Skip to main content
Log in

Alpha-Lipoic Acid Improves Acetic Acid-Induced Gastric Ulcer Healing in Rats

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

To evaluate the role of ALA treatment on the healing of acetic acid-induced gastric ulcer, rats were given ALA (35 mg/kg/day) or saline for 3 days before the induction of ulcer and the treatment was continued twice daily for 2 days (early) or 10 days (late) until they were decapitated. Gastric ulcer index, microscopic score, elevated DNA fragmentation and chemiluminescence levels of the saline-treated ulcer groups were all reduced by ALA treatment. Likewise, ALA treatment inhibited chemiluminescence levels in both early and late ulcer groups. Marked reduction in glutathione levels of the saline-treated early ulcer group was reversed by ALA treatment, while ALA treatment was effective in depressing gastric myeloperoxidase activity in the late ulcer group. In conclusion, ALA treatment shows protective role in the healing of acetic acid-induced gastric injury in rats via the suppression of neutrophil accumulation, preservation of endogenous glutathione, inhibition of reactive oxidant generation and apoptosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Eastwood, G. L. 1997. Is smoking still important in the pathogenesis of peptic ulcer disease? J Clin Gastroenterol. 25:S1–S7. doi:10.1097/00004836-199700001-00003.

    Article  PubMed  Google Scholar 

  2. Ham, M., and J. D. Kaunitz. 2007. Gastroduodenal defense. Curr Opin Gastroenterol. 23:607–11.

    PubMed  Google Scholar 

  3. Tarnawski, A. S. 2005. Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci. 50:S24–S33. doi:10.1007/s10620-005-2803-6.

    Article  PubMed  CAS  Google Scholar 

  4. Taupin, D., D. C. Wu, W. K. Jeon, K. Devaney, T. C. Wang, and D. K. Podolsky. 1999. The trefoil gene family are coordinately expressed immediate-early genes: EGF receptor-and MAP kinase-dependent interregulation. J Clin Invest. 103:R31–R38. doi:10.1172/JCI3304.

    Article  PubMed  CAS  Google Scholar 

  5. Wong, W. M., R. J. Playford, and N. A. Wright. 2000. Peptide gene expression in gastrointestinal mucosal ulceration: ordered sequence or redundancy? Gut 46:286–292. doi:10.1136/gut.46.2.286.

    Article  PubMed  CAS  Google Scholar 

  6. Günal, O., B. K. Oktar, E. Ozçinar, M. Sungur, S. Arbak, and B. Yeğen. 2003. Estradiol treatment ameliorates acetic acid-induced gastric and colonic injuries in rats. Inflammation 27:351–359. doi:10.1023/B:IFLA.0000006703.53427.da.

    Article  PubMed  Google Scholar 

  7. Okabe, S., and K. Amagase. 2005. An overview of acetic acid ulcer models—the history and state of the art of peptic ulcer research. Biol Pharm Bull. 28:1321–1341. doi:10.1248/bpb.28.1321.

    Article  PubMed  CAS  Google Scholar 

  8. Millar, A. H., and C. J. Leaver. 2000. The cytotoxic lipid peroxidation product, 4-hydroxy-2-nonenal, pecifically inhibits decarboxylating dehydrogenases in the matrix of plant mitochondria. FEBS Lett. 481:117–121. doi:10.1016/S0014-5793(00)01976-1.

    Article  PubMed  CAS  Google Scholar 

  9. Reed, L. 1998. From lipoic acid to multi-enzyme complexes. Protein Sci. 7:220–224.

    Article  PubMed  CAS  Google Scholar 

  10. Biewenga, G. P., G. R. Haenen, and A. Bast. 1997. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol. 29:315–331. doi:10.1016/S0306-3623(96)00474-0.

    PubMed  CAS  Google Scholar 

  11. Packer, L., E. H. Witt, and H. J. Tritschler. 1995. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med. 19:227–250. doi:10.1016/0891-5849(95)00017-R.

    Article  PubMed  CAS  Google Scholar 

  12. Savitha, S., and C. Panneerselvam. 2006. Mitochondrial membrane damage during aging process in rat heart: potential efficacy of l-carnitine and dl-alpha-lipoic acid. Mech Ageing Dev. 127:349–355. doi:10.1016/j.mad.2005.12.004.

