Skip to main content
SpringerLink
Log in

Intestinal ischemic preconditioning: Less xanthine accumulation relates with less apoptosis

  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

Ischemic preconditioning has shown to reduce apoptosis in the intestinal mucosa during ischemia/reperfusion. This study evaluated if the decrease of apoptotic events found during preconditioning could be related with a reduction of the substrate (i.e., xanthine/hypoxanthine) available for xanthine oxidase (XO). Animals were randomly assigned to the following study groups: C, control; I/R, ischemia/reperfusion; P+I/R, ischemic preconditioning; P+I/R+H/X, ischemic preconditioning plus hypoxanthine/xanthine, and P+I/R+H/X+Allo, ischemic preconditioning plus hypoxanthine/xanthine plus allopurinol. Caspase-3 activity, DNA fragmentation and TUNEL staining increased in the I/R group compared to control. Ischemic preconditioning (P+I/R group) was able to reverse these apoptotic variables to a level similar to that of control rats. The addition of hypoxanthine/xanthine to rats subjected to ischemic preconditioning (P+I/R+H/X group) showed the highest apoptotic activity; however, further addition of allopurinol (P+I/R+H/X+Allo group) decreased significantly apoptotic activity and events. In conclusion, intestinal ischemic preconditioning is able to reduce apoptosis during the following sustained ischemia/reperfusion event because of a reduced accumulation of xanthine/hypoxanthine nucleotide.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ishida T, Yakimuzu K, Gute DC, Korthuis RJ. Mechanisms of ischemic preconditioning. Shock 1997; 8: 86–94.

    CAS  PubMed  Google Scholar 

  2. Hotter G, Closa D, Prados M, et al. Intestinal preconditioning is mediated by a transient increase in nitric oxide. Biochem Biophys Res Commun 1996; 222: 27–32.

    CAS  PubMed  Google Scholar 

  3. McLaren AJ, Friend PJ. Trends in organ preservation. Transpl Int 2003; 16(10): 701–708.

    Article  PubMed  Google Scholar 

  4. Kosieradzki M. Mechanisms of ischemic preconditioning and its application in transplantation. Ann Transplant 2002; 7(3): 12–20.

    CAS  PubMed  Google Scholar 

  5. Ferencz A, Szanto Z, Borsiczky B, et al. The effects of preconditioning on the oxidative stress in small-bowel autotransplantation. Surgery 2002; 132(5): 877–884.

    Article  PubMed  Google Scholar 

  6. Farber A, Connors JP, Friedlander RM, Wagner RJ, Powell RJ, Cronenwett JL. A specific inhibitor of apoptosis decreases tissue injury after intestinal ischemia-reperfusion in mice. J Vasc Surg 1999; 30(4): 752–760.

    CAS  PubMed  Google Scholar 

  7. Fukuyama K, Iwakiri R, Noda T, et al. Apoptosis induced by ischemia-reperfusion and fasting in gastric mucosa compared to small intestinal mucosa in rats. Dig Dis Sci 2001; 46(3): 545–549.

    CAS  PubMed  Google Scholar 

  8. Genescà M, Sola A, Miquel R, et al. Role of changes in tissular nucleotides on the development of apoptosis during ischemia/reperfusion in rat small bowel. Am J Pathol 2002; 161: 1839–1847.

    PubMed  Google Scholar 

  9. Hotchkiss RS, Schmieg RE, Jr., Swanson PE, et al. Rapid onset of intestinal epithelial and lymphocyte apoptotic cell death in patients with trauma and shock. Crit Care Med 2000; 28(9): 3207–3217.

    CAS  PubMed  Google Scholar 

  10. Ikeda H, Suzuki Y, Suzuki M, et al. Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/reperfusion injury to the rat intestinal epithelium. Gut 1998; 42(4): 530–537.

    CAS  PubMed  Google Scholar 

  11. Noda T, Iwakiri R, Fujimoto K, Matsuo S, Aw TY. Programmed cell death induced by ischemia-reperfusion in rat intestinal mucosa. Am J Physiol 1998; 274(2Pt1): G270–276.

    CAS  PubMed  Google Scholar 

  12. Bedirli A, Soyuer I, Muhtaroglu S, Guler I. Role of granuocyte-macrophage colony-stimulating factor on apoptosis induced by ischemia-reperfusion in the intestinal epithelium. Eur Surg Res 2003; 35: 357–362.

    CAS  PubMed  Google Scholar 

  13. Liu H, McPherson BC, Yao Z. Preconditioning attenuates apoptosis and necrosis: Role of protein kinase C epsilon and-delta isoforms. Am J Physiol Heart Circ Physiol 2001; 281(1): H404–H410.

    CAS  PubMed  Google Scholar 

  14. Zhao ZQ, Vinten-Johansen J. Myocardial apoptosis and ischemic preconditioning. Cardiovasc Res 2002; 55(3): 438–455.

    CAS  PubMed  Google Scholar 

  15. Raymond MA, Vigneault N, Luyckx V, Hebert MJ. Paracrine repercussions of preconditioning on angiogenesis and apoptosis of endothelial cells. Biochem Biophys Res Commun 2002; 291(2): 261–269.

    CAS  PubMed  Google Scholar 

  16. Sindram D, Rudiger HA, Upadhya AG, Strasberg SM, Clavien PA. Ischemic preconditioning protects against cold ischemic injury through and oxidative stress dependent mechanism. J Hepatol 2002; 36(1): 78–84.

    PubMed  Google Scholar 

  17. Cavalieri B, Perrelli MG, Aragno M, et al. Ischemic preconditioning attenuates the oxidant-dependent mechanisms of reperfusion cell damage and death in rat liver. Liver Transpl 2002; 8(11): 990–999.

