The ameliorative effect of fisetin, a bioflavonoid, on ethanol-induced and pylorus ligation-induced gastric ulcer in rats
DOI:
https://doi.org/10.22377/ijgp.v5i3.208Abstract
Fisetin, a tetrahydroxy flavone, exhibits many biological activities such as antioxidant, antibacterial and anti-inflammatory. The aim of present study was to unravel the therapeutic potential of fisetin at a dose of 10, 20, 30 mg/kg, per oral (p.o.), in ethanol-induced gastric ulcer and pylorus ligation-induced gastric ulcer. Omeprazole (20 mg/kg) was used as a standard drug. In ethanol-induced ulcer, after the pretreatment period of 1 hr gastric ulcer was induced with absolute ethanol at a dose of 8 ml/kg (p.o.), where as in pylorus ligation-induced gastric ulcer; after the pretreatment period of 1 hr ulcer was induced by tight ligation of pylorus portion of stomach. In the pylorus ligation-induced ulcer model there was a significant reduction in the ulcer area as well as the total volume, free acidity and total acidity and increase in the pH of gastric content along with the mucous production were found. There was a significant decrease in ulcer area and significant increase in the mucosal production in the ethanol-induced gastric ulcer model. Fisetin significantly lowered the level of lipid peroxidase, neutrophil infiltration along with gastric mucosal nitrite in both models of the gastric ulcer. The present findings elucidate the therapeutic value of fisetin in the prevention of experimental gastric ulcer byvirtue of its antioxidant mechanism.
Key words: Antioxidant, antiulcer, fisetin, lipid peroxidation, nitric oxide
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References
Piper DW, Stiel DD. Pathogenesis of chronic peptic ulcer, current
thinking and clinical implications. Med Prog 1986:2:7-10.
Ray A, Henke PG, Sullivan RM. Noradrenogenic mechanisms in
the central amygdalar nucleus and gastric stress ulcer formation
in rats. Neurosci Lett 1990;110:331-6.
Loguercio C, Taranto D, Beneduce F, del Vecchio Blanco C, de
Vincentilis A, Nardi G, et al. Glutathione prevents ethanol-induced
gastric mucosal damage and depletion of sulfhydryl compounds
in humans. Gut 1993;34:161-5.
Body SC, Sasame HA, Body MR. Gastric glutathione depletion
and acute ulcerogenesis by diethylmaleate given subcutaneously
to rats. Life Sci 1981;28:2987-92.
Das D, Banerjee RK. Effect of stress on antioxidant enzymes and
gastric ulceration. Mol Cell Biochem 1993;125:115-25.
Melchiorri D, Sewerynek E, Reiter RJ, Ortiz GG, Poeggeler B,
Nisticò G. Suppressive effect of melatonin administration
on ethanol-induced gastoduodenal injury in rats in vivo. Br J
Pharmacol 1997;121:264-70.
Szabo S. Mechanisms of mucosal injury in the stomach and
duodenum: Time sequence analysis of morphologic, functional,
biochemical and histochemical studies. Scand J Gastroenterol
Suppl 1987;127:21-8.
Singh S, Khajuria A, Taneja SC, Khajuria RK, Singh J, Johri RK, et al.
The gastric ulcer protective effect of boswellic acids, a leukotriene
inhibitor from Boswelliaserrata in rats. Phytomedicine 2008;15:408-15.
Hoogerwerf WA, Pasricha PJ. Agents used for control of gastric
acidity and treatment of peptic ulcers and gastroesophageal
reflux disease. In: Hardman JG, Limbird LE, Goodman A.G.,
eds. Goodman and Gilmans’s: The Pharmacological Basis of
Therapeutics. 10th ed. New York: McGraw-Hill; 2001:1005-1020.
Rastogi L, Patnaik GK, Dikshit M. Free radicals and antioxidant
status following pylorus ligation induced gastric mucosal injury
in rats. Pharmacol Res 1998;38:125-32.
Pihan G, Regillo C, Szabo S. Free radicals and lipid peroxidation
in ethanol or aspirin-induced gastric mucosal injury. Dig Dis Sci
;32:1395-401.
Mizui T, Sato H, Hirose F, Doteuch M. Effect of antiperoxidative
drugs on gastric damage induced by ethanol in rats. Life Sci
;41:755-63.
Barry H. Antioxidant effects a basis for drug selection. Drugs
;42:569.
Borelli F, Izzo AA. The plant kingdom as a source of anti-ulcer
remedies. Phytother Res2000;14:581-91.
Manonmani S, Viswanathan VP, Subramanian S, Govindasamy S.
Biochemical studies on the antiulcerogenic activity of cauvery
, an ayurvedic formulation in experimental ulcers. Indian J
Pharmacol 1995;27:101-5.
Akhtar MS, Akhtar AH, Khan MA. Antiulcerogenic effects of
Ocimumbasilicumextracts, volatile oils and flavonoid glycosides
in albino rats. Inter J Pharmacogn 1992;30:97-104.
Formica JV, Regelson W. Review of the biology of Quercetinand
related bioflavonoids. Food ChemToxicol 1995;33:1061-80.
ErdenInal M, Kahraman A. The protective effect of flavonolquercetin
against ultraviolet an induced oxidative stress in rats. Toxicology
;154:21-9.