    Article  PubMed  CAS  Google Scholar 

  13. Coombes, J. S., S. K. Powers, H. A. Demirel, J. Jessup, H. K. Vincent, K. L. Hamilton, H. Naito, R. A. Shanely, C. K. Sen, L. Packer, and L. L. Ji. 2000. Effect of combined supplementation with vitamin E and alpha-lipoic acid on myocardial performance during in vivo ischaemia–reperfusion. Acta Physiol Scand. 169:261–269. doi:10.1046/j.1365-201x.2000.00740.x.

    Article  PubMed  CAS  Google Scholar 

  14. Da Ros, R., R. Assaloni, and A. Ceriello. 2005. Molecular targets of diabetic vascular complications and potential new drugs. Curr Drug Targets. 6:503–509. doi:10.2174/1389450054021855.

    Article  PubMed  Google Scholar 

  15. Vincent, A. M., M. J. Stevens, C. Backus, L. L. McLean, and E. L. Feldman. 2005. Cell culture modeling to test therapies against hyperglycemia-mediated oxidative stress and injury. Antioxid Redox Signal 7:1494–506. doi:10.1089/ars.2005.7.1494.

    Article  PubMed  CAS  Google Scholar 

  16. Park, K. G., M. J. Kim, H. S. Kim, S. J. Lee, D. K. Song, and I. K. Lee. 2004. Prevention and treatment of macroangiopathy: focusing on oxidative stress. Diabetes Res Clin Pract. 66:S57–S62. doi:10.1016/j.diabres.2003.08.017.

    Article  PubMed  CAS  Google Scholar 

  17. de Champlain, J., R. Wu, H. Girouard, M. Karas, A. E. L. Midaoui, M. A. Laplante, and L. Wu. 2004. Oxidative stress in hypertension. Clin Exp Hypertens. 26:593–601. doi:10.1081/CEH-200031904.

    Article  PubMed  CAS  Google Scholar 

  18. Pirlich, M., K. Kiok, G. Sandig, H. Lochs, and T. Grune. 2002. Alpha-lipoic acid prevents ethanol-induced protein oxidation in mouse hippocampal HT22 cells. Neurosci Lett. 328:93–96. doi:10.1016/S0304-3940(02)00415-9.

    Article  PubMed  CAS  Google Scholar 

  19. Tastekin, N., N. Aydogdu, D. Dokmeci, U. Usta, M. Birtane, H. Erbas, and M. Ture. 2007. Protective effects of l-carnitine and alpha-lipoic acid in rats with adjuvant arthritis. Pharmacol Res. 56:303–310. doi:10.1016/j.phrs.2007.07.008.

    Article  PubMed  CAS  Google Scholar 

  20. Demir, U., T. Demir, and N. Ilhan. 2005. The protective effect of alpha-lipoic acid against oxidative damage in rabbit conjunctiva and cornea exposed to ultraviolet radiation. Ophthalmologica 219:49–53. doi:10.1159/000081783.

    Article  PubMed  CAS  Google Scholar 

  21. Bilska, A., and L. Włodek. 2005. Lipoic acid—the drug of the future? Pharmacol Rep. 57:570–577.

    PubMed  CAS  Google Scholar 

  22. Sehirli, O., E. Tatlidede, M. Yüksel, C. Erzik, S. Cetinel, B. C. Yeğen, and G. Sener. 2008. Antioxidant effect of alpha-lipoic acid against ethanol-induced gastric mucosal erosion in rats. Pharmacology 81:173–180. doi:10.1159/000111145.

    Article  PubMed  CAS  Google Scholar 

  23. Selvakumar, E., C. Prahalathan, Y. Mythili, and P. Varalakshmi. 2004. Protective effect of dl-alpha-lipoic acid in cyclophosphamide induced oxidative injury in rat testis. Reprod Toxicol. 19:163–7. doi:10.1016/j.reprotox.2004.06.015.

    Article  PubMed  CAS  Google Scholar 

  24. Selvakumar, E., C. Prahalathan, P. T. Sudharsan, and P. Varalakshmi. 2006. Protective effect of lipoic acid on micronuclei induction by cyclophosphamide. Arch Toxicol. 80:115–119. doi:10.1007/s00204-005-0015-7.

    Article  PubMed  CAS  Google Scholar 

  25. Okabe, S., and C. J. Pfeiffer. 1972. Chronicity of acetic acid ulcer in the rat stomach. Am J Dig Dis. 17:619–629. doi:10.1007/BF02231748.

