PL EN
PRACA ORYGINALNA
Wpływ pojedynczej dawki paracetamolu i/lub N-acetylocysteiny na szczury przewlekle eksponowane na trichloroetylen. II. Wpływ na wątrobowy poziom glutationu
 
Więcej
Ukryj
1
Department of Histology, Medical University of Silesia, Katowice Head of Department: Ryszard Wiaderkiewicz MD, PhD, associated professor
 
2
Department of Proteomics, Medical University of Silesia, Sosnowiec Head of Department: Prof. Andrzej Plewka MD PhD
 
3
Department of Toxicology, Medical University, Poznań Head of Department: Prof. Jadwiga Jodynis-Liebert PhD
 
 
Autor do korespondencji
Danuta Plewka   

Department of Proteomics Medical University of Silesia, ul. Ostrogórska 30, 41-200 Sosnowiec tel./fax +48 32 364-14-40
 
 
Med Srod. 2012;15(3)
 
STRESZCZENIE
Wstęp:
Cechą współcześnie występujących zagrożeń, zarówno środowiskowych jak i zawodowych jest narażenie łączne, wielokrotnie prowadzące do nieprzewidzianej odpowiedzi biologicznej organizmu, wynikają-cej 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


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.”

Material and Methods:
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.

 
REFERENCJE (26)
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. Comporti M., Maellaro E., Del Bello B., et. al.: Glutathione.
 
6.
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 hepati 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.
 
eISSN:2084-6312
ISSN:1505-7054
Journals System - logo
Scroll to top