Skip to main content
SpringerLink
Log in

Effects of a cantaloupe melon extract/wheat gliadin biopolymer during aortic cross-clamping

  • Experimental
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Objective

We previously reported in healthy volunteers that a cantaloupe melon extract chemically combined with wheat gliadin (melon extract/gliadin) and containing SOD, catalase and residual glutathione peroxidase (GPx), protected against DNA strand-break damage induced by hyperbaric oxygen (HBO), a well-established model of DNA damage resulting from oxidative stress. Aortic cross-clamping is a typical example of ischemia/reperfusion injury-related oxidative stress, and therefore we investigated whether this melon extract/gliadin would also reduce DNA damage after aortic cross-clamping and reperfusion.

Design

Prospective, randomized, controlled experimental study.

Setting

Animal laboratory.

Patients and participants

18 anesthetized, mechanically ventilated and instrumented pigs.

Interventions

After 14 days of oral administration of 1250 mg of the melon extract/gliadin (n = 9) or vehicle (n = 9), animals underwent 30 min of thoracic aortic cross-clamping and 4 h of reperfusion.

Measurements and results

Before clamping, immediately before declamping, and at 2 and 4 h of reperfusion, we measured blood isoprostane (immunoassay) and malondialdehyde concentrations (fluorimetric thiobarbituric acid test), SOD, catalase and GPx activities (spectrophotometric kits), NO formation (nitrate+nitrite; chemoluminescence), DNA damage in whole blood samples and isolated lymphocytes exposed to hyperbaric oxygen (comet assay). Organ function was also evaluated. Kidney and spinal cord specimen were analysed for apoptosis (TUNEL assay). The melon extract/gliadin blunted the DNA damage, reduced spinal cord apoptosis and attenuated NO release, however, without any effect on lipid peroxidation and organ function.

Conclusions

Pre-treatment with the oral melon extract/gliadin may be a therapeutic option to reduce oxidative cell injury affiliated with aortic cross-clamping.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Gelman S (1995) The pathophysiology of aortic cross-clamping and unclamping. Anesthesiology 82:1026–1060

    Article  PubMed  CAS  Google Scholar 

  2. Gloviczki P (2002) Surgical repair of thoracoabdominal aneurysms: patient selection, techniques and results. Cardiovasc Surg 10:434–441

    Article  PubMed  Google Scholar 

  3. McCord JM (2000) The evolution of free radicals and oxidative stress. Am J Med 108:652–659

    Article  PubMed  CAS  Google Scholar 

  4. Galang N, Sasaki H, Maulik N (2000) Apoptotic cell death during ischemia/reperfusion and its attenuation by antioxidant therapy. Toxicology 148:111–118

    Article  PubMed  CAS  Google Scholar 

  5. Beckmann KB, Ames BN (1997) Oxidative decay of DNA. J Biol Chem 272:19633–19636

    Article  Google Scholar 

  6. Nagel E, Meyer ZU, Vilsendorf A, Bartels M, Pichlmayer R (1997) Antioxidant vitamins in prevention of ischemia/reperfusion injury. Int J Vit Nutr Res 67:298–306

    CAS  Google Scholar 

  7. Kearns SR, Kelly CJ, Barry M, Abdith H, Condron C, Leahy A, Bouchier-Hayes D (1999) Vitamin C reduces ischaemia-reperfusion-induced acute lung injury. Eur J Vasc Endovasc Surg 17:533–536

    Article  PubMed  CAS  Google Scholar 

  8. Dimakakos PB, Kotsis T, Kondi-Pafiti A, Katsenis K, Doufas A, Chondors K, Kouskouni E (2002) Oxygen free radicals in abdominal aortic surgery. An experimental study. J Cardiovasc Surg (Torino) 43:77–82

