Pérez GY, Oyarzábal YA, Jiménez DS, Molina CCV, Mas FR

Language: Spanish
References: 36
Page: 87-96
PDF size: 76.96 Kb.

ABSTRACT

Introduction: the etiology of the gastric ulceration is associated to the imbalance between aggressive and defensive factors acting upon the gastric mucosa. D-002, a mixture of 6 higher primary alcohols purified from the beeswax, cause some multiple mechanism-mediated gastroprotective effects and decrease of lipid peroxidation in the gastric mucosa.
Objective: to determine whether D-002 can scavenge the in vivo added or in vivo generated hydroxyl radical in rats with indometacin-induced gastric ulcer or not.
Methods: For the in vitro experiment, D-002 was added at concentrations 0.9 and 1 000 μg/mL For the in vivo experiment, the rats were randomized into 6 groups: one negative control, and five indometacin-treated groups as follows a positive excipienttreated control, three under D-002 treatment (5, 25 or 100 mg/kg, respectively, p.o.), and another group treated with Omeprazole (20 mg/kg i.p.). These lines of treatment were given 1 hour (excipient and D-002) or 30 min (Omeprazole) prior to inducing the ulcers. In both experiments, aliquots from the gastric mucosa were taken and the damage infringed to 2-deoxiribose by the hydroxyl radical was determined.
Results: oral administration of D-002, rather than in vitro addition, significantly protected 2-desoxiribose from the oxidative damage depending on the dosage as compared to the positive control.
Conclusions: these results indicate that the ability of the orally administered D-002 (25 and 100 mg/kg) to scavenge the hydroxyl radical endogenously generated on the gastric mucosa by indometacin could contribute to its antioxidant and gastroprotective effects against the damage that the non-steroidal anti-inflammatory drugs carry to the gastric mucosa.

REFERENCES

1. Lamarque D. Pathogenesis of gastroduodenal lesions induced by non-steroidal antiinflammatory drugs. Gastroenterol Clin Biol. 2004;28:C18-26.

2. Erkin B, Dokmeci D, Altaner S, Turan FN. Gastroprotective effect of L-carnitine on indomethacin-induced gastric mucosal injury in rats: a preliminary study. Folia Med (Plovdiv). 2006;48:86-9.

3. Farias-Silva E, Cola M, Calvo TR, Barbastefano V, Ferreira AL, De Paula Michelatto D, et al. Antioxidant activity of indigo and its preventive effect against ethanolinduced DNA damage in rat gastric mucosa. Planta Med. 2007;73:1241-6.

4. Kountouras J, Chatzopoulos D, Zavos C. Reactive oxygen metabolites and upper gastrointestinal diseases. Hepatogastroenterology. 2001;48:743-51.

5. Ramakrishnan K, Salinas RC, Peptic Ulcer Disease. Am Fam Physician. 2007;76:1005-1013.

6. Robert A, Nezamis JE, Lancaster C, Davies JP. Field SO, Hanchar A. Mild irritants prevent gastric necrosis through «adaptive cytoprotection» mediated by prostaglandins. J Physiol. 1983;245:G113-G21.

7. Naito Y. Yoshikawa T. Oxidative stress involvement and gene expression in indomethacin-induced gastropathy. Redox Rep. 2006;11:243-53.

8. Augusto AC, Miguel F, Mendonca S, Pedrazzoli J, Gurqueira SA. Oxidative stress expression status associated to Helicobacter pylori virulence in gastric diseases. Clin Biochem. 2007;40:615-22.

9. Biswas K, Bandyopadhyay U, Chattopadhyay I, Varadaraj A, Ali E. A Novel Antioxidant and Antiapoptotic Role of Omeprazole to Block Gastric Ulcer through Scavenging of Hydroxyl Radical. J Biol Chem. 2003;278:10993-1001.

10. Yeo M, Kwak MS, Kim DK, Chung IS, Moon BS, Song KS, et al. The novel acid pump antagonists for anti-secretory actions with their peculiar applications beyond acid suppression. J Clin Biochem Nutr. 2006;8:1-8.

11. Oluwole FS, Ayo JA, Omolaso BO, Emikpe BO, Adesanwo JK. Methanolic extract of Tetracera potatoria, an antiulcer agent increases gastric mucus secretion and endogenous antioxidants. Niger J Physiol Sci. 2008;23:79-83.

12. Mas R. D-002: A product obtained from beeswax. Drugs of the Future. 2001;26:731-44.

13. Carbajal D, Molina V, Valdés S, Arruzazabala ML. Mas R. Anti-ulcer activity of higher primary alcohols of beeswax. J Pharm Pharmacol. 1995;47:731-33.

14. Carbajal D, Molina V, Valdés S, Arruzazabala ML, Rodeiro I, Mas R, et al. Possible cytoprotective mechanism in rats of D-002 an anti-ulcerogenic product isolated from beeswax. J Pharm Pharmacol. 1996;48:858-60.

