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Has reactive oxygen a role in methylglyoxal toxicity? A study on cultured rat hepatocytes

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Abstract

The toxicity of methylglyoxal and its ability to generate reactive oxygen species were investigated in cultured rat hepatocytes. Under aerobic and anaerobic conditions methylglyoxal increased lactate dehydrogenase (LDH) release and trypan blue uptake in a concentration dependent manner. Those concentrations of methylglyoxal causing cell injury (1 mM<) also caused the release of reactive oxygen species as indicated by peroxidase-catalyzed luminol chemiluminescence. Release of reactive oxygen was detectable only under aerobic conditions, and only became significant when a large portion of the cells had already lost their viability. It is concluded that methylglyoxal injures cultured rat hepatocytes and induces the generation of reactive oxygen species. The reactive oxygen species, however, are essentially not involved in methylglyoxal hepatotoxicity but are released by already severely injured cells.

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References

  • Anundi I, Högberg J, Stead AH (1979) Glutathione depletion in isolated hepatocytes: its relation to lipid peroxidation and cell damage. Acta Pharmacol Toxicol 45: 45–51

    Google Scholar 

  • Cadenas E, Sies H (1984) Low-level chemiluminescence as an indicator of singlet molecular oxygen in biological systems. Methods Enzymol 105: 221–231

    PubMed  Google Scholar 

  • Casazza JP, Felver ME, Veech RL (1984) Acetone metabolism in rat. J Biol Chem 259: 231–236

    PubMed  Google Scholar 

  • Cooper RA (1984) Metabolism of methylglyoxal in microorganisms. Annu Rev Microbiol 38: 49–68

    PubMed  Google Scholar 

  • de Groot H, Brecht M (1991) Reoxygenation injury in rat hepatocytes: mediation by O2−s/H2O2 liberated by sources other than xanthine oxidase. Biol Chem Hoppe-Seyl 372: 35–41

    Google Scholar 

  • de Groot H, Anundi I, Sies H (1991) Cytochrome P-450 and lipid peroxidation. In: Ruckpaul K, Rein H (eds) Membrane organization and phospholipid interaction of cytochrome P-450. Akademie Verlag, Berlin, pp 184–205

    Google Scholar 

  • Jauregui HO, Hayner NT, Driscoll JL, Williams-Holland R, Lipsky MH, Galletti PM (1981) Trypan blue dye uptake and lactate dehydrogenase in adult rat hepatocytes — freshly isolated cells, cell suspensions, and primary monolayer cultures. In Vitro 17: 1100–1110

    PubMed  Google Scholar 

  • Kalapos MP (1992) Mechanisms leading to complications in diabetes mellitus: possible role of alpha-oxoaldehydes. Biochem Education 20: 27–29

    Article  Google Scholar 

  • Kalapos MP, Garzó T, Antoni F, Mandl J (1991) Effect of methylglyoxal on glucose formation, drug oxidation and glutathione content in isolated murine hepatocytes. Biochim Biophys Acta 1092: 284–290

    Article  PubMed  Google Scholar 

  • Kalapos MP, Garzó T, Antoni F, Mandl J (1992) Accumulation of S-d-lactoylglutathione and transient decrease of glutathione level caused by methylglyoxal load in isolated hepatocytes. Biochim Biophys Acta 1135: 159–164

    Article  PubMed  Google Scholar 

  • Kun E (1950) Inhibition of succinic dehydrogenase by methylglyoxal. J Biol Chem 187: 289–297

    PubMed  Google Scholar 

  • Leoncini G (1979) The role of alpha-ketoaldehydes in biological systems. Ital J Biochem 28: 285–294

    PubMed  Google Scholar 

  • Leoncini G, Maresca M, Bonsignore A (1980) The effect of methylglyoxal on the glycolytic enzymes. FEBS Lett 117: 17–18

    Article  PubMed  Google Scholar 

  • Meister A (1988) Glutathione metabolism and its selective modification. J Biol Chem 263: 17205–17208

    PubMed  Google Scholar 

  • Mira ML, Martinho F, Azevedo MS, Manso CF (1991) Oxidative inhibition of red blood cell ATP-ases by glyceraldehyde. Biochim Biophys Acta 1060: 257–261

    PubMed  Google Scholar 

  • Peinado J, López-Sariano FJ, Argiles JM (1986) The metabolism of acetone in the pregnant rat. Biosci Rep 6: 983–989

    Article  PubMed  Google Scholar 

  • Puget K, Michelson AM (1976) Microestimation of glucose and glucose oxidase. Biochemie 58: 757–758

    Google Scholar 

  • Racker E (1951) The mechanism of action of glyoxalase. J Biol Chem 190: 685–696

    PubMed  Google Scholar 

  • Seglen PO (1973) Preparation of rat liver cells. Exp Cell Res 82: 391–398

    Article  PubMed  Google Scholar 

  • Seitz WR (1978) Chemiluminescence detection of enzymically generated peroxide. Methods Enzymol 57: 737–758

    Google Scholar 

  • Sulway MJ, Malins JM (1970) Acetone in diabetic ketoacidosis. Lancet ii: 736–740

    Article  Google Scholar 

  • Thornalley PJ (1990) The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life. Biochem J 269: 1–11

    PubMed  Google Scholar 

  • Thornalley PJ and Bellavite P (1988) Modification of the glyoxalase system during the functional activation of human neutrophils. Biochim Biophys Acta 931: 120–129

    Google Scholar 

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  1. Miklós Péter Kalapos

    Present address: Department of Metabolic Regulation, Boston Biomedical Research Institute, 20 Staniford Street, 02114, Boston, MA, USA

Authors and Affiliations

  1. Klinische Forschergruppe Leberschädigung, Institut für Physiologische Chemie I und Abteilung für Gastroenterologie, Heinrich-Heine-Universität Düsseldorf, Germany

    Miklós Péter Kalapos, Andrea Littauer & Herbert qde Groot

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  1. Miklós Péter Kalapos
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  2. Andrea Littauer
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  3. Herbert qde Groot
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Kalapos, M.P., Littauer, A. & qde Groot, H. Has reactive oxygen a role in methylglyoxal toxicity? A study on cultured rat hepatocytes. Arch Toxicol 67, 369–372 (1993). https://doi.org/10.1007/BF01973710

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  • DOI: https://doi.org/10.1007/BF01973710

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