    PubMed  Google Scholar 

  18. Chien CT, Hsu SM, Chen CF, Lee PH, Lai MK. Hypoxic preconditioning reduces ischemia/referfusion-induced apoptosis cell death in rat kidney. Transplant Proc 2000; 32(7): 1653–1654.

    CAS  PubMed  Google Scholar 

  19. Ravati A, Ahlemeyer B, Becker A, Krieglstein J. Preconditioning-induced neuroprotection is mediated by reactive oxygen species. Brain Res 2000: 23–32.

  20. Zhang C, Rosenbaum DM, Shaikh AR, et al. Ischemic preconditioning attenuates apoptotic cell death in the rat retina. Invest Ophthalmol Vis Sci 2002; 43(9): 3059–3066.

    PubMed  Google Scholar 

  21. Cinel I, Avalan D, Cinel L, et al. Ischemic preconditioning reduces intestinal epithelial apoptosis in rats. Shock 2003; 19(6): 588–592.

    CAS  PubMed  Google Scholar 

  22. Fox IH. Metabolic basis for disorders of purine nucleotide degradation. Metabolism 1981; 30: 616–634.

    CAS  PubMed  Google Scholar 

  23. Saugstad OD. Hypoxanthrine as an indicator of hypoxia: Its role in health and disease through free radical production. Pediatr Res 1988; 23: 143–150.

    CAS  PubMed  Google Scholar 

  24. Buttke TM, Sandstrom PA. Oxidative stress as a mediator of apoptosis. Immunol Today 1994; 15: 1–4.

    PubMed  Google Scholar 

  25. Cai J, Jones DP. Superoxide in apoptosis: Mitochondrial generation triggered by cytochrome c loss. J Biol Chem 1998; 273: 11401–11404.

    CAS  PubMed  Google Scholar 

  26. Ramachandran A, Madesh M, Balasubramanian KA. Apoptosis in the intestinal epithelium: Its relevance in normal and pathophysiological conditions. J Gastroenterol Hepatol 2000; 15: 109–120.

    CAS  PubMed  Google Scholar 

  27. Sola A, Hotter G, Prats N, Xaus C, Gelpi E, Rosello-Catafau J. Modification of oxidative stress in response to intestinal preconditioning. Transplantation 2000; 69(5): 767–772.

    CAS  PubMed  Google Scholar 

  28. Hotter G, Closa D, Prats N, Pi F, Gelpi E, Rosello-Catafau J. Free radical enhancement promotes leucocyte recruitment through a PAF and LTB4 dependent mechanism. Free Radic Biol Med 1997; 22(6): 947–954.

    CAS  PubMed  Google Scholar 

  29. Hotter G, Closa D, Gelpi E, Prats N, Rosello-Catafau J. Role of xanthine oxidase and eicosanoids in development of pancreatic ischemia-reperfusion injury. Inflammation 1995; 19(4): 469–478.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  31. Jha HC, von Recklinghausen G, Zilliken F. Inhibition of in vitro microsomal lipid peroxidation by isoflavonoids. Biochem Pharmacol 1985; 34(9): 1367–1369.

    CAS  PubMed  Google Scholar 

  32. Haglund U. Gut ischemia. Gut 1994; 35(Suppl 1): 73–76.

    PubMed  Google Scholar 

  33. Shah KA, Shurey S, Green CJ. Apoptosis after intestinal ischemia-reperfusion injury: A morphological study. Transplantation 1997; 64(10): 1393–1397.

    CAS  PubMed  Google Scholar 

  34. Wells CL. Colonization and translocation of intestinal bacterial flora. Transplant Proc 1996; 28(5): 2653–2656.

    CAS  PubMed  Google Scholar 

  35. Parks D, Granger D. Xanthine oxidase: Biochemistry, distribution and physiology. Acta Physiol Scand 1986; 548: 87–99.

    CAS  Google Scholar 

  36. Hockenbery DM, Oltvai ZN, Yin XM, Milliman C, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 1993; 75: 241–251.

    CAS  PubMed  Google Scholar 

  37. Borges F, Fernandes E, Roleira F. Progress towards the discovery of xanthine oxidase inhibitors. Curr Med Chem 2002; 9: 195–217.

    CAS  PubMed  Google Scholar 

  38. Ciz M, Cizova H, Lojek A, Kubala L, Papezikova I. Ischemia/reperfusion injury of rat small intestine: The effect of allopurinol dosage. Transplant Proc 2001; 33: 2871–2873.

    CAS  PubMed  Google Scholar 

  39. Albuquerque RG, Sanson AJ, Malangoni AM. Allopurinol protects enterocytes from hypoxia-induced apoptosis in vivo. J Trauma 2002; 53: 415–421.

    CAS  PubMed  Google Scholar 

  40. Parra E, Gota R, Gamen A, Moros M, Azuara M, Granulomatous interstitial nephritis secondary to allopurinol treatment. Clin Nephrol 1995; 43(5): 350.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Experimental Pathology, Instituto de Investigaciones Biomédicas, IIBB-CSIC, IDIBAPS, Barcelona, Spain

    A. Sola & G. Hotter

  2. Department of Physiology, Faculty of Biology, University of Barcelona, Spain

    V. Alfaro

Authors
  1. A. Sola
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. Alfaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Hotter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Hotter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sola, A., Alfaro, V. & Hotter, G. Intestinal ischemic preconditioning: Less xanthine accumulation relates with less apoptosis. Apoptosis 9, 353–361 (2004). https://doi.org/10.1023/B:APPT.0000025812.45382.4d

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:APPT.0000025812.45382.4d

Search

Navigation