Inal ME, Kahraman A, Koken T. Beneficial effects of quercetin
on oxidative stress induced by ultraviolet A. Clin Exp Dermatol
;26:536-9.
Robak J, Gryglewski RJ. Bioactivity of flavonoids. Pol J Pharmacol
;48:555-64.
Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant
activity relationships of flavonoids and phenolic acids. Free Radic
Bio Med 1996;20:933-56.
Constantin RP, Constantin J, Pagadigorria CL, Ishii- Iwamoto EL,
Bracht A, Ono MdeK, et al. The actions of fisetin on glucose
metabolism in the rat liver. Cell BiochemFunct 2010;28:149-58.
Suh Y, Afaq F, Khan N, Johnson JJ, Khusro FH, Mukhtar H.
Fisetin induces autophagic cell death through suppression of
mTOR signaling pathway in prostate cancer cells. Carcinogenesis
;31:1424-33.
Cheong H, Ryu SY, Oak MH, Cheon SH, Yoo GS, Kim KM. Studies
of structure activity relationship of flavonoids for the anti-allergic
actions. Arch Pharm Res 1998;21:478-80.
Divi RL, Doerge DR. Inhibition of thyroid peroxidase by dietary
flavonoids. Chem Res Toxicol1996;9:16-23.
Sriram G, Subramanian S. Fisetin, a bioflavonoid ameliorates
hyperglycemia in STZ-induced experimental diabetes in rats. Int
J Pharm Sci RevRes 2011;6:68-74.
Yao K, Zhang L, Zhang Y, Ye P, Zhu N. The flavonoid, fisetin,
inhibits UV radiation-induced oxidative stress and the activation
of NF-КB and MAPK signaling in human lens epithelial cells.Mol
Vis 2008;14:1865-71.
Ozbakis DG, Gursan N. Effects of Momordicacharantia L.
(Cucurbitaceae) on indomethacin-induced ulcer model in rats.
Turk J Gastroenterol 2005;16:85-8.
Shay H, Komarov SA, Fels SS, Meranze D, Gruenstein M, Siplet H.
A simple method for the uniform production of gastric ulceration
in rat. Gastroenterology 1945;5:43-61.
Tan PV, Nyasse B, Dimo T, Mezui C. Gastric cytoprotective
anti-ulcer effects of the leaf methanol extract of Ocimum suave
(Lamiaceae) in rats. J Ethnopharmacol2002;82:69-74.
Slater TF, Sawyer BC. The stimulatory effects of carbon
tetrachloride and other halogenoalkanesonperoxidative reactions
in rat liver fractions in vitro. General features of the systems used.
Biochem J 1971;123:805-14.
Krawisz JE, Sharon P, Stenson WF. Quantitative assay for acute
intestinal inflammation based on myeloperoxidase activity.
Assessment of inflammation in rat and hamster models.
Gasteroenterology 1984;87:1344-50.
Lowry OH, Rosenbrough NJ, Farr AL, Randell RJ. Protein
measurement with folin-phenol reagent. J BiolChem 1951;193:265-75.
Miranda K, Espy MG, Wink DA. A rapid and simple
spectrophotometric method for simultaneous detection of nitrate
and nitrite. Nitric Oxide 2001;5:62-71.
Vatier J, Vallot T. Antacids.In: Michel Schorderet et al. Pharmacology.
Fundamental concepts to therapeutic applications. Paris: Frisianrock,
Geneva: Slatkine, 1992: 565-570.
Sahin E, Gumuslu S. Immobilization stress in rat tissues: Alterations
in protein oxidation, lipid peroxidation and antioxidant defense
system. Comp Biochem Physiol C Toxicol Pharmacol 2007;
:342-7.
Bayir Y, Odabasoglu F, Cakir A, Aslan A, Suleyman H, Halici M,
et al. The inhibition of gastric mucosal lesion, oxidative stress and
neutrophil-infiltration in rats by the lichen constituent diffractaic
acid. Phytomedicine 2006;13:584-90.
Tariq M, Khan HA, Elfaki I, Arshaduddin M, Al Moutaery M,
Al Rayes H, et al. Gastric antisecretory and antiulcer effects of
simvastatin in rats. J Gastroenterol Hepatol 2007;22:2316-23.
Cheesman KH. Lipid peroxidation in biological systems. In:
Halliwell B, Aruoma OI,editors.DNA and Free Radicals. London:
Ellis Horwood; 1993. p.12-7.
Hiramoto K, Ohkawa T, Oikawa N, Kikugawa K. Is nitric oxide
(NO) an antioxidant or a prooxidant for lipid peroxidation? Chem
Pharm Bull (Tokyo) 2003;51:1046-50.
O’Donnell VB, Chumley PH, Hogg N, Bloodsworth A,
Darley-Usmar VM, Freeman BA. Nitric oxide inhibition of
lipid peroxidation: Kinetics of reaction with lipid peroxyl
radicals and comparison with alpha-tocopherol. Biochemistry
;36:15216-23.
O’Donnell VB, Eiserich JP, Bloodsworth A, Chumley PH, Kirk M,
Barnes S, et al. Nitration of unsaturated fatty acids by nitric oxidederived
reactive species. Methods Enzymol 1999;301:454-70.