluation of anti-inflammatory activity of aqueous extract of Mangifera indica leaves in albino rats. Int. J Bas Clini Pharmacol. 2016;5(3):635-8.

Pablos RM, Sarmiento M, Espinosa AM. Creating a Rat Model of Chronic Variate Stress. J Bio-Protocol. 2014;4(23):1-5.

Bourin M, Hascoet M. The mouse light/dark box test. Europ. J Pharmacol. 2003;463(1):55-65.

Yadav R, Franko M, Huly A, Doron R. The Forced Swim Test as a Model of Depressive-like Behavior. Jove-J Vis Exp. 2015;97:1-7.

Arab HH, El-Sawalhi MM. Carvedilol alleviates adjuvant- induced Arthritis and Subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators. Toxicol Appl Pharm. 2013;268(1):241-8.

Verma AK, Dubey G.P, Tripathi AK. Quantitative Estimation Of 5-HT (Serotonin) In Stressed Rat’s Brain Regions Under Influence of T. Orientalis And H. Rhammoides Plant Extracts. J Biotechnol. 2014;3(4):72-6.

Chalmers JP, Baldessarini RJ, Wurtman RJ. Effects of L-Dopa on norepinephrine Metabolism in the brain. J Proc Nat Acad Sci. 1971;68(3):662-6.

Vogel GH. Drug Discovery and Evaluation-Pharmacological Assays. 2nd ed. Springer-Verlog Berlin Heidelberg: Germa. 2002;600-3.

University of Nairobi. Projects. Documents. Available at: www.uonbi.ac.ke>ibro>workshops 2005. Assessed on 23 March 2019.

Steru L, Chermat R, Thierry B, Simom P. The tail suspension test: A new method for screening antidepressant in mice. J Psycho Pharmacol. 1985;85(1):367-70

Al-Khotani A, Alstergren. Acetylcholine Supresses Release of Interleukin-6 in Fibroblast-Like Synoviocytes in Rheumatoid Arthritis. J Dent Oro Surg. 2017;2(1):1-3.

Leonard BE. The concept of depression as a dysfunction of the immune system. Curr Immunol Rev. 2010;6(3):205-12.

Kakeda S, Watanabe K, Katsuki A, Sugimoto K, Igata N, Ueda I et al. Relationship between interleukin (IL)-6 and brain morphology in drug-naïve, first-episode major depressive disorder using surface-based morphometry. Sci. Rep. 2018;8(1):1-9.

Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27(1):24-31.

Khan SA, Chatterjee SS, Kumar V. Potential Anti- Stress, Anxiolytic and Antidepressant Like Activities of Mono-Hydroxybenzoic Acids and Aspirin in Rodents: A Comparative study. Aus J Pharmacol Ther. 2015;3(3):1-10.

Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neuroscience. 2008;9(1):46-56.

Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol. Psychiatry. 2009;65(9):732-41.

Zunszain PA, Anacker C, Cattaneo A, Carvalho LA, Pariante CM. Glucocorticoids, cytokines and brain abnormalities in depression. Prog Neuro-Psychoph. 2011;35(3):722-29.

Kaster MP, Gadotti VM, Calixto JB, Santos AR, Rodrigues AL. Depressive-like behavior induced by tumor necrosis factor-α in mice. Neuropharmacology. 2012;62(2012):419-26.

Maes M, Vandoolaeghe E, Ranjan R, Bosmans E, Bergmans R, Desnyder R. Increased serum interleukin-1-receptor-antagonist concentrations in major depression. J Affect Disord. 1995;36(1):29-36.

Kabiersch A, del Rey A, Honegger CG, Besedovsky HO. Interleukin-1 induces changes in norepinephrine metabolism in the rat brain. Brain Behav Immun. 1988;2(1):267-74.

Brown JA, Sherrod SD, Goodwin CR, Brewer B, Yang L, Garbett KA, et al. Metabolic consequences of interleukin-6 challenge in developing neurons and astroglia. J. Neuroinflammation. 2014;11(1):1-12.

Szelenyi J, Vizi ES. The catecholamine–cytokine balance: interaction between the brain and the immune system. Ann N Y Acad Sci. 2007;1113(1): 311-24.