The effects of galactosamine on UTP levels in the livers of young, adult and old rats.
Languages of publication
Galactosamine (GalN), a well-known hepatotoxin that depletes the cellular pool of uracil nucleotides, was previously shown to have greater impact on the inhibition of protein synthesis in hepatocytes of old rats as compared with young animals (Kmieć 1994, Ann. N.Y. Ac. Sci. 717, 216-225). In the present study we compared the effects of GalN on the nucleotide content (measured by ion-exchange HPLC) in the livers of young (4 months), adult (12 months), and old (24-26 months old) rats two hours after its intraperitoneal administration. UTP content of the livers of old control rats was significantly lower (by 28%) than that of young animals. GalN administration decreased the UTP content in the livers of young, adult and old rats by, respectively, 55%, 65% and 89%, and increased the content of UDP-sugars by 189%, 175% and 305%. The hepatic content of ATP, ADP, AMP, NAD, GTP except CTP did not differ significantly among the age groups of rats studied, and was not changed by GalN treatment. The content of CTP was significantly higher in old rats (P < 0.03) upon GalN treatment. The lower hepatic content of UTP may partially explain the increased sensitivity of hepatocytes and livers of old rats to the action of galactosamine, and possibly to other hepatotoxic compounds that decrease transcription in the liver.
- 1. Kmiec, Z. (1994) Prostaglandin cytoprotection of galactosamine-incubated hepatocytes isolated from young and old rat. Ann. N.Y. Acad. Sci. 717, 216-225.
- 2. Keppler, D., Pausch, J. & Decker, K. (1974) Selective uridine triphosphate deficiency induced by D-galactosamine in liver and reversed by pyrimidine nucleotide precursors. Effect on ribonucleic acid synthesis. J. Biol. Chem. 249, 211-216.
- 3. Kmieć, Z., Marlewski, M., Smoleński, R.T. & Simmons, H.A. (1995) Effect of galactosamine on adenine and uracil nucleotides levels in isolated hepatocytes of young and old rats; in Purine and Pyrimidine Metabolism in Man VIII (Sahota, A. & Taylor, M., eds.) pp. 523-526, Plenum Press, New York.
- 4. Kmieć, Z. & Myśliwski, A. (1985) Urea synthesis in hepatocytes isolated from young and old rats. Exp. Gerontol. 20, 271-277.
- 5. Myśliwski, A. & Kmieć, Z. (1992) Effect of aging on glycogen synthesis in liver of starved- refed rats. Arch. Gerontol. Geriatr. 14, 85-92.
- 6. Żydowo, M., Smoleński, R.T. & Świerczyński, J. (1993) Acetate-induced changes of adenine nucleotides levels in rat liver. Metabolism 42, 644-648.
- 7. Simmonds, H.A., Duley, J.A. & Davies, P.M. (1991) Analysis of purines and pyrimidines in blood, urine and other physiological fluids; in Techniques in Diagnostic Human Biochemical Genetics (White, W.F., ed.) pp. 397-424, Wiley, New York.
- 8. Bergmeyer, H.U., Horder, M. & Rej, R. (1986) Approved recommendation (1985) on IFCC methods for the measurement of catalytic concentrations of enzymes. Part 3. IFCC method for alanine aminotransferase. J. Clin. Chem. Clin. Biochem. 24, 481-489.
- 9. Mandl, J., Meszaros, K., Antoni, F., Spolarics, Z. & Garzo, T. (1982) Reversible inhibition of RNA synthesis and irreversible inhibition of protein synthesis by D-galactosamine in isolated mouse hepatocytes. Mol. Cell. Biochem. 46, 25-30.
- 10. Leist, M., Gantner, F., Bohlinger, I., Germann, P.G., Tiegs, G. & Wendel, A. (1994) Murine hepatocyte apoptosis induced in vitro and in vivo by TNF-α requires transcriptional arrest. J. Immunol. 153, 1778-1788.
- 11. Decker, K. & Keppler, D. (1974) Galactosamine hepatitis: Key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death. Rev. Physiol. Biochem. Pharmacol. 71, 77-106.
- 12. Platt, D., Forster, K. & Forster, L.C. (1978) Age-dependent kinetic studies of cytoplasmic and lysosomal enzymes of the normal and D-galactosamine-injured rat liver. Mech. Ageing Dev. 7, 183-188.
- 13. Rikans, L.E. (1989) Influence of aging on chemically induced hepatotoxicity: Role of age-related changes in metabolism. Drug Metab. Rev. 20, 87-110.
- 14. Galanos, Ch., Freudenberg, M.A. & Reutter, W. (1979) Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc. Natl. Acad. Sci. U.S.A. 76, 5939-5943.
- 15. Decker, K. (1990) Biologically active products of stimulated liver macrophages (Kupffer cells). Eur. J. Biochem. 192, 245-261.
- 16. Kmieć, Z., Hughes, R.D., Moore, K.P., Sheron, N., Gove, C.D., Nouri-Aria, K.T. & Williams, R. (1993) Effect of supernatants from Kupffer cells stimulated with galactosamine and endotoxin on the function of isolated rat hepatocytes. Hepato-Gastroenterol. 40, 259- 261.
- 17. Horan, M.A., Brouwer, A., Barelds, R.J., Wientjens, R., Durham, S.K. & Knook, D.L. (1991) Changes in endotoxin sensitivity in ageing. Absorption, elimination and mortality. Mech. Ageing Dev. 57, 145-162.
Publication order reference