15. Carbajal D, Molina V, Noa M, Valdés S, Arruzazabala ML, Aguiar A, et al. Effects of D-002 on gastric mucus composition in ethanol induced ulcer. Pharmacol Res. 2000;33:85-90.

16. Molina V, Valdés S, Carvajal. Arruzazabala ML, Mas R. Antioxidant effects of D- 002 on gastric mucosa of rats with experimentally-induced injury. J Med Food. 2000;4:79-83.

17. Hano O, Illnait J, Mas R. Fernández L, Piñol F, Fernández J. Effects of D-002, a Product Isolated from Beeswax, on Duodenal Ulcer: A Double-Blind, Placebo- Controlled Study. Curr Ther Res. 2001;62:394-407.

18. Illnait J, Terry H, Mas R, Fernández L, Carbajal D. Effects of D-002, a product isolated from beeswax, on gastric symptoms of patients with osteoarthritis treated with piroxicam: a pilot study. J Med Food. 2005;8:63-8.

19. Fernández L, Terry H, Quiñones AM, Díaz B, Hernández ML, Illnait J, et al. Effects of Abexol® in middle-aged and older subjects: an open follow-up. Rev CENIC Cien Biol. 2008;39:3-8.

20. Rodríguez I, Illnait J, Terry H, Mas R, Fernández L, Fernández JC, et al. Effects of Abexol® (beeswax alcohols) on gastrointestinal symptoms of middle-aged and older subjects assessed Rev CENIC Cien Biol. 2009;40:147-54.

21. Ohara A, Sugiyama S, Hoshino H. Reduction of adverse effects of indomethacin by anti-allergic drugs in rat stomachs. Arzneim-Forsch Drug Res. 1992;42:1115-8.

22. Burdon RH, Knippenberg PH. Laboratory Techniques in Biochemistry and Molecular Biology. Vol. 22. Techniques in Free Radical Research. Amsterdam: Elsevier; 1991;3:50-5.

23. Ohkawa Y, Ohishi J, Yagi K. Assay fo lipid peroxides in animal tissues by the thiobarbituric acid reaction. Anal Biochem. 1979;95:351-8.

24. Marxwell MA, Haas SM, Beiber LL, Tolbert NE. A modification of the Lowry procedure to simplify protein determination in membrane lipoprotein samples. Anal Biochem. 1987;87:206-9.

25. Gutteridge JM, Halliwell B. The deoxyribose assay: and both for free hydroxyl radical and for site-specific hydroxyl radical production. Biochem J. 1988;253:932-3.

26. Menéndez R, Amor AM, González RM, Jiménez S, Mas R. Inhibition of rat microsomal lipid peroxidation by the oral administration of D-002. Brazil J Med Biol Res. 2000;33:85-90.

27. Menéndez R, Pérez Y, González RM, Amor AM, Jiménez S, Mas R. Antioxidant effects of D002 on the in vitro susceptibility of whole plasma in healthy volunteers. Arch Med Res. 2001;32:436-41.

28. Menéndez R, Mas R, Illnait J, Peréz Y, Amor AM, Fernández J, González RM. Effects of D002 on lipid peroxidation in older subjects. J Med Food. 2001;4:81-6.

29. López E, Illnait J, Molina V, Oyárzabal A, Fernández L, Pérez Y, et al. Effects of D- 002 (beeswax alcohols) on lipid peroxidation in middle-aged and older subjects. LAJP. 2008;27:695-703.

30. Rodríguez I, Illnait J, Molina V, Oyarzábal A, Fernández L, Fernández J, et al. Comparative antioxidant effects of beeswax alcohols and grape seed extract in healthy persons. LAJP. 2010;29:255-62.

31. Rizzo E, Craft D, Dammann A. Fatty alcohol metabolism in cultured human fibroblasts. Evidence for a fatty alcohol cycle. J Biol Chem. 1987;262:17412-9.

32. Kabir Y, Kimura S. Tissue distribution of (14C)-octacosanol in liver and muscle of rats after serial administration. Ann Nutr Metab. 1995;39:279-84.

33. Kabir Y, Kimura S. Metabolism of octacosanol in liver and muscle of rat. Acta Alimentaria. 1995;4:39-44.

34. Menéndez R, Marrero D, Mas R. González RM. In vitro and in vivo study of octacosanol metabolism. Arch Med Res. 2005;6:113-9.

35. Banerjee S, Ghoshal S, Porter TD. Activation of AMP-kinase by Policosanol Requires Peroxisomal Metabolism. Lipids. 2011;46:311-21.

36. Kim JM, Choi SM, Kim DH, Oh TY, Ahn BO, Kwon JW, et al. Combined use of omeprazole and a novel antioxidative cytoprotectant for the treatment of peptic ulcer. Facilitation of ulcer healing in experimental animals. Arzneimittelforschung. 2005;55:387-93.