Betaine improves gastroprotective effects of ranitidine and omeprazole against Indomethacin-induced gastric ulcer in rats

Vahid Jaldani, Omid Dezfoulian, Gholamreza Shahsavari*

Abstract


Background and Aim: Antioxidant capacity of betaine has been indicated in our recent studies. Thus, we examined oral betaine as an antioxidant agent in combination with antisecretory drugs to prevent indomethacin-induced gastric damages in rats.

Materials and Methods: Fifty-six adult male Sprague–Dawley rats were divided into two controls (negative and normal) and five experimental groups as follows: betaine-indomethacin (Bet.-Ind.), ascorbic acid-indomethacin (Asc.-Ind.), omeprazole-indomethacin (Ome.-Ind.), betaine-omeprazole plus indomethacin (Bet.-Ome.-Ind.) and betaine-ranitidine plus indomethacin (Bet.-Ran.-Ind.).

Results: The betaine pretreated groups received betaine at a dosage of 1.5% (w/w) in their diet, whereas 50 mg/kg of ascorbic acid was administered orally to the Asc.-Ind., group for 15 consecutive days. After a 24 hour fast, all the groups received 48 mg/kg of indomethacin once except for normal control group. The omeprazole and ranitidine groups also received one dose of omeprazole (10 mg/kg) and ranitidine (50 mg/kg), 120 minutes before receiving indomethacin. Histopathological findings indicated the gastroprotective effects of betaine and ranitidine in pretreated rats. Pretreatment by betaine and ranitidine increased significantly the ulcer index inhibition (%), in comparison with ascorbic acid and omeprazole (alone) treatment. Glutathione peroxidase (GPx) activity was significantly higher in the Bet.-Ran.-Ind., group as compared to the Asc.-Ind., and Ome.-Ind., treated rats. GPx activity also increased significantly in Bet.-Ind., treated rats as compared to the Asc.-Ind. group. Catalase (CAT) activity was remarkably higher in the Bet.-Ran.-Ind., treated rats than the Asc.-Ind., and Ome.-Ind., groups. TBARS concentration as a lipid peroxidation marker increased significantly in Ome.-Ind., group as compared to the Bet.-Ind., and Bet.-Ran.-Ind., treated rats.

Conclusion: Thus, it seems that betaine as an antioxidant agent, is able to improve the effects of ranitidine and omeprazole against indomethacin-mediated gastric damages in rats. It may also be promising in the prevention of NSAIDs side effects.


Keywords


Betaine, Indomethacin, Omeprazole, Ranitidine, Ulcer, Rat

Full Text:

PDF

References


Alirezaei M, Dezfoulian O, Neamati S, Rashidipour M, Tanideh N, Kheradmand A. Oleuropein prevents ethanol-induced gastric ulcers via elevation of antioxidant enzyme activities in rats. J Physiol Biochem. 2012;68:583-92.

Ganesan B, Yathavamoorthy R, Farvin KSH, Anandan R. Supplementation of betaine attenuates HCI-ethanol induced gastric ulcer in rats. Int J Biol Chem. 2010;4:79-89.

Bandyopadhyay SK, Pakrashi SC, Pakrashi A. The role of antioxidant activity of Phyllanthus emblica fruits on prevention from indomethacin induced gastric ulcer. J Ethnopharmacol. 2000;70:171-6.

Lee JH, Lee DU, Jeong CS. Gardenia jasminoides Ellis ethanol extract and its constituents reduce the risks of gastritis and reverse gastric lesions in rats. Food Chem Toxicol. 2009;47:1127-31.

Leirisalo-Repo M, Paimela L, Koskimies S, Repo H. Functions of polymorphonuclear leukocytes in early rheumatoid arthritis. Inflammation. 1993;17:427-42.

Alirezaei M, Jelodar G, Niknam P, Ghayemi Z, Nazifi S. Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum. J Physiol Biochem. 2011;67:605-12.

Das D, Banerjee RK. Effect of stress on the antioxidant enzymes and gastric ulceration. Mol Cell Biochem. 1993;125:115-25.