    Article  PubMed  CAS  Google Scholar 

  26. Okabe, S., J. L. Roth, and C. J. Pfeiffer. 1971. A method for experimental, penetrating gastric and duodenal ulcers in rats. Observations on normal healing. Am J Dig Dis. 16:277–284. doi:10.1007/BF02235252.

    Article  PubMed  CAS  Google Scholar 

  27. Ozveri, E. S., A. Bozkurt, G. Haklar, S. Cetinel, S. Arbak, C. Yeğen, and B. C. Yeğen. 2001. Estrogens ameliorate remote organ inflammation induced by burn injury in rats. Inflamm Res. 50:585–591. doi:10.1007/PL00000238.

    Article  PubMed  CAS  Google Scholar 

  28. Wyllie, A. H. 1980. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284:555–556. doi:10.1038/284555a0.

    Article  PubMed  CAS  Google Scholar 

  29. Burton, K. 1956. A study of the conditions and mechanism of the diphenylamine reaction for the calorimetric estimation of deoxyribonucleic acid. Biochem J. 62:315–323.

    PubMed  CAS  Google Scholar 

  30. Bradley, P. P., D. A. Priebat, R. D. Christensen, and G. Rothstein. 1982. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 78:206–209. doi:10.1111/1523-1747.ep12506462.

    Article  PubMed  CAS  Google Scholar 

  31. Hillegass, L. M., D. E. Griswold, B. Brickson, and C. Albrightson-Winslow. 1990. Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods 24:285–295. doi:10.1016/0160-5402(90)90013-B.

    Article  PubMed  CAS  Google Scholar 

  32. Davies, G. R., N. J. Simmonds, T. R. Stevens, A. Grandison, D. R. Blake, and D. S. Rampton. 1992. Mucosal reactive oxygen metabolite production in duodenal ulcer disease. Gut 33:1467–1472. doi:10.1136/gut.33.11.1467.

    Article  PubMed  CAS  Google Scholar 

  33. Aykac, G., M. Uysal, A. S. Yalcin, N. Koçak-Toker, A. Sivas, and H. Öz. 1985. The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology 36:71–76. doi:10.1016/0300-483X(85)90008-3.

    Article  PubMed  CAS  Google Scholar 

  34. Yoshikawa, T., Y. Naito, S. Ueda, H. Oyamada, T. Takemura, N. Yoshida, S. Sugino, and M. Kondo. 1990. Role of oxygen-derived free radicals in the pathogenesis of gastric mucosal lesions in rats. J Clin Gastroenterol. 12:S65–S71. doi:10.1097/00004836-199001001-00012.

    Article  PubMed  Google Scholar 

  35. Hahm, K. B., I. S. Park, Y. S. Kim, J. H. Kim, S. W. Cho, S. I. Lee, and J. K. Youn. 1997. Role of rebamipide on induction of heat-shock proteins and protection against reactive oxygen metabolite-mediated cell damage in cultured gastric mucosal cells. Free Radic Biol Med. 22:711–716. doi:10.1016/S0891-5849(96)00406-6.

    Article  PubMed  CAS  Google Scholar 

  36. Arangon, K., S. Deveraj, O. Tirosh, L. Packer, and I. Jialal. 1999. Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress. Free Radic Biol Med. 27:1114–1121. doi:10.1016/S0891-5849(99)00155-0.

    Article  Google Scholar 

  37. Petersen Shay, K., R. F. Moreau, E. J. Smith, and T. M. Hagen. 2008. Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity. IUBMB Life 60:362–367. doi:10.1002/iub.40.

    Article  PubMed  CAS  Google Scholar 

  38. Vázquez-Ramírez, R., M. Olguín-Martínez, C. Kubli-Garfias, and R. Hernández-Muñoz. 2006. Reversing gastric mucosal alterations during ethanol–induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage. World J Gastroenterol. 12:4318–4324.

    PubMed  Google Scholar 

  39. Naito, Y., and T. Yoshikawa. 2006. Oxidative stress involvement and gene expression in indomethacin–induced gastropathy. Redox Rep. 11:243–253. doi:10.1179/135100006X155021.

    Article  PubMed  CAS  Google Scholar 

  40. Biewenga, G., J. de Jong, and A. Bast. 1994. Lipoic acid favors thiolsulfinate formation after hypochlorous acid scavenging: a study with lipoic acid derivatives. Arch Biochem Biophys. 312:114–120. doi:10.1006/abbi.1994.1288.

