MODULATORY ANTI-DIARRHEAL EFFECTS OF ASCORBIC ACID IN SWISS ALBINO MICE
DOI:
https://doi.org/10.53808/KUS.2021.18.01.2103-LKeywords:
Ascorbic acid; Castor oil; Diarrhea; Mus musculus; PrazosinAbstract
Ascorbic acid (AA) has been reported for the management of diarrhea. The anti-diarrheal potential and modulatory activities of AA on some commonly used anti-diarrheal drugs were investigated. For this purpose, the activities of AA on castor oil-induced diarrhea in Swiss mice were examined. As standard anti-diarrheal agents, we used prazosin, propranolol, loperamide, and nifedipine with or without AA. The results revealed that AA at 25 mg/kg (i.p.) and all other standard drugs exhibited significant (p < 0.05) diarrheal attenuating activities in mice. However, the impact was more pronounced in the loperamide and propranolol groups. AA administrated with prazosin and propranolol had a higher rate of latent periods and a lower rate of diarrheic secretion during the study period (4 h) than that of the other single or mixed groups. Furthermore, a molecular docking study illustrated that AA displayed good binding affinities with (α1) (–5.2 Kcal/mol), α2b (–5.4 Kcal/mol), α2c (-5.6 Kcal/mol), β1(–5.3 Kcal/mol) and β2(–6.4 Kcal/mol) adrenoceptors. Of note, AA exerted a significant anti-diarrheal effect and it was seen to modulate the anti-diarrheal effects of α- and β-adrenergic receptor blocking agents in Swiss mice.
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Awouters, F., Niemegeers, C. J. E., Lenaerts, F. M., & Janssen, P. A. J. (1978). Delay of castor oil diarrhoea in rats: a new way to evaluate inhibitors of prostaglandin biosynthesis. Journal of Pharmacy and Pharmacology, 30(1), 41-45.
Bello, F. H., Maiha, B. B., & Anuka, J. A. (2016). The effect of methanol rhizome extract of Nymphaea lotus Linn.(Nymphaeaceae) in animal models of diarrhoea. Journal of ethnopharmacology, 190, 13-21.
Bricker, L., Such, F., Loehrke, M., & Kavanaugh, K. (2001). Intractable Diarrhea in Hyperthyroidism: Management with β-Adrenergic Blockade. Endocrine Practice, 7(1), 28-31.
Candelario-Jalil, E., Akundi, R. S., Bhatia, H. S., Lieb, K., Appel, K., Muñoz, E., ... & Fiebich, B. L. (2006). Ascorbic acid enhances the inhibitory effect of aspirin on neuronal cyclooxygenase-2-mediated prostaglandin E2 production. Journal of neuroimmunology, 174(1-2), 39-51.
Cavalcanti, P., MARTINS, M., Do Carmo, C., NUNES, P. H., ALVES, F. C., SILVA, J. D., & CAVALCANTI, S. M. (2019). Antidiarrheal effect of extract from the bark of Combretum leprosum in mice. Anais da Academia Brasileira de Ciências, 91.
Chang, E. B., Bergenstal, R. M., & Field, M. (1985). Diarrhea in streptozocin-treated rats. Loss of adrenergic regulation of intestinal fluid and electrolyte transport. The Journal of clinical investigation, 75(5), 1666-1670.
Child, R., Brown, S., Day, S., Donnelly, A., Roper, H., & Saxton, J. (1999). Changes in indices of antioxidant status, lipid peroxidation and inflammation in human skeletal muscle after eccentric muscle actions. Clinical science, 96(1), 105-115.
Connor, M., & Christie, M. J. (1999). Opioid receptor signalling mechanisms. Clinical and experimental pharmacology and physiology, 26(7), 493-499.
Diatchenko, L., Anderson, A. D., Slade, G. D., Fillingim, R. B., Shabalina, S. A., Higgins, T. J., ... & Maixner, W. (2006). Three major haplotypes of the β2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 141(5), 449-462.
Dietis, N., Rowbotham, D. J., & Lambert, D. G. (2011). Opioid receptor subtypes: fact or artifact?. British journal of anaesthesia, 107(1), 8-18.
DuPont, H. L. (2014). Acute infectious diarrhea in immunocompetent adults. New England Journal of Medicine, 370(16), 1532-1540.
Fiebich, B. L., Lieb, K., Kammerer, N., & Hüll, M. (2003). Synergistic inhibitory effect of ascorbic acid and acetylsalicylic acid on prostaglandin E2 release in primary rat microglia. Journal of neurochemistry, 86(1), 173-178.
Guandalini, S., & Vaziri, H. (Eds.). (2010). Diarrhea: diagnostic and therapeutic advances. Springer Science & Business Media.
Hemingway, D. C. (1991). Vitamin C in the prevention of neonatal calf diarrhea. The Canadian Veterinary Journal, 32(3), 184.
Ide, S., Sora, I., Ikeda, K., Minami, M., Uhl, G. R., & Ishihara, K. (2010). Reduced emotional and corticosterone responses to stress in μ-opioid receptor knockout mice. Neuropharmacology, 58(1), 241-247.
Ivanov, V., Ivanova, S., Kalinovsky, T., Niedzwiecki, A., & Rath, M. (2016). Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate. American journal of cardiovascular disease, 6(2), 26.
Knight, J., Madduma-Liyanage, K., Mobley, J. A., Assimos, D. G., & Holmes, R. P. (2016). Ascorbic acid intake and oxalate synthesis. Urolithiasis, 44(4), 289-297.
Koul, V., Kaur, A., & Singh, A. P. (2015). Investigation of the role of nitric oxide/soluble guanylyl cyclase pathway in ascorbic acid-mediated protection against acute kidney injury in rats. Molecular and cellular biochemistry, 406(1), 1-7.