    CAS  Google Scholar 

  9. Halliwell B (2002) The antioxidant paradox. Lancet 355:1179–1180

    Article  Google Scholar 

  10. Bailey DM, Raman S, McEneny J, Young IS, Parham KL, Hullin DA, Davies B, McKeeman G, McCord JM, Lewis MH (2006) Vitamin C prophylaxis promotes oxidative lipid damage during surgical ischemia-reperfusion. Free Radic Biol Med 40:591–600

    Article  PubMed  CAS  Google Scholar 

  11. Crimi E, Sica V, Williams-Ignarro S, Zhang H, Slutsky AS, Ignarro LJ, Napoli C (2006) The role of oxidative stress in critical care. Free Radic Biol Med 40:398–406

    Article  PubMed  CAS  Google Scholar 

  12. Nelson SK, Bose SK, Grunwald GK, Myhill P, McCord JM (2006) The induction of human superoxide dismutase and catalase in vivo: a fundamentally new approach to antioxidant therapy. Free Radic Biol Med 40:341–347

    Article  PubMed  CAS  Google Scholar 

  13. McCord JM, Edeas MA (2005) SOD, oxidative stress and human pathologies: a brief history and a future vision. Biomed Pharmacother 59:139–142

    Article  PubMed  CAS  Google Scholar 

  14. Svensson LG, Ritter CM von, Groeneveld HT, Rickards ES, Hunter SJ, Robinson MF, Hinder RA (1986) Cross-clamping of the thoracic aorta. Influence of aortic shunts, laminectomy, papaverine, calcium channel blocker, allopurinol, and superoxide dismutase on spinal cord blood flow and paraplegia in baboons. Ann Surg 204:38–47

    Article  PubMed  CAS  Google Scholar 

  15. Lim KH, Conolly M, Rose D, Siegman F, Jacobowitz I, Acinapura A, Cunningham JN (1986) Prevention of reperfusion injury of the ischemic spinal cord: use of recombinant superoxide dismutase. Ann Thorac Surg 42:282–286

    Article  PubMed  CAS  Google Scholar 

  16. Grabitz K, Freye E, Prior R, Schrör K, Sandmann W (1990) Does prostaglandin E1 and superoxide dismutase prevent ischaemic spinal cord injury after thoracic aortic cross-clamping? Eur J Vasc Surg 4:19–24

    Article  PubMed  CAS  Google Scholar 

  17. Chen HJ, Wu CF, Huang JL (2005) Measurement of urinary excretion of 5-hydroxymethyluracil in human by GC/NICI/MS: correlation with cigarette smoking, urinary TBARS and etheno DNA adduct. Toxicol Lett 155:403–410

    Article  PubMed  CAS  Google Scholar 

  18. Vouldoukis I, Lacan D, Kamate C, Coste P, Calenda A, Mazier D, Conti M, Dugas B (2004) Antioxidant and anti-inflammatory properties of a Cucumis melo LC extract rich in superoxide dismutase activity. J Ethnopharmacol 94:67–75

    Article  PubMed  Google Scholar 

  19. Vouldoukis I, Conti M, Krauss P, Kamate C, Blazquez S, Tefit M, Mazier D, Calenda A, Dugas B (2004) Supplementation with gliadin-combined plant superoxide dismutase extract promotes antioxidant defences and protects against oxidative stress. Phytother Res 18:957–962

    Article  PubMed  CAS  Google Scholar 

  20. Muth CM, Glenz Y, Klaus M, Radermacher P, Speit G, Leverve X (2004) Influence of an orally effective SOD on hyperbaric oxygen-related cell damage. Free Rad Res 38:927–932

    Article  CAS  Google Scholar 

  21. Naito Y, Akagiri S, Uchiyama K, Kokura S, Yoshida N, Hasegawa G, Nakamura N, Ichikawa H, Toyokuni S, Ijichi T, Yoshikawa T (2005) Reduction of diabetes-induced renal oxidative stress by a cantaloupe melon extract/gliadin biopolymer, oxykine, in mice. Biofactors 23:85–95

