The influence of single application of paracetamol and/or N-acetylcysteine on rats in subchronic exposition to trichloroethylene vapours. II. Effect on hepatic glutathione level

• Authors: Danuta Plewka , Andrzej Plewka , Joanna Kowalówka-Zawieja , Barbara Zielińska-Psuja , Jędrzej Przystanowicz

Title variants

PL

Wpływ pojedynczej dawki paracetamolu i/lub N-acetylocysteiny na szczury przewlekle eksponowane na trichloroetylen. II. Wpływ na wątrobowy poziom glutationu

• Languages of publication: EN

Abstracts

EN

Background: Feature of modern existing hazards
both environmental and occupational is cumulative
exposure often leading to unexpected response of the
organism resulting, among other things, in interactions
with cytochrome P450 system involved in biotransformation
of trichloroethylene and paracetamol. Hepatotoxity
of paracetamol is closely connected with hepatic
glutathione level. „In therapy of acute paracetamol poisoning
application of N-acetylcysteine as a factor, which
protects GSH level in cells, is recommended.”
Materials and method: Tests were performed on rats
which were treated with trichloroethylene, paracetamol
and/or N-acetylcysteine. In rat liver total level of glutathione
was determined i.e. reduced and oxidized form.
Results: Paracetamol just after completion of the
exposure affected the glutathione level. Trichloroethylene
throughout the period of observation stimulated
growth of glutathione level in liver. N-acetylcysteine
didn’t have any influence on the level of investigated
tripeptyde.
Conclusions: N-acetylcysteine removes negative
effect of paracetamol especially when it’s applied with
2-hour delay. After exposure for trichloethylene immediate
application of N-acetylcysteine caused noticeable
lowering of glutathione level. Cumulative exposure for
three xenobiotics had positive influence for glutathione
level in rat liver.

PL

Wstęp: Cechą współcześnie występujących zagrożeń,
zarówno środowiskowych jak i zawodowych jest narażenie
łączne, wielokrotnie prowadzące do nieprzewidzianej
odpowiedzi biologicznej organizmu, wynikającej między innymi z oddziaływań na układ cytochromu
P450 biorący udział w biotransformacji trichloroetylenu
i paracetamolu. Hepatotoksyczność paracetamolu jest
między innymi ściśle związana z wątrobowym poziomem
glutationu. W terapii zatruć ostrych paracetamolem
zalecane jest podawanie N-acetylocysteiny jako
czynnika ochraniającego poziom GSH w komórkach.
Materiał i metody: Badania wykonano na szczurach,
które traktowano trichloroetylenem, paracetamolem
i/lub N-acetylocysteiną. W wątrobie szczura oznaczano
poziom całkowity glutationu, tj. formę zredukowaną
i utlenioną.
Wyniki: Paracetamol tuż po zakończeniu ekspozycji
negatywnie wpływał na poziom glutationu. Trichloroetylen
przez cały czas obserwacji stymulował wzrost poziomu
glutationu w wątrobie. N-acetylocysteina nie miała
żadnego wpływu na poziom badanego tripeptydu.
Wnioski: N-acetylocysteina usuwała negatywny
wpływ paracetamolu, szczególnie wtedy, kiedy podano
ją z 2-godzinnym opóźnieniem. Po narażeniu na trichloroetylen
natychmiastowe podanie N-acetylocysteiny
niosło za sobą wyraźnie obniżenie poziomu glutationu.
Narażenie łączne na trzy oceniane ksenobiotyki.

Keywords

EN

N-acetylcysteine   glutathione   liver   paracetamol   trichloroethylene  

• Publisher: Polish Society of Environmental Medicine, Institute of Occupational Medicine and Environmental Health
• Journal: Medycyna Środowiskowa - Environmental Medicine
• Year: 2012
• Volume: 15
• Issue: 3
• Pages: 91-95

