THE ANTIDEPRESSANT DRUG DOXEPIN: A PROMISING ANTIOXIDANT
Objective: Oxidative stress contributes to the pathophysiology of exposure to environmental pollutants and to different free radical generating
biochemical reactions in a human system leading to various types of age-related ailments. An antioxidant is a substance capable of preventing
or slowing down oxidation of other molecules. Administration of different natural or synthetic antioxidants can ably lead to prevention and
attenuation of such stress-induced biochemical alterations. Best examples of natural antioxidants are plant-derived flavonoids. The present
study has been designated to determine antioxidant properties in antidepressant compound doxepin which is structurally similar to flavonoid
Methods: Antioxidant capacity in doxepin was determined with help of several standard conventional procedures such as phosphomolybdenum
assay, Ferric ion and cupric ion reducing power assays, ferrous ion chelating activity assay, hydrogen peroxide, and nitric oxide scavenging activity
Results: Doxepin showed a stable rise in its antioxidant activity in a dose-dependent manner as determined by ferric as well as cupric ion reducing
capacity and by phosphomolybdenum assay. An almost identical observation was noted while determining ferrous ion chelating activity. Furthermore,
doxepin showed a strong nitric oxide scavenging activity in all the concentrations used in the study while its hydrogen peroxide scavenging activity
was only observed at 500 Î¼g/ml of doxepin.
Conclusion: Thus, our study opens up a new vista in search for antioxidants not only from plant sources but also from clinically established
pharmaceutical compounds that are already in practical use among patients.
Keywords: Antioxidant, Antidepressant, Doxepin, Quercetin, Flavanol, Flavonoids.
Herman D. The free radical theory of aging. In: Pryor WA, editor. Free Radicals in Biology. New York: Academic Press; 1982. p. 255-75.
Ames BN. Pollution, pesticides and cancer. J AOAC Int 1992;75:1-5. Available from: http://www.heinonline.org/hol/landingpage?handle=hein.journals/environs16&div=16&id=&page.
Kehrer JP. Free radicals as mediators of tissue injury and disease. Crit Rev Toxicol 1993;23(1):21-48.
Stohs SJ, Bagchi D. Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 1995;18(2):321-36.
Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA, et al. Free radicals and grape seed proanthocyanidin extract: Importance in human health and disease prevention. Toxicology 2000;148(2-3):187-97.
Halliwell B. Biochemistry of oxidative stress. Biochem Soc Trans 2007;35:1147-50.
Palchoudhuri S, Roy D, Rahman KA, Roy DS, Dasgupta P, Das S, et al. Evaluation of anti-oxidant and free radical scavenging potential of Withania somnifera water extract. Int J Phytother 2016;6:1-8.
Halliwell B, Gutteridge JM, Cross CE. Free radicals, antioxidants, and human disease: Where are we now? J Lab Clin Med 1992;119(6):598-620.
Sies H, Stahl W, Sevanian A. Nutritional, dietary and postprandial oxidative stress. J Nutr 2005;135(5):969-72.
Darmanyan AP, Gregory DD, Guo Y, Jenks WS, Burel L, Eloy D, et al. Quenching of singlet oxygen by oxygen-and sulfur-centered radicals: Evidence for energy transfer to peroxyl radicals in solution. J Am Chem Soc 1998;120:396-403. Available from: http://www.pubs.acs.org/doi/abs/10.1021/ja9730831.
Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: Chemistry, metabolism and structure-activity relationships. J Nutr Biochem 2002;13(10):572-84.
Min DB, Boff JM. Chemistry and reaction of singlet oxygen in foods. Compr Rev Food Sci Food Saf 2002;1:58-72. Available from: http://www.onlinelibrary.wiley.com/doi/10.1111/j.1541-4337.2002.tb00007.x/full.
Pokorny J. Are natural antioxidants better â€“ And safer â€“ That synthetic antioxidants? Eur J Lipid Sci Technol 2007;109:629-42. Available from: http://www.onlinelibrary.wiley.com/doi/10.1002/ejlt.200700064/full.
