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Vol. 107, No. 1, 2007
Issue release date: September 2007
Nephron Clin Pract 2007;107:c26–c34

Antiglycation and Antioxidant Effect of Carnosine against Glucose Degradation Products in Peritoneal Mesothelial Cells

Alhamdani M.-S.S. · Al-Kassir A.-H.A.-M. · Abbas F.K.H. · Jaleel N.A. · Al-Taee M.F.
aDepartment of Medical Sciences, College of Pharmacy, and bDepartment of Internal Medicine, College of Medicine, Al-Mustansiriya University; cArtificial Kidney Unit, Al-Karama Teaching Hospital, dArtificial Kidney Unit, Al-Yarmuk Teaching Hospital, and eBiotechnology Department, College of Sciences, Al-Nahrain University, Baghdad, Iraq

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Background/Aim:Toxicity with advanced glycation end products (AGEs) is a major problem in uremic patients. Treatment with peritoneal dialysis (PD) exacerbates AGE formation as a result of bioincompatibility of the conventional peritoneal dialysis fluid (PDF). The presence of glucose degradation products (GDPs) in PDF is the main cause of its bioincompatibility. Carnosine is an endogenous dipeptide with a powerful antiglycation/antioxidant activity. In an attempt to improve PDF biocompatibility, we evaluated the effect of carnosine in human peritoneal mesothelial cells (HPMC) incubated with PDF or GDPs in vitro. Methods: HPMC were incubated for short or prolonged time with PDF in the presence or absence of carnosine. Similarly, HPMC were incubated in the same condition but with a combination of GDPs. Following the incubation, cells were tested for their viability, protein carbonyl content and reactive oxygen species (ROS) production. Results: Results demonstrated a significant protective effect of carnosine to HPMC in both acute and chronic conditions with PDF or GDPs as judged by the enhancement of cell viability, preserved protein from modification and decreased ROS production. Conclusion: Carnosine enhanced HPMC viability against the toxic effect of GDPs probably through protection of cellular protein from modification and from ROS-mediated oxidative damage. The salutary effect of carnosine may render it a desirable candidate for improving PDF biocompatibility and reducing AGE complications in PD patients.

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  1. Inagi R, Miyata T: Oxidative protein damage with carbohydrates and lipids in uremia: ‘carbonyl stress’. Blood Purif 1999;17:95–98.
  2. Lapolla A, Flamini R, Lupo A, Arico NC, Rugiu C, Reitano R, Tubaro M, Ragazzi E, Seraglia R, Traldi P: Evaluation of glyoxal and methylglyoxal levels in uremic patients under peritoneal dialysis. Ann NY Acad Sci 2005;1043:217–224.
  3. Miyata T, Kurokawa K, van Ypersele de Strihou C: Advanced glycation and lipoxidation end products: role of reactive carbonyl compounds generated during carbohydrate and lipid metabolism. J Am Soc Nephrol 2000;11:1744–1752.
  4. Linden T, Cohen A, Deppisch R, Kjellstrand P, Wieslander A: 3,4-Dideoxyglucosone-3-ene (3,4-DGE): a cytotoxic glucose degradation product in fluids for peritoneal dialysis. Kidney Int 2002;62:697–703.
  5. Alhamdani MSS, Al-Kassir AAM, Jaleel NA, Hmood AM, Ali HM: Elevated levels of alkanals, alkenals and 4-hydroxyalkenals in plasma of hemodialysis patients. Am J Nephrol 2006;26:299–303.
  6. Miyata T, van Ypersele de Strihou C, Kurokawa K, Baynes JW: Alterations in non-enzymatic biochemistry in uremia: origin and significance of ‘carbonyl stress’ in long-term uremic complications. Kidney Int 1999;55:389–399.
  7. Nilsson-Thorell CB, Muscalu N, Andrén AH, Kjellstrand PT, Wieslander AP: Heat sterilization of fluids for peritoneal dialysis gives rise to aldehydes. Perit Dial Int 1993;13:208–213.
  8. Wieslander AP, Andrén AH, Nilsson-Thorell C, Muscalu N, Kjellstrand PT, Rippe B: Are aldehydes in heat-sterilized peritoneal dialysis fluids toxic in vitro? Perit Dial Int 1995;15:348–352.
  9. Witowski J, Korybalska K, Wisniewska J, Breborowicz A, Gahl GM, Frei U, Passlick-Deetjen J, Jorres A: Effect of glucose degradation products on human peritoneal mesothelial cell function. J Am Soc Nephrol 2000;11:729–739.
  10. Witowski J, Wisniewska J, Korybalska K, Bender TO, Breborowicz A, Gahl GM, Frei U, Passlick-Deetjen J, Jorres A: Prolonged exposure to glucose degradation products impairs viability and function of human peritoneal mesothelial cells. J Am Soc Nephrol 2001;12:2434–2441.
  11. Breborowicz A, Witowski J, Polubinska A, Pyda M, Oreopoulos D: L-2-Oxothiazolidine-4-carboxylic acid reduces in vitro cytotoxicity of glucose degradation products. Nephrol Dial Transplant 2004;19:3005–3011.
  12. Welten AG, Schalkwijk CG, ter Wee PM, Meijer S, van den Born J, Beelen RJ: Single exposure of mesothelial cells to glucose degradation products yields early advanced glycation end products and a proinflammatory response. Perit Dial Int 2003;23:213–221.
  13. Inagi R, Miyata T, Yamamoto T, Suzuki D, Urakami K, Saito A, van Ypersele de Strihou C, Kurokawa K: Glucose degradation product methylglyoxal enhances the production of vascular endothelial growth factor in peritoneal cells: role in the functional and morphological alterations of peritoneal membranes in peritoneal dialysis. FEBS Lett 1999;463:260–264.
  14. Linden T, Musi B, Jarkelid L, Forsback G, Kjellstrand P, Deppisch R, Wieslander A: Glucose degradation products in peritoneal dialysis fluids may have both local and systemic effects: a study of residual fluid and mesothelial cells. Perit Dial Int 2001;21:607–610.
  15. Lage C, Pischetsrieder M, Aufricht C, Jorres A, Schilling H, Passlick-Deetjen J: First in vitro and in vivo experiences with Stay-Safe Balance, a pH-neutral solution in a dual-chambered bag. Perit Dial Int 2000;20(suppl 5):S28–S32.