References

• 1. Winiarska K.: Glutation: niezwykłe funkcje pospolitego peptydu. Post Biochem 2000; 46: 318–326.
• 2. Sies H.: Glutathione and its role in cellular functions. Free Radic Biol Med 1999; 27: 916–921.
• 3. De Nicola M., Gualandi G., Alfonsi A., et. al.: Different fates of intracellular glutathione determine different modalities of apoptotic nuclear vesiculation. Biochem Pharmacol 2006; 72: 1405-1416.
• 4. Kuralay F., Akarca U.S., Ozutemitz O., et. al.: Possible role of glutathione in prevention of acetaminophen-induced hepatotoxicity enhanced by fish oil in male Wistar rats. J Toxicol Environm Health 1998 Part A; 53: 223-229.
• 5. Amimoto T., Matsura T., Koyama S.-Y., et. al.: Acetaminophen- induced hepatic injury in mice: The role of lipid peroxidation and effects of pretreatment with coenzyme Q10 and ?-tocopherol. Free Radic Biol Med 1995; 19: 169-176.
• 6. Comporti M., Maellaro E., Del Bello B., et. al.: Glutathione depletion: its effects on other antioxidant systems and hepatocellular damage. Xenobiotica 1991; 21: 1067-1076.
• 7. Tran A., Treluyer J.M., Rey E., et. al.: Protective effect of stiripentol on acetaminophen-induced hepatotoxicity in rat. Toxicol Appl Pharmacol 2001; 170: 145-152.
• 8. Woo O.F., Mueller P.D., Olson K.R., et. al.: Shorter duration of oral N-acetylcysteine therapy for acute acetaminophen overdose. Ann Emerg Med 2000; 35: 363-368.
• 9. Buckley N.A., Whyte I.M., O’Connell D.L., et. al.: Oral or intravenous N-acetycysteine: Which is the treatment of choice for acetaminophen (paracetamol) poisoning? J Toxicol Clin Toxicol 1999; 37: 759-767.
• 10. Dahlin D.C., Miwa G.T., Lu A.Y., et. al.: N-acetyl-p-benzoquinone imine: A cytochrome P-450-mediated oxidation product of acetaminophen. Proc Natl Acad Sci USA 1984; 81: 1327-1331.
• 11. Adams J.D., Lauterburg B.H., Mitchell J.R.: Plasma glutathione and glutathione disulfide in the rat: regulation and response to oxidative stress. J Pharmacol Exp Ther 1983; 227: 745-754.
• 12. Bloemen L.J., Monster A.C., Kezic S., et. al.: Study on the cytochrome P-450– and glutathione-dependent biotransformation of trichloroethylene in humans. Int Arch Occup Environ Health 2001; 74: 102-108.
• 13. Lash L.H., Qian W., Putt D.A., et. al.: Renal and hepatic toxicity of trichloroethylene and its glutathione-derived metabolites in rats and mice: sex-, species-, and tissuedependent differences. J Pharmacol Exp Ther 2001; 297: 155-164.
• 14. Lash L.H., Putt D,A., Huang P., et. al.: Modulation of hepatic and renal metabolism and toxicity of trichloroethylene and perchloroethylene by alterations in status of cytochrome P450 and glutatione. Toxicology 2007; 235: 11-26.
• 15. Henschler D., Vamvakas S., Lammert M., et. al.: Increased incidence of renal cell tumors in a cohort of cardboard workers exposed to trichloroethene. Arch Toxicol 1995; 69: 291-299.
• 16. Lash LH, Putt DA, Parker JC.: Metabolism and tissue distribution of orally administered trichloroethylene in male and female rats: identification of glutathione– and cytochrome P-450-derived metabolites in liver, kidney, blood, and urine. J Toxicol Environ Health A 2006; 69: 1285-1309.
• 17. Lash L.H., Lipscomb J.C., Putt D.A., et. al.: Glutathione conjugation of trichloroethylene in human liver and kidney: kinetics and individual variation. Drug Metab Dispos 1999; 27: 351-359.
• 18. Ryu B.K., Ahn B.O., Oh T.Y., et. al.: Studies on protective effect of DA-9601, Artemisia asiatica extract, on acetaminophen– and CCl4-induced liver damage in rats. Arch Pharm Res 1998; 21: 508-513.
• 19. Abdel Salam OM., Baiuomy A..R, El-Shenawy S.M., et. al.: Effect of pentoxifylline on hepatic injury caused in the rat by the administration of carbon tetrachloride or acetaminophen. Pharmacol Rep 2005; 57: 596-603.
• 20. Plewka A., Grażyna Nowaczyk G., Plewka D., et. al.: N-acethylcysteine effect on microsomal monooxygenase system and glutathione levels in rat after acute trichloroethylene intoxications. Acta Toxicol 2003; 11: 99-111.
• 21. Zhao C., Shichi H.: Prevention of acetaminophen-induced cataract by a combination of diallyl disulfide and N-acetylcysteine, J Ocul Pharmacol Ther 1998; 14: 345-355.
• 22. Halliwell B., Gutteridge J.M.C.: Protection against oxidants in biological systems: The superoxide theory of oxygen toxicity. In: Halliwell B., Gutteridge J.M.C., eds. Free radicals in biology and medicine, Oxford University Press, New York, 1989; pp. 86-187.
• 23. Cummings B.S., Parker J.C., Lash LH.: Role of cytochrome P450 and glutathione S-transferase alpha in the metabolism and cytotoxicity of trichloroethylene in rat kidney. Biochem Pharmacol 2000; 59: 531-543.
• 24. Bilska A., Krypczyk A., Włodek L.: Różne oblicza biologicznej roli glutationu. Post Hig Med Dosw 2007; 61: 438-453.
• 25. Moore M., Thor H., Moore G., et. al.: The toxicity of acetaminophen and N-acetyl-p-benzoquinone imine in isolated hepatocytes is associated with tiol depletion and increased cytosolic Ca2+. J Biol Chem 1985; 260: 13035-13040.
• 26. Corcoran G.B., Wong B.K. Role of glutathione in prevention of acetaminophen-induced hepatotoxicity by N-acetyl-Lcysteine in vivo: studies with N-acetyl-D-cysteine in mice. J Pharmacol Exp Ther 1986; 238: 54-61.

• Document Type: paper