Kancheva VD. Phenolic antioxidants â€“ Radical-scavenging and chain breaking activity: A comparative study. Eur J Lipid Sci Technol 2009;111:1072-89. Available from: http://www.onlinelibrary.wiley.com/doi/10.1002/ejlt.200900005/full.
Asian J Pharm Clin Res, Vol 10, Issue 3, 2017, 97-102
Palchoudhuri et al.
Hollman PC, van Trijp JM, Buysman MN, van der Gaag MS, Mengelers MJ, de Vries JH, et al. Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Lett 1997;418(1-2):152-6.
Pietta PG. Flavonoids as antioxidants. J Nat Prod 2000;63(1):1035-42.
Murota K, Terao J. Antioxidative flavonoid quercetin: Implication of its intestinal absorption and metabolism. Arch Biochem Biophys 2003;417(1):12-7.
Martins M, Dastidar SG, Fanning S, Kristiansen JE, Molnar J, PagÃ¨s JM, et al. Potential role of non-antibiotics (helper compounds) in the treatment of multi-drug resistant Gram negative infections: Mechanisms for their direct and indirect activities. Int J Antimicrob Agents 2008;31(3):198-208.
Dastidar SG, Kristiansen JE, Molnar J, Amaral L. Role of phenothiazines and structurally similar compounds of plant origin in the fight against infections by drug resistant bacteria. Antibiotics (Basel) 2013;2(1):58-72.
Kristiansen JE, Dastidar SG, Palchoudhuri S, Roy DS, Das S, Hendricks O, et al. Phenothiazines as a solution for multidrug resistant tuberculosis: From the origin to present. Int Microbiol 2015;18(1):1-12.
Karak P, Palchoudhuri S, Roy DS, Mookerjee M, Ghosh B, Das S, et al. Experimentally potent synergism resulting from combination of the antibiotic streptomycin with the non-antibiotic dicyclomine hydrochloride. Eur J Biomed Pharm Sci 2016;3:237-44.
Prieto P, Pineda M, Aguilar M. Spectrophotometric quantification of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application of vitamin E. Anal Biochem 1999;269(2):337-41.
Apak R, GÃ¼Ã§lÃ¼ K, OzyÃ¼rek M, Bektasoglu B, Bener M. Cupric ion reducing antioxidant capacity assay for antioxidants in human serum and for hydroxyl radical scavengers. Methods Mol Biol 2010;594:215-39.
Mukhopadhyay D, Rahman KA, Roy D, Dasgupta P. Evaluation of in vitro antioxidant activity and phytochemical constituents of kulekhara (hygrophiliaspinosa). Int J Pharmacogn Phytochem Res 2015;7:1-7. Available from: http://www.impactfactor.org/pdf/ijppr/7/ijppr,vol7,issue5,article17.pdf.
Miller HE, Rigelhof F, Marquart L, Prakash A, Kanter M. Antioxidant content of whole grain breakfast cereals, fruits and vegetables. J Am Coll Nutr 2000;19 3 Suppl:312S-9.
Mukhopadhyay D, Dasgupta P, Roy DS, Palchoudhuri S, Chatterjee I, Ali S, et al. A sensitive in vitro spectrophotometric hydrogen peroxide scavenging assay using 1,10-phenanthroline. Free Radic Antioxid 2016;6:123-31. Available from: http://www.antiox.org/sites/default/files/10.5530fra.2016.1.15_0.pdf.
Taylor BS, Kim YM, Wang Q, Shapiro RA, Billiar TR, Geller DA. Nitric oxide down-regulates hepatocyte-inducible nitric oxide synthase gene expression. Arch Surg 1997;132(11):1177-83.
Chaudhuri D, Ghate NB, Sarkar R, Mandal N. Phytochemical analysis and evaluation of antioxidant and free radical scavenging activity of Withania somnifera root. Asian J Pharm Clin Res 2012;5:193-9. Available from: http://www.ajpcr.com/Vol5Suppl4/1429.pdf.