    External Resources

  16. Inagi R, Miyata T, Ueda Y, Yoshino A, Nangaku M, van Ypersele de Strihou C, Kurokawa K: Efficient in vitro lowering of carbonyl stress by the glyoxalase system in conventional glucose peritoneal dialysis fluid. Kidney Int 2002;62:679–687.
  17. Ishikawa N, Miyata T, Ueda Y, Inagi R, Izuhara Y, Yuzawa H, Onogi H, Nishina M, Nangaku M, Van Ypersele De Strihou C, Kurokawa K: Affinity adsorption of glucose degradation products improves the biocompatibility of conventional peritoneal dialysis fluid. Kidney Int 2003;63:331–339.
  18. Sakai A, Nakayama M, Numata M, Takesawa S, Nakamoto M: Sodium sulfite and N-acetylcysteine: new additives to dialysate for inhibiting formation of glucose degradation products and advanced glycation end products. Adv Perit Dial 2001;17:66–70.
  19. Quinn PJ, Boldyrev AA, Formazuyk VE: Carnosine: its properties, functions and potential therapeutic applications. Mol Aspects Med 1992;13:379–444.
  20. Abe H: Role of histidine-related compounds as intracellular proton buffering constituents in vertebrate muscle. Biochemistry (Mosc) 2000;65:757–765.
  21. Shimada T, Watanabe N, Ohtsuka Y, Endoh M, Kojima K, Hiraishi H, Terano A: Polaprezinc down-regulates proinflammatory cytokine-induced nuclear factor-κB activation and interleukin-8 expression in gastric epithelial cells. J Pharmacol Exp Ther 1999;291:345–352.
  22. Nagai K, Suda T: Realization of spontaneous healing function by carnosine. Methods Find Exp Clin Pharmacol 1988;10:497–507.
  23. McFarland GA, Holliday R: Retardation of the senescence of cultured human diploid fibroblasts by carnosine. Exp Cell Res 1994;212:167–175.
  24. McFarland GA, Holliday, R: Further evidence for the rejuvenating effects of the dipeptide L-carnosine on cultured human diploid fibroblasts. Exp Geront 1999;34:35–45.
  25. Hartman PE, Hartman Z: Direct interception of mutagens and carcinogens by biomolecules. Basic Life Sci 1993;61:351–366.
  26. Guiotto A, Calderan A, Ruzza P, Borin G: Carnosine and carnosine-related antioxidants: a review. Curr Med Chem 2005;12:2293–2315.
  27. Aldini G, Facino RM, Beretta G, Carini M: Carnosine and related dipeptides as quenchers of reactive carbonyl species: from structural studies to therapeutic perspectives. Biofactors 2005;24:77–87.
  28. Price DL, Rhett PM, Thorpe SR, Baynes JW: Chelating activity of advanced glycation end product inhibitors. J Biol Chem 2001;276:48967–48972.
  29. Hipkiss AR, Michaelis J, Syrris P: Non-enzymic glycosylation of the dipeptide L-carnosine, a potential anti-protein cross-linking agent. FEBS Lett 1995;371:81–85.
  30. Hipkiss AR, Brownson C, Bertani MF, Ruiz E, Ferro A: Reaction of carnosine with aged proteins: another protective process? Ann NY Acad Sci 2002;959:285–294.
  31. Seidler NW, Yeargans GS, Morgan TG: Carnosine disaggregates glycated α-crystallin: an in vitro study. Arch Biochem Biophys 2004;427:110–115.
