In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds

S. de Flora, C. Bennicelli, A. Camoirano, D. Serra, M. Romano, G. A. Rossi, A. Morelli

Research output: Contribution to journalArticle

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Abstract

N-acetylcysteine (NAC) was administered to rats in various combinations with an enzyme inducer (Aroclor 1254) and with depletors of reduced glutathione (GSH), i.e., diethyl maleate (DEM) and buthionine sulfoximine (BSO). NAC increased intracellular glutathione levels in erythrocytes and in liver and lung cells, and replenished its stores following depletion. It did not affect the concentrations nor the spectral properties of cytochromes P-450 in hepatic and pulmonary microsomes, whereas it stimulated, especially in Aroclor-pre-treated animals, cytosolic enzyme activities involved in NADP reduction (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), in glutathione reduction (GSSG-reductase) and in the reductive detoxication of xenobiotics by-passing formation of reactive oxygen species (DT-diaphorase). In vivo treatment with the drug enhanced detoxication by liver and lung S-12 fractions of direct-acting mutagens (ICR 191, epichlorohydrin, 4-nitroquinolino-N-oxide and dichromate) and counteracted opposite effects triggered by administration of GSH depletors. The metabolic activation of procarcinogens (aflatoxin B1, 2-aminofluorene, cyclophosphamide, benzo[a]pyrene, a tryptophan pyrolysate product and cigarette smoke condensate) was inhibited by NAC in uninduced rats, while it was further stimulated in Aroclor-pre-treated animals. Additional assays, performed also with other enzyme inducers (phenobarbital and 3-methylcholanthrene) suggested that the effect of NAC on the metabolic activation of procarcinogens depends on the balance between an increased production of mutagenic metabolites (prevailing in induced animals) and their binding by intracellular thiols (prevailing under normal conditions). Thus, due to its dual role as a nucleophile and as a SH donor, NAC appears to exert protective effects by modulating glutathione metabolism and the biotransformation of mutagenic/carcinogenic compounds. This may have clinical relevance, since NAC is administered to individuals, such as cigarette smokers, who are more heavily exposed to GSH depletors and to carcinogenic agents.

Original languageEnglish
Pages (from-to)1735-1745
Number of pages11
JournalCarcinogenesis
Volume6
Issue number12
Publication statusPublished - 1985

Fingerprint

Acetylcysteine
Glutathione
Biotransformation
Metabolism
Animals
Enzymes
Lung
Aroclors
Liver
Activation
diethyl maleate
Reactive Oxygen Species
Tobacco Products
Erythrocyte
Rats
Condensate
Depletion
Chemical activation
Glucose
Epichlorohydrin

ASJC Scopus subject areas

  • Cancer Research
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology
  • Behavioral Neuroscience

Cite this

de Flora, S., Bennicelli, C., Camoirano, A., Serra, D., Romano, M., Rossi, G. A., & Morelli, A. (1985). In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds. Carcinogenesis, 6(12), 1735-1745.

In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds. / de Flora, S.; Bennicelli, C.; Camoirano, A.; Serra, D.; Romano, M.; Rossi, G. A.; Morelli, A.

In: Carcinogenesis, Vol. 6, No. 12, 1985, p. 1735-1745.

Research output: Contribution to journalArticle

de Flora, S, Bennicelli, C, Camoirano, A, Serra, D, Romano, M, Rossi, GA & Morelli, A 1985, 'In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds', Carcinogenesis, vol. 6, no. 12, pp. 1735-1745.
de Flora S, Bennicelli C, Camoirano A, Serra D, Romano M, Rossi GA et al. In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds. Carcinogenesis. 1985;6(12):1735-1745.
de Flora, S. ; Bennicelli, C. ; Camoirano, A. ; Serra, D. ; Romano, M. ; Rossi, G. A. ; Morelli, A. / In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds. In: Carcinogenesis. 1985 ; Vol. 6, No. 12. pp. 1735-1745.
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