Mandal S, Hazra B, Sarkar R, Biswas S, Mandal N. Assessment of the antioxidant and reactive oxygen species scavenging activity of methanolic extract of Caesalpinia crista Leaf. Evid Based Complement Alternat Med 2011;2011:173768.
Shahriar M, HossainMI, Sharmin FA, Akhter S, Haque MA, Bhuiyan MA. In vitro antioxidant and free radical scavenging activity of Withania somnifera root. IOSR J Pharm 2013;3(2):38-47.
Yen GC, Chen HY. Antioxidant activity of various tea extracts in relation to their antimutagenicity. J Agric Food Chem 1995;43:27-32. Available from: http://www.pubs.acs.org/doi/abs/10.1021/jf00049a007.
Decker EA, Welch B. Role of ferritin as a lipid oxidation catalyst in muscle food. J Agric Food Chem 1990;38:674-7. Available from: http://www.pubs.acs.org/doi/abs/10.1021/jf00093a019.
Lien AP, Hua H, Chuong PH. Free radicals, antioxidants in diseases and health. Int J Biomed Sci 2008;4(2):89-96. Available from: http://www.ijbs.org/user/contentfulltext.aspx?volumeno=4&startpage=89&.
Valko M, Leibfritz D, Moncola J, Cronin MT, Mazura M, Tesler J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39(1):44-84.
Jena S, Jena RC, Bhol R, Agarwal K, Sarangi A, Sahu PK, et al. A comparative study of the anti-oxidative and anti-diabetic potential of in vitro and in vivo root and leaf extracts of Withania somnifera on streptozotocin induced diabetic rats. Int J Pharm Pharm Sci 2016;8(10):85-91. Available from: http://www.innovareacademics.in/journals/index.php/ijpps/article/view/8103/7391.
Mahapatra SK, Mookerjee M, Roy DS, Karak P, Das S, Dastidar SG. Evaluation of antimicrobial potentiality of a flavonoid isolated from the leaf of the plant Colebrookea oppositifolia. Int J Biol Pharm Res 2013;4(4):225-30. Available from: http://www.ijbpr.com/cadmin/article/298_225-230.pdf.
Lavanya J, Periyar SS, Jeevitha PM, Jacintha P, Aradana M. Antioxidant and antimicrobial activity of selected medicinal plants against human oral pathogens. Int J Pharm Pharm Sci 2016;8(9):71-8. Available from: http://www.innovareacademics.in/journals/index.php/ijpps/article/view/11989/70090.
Bharti V, Vasudeva N, Kumar S. Antioxidant studies and antimicrobial effect of Origanum vulgare Linn in combination with standard antibiotics. Int Quat J Res Ayurveda 2014;35:71-8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213973.
Nabavi SM, Ebrahimzadeh MA, Nabavi SF, Hamidinia A, Bekhradnia AR. Determination of antioxidant activity, phenol and flavonoids content of Parrotia persica Mey. Pharm Online 2008;2:560-7.
Flora SJ. Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxid Med Cell Longev 2008;2(4):191-206. Available from: https://www.hindawi.com/journals/omcl/2009/873634/abs.
Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, et al. Vitamin C as an antioxidant: Evaluation of its role in disease prevention. J Am Coll Nutr 2003;22(1):18-35.
Traber MG, Atkinson J. Vitamin E, antioxidant and nothing more. Free Radic Biol Med 2007;43(1):4-15.
Green AR, Ashwood T. Free radical trapping as a therapeutic approach to neuroprotection in stroke: Experimental and clinical studies with NXY-059 and free radical scavengers. Curr Drug Targets CNS Neurol Disord 2005;4(2):109-18.
Zhang S, Wang L, Liu M, Wu B. Tirilazad for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2010;2:CD006778.
Roy DS, Mukhopadhyay D, Palchoudhuri S, Ghosh B, Das S, Dastidar SG. Distinct antioxidant activity of a common antidepressant drug imipramine. Free Radic Antioxid 2016;6(2):151-4. Available from: http://www.antiox.org/sites/default/files/10.5530fra.2016.2.4.pdf.
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