  32. Stylianou E, Jenner LA, Davies M, Coles GA, Williams JD: Isolation, culture and characterization of human peritoneal mesothelial cells. Kidney Int1990;37:1563–1570.
  33. Van de Loosdrecht AA, Beelen RH, Ossenkoppele GJ, Broekhoven MG, Langenhuijsen MM: A tetrazolium-based colorimetric MTT assay to quantitate human monocyte-mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leukemia. J Immunol Methods 1994;174:311–320.
  34. Vassault, A: Lactate dehydrogenase: UV method with pyruvate and NADH; in Bergmeyer HU, Bergmeyer J, Grassi M (eds): Methods of Enzymatic Analysis. New York, Verlag Chemie/Academic Press, 1983, vol 3, pp 118–126.
  35. Hartley DP, Kroll DJ, Petersen DR: Prooxidant-initiated lipid peroxidation in isolated rat hepatocytes: detection of 4-hydroxynonenal- and malondialdehyde-protein adducts. Chem Res Toxicol 1997;10:895–905.
  36. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn B, Shaltiel S, Stadtman ER: Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 1990;186:464–478.
  37. Gouazé V, Andrieu-Abadie N, Malagarie-Cazenave O, Frisach MF, Mirault ME, Levade T: Glutathione peroxidase-1 protects from CD95-induced apoptosis. J Biol Chem 2002;277:42867–42874.
  38. Breborowicz A, Breborowicz M, Oreopoulos DG: Glucose-induced changes in the phenotype of human peritoneal mesothelial cells: effect of L-2-oxothiazolidine carboxylic acid. Am J Nephrol 2003;23:471–476.
  39. Hu Y, Ocheltree SM, Xiang J, Keep RF, Smith DE: Glycyl-L-glutamine disposition in rat choroid plexus epithelial cells in primary culture: role of PEPT2. Pharm Res 2005;22:1281–1286.
  40. Miyata T, Horie K, Ueda Y, Fujita Y, Izuhara Y, Hirano H, Uchida K, Saito A, van Ypersele de Strihou C, Kurokawa K: Advanced glycation and lipid oxidation of the peritoneal membrane: respective roles of serum and peritoneal fluid reactive carbonyl compounds. Kidney Int 2000;58:425–435.
  41. Alhamdani MSS, Al-Azzawie HF, Abbas FKH: Decreased formation of advanced glycation end products in peritoneal fluid by carnosine and related peptides. Perit Dial Int 2007;27:86–89.
  42. Decker EA, Livisay SA, Zhou S: A re-evaluation of the antioxidant activity of purified carnosine. Biochemistry (Mosc) 2000;65:766–770.
  43. Boldyrev AA, Dupin AM, Pindel EV, Severin SE: Antioxidative properties of histidine-containing dipeptides from skeletal muscles of vertebrates. Comp Biochem Physiol B 1988;89:245–250.
  44. Werynski A, Waniewski J, Wang T, Anderstam B, Lindholm B, Bergstrom J: Kinetic studies of dipeptide-based and amino acid-based peritoneal dialysis solutions. Kidney Int 2001;59:363–371.
  45. Bergstrom J, Furst P, Noree LO, Vinnars E: Intracellular free amino acids in muscle tissue of patients with chronic uraemia: effect of peritoneal dialysis and infusion of essential amino acids. Clin Sci Mol Med 1978;54:51–60.

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