De Barros MP, Sousa JPB, Bastos JK, De Andrade SF. Effect of Brazilian green propolis on experimental gastric ulcers in rats. J Ethnopharmacol. 2007;110:567-71.

Hetil O. Mechanism of free radicals in gastrointestinal and liver diseases. J Clin Biol. 1993;134:675-83.

Isenberg JI, McQuaid KR, Laine L, Walsh JH. Acid-peptic disorders. Textbook of gastroenterology. 1995;1:1.347-1.430.

Itoh M, Guth PH. Role of oxygen-derived free radicals in hemorrhagic shock-induced gastric lesions in the rat. Gastroenterology. 1985;88:1165-7.

Biswas K, Bandyopadhyay U, Chattopadhyay I, Varadaraj A, Ali E, Banerjee RK. A novel antioxidant and antiapoptotic role of omeprazole to block gastric ulcer through scavenging of hydroxyl radical. J Biol Chem. 2003;278:10993-1001.

Das D, Bandyopadhyay D, Bhattacharjee M, Banerjee RK. Hydroxyl radical is the major causative factor in stress-induced gastric ulceration. Free Radical Biol Med. 1997;23:8-18.

Elliott SN, Wallace JL. Neutrophil-mediated gastrointestinal injury. Can J Gastroenterol. 1998;12:559-68.

Miura T, Muraoka S, Fujimoto Y. Lipid peroxidation induced by indomethacin with horseradish peroxidase and hydrogen peroxide: involvement of indomethacin radicals. Biochem Pharmacol. 2002;63:2069-74.

Odabasoglu F, Cakir A, Suleyman H, Aslan A, Bayir Y, Halici M, Kazaz C. Gastroprotective and antioxidant effects of usnic acid on indomethacin-induced gastric ulcer in rats. J Ethnopharmacol. 2006;103:59-65.

Smith SM, Kvietys PR. Gastric ulcers: role of oxygen radicals. Crit. Care Med. 1988;16:892-8.

Wallace JL. Mechanisms of protection and healing: current knowledge and future research. American J Med. 2001;110:19-23.

De Souza GEP, Cardoso RA, Melo MCC, Fabricio ASC, Silva VMS, Lora M, De Brum-Fernandes AJ, Rae GA, Ferreira SH, Zampronio AR. A comparative study of the antipyretic effects of indomethacin and dipyrone in rats. Inflammation Res. 2002;51:24-32.

Ganesan B, Anandan R, Lakshmanan PT. Studies on the protective effects of betaine against oxidative damage during experimentally induced restraint stress in Wistar albino rats. Cell Stress Chaperones. 2011;16:641-52.

Langtry HD, Wilde MI. Omeprazole. Drugs 1998;56:447-86.

Garnett WR. Lansoprazole: a proton pump inhibitor. Ann Pharmacother. 1996;30:1425-36.

Zimmermann AE, Katona BG. Lansoprazole: a comprehensive review. Pharmacotherapy: J Human Pharmacol Drug Therapy. 1997;17:308-26.

Wolfe MM, Sachs G. Acid suppression: optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome. Gastroenterology. 2000;118:S9-S31.

Fellenius E, Berglindh T, Sachs G, Olbe L, Elander B, Sjostrand S-E, Wallmark B. Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+) ATPase. Nature. 1981;290:159-61.

Sachs G. Proton pump inhibitors and acid-related diseases. Pharmacotherapy: J Human Pharmacol Drug Therapy. 1997;17:22-37.

Wallmark B, Larsson H, Humble L. The relationship between gastric acid secretion and gastric H+, K+-ATPase activity. J Biol Chem. 1985;260:13681-4.

Ahn M, Kang Y, Moon J, Kim S, Moon C, Shin T. Oral administration of betaine ameliorates ethanol-induced gastric injury in rats through its antioxidant effects. Orient Pharm Exp Med. 2014;14:237-43.

Alirezaei M. Betaine as a methyl donor and an antioxidant agent in levodopa-induced hyperhomocysteinemia and oxidative stress in rat's kidney. Iranian Journal of Veterinary Medicine 2014;8:91-9.