    PubMed  CAS  Google Scholar 

  22. Hauser B, Fröba G, Bracht H, Sträter J, Chkhotua AB, Vassilev D, Schoaff M, Huber-Lang M, Brückner UB, Radermacher P, Schelzig H (2005) Effects of intrarenal administration of the COX-2-inhibitor parecoxib during porcine suprarenal aortic-cross clamping. Shock 24:476–481

    Article  PubMed  CAS  Google Scholar 

  23. Hauser B, Gröger M, Ehrmann U, Albicini M, Brückner UB, Schelzig H, Venkatesh B, Li H, Szabó C, Speit G, Radermacher P, Kick J (2006) The PARP-inhibitor IN1001 facilitates hemodynamic stabilization without affecting DNA repair in porcine thoracic aortic cross-clamping-induced ischemia-reperfusion. Shock 25:633–640

    Article  PubMed  CAS  Google Scholar 

  24. Mastaloudis A, Yu TW, O'Donnell RP, Frei B, Dashwood RH, Traber MG (2004) Endurance exercise results in DNA damage as detected by the comet assay. Free Radic Biol Med 36:966–975

    Article  PubMed  CAS  Google Scholar 

  25. Hoffmann H, Hogel J, Speit G (2005) The effect of smoking on DNA effects in the comet assay: a meta-analysis. Mutagenesis 20:455–466

    Article  PubMed  CAS  Google Scholar 

  26. Glei M, Habermann N, Osswald K, Seidel C, Persin C, Jahreis G, Pool-Zobel BL (2005) Assessment of DNA damage and its modulation by dietary and genetic factors in smokers using the Comet assay: a biomarker model. Biomarkers 10:203–217

    Article  PubMed  CAS  Google Scholar 

  27. Godin DV, Garnett ME (1992) Species-related variations in tissue antioxidant status, II. Differences in susceptibility to oxidative challenge. Comp Biochem Physiol B 103:743–748

    Article  PubMed  CAS  Google Scholar 

  28. Godin DV, Garnett M (1992) Species-related variations in tissue antioxidant status, I. Differences in antioxidant enzyme profiles. Comp Biochem Physiol B 103:737–742

    Article  PubMed  CAS  Google Scholar 

  29. Gröger M, Speit G, Radermacher P, Muth CM (2005) Interaction of hyperbaric oxygen, nitric oxide, and heme oxygenase on DNA strand breaks in vivo. Mutat Res 572:167–172

    PubMed  Google Scholar 

  30. Matejovic M, Krouzecky A, Martinkova V, Rokyta R, Radej J, Kralova H, Treska V, Radermacher P, Novak I (2005) Effects of tempol, a free radical scavenger, on long-term hyperdynamic porcine bacteremia. Crit Care Med 33:1057–1063

    Article  PubMed  CAS  Google Scholar 

  31. Meylaerts SA, De-Haan P, Kalkman CJ, Jaspers J, Vanicky I, Jacobs MJ (2000) Prevention of paraplegia in pigs by selective segmental artery perfusion during aortic cross-clamping. J Vasc Surg 32:160–170

    Article  PubMed  CAS  Google Scholar 

  32. Maharajh GS, Pascoe EA, Halliday WC, Grocott HP, Thiessen DB, Girling LG, Cheang MS, Mutch WA (1996) Neurological outcome in a porcine model of descending thoracic aortic surgery. Left atrial–femoral artery bypass versus clamp/repair. Stroke 27:2095–2100

    PubMed  CAS  Google Scholar 

  33. Maulik G, Cordis GA, Das DK (1996) Oxidative damage to myocardial proteins and DNA during ischemia and reperfusion. Ann NY Acad Sci 793:431–436

    Article  PubMed  CAS  Google Scholar 

  34. Liu PK (2001) DNA damage and repair in the brain after cerebral ischemia. Curr Top Med Chem 1:483–495

    Article  PubMed  CAS  Google Scholar 

  35. Loft S, Larsen PN, Rasmussen A, Fischer-Nielsen A, Bondesen S, Kirkegaard P, Rasmussen LS, Ejlersen E, Tornoe K, Bergholdt R (1995) Oxidative DNA damage after transplantation of the liver and small intestine in pigs. Transplantation 59:16–20

