Molina CV, Valle CM, Ravelo CY, Carbajal QD, Mas FR

Language: Spanish
References: 30
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ABSTRACT

Introduction: non-steroidal anti-inflammatory drugs are very useful to treat acute and chronic inflammatory processes, being relevant among them the extended use of Aspirin. Their main limitation,however, are the induced gastrointestinal adverse effects, so it is justified the search of new substances with antiinflammatory effects devoided of gastrotoxicity, as D-002, a mixture of aliphatic primary alcohols purified from bees wax.
Objective: to evaluate the effect of D-002 on the Aspirin-induced gastrotoxicity.
Methods: Experiment 1: Rats were distributed into 4 groups: one vehicle control, treated with D-002 (50 mg/kg), one treated with Aspirin (150 mg/kg) and other with D-002 plus Aspirin (50 mg/kg plus 150 mg/kg). Experiment 2: Rats were distributed into 5 groups: a negative vehicle and four with Aspirin (300 mg/kg)-induced ulcer: a positive control (vehicle), two treated with D-002 (50 and 100 mg/kg) and one with Omeprazole (10 mg/kg). Treatments were orally administered for 6 days and gastric lesions were quantified. In the second experiment the neutrophil infiltration grade was evaluated too.
Results: all Aspirin-, but none of the D-002-treated animals exhibited typical gastric ulcers. The administration of D-002 (50 mg/kg) plus Aspirin (100 mg/kg) reduced the ulcers (67 % reduction) as compared to Aspirin monotherapy. In the model of Aspirin-induced ulcer, D-002 (50 and 100 mg/kg) reduced the ulcers (70 and 75 %), and also neutrophil infiltration (75 and 82 %, respectively), Omeprazole reduced both variables (90 and 92 %, respectively).
Conclusion: D-002 reduced the Aspirin-induced gastrotoxicity and the characteristic neutrophil infiltration of these gastric lesions in rats.

REFERENCES

1. Ramakrishnan K, Salinas RC. Peptic ulcer disease. Am Fam Physician. 2007;76:1005-13.

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

3. Allen A, Flemström G. Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin. Am J Cell Physiol. 2005;288:C1-19.

4. Tsumura H, Tamura I, Tanaka H, Chinzei R, Ishida T, Masuda A. Prescription of non-steroidal anti-inflammatory drugs and co-prescribed drugs for mucosal protection: analysis of the present status based on questionnaires obtained from orthopaedists in Japan. Intern Med. 2007;46:927-31.

5. Whittle BJ. Gastrointestinal effects of non-steroidal anti-inflammatory drugs. Fundam Clin Pharmacol. 2003;17:301-13

6. Fernández Lanas A. NSAID-induced gastrointestinal damage: current clinical management and recommendations for prevention. Chin J Dig Dis. 2006;7:127-33.

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

8. Pohle T, Brzozowski T, Becker JC, Van Der Voort IR. Role of reactive oxygen metabolites in aspirin-induced gastric damage in humans: gastroprotection by vitamin C. Aliment Pharmacol Ther. 2001;15:677-87.

9. Sener-Muratoglu G, Paskaloglu K, Arbak S. Protective effect of famotidine, omeprazole, and melatonin against acetylsalicylic acid-induced gastric damage in rats. Dig Dis Sci. 2001;46:318-30.

10. Fries JF, Bruce B. Rates of serious gastrointestinal events from low dose use of acetylsalicylic acid, acetaminophen, and ibuprofen in patients with osteoarthritis and rheumatoid arthritis. J. Rheumatol. 2003;30:2226-33.

11. Jainu M, Devi S. Attenuation of neutrophil infiltration and proinflammatory cytokines by Cissus quadrangularis: a possible prevention against gastric ulcerogenesis. J Herb Pharmacother. 2005;5:33-42.

12. Jainu M, Mohan V. Devi S. Protective effect of Cissus quadrangularis on neutrophil mediated tissue injury induced by aspirin in rats. J Ethnopharmacol. 2006:104;302-5.

13. Yajima H, Yamao J, Fukui H, Takakura Y. Up-to-date information on gastric mucosal lesions from long-term NSAID therapy in orthopaedic outpatients: a study using logistic regression analysis. J Orthop Sci. 2007;12:341-6.

14. Hyllested M, Jones S, Pedersen JL, Kehlet H. Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review. Br J Anaesth. 2002;88:199-214.

15. Kalra BS, Shalini, Chaturvedi S, Tayal V, Gupta U. Evaluation of gastric tolerability, antinociceptive and antiinflammatory activity of combination NSAIDs in rats. Indian J Dent Res 2009;20:418-22.

16. Carbajal D, Molina V, Valdés S. Anti-inflammatory activity of D-002: an active product isolated from beeswax. Prostagl Leukotr Essent Fatty Acids. 1998;59:235-8.

17. Carbajal D, Molina V, Valdés S, Arruzazabala ML, Más R. Anti-ulcer activity of higher primary alcohols of beeswax. J Pharm. Phamacol. 1995;47:731-3.

18. 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;42:329-32.

19. Carbajal D, Molina V, Valdés S. Possible cytoprotective mechanism in rats of D-002 an anti-ulcerogenic product isolated from beeswax. J Pharm Pharmacol. 1996;48:858-60.

20. Carbajal D, Molina V, Noa M, Valdés S. Effects of D-002 on gastric mucus composition in ethanol-induced ulcer. Pharmacol Res. 2000;42:329-32.

21. Molina V, Valdés S, Carbajal D. Antioxidant effects of D-002 on gastric mucosa of rats with experimentally-induced injury. J Med Food. 2001;4:79-83.

22. 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.

23. Nygard G, Amthony A, Piasecki C, Trevethick M, Hudson M, Dhilon A, et al. Acute indomethacin-induced jejunum injury in the rat. Early morphological and biochemical changes. Gastroenterology 1994;106:567-75.

24. Cheng CL, Koo MWL. Effect of Centella asiatica on ethanol induced gastric mucosal lesions in rats. Life Sci. 2000;67:2647-53.

25. Bou-Abboud CF, Wayland H, Panlsen G, Guth PH. Microcirculatory stasis precedes tissue necrosis in ethanol-induced gastric mucosal injury in rat. Dig Dis Sci. 1988;33:872-7.

26. Shimizu N, Watanabe T, Arakawa T, Fujiwara Y, Higuchi K, Kuroki T. Pentoxifylline accelerates gastric ulcer healing in rats: roles of tumour necrosis factor alpha and neutrophils during the early phase of ulcer healing. Dig. 2000;6:157-64.

27. Paul AD, Chauhan CK. Study of usage pattern of nonsteroidal anti-inflammatory drugs (NSAIDs) among different practice categories in Indian clinical setting. Eur J Clin Pharmacol. 2005;60:889-92.

28. Lanas A, García-Rodríguez LA, Arroyo MT, Gomollon F, Feu F, González- Pérez A, et al. Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations. Gut. 2006;55:1731-8.

29. Rostom A, Dube C, Wells G, Tugwell P, Welch V, Jolicoeur E, et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev. 2002; CD002296.

30. Lanas A, Hunt R. Prevention of anti-inflammatory drug-induced gastrointestinal damage: benefits and risks of therapeutic strategies. Ann Med. 2006;38:415-28.