    Article  PubMed  CAS  Google Scholar 

  41. Boyd, S. C., H. A. Sasame, and M. R. Boyd. 1979. High concentrations of glutathione in glandular stomach: possible implications for carcinogenesis. Science 205:1010–1012. doi:10.1126/science.572989.

    Article  CAS  Google Scholar 

  42. Hayes, J. D., and L. I. McLellan. 1999. Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defense against oxidative stress. Free Radic Res. 31:273–300. doi:10.1080/10715769900300851.

    Article  PubMed  CAS  Google Scholar 

  43. La Casa, C., I. Villegas, C. Alarcón de la Lastra, V. Motilva, and M. J. Martín Calero. 2000. Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions. J Ethnopharmacol. 71:45–53. doi:10.1016/S0378-8741(99)00174-9.

    Article  PubMed  Google Scholar 

  44. Moungjaroen, J., U. Nimmannit, P. S. Callery, L. Wang, N. Azad, V. Lipipun, P. Chanvorachote, and Y. Rojanasakul. 2006. Reactive oxygen species mediate caspase activation and apoptosis induced by lipoic acid in human lung epithelial cancer cells through Bcl-2 down-regulation. J Pharmacol Exp Ther. 319:1062–1069. doi:10.1124/jpet.106.110965.

    Article  PubMed  CAS  Google Scholar 

  45. Shi, D. Y., H. L. Liu, J. S. Stern, P. Z. Yu, and S. L. Liu. 2008. Alpha-lipoic acid induces apoptosis in hepatoma cells via the PTEN/Akt pathway. FEBS Lett. 582:1667–1671. doi:10.1016/j.febslet.2008.04.021.

    Article  PubMed  CAS  Google Scholar 

  46. Artwohl, M., K. Muth, K. Kosulin, R. de Martin, T. Hölzenbein, G. Rainer, A. Freudenthaler, N. Huttary, L. Schmetterer, W. K. Waldhäusl, and S. M. Baumgartner-Parzer. 2007. R-(+)-alpha-lipoic acid inhibits endothelial cell apoptosis and proliferation: involvement of Akt and retinoblastoma protein/E2F-1. Am J Physiol Endocrinol Metab. 293:E681–E689. doi:10.1152/ajpendo.00584.2006.

    Article  PubMed  CAS  Google Scholar 

  47. Kim, H. S., H. J. Kim, K. G. Park, Y. N. Kim, T. K. Kwon, J. Y. Park, K. U. Lee, J. G. Kim, and I. K. Lee. 2007. Alpha-lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF-kappaB transcriptional activity. Exp Mol Med. 39:106–113.

    PubMed  CAS  Google Scholar 

  48. Karin, M., and F. R. Greten. 2005. NF-κB: Linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 5:749–759. doi:10.1038/nri1703.

    Article  PubMed  CAS  Google Scholar 

  49. Zhang, W. J., and B. Frei. 2001. Alpha-lipoic acid inhibits TNF-alpha induced NF-kappaB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J. 15:2423–2432. doi:10.1096/fj.01-0260com.

    Article  PubMed  CAS  Google Scholar 

  50. Dinçer, Y., A. Telci, R. Kayali, I. A. Yilmaz, U. Cakatay, and T. Akçay. 2002. Effect of alpha-lipoic acid on lipid peroxidation and anti-oxidant enzyme activities in diabetic rats. Clin Exp Pharmacol Physiol. 29:281–284. doi:10.1046/j.1440-1681.2002.03642.x.

    Article  PubMed  Google Scholar 

  51. Vincent, A. M., L. L. McLean, C. Backus, and E. L. Feldman. 2005. Short-term hyperglycemia produces oxidative damage and apoptosis in neurons. FASEB J. 19:638–640.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The study was presented at Digestive Disease Week 2008 and published in abstract from in Gastroenterology 2008;134(4): A239.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Berna Karakoyun.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karakoyun, B., Yüksel, M., Ercan, F. et al. Alpha-Lipoic Acid Improves Acetic Acid-Induced Gastric Ulcer Healing in Rats. Inflammation 32, 37–46 (2009). https://doi.org/10.1007/s10753-008-9100-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-008-9100-4

KEY WORDS

Navigation