Distribution of radio-labeled N-acetyl-L-cysteine in sprague-dawley rats and its effect on glutathione metabolism following single and repeat dosing by oral gavage

Cutaneous and Ocular Toxicology

Volumn 26, Issue 2, 2007, Pages 113-134

  Arfsten, Darryl P ^a,b   Johnson, Eric W ^a   Wilfong, Erin R ^a   Jung, Anne E ^a   Bobb, Andrew J ^a  

^a AIR FORCE RESEARCH LABORATORY   (United States)

^b Navy Drug Screening Laboratory   (United States)

Author keywords

Distribution; Glutathione; Glutathione peroxidase; Glutathione reductase; Glutathione S transferase; N acetyl L cysteine; Oral gavage; Oxidative stress; Rats; Toxicity

Indexed keywords

ACETYLCYSTEINE; ACETYLCYSTEINE C 14; GLUTATHIONE; GLUTATHIONE PEROXIDASE; GLUTATHIONE REDUCTASE; GLUTATHIONE TRANSFERASE; MUSTARD GAS; RADIOISOTOPE; UNCLASSIFIED DRUG;

AMINO ACID METABOLISM; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; COMPARATIVE STUDY; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DRUG DOSE COMPARISON; ENZYME ACTIVITY; EYE; FEEDING; FEMALE; KIDNEY; LIVER; MALE; MULTIPLE CYCLE TREATMENT; NONHUMAN; RADIOACTIVITY; RADIOISOTOPE DISTRIBUTION; RAT; SERUM; SKIN; SPLEEN; THYMUS;

ACETYLCYSTEINE; ANIMALS; FEMALE; FREE RADICAL SCAVENGERS; GLUTATHIONE; GLUTATHIONE PEROXIDASE; GLUTATHIONE REDUCTASE; GLUTATHIONE TRANSFERASE; INTUBATION, GASTROINTESTINAL; MALE; RATS; RATS, SPRAGUE-DAWLEY; SKIN; TISSUE DISTRIBUTION;

ANIMALIA; RATTUS;

EID: 34347374644     PISSN: 15569527     EISSN: 15569535     Source Type: Journal    
DOI: 10.1080/15569520701212233     Document Type: Article

References (57)