    Article  PubMed  CAS  Google Scholar 

  36. Miller Q, Peyton BD, Cohn EJ, Holmes GF, Harlin SA, Bird ET, Harre JG, Miller ML, Riley KD, Hogan MB, Taylor A (2003) The effects of intraoperative fenoldopam on renal blood flow and tubular function following suprarenal aortic cross-clamping. Ann Vasc Surg 17:656–662

    Article  PubMed  Google Scholar 

  37. Bäckström T, Saether OD, Norgren L, Aadahl P, Myhre HO, Ungerstedt U (2001) Spinal cord metabolism during thoracic aortic cross-clamping in pigs with special reference to the effect of allopurinol. Eur J Vasc Endovasc Surg 22:410–417

    Article  PubMed  Google Scholar 

  38. Juel IS, Solligard E, Lyng O, Stromholm T, Tvedt KE, Johnsen H, Jynge P, Saether OD, Aadahl P, Gronbech JE (2004) Intestinal injury after thoracic aortic cross-clamping in the pig. J Surg Res 117:283–295

    Article  PubMed  Google Scholar 

  39. Willy C, Dahouk S, Starck C, Kaffenberger W, Gerngross H, Plappert UG (2000) DNA damage in human leukocytes after ischemia/reperfusion injury. Free Radic Biol Med 28:1–12

    Article  PubMed  CAS  Google Scholar 

  40. Andreassi MG, Botto N, Rizza A, Colombo MG, Palmieri C, Berti S, Manfredi S, Masetti S, Clerico A, Biagini A (2002) Deoxyribonucleic acid damage in human lymphocytes after percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 40:862–868

    Article  PubMed  CAS  Google Scholar 

  41. Harkema JM, Chaudry IH (1992) Magnesium-adenosine triphosphate in the treatment of shock, ischemia, and sepsis. Crit Care Med 20:263–275

    Article  PubMed  CAS  Google Scholar 

  42. Nalos M, Asfar P, Ichai C, Radermacher P, Leverve XM, Fröba G (2003) Adenosine triphosphate-magnesium chloride: relevance for intensive care. Intensive Care Med 29:10–18

    PubMed  Google Scholar 

  43. Chien CT, Lee PH, Chen CF, Ma MC, Lai MK, Hsu SM (2001) De novo demonstration and co-localization of free-radical production and apoptosis formation in rat kidney subjected to ischemia/reperfusion. J Am Soc Nephrol 12:973–982

    PubMed  CAS  Google Scholar 

  44. Ambrosio G, Zweier JL, Becker LC (1998) Apoptosis is prevented by administration of superoxide dismutase in dogs with reperfused myocardial infarction. Basic Res Cardiol 93:94–96

    Article  PubMed  CAS  Google Scholar 

  45. Warner DS, Sheng H, Batinic-Haberle I (2004) Oxidants, antioxidants and the ischemic brain. J Exp Biol 207:3221–3231

    Article  PubMed  CAS  Google Scholar 

  46. Speit G, Dennog C, Radermacher P, Rothfuss A (2002) Genotoxicity of hyperbaric oxygen. Mutat Res 512:111–119

    Article  PubMed  CAS  Google Scholar 

  47. Hicks RG, Unsworth IP, Lethlean AK (1974) Electroencephalographic responses in the pig subjected to hyperbaric oxygenation. Am J Vet Res 35:1301–1313

    PubMed  CAS  Google Scholar 

  48. Carraway MS, Piantadosi CA (1999) Oxygen toxicity. Respir Care Clin N Am 5:265–295

    PubMed  CAS  Google Scholar 

  49. Basu S, Eriksson M (1998) Oxidative injury and survival during endotoxemia. FEBS Lett 438:159–160

    Article  PubMed  CAS  Google Scholar 

  50. Longmire AW, Swift LL, Roberts LJ, Awad JA, Burk RF, Morrow JD (1994) Effect of oxygen tension on the generation of F2-isoprostanes and malondialdehyde in peroxidizing rat liver microsomes. Biochem Pharmacol 47:1173–1177