Maltz, F., & Fidler, B. (2017). Eluxadoline (ViberzI): a mu-opioid receptor agonist for the treatment of irritable bowel syndrome with diarrhea. Pharmacy and Therapeutics, 42(7), 438.
Mascolo, N., Izzo, A. A., Barbato, F., & Capasso, F. (1993). Inhibitors of nitric oxide synthetase prevent castor‐oil‐induced diarrhoea in the rat. British journal of pharmacology, 108(4), 861-864.
Molinoff, P. B. (1984). α-and β-Adrenergic Receptor Subtypes. Drugs, 28(2), 1-15.
Palhares, D. B., Nascimento, D. R., Palhares, M. G., Balaniuc, S. L. B., de Rosso Giuliani, L., Xavier, P. C. N., ... & Martins, A. S. (2019). Propranolol and ascorbic acid in control of fibrodysplasia ossificans progressiva flare-ups due to accidental falls. Intractable & rare diseases research, 8(1), 24-28.
Philipp, M., & Hein, L. (2004). Adrenergic receptor knockout mice: distinct functions of 9 receptor subtypes. Pharmacology & therapeutics, 101(1), 65-74.
Pierce, K. L., Premont, R. T., & Lefkowitz, R. J. (2002). Seven-transmembrane receptors. Nature reviews Molecular cell biology, 3(9), 639-650.
Rawat, P., Singh, P. K., & Kumar, V. (2017). Evidence based traditional anti-diarrheal medicinal plants and their phytocompounds. Biomedicine & pharmacotherapy, 96, 1453-1464.
Riviere, P. J., Farmer, S. C., Burks, T. F., & Porreca, F. (1991). Prostaglandin E2-induced diarrhea in mice: importance of colonic secretion. Journal of Pharmacology and Experimental Therapeutics, 256(2), 547-552.
Robert, A., Nezamis, J. E., Lancaster, C., Hanchar, A. J., & Klepper, M. S. (1976). Enteropooling assay: a test for diarrhea produced by prostaglandins. Prostaglandins, 11(5), 809-828.
Rokosh, D. G., & Simpson, P. C. (2002). Knockout of the α1A/C-adrenergic receptor subtype: the α1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure. Proceedings of the National Academy of Sciences, 99(14), 9474-9479.
Seifi, H. A., Dezfuly, M. M., & Bolurchi, M. (1996). The effectiveness of ascorbic acid in the prevention of calf neonatal diarrhoea. Journal of Veterinary Medicine, Series B, 43(1‐10), 189-191.
Shah, A. J., Bhulani, N. N., Khan, S. H., ur Rehman, N., & Gilani, A. H. (2010). Calcium channel blocking activity of Mentha longifolia L. explains its medicinal use in diarrhoea and gut spasm. Phytotherapy Research, 24(9), 1392-1397.
Shook, J. E., Lemcke, P. K., Gehrig, C. A., Hruby, V. J., & Burks, T. F. (1989). Antidiarrheal properties of supraspinal mu and delta and peripheral mu, delta and kappa opioid receptors: inhibition of diarrhea without constipation. Journal of Pharmacology and Experimental Therapeutics, 249(1), 83-90.
Sorice, A., Guerriero, E., Capone, F., Colonna, G., Castello, G., & Costantini, S. (2014). Ascorbic acid: its role in immune system and chronic inflammation diseases. Mini reviews in medicinal chemistry, 14(5), 444-452.
Stein, C., Schäfer, M., & Machelska, H. (2003). Attacking pain at its source: new perspectives on opioids. Nature medicine, 9(8), 1003-1008.
Stickel, F., Meydani, M., Wu, D., Bronson, R., Martin, A., Smith, D., ... & Russell, R. M. (1997). Effect of vitamin E supplementation on prostaglandin concentrations in aspirin-induced acute gastric injury in aged rats. The American journal of clinical nutrition, 66(5), 1218-1223.
Toth, C. (2009). Poor tolerability of high dose ascorbic acid in a population of genetically confirmed adult Charcot‐Marie‐Tooth 1A patients. Acta Neurologica Scandinavica, 120(2), 134-138.
Uchida, M., Kato, Y., Matsueda, K., Shoda, R., Muraoka, A., & Yamato, S. (2000). Involvement of nitric oxide from nerves on diarrhea induced by castor oil in rats. The Japanese Journal of Pharmacology, 82(2), 168-170.
Umukoro, S., & Ashorobi, R. B. (2005). Effect of aframomum melegueta. seed extract on castor oil–induced diarrhea. Pharmaceutical biology, 43(4), 330-333.
Wolfman, C., de Stein, M. L., & De Robertis, E. (1983). Time course of changes in [3H] prazosin binding after catecholaminergic denervation by 6-hydroxydopamine in rat cerebral cortex: Inhibitory effects of ascorbic acid on the α1-adrenoceptor. Neuropharmacology, 22(9), 1061-1064.
Yamamoto, T., Kinoshita, M., Shinomiya, N., Hiroi, S., Sugasawa, H., Matsushita, Y., ... & Seki, S. (2010). Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation. Journal of radiation research, 51(2), 145-156.
Kase, Y., Saitoh, K., Makino, B., Hashimoto, K., Ishige, A., & Komatsu, Y. (1999). Relationship between the antidiarrhoeal effects of Hange‐Shashin‐To and its active components. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 13(6), 468-473.
Zimmermann, M., Kotloff, K., Nasrin, D., Roose, A., Levine, M. M., Rheingans, R., ... & Pecenka, C. (2019, April). Household Costs of Diarrhea by Etiology in 7 Countries, The Global Enterics Mulitcenter Study (GEMS). In Open forum infectious diseases (Vol. 6, No. 4, p. ofz150). US: Oxford University Press.
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