1. AMR. N-acetyl-L-cysteine. Altern Med Rev 2000; Oct; 5(5):467-471.
2. Bobb AJ, Arfsten DP, Jederberg WW. N-acetyl-L-cysteine as prophylaxis against sulfur mustard. Mil Med 2005; 170:52-56.
3. De Rosa SC, Zaretsky MD, Dubs JG, Roederer M, Anderson M, Green A, Mitra D, Watanabe N, Nakamura H, Tjioe I, Deresinski SC, Moore WA, Ela SW, Parks D, Herzenberg LA, Herzenberg LA. N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest 2000; 30:915-929.
4. Lailey AF. Oral N-acetylcysteine protects against perfluoroisobutene toxicity in rats. Hum Exp Toxicol 1997; 16:212-216.
5. Lailey AF, Hill L, Lawston IW, Stanton D, Upshall DG. Protection by cysteine esters against chemically induced pulmonary oedema. Biochem Pharmacol 1991; 42:S47-S54.
6. Rhoden CR, Lawrence J, Godleski JJ, Gonzalez-Flecha B. N-acetylcysteine prevents lung inflammation after short-term inhalation exposure to concentrated ambient particles. Toxicol Sci 2004; 79:296-303.
7. Neal R, Matthews RH, Lutz P, Ercal N. Antioxidant role of N-acetyl cysteine isomers following high dose irradiation. Free Radic Biol Med 2003; 34:689-695.
8. Afaq F, Abidi P, Rahman Q. N-acetyl L-cysteine attenuates oxidant-mediated toxicity induced by chrysotile fibers. Toxicol Lett 2000; 117:53-60.
9. De Flora S, Rossi GA, De Flora A. Metabolic, desmutagenic and anticarcinogenic effects of N-acetylcysteine. Respiration 1986; 50:43-49.
10. Izzotti A, Balansky RM, Dagostini F, Bennicelli C, Myers SR, Grubbs CJ, Lubet RA, Kelloff GJ, De Flora S. Modulation of biomarkers by chemopreventive agents in smoke-exposed rats. Cancer Res 2001; 61:2472-2479.
11. Rogers DF, Jeffery PK. Inhibition by oral N-acetylcysteine of cigarette smoke-induced bronchitis in the rat. Exp Lung Res 1986; 10:267-283.
12. Smilkstein MJG, Knapp L, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med 1988; 319:1557-1562.
13. Guru V, Fremes SE. The role of N-acetylcysteine in preventing radiographic contrast-induced nephropathy. Clin Nephrol 2004; 62:77-83.
14. Kasielski M, Nowak D. Long-term administration of N- acetylcysteine decreases hydrogen peroxide exhalation in subjects with chronic obstructive pulmonary disease. Respir Med 2001; 95:448-456.
15. Hoffer E, Baum Y, Nahir AM. N-Acetylcysteine enhances the action of anti-inflammatory drugs as suppressors of prostaglandin production in monocytes. Mediators Inflamm 2002; 11:321-323.
16. Abe S, Takizawa H, Sugawara I, Kudoh S. Diesel exhaust (DE)-induced cytokine expression in human bronchial epithelial cells: A study with a new cell exposure system to freshly generated DE in vitro. Am J Respir Cell Mol Biol 2000; 22:296-303.
17. Xia C, Hu J, Ketterer B, Taylor JB. The organization of the human GSTP1-1 gene promoter and its response to retinoic acid and cellular redox status. Biochem J 1996; 313:155-161.
18. Henderson JT, Javaheri M, Kopko S, Roder JC. Reduction of lower motor neuron degeneration in wobbler mice by N-acetyl-L-cysteine. J Neurosci 1996; 16:7574-7582.
19. Anderson DR, Byers SL, Vesely KR. Treatment of sulfur mustard (HD)-induced lung injury. J Appl Toxicol 2000; 20 (Suppl. 1):S129-32.
20. McClintock SD, Till GO, Smith MG, Ward PA. Protection from half-mustard-gas-induced acute lung injury in the rat. J Appl Toxicol 2002; 22:257-262.
21. Das SK, Mukherjee S, Smith MG, Chatterjee D. Prophylactic protection by N-acetylcysteine against the pulmonary injury induced by 2-chloroethyl ethyl sulfide, a mustard analogue. J Biochem Mol Toxicol 2003; 17:177-184.
22. Borgstrom L, Kagedal B, Paulsen O. Pharmacokinetics of N-acetylcysteine in man. Eur J Clin Pharmacol 1986; 31:217-222.
23. Olsson B, Johansson M, Gabrielsson J, Bolme P. Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. Eur J Clin Pharmacol 1988; 34:77-82.
24. Cotgreave IA, Berggren M, Jones TW, Dawson J, Moldéus P. Gastrointestinal metabolism of N-acetylcysteine in the rat, including an assay for sulfite in biological systems. Biopharm Drug Dispos 1987; 8:377-386.
25. Sjodin K, Nilsson E, Hallberg A, Tunek A. Metabolism of N-acetyl-L-cysteine. Some structural requirements for the deacetylation and consequences for the oral bioavailability. Biochem Pharmacol 1989; 38:3981-3985.
26. Bonanomi L, Gazzaniga A. Toxicological, pharmacokinetic and metabolic studies on acetylcysteine. Eur J Respir Dis 1980; 61:(Suppl. 111):45-51.
27. Streeter AJ, Dahlin DC, Nelson SD, Baillie TA. The covalent binding of acetaminophen to protein. Evidence for cysteine residues as major sites of arylation in vitro. Chem Biol Interact 1984; 48:349-366.
28. Yamauchi A, Ueda N, Hanafusa S, Yamashita E, Kihara M, Naito S. Tissue distribution of and species differences in deacetylation of N-acetyl- L-cysteine and immunohistochemical localization of acylase I in the primate kidney. J Pharm Pharmacol 2002; 54:205-212.