Alirezaei M. Betaine protects cerebellum from oxidative stress following levodopa and benserazide administration in rats. Iran J Basic Med Sci. 2014;18:950.

Alirezaei M, Khoshdel Z, Dezfoulian O, Rashidipour M, Taghadosi V. Beneficial antioxidant properties of betaine against oxidative stress mediated by levodopa/benserazide in the brain of rats. J Physiol Sci. 2015;65:243-52.

Alirezaei M, Niknam P, Jelodar G. Betaine elevates ovarian antioxidant enzyme activities and demonstrates methyl donor effect in non-pregnant rats. Int J Peptide Res Therap. 2012;18:281-90.

Farris PK. Topical vitamin C: a useful agent for treating photoaging and other dermatologic conditions. Dermatol Surg. 2005;31:814-8.

Dekanski D, Janicijevic-Hudomal S, Ristic S, Radonjic NV, Petronijevic ND, Piperski V, Mitrovic DM. Attenuation of cold restraint stress-induced gastric lesions by an olive leaf extract. Gen Physiol Biophys 2009;28:135-42.

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265-75.

Claiborn A. CRC handbook of methods for oxygen radical research. CRC press Boca Raton FL; 1986.

Subbarao KV, Richardson JS, Ang LC. Autopsy samples of Alzheimer's cortex show increased peroxidation in vitro. J Neur. 1990;55:342-5.

Alirezaei M, Gheisari HR, Ranjbar VR, Hajibemani A. Betaine: a promising antioxidant agent for enhancement of broiler meat quality. Br Poult Sci. 2012;53:699-707.

Craig SAS. Betaine in human nutrition. Amr J Clin Nut. 2004;80:539-49.

Dekanski D, Ristic S, Mitrovic DM. Antioxidant effect of dry olive (Olea europaea L.) leaf extract on ethanol-induced gastric lesions in rats. Med J Nut Met. 2009;2:205-11.

Evbuomwan MI, Bolarinwa Y. Role of indomethacin-induced peptic ulceration in gastric acid secretion in pregnant rats. Afr J Med Med Sci. 1993;22:29-31.

Mattsson H, Andersson K, Larsson Hk. Omeprazole provides protection against experimentally induced gastric mucosal lesions. Eur. J. Pharmacol. 1983;91:111-4.

Alirezaei M, Kheradmand A, Heydari R, Tanideh N, Neamati S, Rashidipour M. Oleuropein protects against ethanol-induced oxidative stress and modulates sperm quality in the rat testis. Med J Nut Met. 2011:1-7.

Neamati S, Alirezaei M, Kheradmand A. Ghrelin Acts as an Antioxidant Agent in the Rat Kidney. Int J Pep Res Therap. 2011;17:239-45.

Kheradmand A, Alirezaei M, Birjandi M. Ghrelin promotes antioxidant enzyme activity and reduces lipid peroxidation in the rat ovary. Regulatory Peptides 2010;162:84-9.

Turner TT, Lysiak JJ. Oxidative stress: a common factor in testicular dysfunction. J Androl. 2008;29:488-98.

Kheradmand A, Alirezaei M, Asadian P, Alavi ER, Joorabi S. Antioxidant enzyme activity and MDA level in the rat testis following chronic administration of ghrelin. Andrologia. 2009;41:335-40.

Peltola V, Huhtaniemi I, Metsa-Ketela T, Ahotupa M. Induction of lipid peroxidation during steroidogenesis in the rat testis. Endocrinology. 1996;137:105-12.




DOI: https://doi.org/10.22087/hmj.v1i2.592

Refbacks

  • There are currently no refbacks.


This journal provides immediate open access to its content on the principle that making research freely available to the public supports a greater global exchange of knowledge.

                               

This work is licensed under a Creative Commons license (CC-BY).  However, the license permits any user to read, copy, redistribute and and make derivative the material in any medium or format for any purpose, even commercially.


 

Lorestan University of Medical Sciences, Khorramabad, Iran.

ISSN: 2538-2144