Gastroprotective effects of irsogladine maleate on ethanol/hydrochloric acid induced gastric ulcers in mice
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background/Aims: This study was conducted to investigate the inhibitory effect of irsogladine maleate (IM) on gastric ulcers induced by ethanol and hydrochloric acid (HCl). Methods: Mice were pretreated with IM for 1 hours before ulcer induction. Gastric ulcers were induced by oral administration of an ethanol/HCl mixture. To clarify the action mechanism of IM, the roles of 3ʹ5ʹ-cyclic adenosine monophosphate (cAMP), nitric oxide (NO), adenosine triphosphate-sensitive potassium (KATP) channels, prostaglandins and transient receptor potential cation channel subfamily V member 1 (TRPV1) were investigated, and lipid peroxidation in the stomach of IM-treated and -untreated animals was also measured. Results: IM significantly reduced the extent of ethanol/HCl mixture-induced gastric ulceration. It exhibited dose-related gastroprotection against the ethanol/ HCl-induced lesions, while pretreatment with glibenclamide but not N(ω)-nitro- L-arginine methyl ester, reversed this action. While pretreatment with the TRPV1 antagonist capsazepine failed to effectively block the gastroprotective effect of IM, the non-selective cyclooxygenase inhibitor indomethacin almost abolished it. IM also decreased the level of thiobarbituric acid reactive substances. Conclusions: We concluded that IM exhibited significant gastroprotective effects in an ethanol/HCl-induced ulcer model, which appear to be mediated, at least in part, by NO, cAMP, endogenous prostaglandins, KATP channel opening, activation of TRPV1 channels, and antioxidant properties.
Abstract
Background/Aims: This study was conducted to investigate the inhibitory effect of irsogladine maleate (IM) on gastric ulcers induced by ethanol and hydrochloric acid (HCl). Methods: Mice were pretreated with IM for 1 hours before ulcer induction. Gastric ulcers were induced by oral administration of an ethanol/HCl mixture. To clarify the action mechanism of IM, the roles of 3ʹ5ʹ-cyclic adenosine monophosphate (cAMP), nitric oxide (NO), adenosine triphosphate-sensitive potassium (KATP) channels, prostaglandins and transient receptor potential cation channel subfamily V member 1 (TRPV1) were investigated, and lipid peroxidation in the stomach of IM-treated and -untreated animals was also measured. Results: IM significantly reduced the extent of ethanol/HCl mixture-induced gastric ulceration. It exhibited dose-related gastroprotection against the ethanol/ HCl-induced lesions, while pretreatment with glibenclamide but not N(ω)-nitro- L-arginine methyl ester, reversed this action. While pretreatment with the TRPV1 antagonist capsazepine failed to effectively block the gastroprotective effect of IM, the non-selective cyclooxygenase inhibitor indomethacin almost abolished it. IM also decreased the level of thiobarbituric acid reactive substances. Conclusions: We concluded that IM exhibited significant gastroprotective effects in an ethanol/HCl-induced ulcer model, which appear to be mediated, at least in part, by NO, cAMP, endogenous prostaglandins, KATP channel opening, activation of TRPV1 channels, and antioxidant properties.