29. Arfsten DP, Johnson EW, Thitoff AR, Jung AE, Wilfong ER, Lohrke SM, Bausman TA, Eggers JS, Bobb AJ. Impact of 30-day oral dosing with N-Acetyl-L-Cysteine on Sprague-Dawley rat physiology. Int J Toxicol 2004; 23:239-247.
30. McLellan LI, Lewis AD, Hall DJ, Ansell JD, Wolf CR. Uptake and distribution of N-acetylcysteine in mice: Tissue-specific effects on glutathione concentrations. Carcinogenesis 1995; 16:2099-2106.
31. Pendyala L, Creaven PJ. Pharmacokinetic and pharmacodynamic studies of N-acetylcysteine, a potential chemopreventive agent during a phase I trial. Cancer Epidemiol Biomarkers Prev 1995; 4:245-251.
32. Goldenthal EI. A compilation of LD50 values in newborn and adult animals. Toxicol Appl Pharmacol 1971; 18:185-207.
33. Thompson J, Burns DA. LSC Sample Preparation by Solubilization. CS-003. 03/06/96. http://las.perkinelmer.com/content/ApplicationNotes/CS-003. pdf.
34. Ott L. An Introduction to Statistical Methods and Data Analysis. 3rd ed. Boston, MA: PWS-Kent Publishing Company, 1988.
35. Borgstrom L, Kagedal B. Dose dependent pharmacokinetics of N-acetylcysteine after oral dosing to man. Biopharm Drug Dispos 1990; 11:131-136.
36. De Flora S, Izzotti A, D'Agostini F, Balansky RM. Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points. Carcinogenesis 2001; 22:999-1013.
37. De Flora S, Cesarone CF, Balansky RM, Albini A, D'Agostini F, Bennicelli C, Bagnasco M, Camoirano A, Scatolini L, Rovida A. Chemopreventive properties and mechanisms of N-Acetylcysteine. The experimental background. J Cell Biochem Suppl 1995; 22:33-41.
38. Zafarullah M, Li WQ, Sylvester J, Ahmad M. Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci 2003; 60:6-20.
39. De Flora S, Bennicelli C, Camoirano A, Serra D, Romano M, Rossi GA, Morelli A, De Flora A. In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds. Carcinogenesis 1985; 6:1735-1745.
40. Pendyala L, Schwartz G, Bolanowska-Higdon W, Hitt S, Zdanowicz J, Murphy M, Lawrence D, Creaven PJ. Phase I/pharmacodynamic study of N- acetylcysteine/oltipraz in smokers: Early termination due to excessive toxicity. Cancer Epidemiol Biomarkers Prev 2001; 10:269-272.
41. Morrison JP, Coleman MC, Aunan ES, Walsh SA, Spitz DR, Kregel KC. Aging reduces responsiveness to BSO- and heat stress-induced perturbations of glutathione and antioxidant enzymes. Am J Physiol Regul Integr Comp Physiol 2005; 289:R1035-1041.
42. Rana SV, Allen T, Singh R. Inevitable glutathione, then and now. Indian J Exp Biol 2002; 40:706-716.
43. Ookhtens M, Kaplowitz N. Role of the liver in interorgan homeostasis of glutathione and cyst(e)ine. Semin Liver Dis 1998; 18:313-329.
44. Larsson A, Mattsson B, Hagenfeldt L, Moldeus P. Glutathione synthetase deficient human fibroblasts in culture. Clin Chim Acta 1983; 135:57-64.
45. Oshima RG, Rhead WJ, Thoene JG, Schneider JA. Cystine metabolism in human fibroblasts. Comparison of normal, cystinotic, and gamma-glutamylcysteine synethetase-deficient cells. J Biol Chem 1976; 251:4287-4293.
46. Lash LH. Role of glutathione transport processes in kidney function. Toxicol Appl Pharmacol 2005; 204:329-342.
47. Liu RM, Dickinson DA. Decreased synthetic capacity underlies the age-associated decline in glutathione content in Fisher 344 rats. Antioxid Redox Signal 2003; 5:529-536.
48. Levonen AL, Lapatto R, Saksela M, Raivio KO. Expression of gamma-glutamylcysteine synthetase during development. Pediatr Res 2000; 47:266-270.
49. Liu RM, Dickinson DA. Decreased synthetic capacity underlies the age-associated decline in glutathione content in Fisher 344 rats. Antioxid Redox Signal 2003; 5:529-536.
50. Rahman I, Li XY, Donaldson K, Harrison DJ, MacNee W. Glutathione homeostasis in alveolar epithelial cells in vitro and lung in vivo under oxidative stress. Am J Physiol 1995; 269:L285-292.
51. Berggren M, Dawson J, Moldeus P. Glutathione biosynthesis in the isolated perfused rat lung: Utilization of extracellular glutathione. FEBS Lett 1984; 176:189-192.
52. Weinander R, Anderson C, Morgenstern R. Identification of N-acetylcysteine as a new substrate for rat liver microsomal glutathione transferase. A study of thiol ligands. J Biol Chem 1994; 269:71-76.
53. Childs A, Jacobs C, Kaminski T, Halliwell B, Leeuwenburgh C. Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise. Free Radic Biol Med 2001; 31:745-753.
54. Kleinveld HA, Demacker PN, Stalenhoef AF. Failure of N- acetylcysteine to reduce low density lipoprotein oxidizability in healthy subjects. Eur J Clin Pharmacol 1992; 43:639-642.
55. Lopez RA, Tornwall MS, Henagan JM, Smith GS, Miller TA. N-acetylcysteiene: Protective agent or promoter of genetic damage. Proc Soc Exp Biol Med 1991; 197:273-278.
56. Romert L, Jenssen D. Mechanisms of N-acetylcysteine (NAC) and other thiols as both positive and negative modifiers of MNNG-induced mutagenicity in V79 Chinese hamster cells. Carcinogenesis 1987; 8:1531-1535.
57. Reed DJ. Glutathione: Toxicological implications. Annu Rev Pharmacol Toxicol 1990; 30:603-631.