    Article  PubMed  CAS  Google Scholar 

  51. Magnani M, Rossi L, Stocchi V, Cucchiarini L, Piacentini G, Fornaini G (1988) Effect of age on some properties of mice erythrocytes. Mech Age Dev 42:37–47

    Article  CAS  Google Scholar 

  52. Clemente MG, Virgiliis S de, Kang JS, Macatagney R, Musu MP, Pierro MR di, Drago S, Congia M, Fasano A (2003) Early effects of gliadin on intracellular signalling involved in intestinal barrier function. Gut 52:218–223

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the Deutsche Forschungsgemeinschaft (DFG Sche 899/2–1). B. Hauser was the recipient of a Roman Herzog research fellowship of the Alexander von Humboldt Stiftung and the Gemeinnützige Hertie Stiftung, and S. Öter was supported by an educational and research grant of the Turkish Air Force. Glisodine was kindly provided by B. Montanari (Isocell Nutra S. A., France). Very special thanks are dedicated to W. Siegler, T. Schulz, I. Eble, A. Söll, S. Schunter, U. Biel, T. Schaller, S. Geisler and T. Seiferlein for their skilful technical assistance.

Author information

Authors and Affiliations

  1. Abteilung Thorax- und Gefässchirurgie, Universitätsklinikum Ulm, Steinhövelstrasse 9, 89075, Ulm, Germany

    Jochen Kick, Florian Simon & Hubert Schelzig

  2. Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum Ulm, Parkstrasse 11, 89073, Ulm, Germany

    Jochen Kick, Balázs Hauser, Hendrik Bracht, Maura Albicini, Sükrü Öter, Florian Simon, Ulrich Ehrmann, Peter Radermacher & Claus-Martin Muth

  3. Département de Biologie Intégrée, Centre Hospitalier Universitaire, Université Joseph Fourier, BP 217, 38043, Grenoble, France

    Catherine Garrel

  4. Abteilung Pathologie, Universitätsklinikum Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany

    Jörn Sträter

  5. Sektion Chirurgische Forschung, Universitätsklinikum Ulm, Parkstrasse 11, 89073, Ulm, Germany

    Uwe B. Brückner

  6. Laboratoire de Bioénergétique Fondamentale et Appliquée, Université Joseph Fourier, BP 53X, 38041, Grenoble, France

    Xavier M. Leverve

  7. Abteilung Humangenetik, Universitätsklinikum Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany

    Günter Speit

  8. Semmelweis Egyetem, Aneszteziológiai és Intenzív Terápiás Klinika, Kútvölgyi ut 4, 1125, Budapest, Hungary

    Balázs Hauser

  9. Istituto di Anestesiologia e Rianimazione dell’Universita degli Studi di Milano, Azienda Ospedaliera, Polo Universitario San Paolo, Via Di Rudini 8, 20154, Milano, Italy

    Maura Albicini

  10. Fizyoloji Anabilim Dali, Gülhane Askeri Tip Akademisi, General Tevfik Saglam Caddesi, 06018 Etlik, Ankara, Turkey

    Sükrü Öter

Authors
  1. Jochen Kick
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Balázs Hauser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hendrik Bracht
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maura Albicini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sükrü Öter
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Florian Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ulrich Ehrmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Catherine Garrel
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jörn Sträter
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Uwe B. Brückner
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xavier M. Leverve
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Hubert Schelzig
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Günter Speit
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Peter Radermacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Claus-Martin Muth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Radermacher.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kick, J., Hauser, B., Bracht, H. et al. Effects of a cantaloupe melon extract/wheat gliadin biopolymer during aortic cross-clamping. Intensive Care Med 33, 694–702 (2007). https://doi.org/10.1007/s00134-006-0518-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-006-0518-6

Keywords

Search

Navigation