참고문헌 (25)
- Franke A, "Alcohol-related diseases of the esophagus and stomach", Dig Dis, 23, pp.204~213 (2005)
- Li CY, "Gastroprotective effect of cyanidin 3-glucoside on ethanol-induced gastric lesions in rats", Alcohol, 42, pp.683~687 (2008)
- Jang SH, "Beta-carotene inhibits Helicobacter pylori-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in human gastric epithelial AGS cells", J Physiol Pharmacol, 60, pp.131~137 (2009)
- Das D, "Effect of stress on the antioxidant enzymes and gastric ulceration", Mol Cell Biochem, 125, pp.115~125 (1993)
- Hamaishi K, "Anti-ulcer effect of tea catechin in rats", Biol Pharm Bull, 29, pp.2206~2213 (2006)
- Jaarin K, "Comparative effect of palm vitamin E and ranitidine on the healing of ethanol-induced gastric lesions in rats", Int J Exp Pathol, 80, pp.259~263 (1999)
- Takahashi N, "Importance of gap junction in gastric mucosal restitution from acid-induced injury", J Lab Clin Med, 136, pp.93~99 (2000)
- Kamei K, "Prophylactic effect of irsogladine maleate against indomethacin-induced small intestinal lesions in rats", Dig Dis Sci, 53, pp.2657~2666 (2008)
- Ueda F, "Effect of 2, 4-diamino-6-(2, 5-dichlorophenyl)-s-triazine maleate(MN-1695)on gastric mucosal blood flow in dogs", Arzneimittelforschung, 34, pp.485~491 (1984)
- Kyoi T, "Irsogladine prevents monochloramine-induced gastric mucosal lesions by improving the decrease in mucosal blood flow due to the disturbance of nitric oxide synthesis in rats", J Pharmacol Sci, 93, pp.314~320 (2003)
- Kyoi T, "Phosphodiesterase inhibition by a gastroprotective agent irsogladine : preferential blockade of cAMP hydrolysis", Life Sci, 75, pp.1833~1842 (2004)
- Yao J, "Irsogladine maleate potentiates the effects of nitric oxide on activation of cAMP signalling pathways and suppression of mesangial cell mitogenesis", Br J Pharmacol, 151, pp.457~466 (2007)
- Laine L, "Gastric mucosal defense and cytoprotection : bench to bedside", Gastroenterology, 135, pp.41~60 (2008)
- 심기남, "The efficacy and safety of irsogladine maleate in nonsteroidal anti-inflammatory drug or aspirin-induced peptic ulcer and gastritis", The Korean Journal of Internal Medicine, 34(5), pp.1008~1021 (2019), 대한내과학회[DOI]
- Ohkawa H, "Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction", Anal Biochem, 95, pp.351~358 (1979)
- Kurebayashi Y, "Cytoprotective action of cetraxate against HCl. ethanol-induced gastric lesion in rats", Jpn J Pharmacol, 46, pp.17~25 (1988)
- Asai M, "Protective effect of a molecular chaperone inducer, paeoniflorin, on the HCl-and ethanol-triggered gastric mucosal injury", Life Sci, 88, pp.350~357 (2011)
- Suo H, "Lactobacillus fermentum Suo attenuates HCl", Ethanol induced gastric injury in mice through its antioxidant effects, 2016, pp.8, 155~
- Ogawa K, "The protective effect and action mechanism of Vaccinium myrtillus L. on gastric ulcer in mice", Phytother Res, 25, pp.1160~1165 (2011)
- Wallace JL, "Nitric oxide, aspirin-triggered lipoxins and NO-aspirin in gastric protection", Inflamm Allergy Drug Targets, 5, pp.133~137 (2006)
- Santos Cerqueira G, "Effects of hecogenin and its possible mechanism of action on experimental models of gastric ulcer in mice", Eur J Pharmacol, 683, pp.260~269 (2012)
- Morais TC, "Protective effect of anacardic acids from cashew(Anacardium occidentale)on ethanol-induced gastric damage in mice", Chem Biol Interact, 183, pp.264~269 (2010)
- Fukushima K, "Gastro-protective action of lafutidine mediated by capsaicin-sensitive afferent neurons without interaction with TRPV1 and involvement of endogenous prostaglandins", World J Gastroenterol, 12, pp.3031~3037 (2006)
- Sepulveda B, "Gastroprotective activity of synthetic coumarins : role of endogenous prostaglandins, nitric oxide, non-protein sulfhydryls and vanilloid receptors", Bioorg Med Chem Lett, 26, pp.5732~5735 (2016)
- Perez S, "Redox signaling in the gastrointestinal tract", Free Radic Biol Med, 104, pp.75~103 (2017)