Summary
Effect ofN-acetyl-l-cysteine (NAC) administration on cysteine and glutathione (GSH) contents in rat liver and kidney was studied using intact and diethyl maleate (DEM)-treated rats and perfused rat liver. Cysteine contents increased rapidly, reaching peak at 10 min after intraperitoneal NAC administration. In liver mitochondria it increased slowly, reaching peak at 60 min. GSH content did not change significantly in these tissues. However, in liver and kidney depleted of GSH with DEM, NAC administration restored GSH contents in 60 and 120 min, respectively. Perfusion with 10 mM NAC resulted in 76% increase in liver cysteine content, but not in GSH content. Liver perfusion of DEM-injected rats with 10 mM NAC restored GSH content by 15%. Present findings indicate that NAC is an effective precursor of cysteine in the intact liver and kidney and in the perfused rat liver, and that NAC stimulated GSH synthesis in GSH-depleted tissues.
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References
Birnbaum SM, Levintow L, Kingsley RB, Greenstein JP (1952) Specificity of amino acid acylases. J Biol Chem 194: 455–470
Borgström L, Kågedal B, Paulsen O (1986) Pharmacokinetics ofN-acetylcysteine in man. Eur J Clin Pharmacol 31: 217–222
Boyland E, Chasseaud LF (1970) The effect of some carbonyl compounds on rat liver glutathione levels. Biochem Pharmacol 19: 1526–1528
Burgunder JM, Varriale A, Lauterburg BH (1989) Effect ofN-acetylcysteine on plasma cysteine and glutathione following paracetamol administration. Eur J Clin Pharmacol 36: 127–131
Gaitonde MK (1967) A spectrophotometric method for the direct determination of cysteine in the presence of other naturally occurring amino acids. Biochem J 104: 627–633
Grassi C, Morandini GC (1976) A controlled trial of intermittent oral acetylcysteine in the long-term treatment of chronic bronchitis. Eur J Clin Pharmacol 9: 393–396
Griffith OW, Meister A (1985) Origin and turnover of mitochondrial glutathione. Proc Natl Acad Sci USA 82: 4668–4672
Jaworek D, Welsch J (1985) UV-method. In: Bergmeyer HU, Bergmeyer J, Grassl M (eds) Methods in enzymatic analysis, 3rd edn, vol 7. VCH, Weinheim, pp 365–370
Jocelyn PC (1972) Biochemistry of the SH group. Academic Press, London, pp 170–173
Lauterburg BH, Corcoran GB, Mitchell JR (1983) Mechanism of action ofN-acetylcysteine in the protection against the hepatotoxicity of acetaminophen in ratsin vivo. J Clin Invest 71: 980–991
Layne E (1957) Spectrophotometric and turbidimetric methods for measuring proteins. Methods Enzymol 3: 447–454
Meister A (1988) Glutathione metabolism and its selective modification. J Biol Chem 263: 17205–17208
Meister A, Anderson ME, Hwang O (1986) Intracellular cysteine and glutathione delivery systems. J Am Coll Nutr 5: 137–151
Plummer JL, Smith BR, Sies H, Bend JR (1981) Chemical depletion of glutathionein vivo. Methods Enzymol 77: 50–59
Porta P, Aebi S, Summer K, Lauterburg BH (1991)l-2-Oxothiazolidine-4-carboxylic acid, a cysteine prodrug: Pharmacokinetics and effects on thiols in plasma and lymphocytes in human. J Pharmacol Exp Ther 257: 331–334
Prescott LF, Park J, Ballantyne A, Adriaenssens P, Proudfoot AT (1977) Treatment of paracetamol (acetaminophen) poisoning withN-acetylcysteine. Lancet ii: 432–434
Sugano T, Suda K, Shimada M, Oshino N (1978) Biochemical and ultrastructural evaluation of isolated rat liver system perfused with a hemoglobin-free medium. J Biochem 83: 995–1007
Thor H, Moldéus P, Orrenius S (1979) Metabolic activation and hepatotoxicity. Effect of cysteine,N-acetylcysteine, and methionine on glutathione biosynthesis and bromobenzene toxicity in isolated rat hepatocyte. Arch Biochem Biophys 192: 405–413
Tietze F (1969) Enzymatic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Application to mammalian blood and other tissues. Anal Biochem 27: 502–522
Traber J, Suter M, Walter P, Richter C (1992)In vivo modulation of total and mitochondrial glutathione in rat liver. Depletion by phorone and rescue byN-acetylcyteine. Biochem Pharmacol 43: 961–964
Trautschold I, Lamprecht W, Schweitzer G (1985) UV-method with hexokinase and glucose-6-phosphate dehydrogenase. In: Bergmeyer HU, Bergmeyer J, Grassl M (eds) Methods of enzymatic analysis, 3rd edn, vol 7. VCH, Weinheim, pp 346–357
Ubuka T, Yuasa S, Ohta J, Masuoka N, Yao K, Kinuta M (1990) Formation of sulfate froml-cysteine in rat liver mitochondria. Acta Med Okayama 44: 55–64
Ubuka T, Ohta J, Yao W-B, Abe T, Teraoka T, Kurozumi Y (1992)l-Cysteine metabolism via 3-mercaptopyruvate pathway and sulfate formation in rat liver mitochondria. Amino Acids 2: 143–155
Viña J, Romero FJ, Estrela JM, Viña JR (1980) Effect of acetaminophen (paracetamol) and its antagonists on glutathione (GSH) content in rat liver. Biochem Pharmacol 29: 1968–1970
Wahlländer A, Soboll S, Sies H (1979) Hepatic mitochondrial and cytosolic glutathione content and the subcellular distribution of GSH-S-transferase. FEBS Lett 97: 138–140
Yamada S, Abe T, Ohta J, Masuoka N, Ubuka T (1995) Increase in tissue cysteine level and excretion of sulfate and taurine after intragastric administration ofl-2-oxothiazolidine-4-carboxylate in rats. Amino Acids (to be published)
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Yao, W.B., Zhao, Y.Q., Abe, T. et al. Effect ofN-acetylcysteine administration on cysteine and glutathione contents in liver and kidney and in perfused liver of intact and diethyl maleate-treated rats. Amino Acids 7, 255–266 (1994). https://doi.org/10.1007/BF00807701
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DOI: https://doi.org/10.1007/BF00807701