CASE REPORT
The influence of single application of paracetamol and/or N-acetylcysteine on rats subchronic exposed to trichloroethylene vapours. I. Effect on hepatic moonooxygenase system dependent of cytochrome P450
1
Department of Proteomics, Medical University of Silesia, Sosnowiec
2
Department of Histology, Medical University of Silesia, Katowice
3
Department of Toxicology, Medical University, Poznań
Corresponding author
Andrzej Plewka
Department of Proteomics, Medical University of Silesia, ul. Ostrogórska 30, 41-200 Sosnowiec tel./fax +48 32 364-14-40
Department of Proteomics, Medical University of Silesia, ul. Ostrogórska 30, 41-200 Sosnowiec tel./fax +48 32 364-14-40
Med Srod. 2012;15(2)
KEYWORDS
ABSTRACT
Introduction:
There is a number of factors which potentially affect occurrence of toxic change in liver after overdosing of paracetamol. Hepatic metabolism of trichloroethylene has primary impact on hepatotoxic effect of this solvent. This means that the combined exposure to these xenobiotics can be particularly harmful for human. The influence of N-acetylcysteine (NAC) as a protective factor after paracetamol intoxication was studies.
Material and Methods:
Tests were carried out on rats which were treated with trichloroethylene, paracetamol and/or N-acetylcysteine. In the hepatic microsomal fraction activity of the components of cytochrome P450- dependent monooxygenases was determined
Results:
Paracetamol slightly stimulated cytochrome P450 having no effect on reductase activity cooperating with it. Cytochrome b5 and its reductase were inhibited by this compound. Trichloroethylene was the inhibitor of compounds of II microsomal electron transport chain. N-acetylcysteine inhibited activity of reductase of NADH-cytochrome b5.
Conclusions:
Tested doses of the xenobiotics influenced on II microsomal electron transport chain. Protective influence of N-acetylcysteine was better if this compound was applied 2 hours after exposure on xenobiotics.
There is a number of factors which potentially affect occurrence of toxic change in liver after overdosing of paracetamol. Hepatic metabolism of trichloroethylene has primary impact on hepatotoxic effect of this solvent. This means that the combined exposure to these xenobiotics can be particularly harmful for human. The influence of N-acetylcysteine (NAC) as a protective factor after paracetamol intoxication was studies.
Material and Methods:
Tests were carried out on rats which were treated with trichloroethylene, paracetamol and/or N-acetylcysteine. In the hepatic microsomal fraction activity of the components of cytochrome P450- dependent monooxygenases was determined
Results:
Paracetamol slightly stimulated cytochrome P450 having no effect on reductase activity cooperating with it. Cytochrome b5 and its reductase were inhibited by this compound. Trichloroethylene was the inhibitor of compounds of II microsomal electron transport chain. N-acetylcysteine inhibited activity of reductase of NADH-cytochrome b5.
Conclusions:
Tested doses of the xenobiotics influenced on II microsomal electron transport chain. Protective influence of N-acetylcysteine was better if this compound was applied 2 hours after exposure on xenobiotics.
REFERENCES (36)
1.
Plewka A., Kamiński M.: Influence of cholesterol and protein diet on liver cytochrome P450-dependent monooxygenase system in rats. Exp Toxic Pathol 1996; 47: 249-253.
2.
Plewka A., Kamiński M., Plewka D.: Ontogenesis of hepatocyte respiration processes in relation to metabolism of xenobiotics. Mech Ageing Develop 1998; 105: 197-207.
3.
Guengerich F. P.: Influence of nutritients and other dietary materials no cytochrome P450 enzymes. Am J Clin Nutr 1995; 61 (supple): 651S-658S.
4.
Geoptar A. R., Scheerens H., Vermeulen N. P. E.: Oxygen and xenobiotics reductase activities of cytochrome P450. Crit Rev Toxicol 1995; 25: 25-65.
5.
Lavonas EJ, Reynolds KM, Dart RC.: Therapeutic acetaminophen is not associated with liver injury in children: a systematic review. Pediatrics 2010; 126: 1430-1444.
6.
Lee W. M.: The case for limiting acetaminophen-related deaths: smaller doses and unbundling the opioid-acetaminophen compounds. Clin Pharmacol Ther 2010; 88: 289-292.
7.
Dahlin D. C., Miwa G. T., Lu A. Y., et. al.: N-acetyl-p-benzoquinone imine: A cytochrome P450-mediated oxidation product of acetaminophen. Proc Natl Acad Sci USA 1984; 81: 1327-1331.
8.
Verma Y, Rana S. V.: Gender differences in the metabolism of benzene, toluene and trichloroethylene in rat with special reference to certain biochemical parameters. J Environ Biol 2003; 24: 135-140.
9.
Lash L. H., Fisher J. W., Lipscomb J. C., et. al.: Metabolism of trichloroethylene. Environ Health Perspect 2000; 108 Suppl 2: 177-200.
10.
Caldwell J. C., Keshava N., Evans M. V.: Difficulty of mode of action determination for trichloroethylene: An example of complex interactions of metabolites and other chemical exposures. Environ Mol Mutagen 2008; 49: 142-154.
11.
Hanioka N., Omae E., Yoda R., et. al.: Effect of trichloroethylene on cytochrome P450 enzymes in the rat liver. Bull Environm Contam Toxicol 1997; 58: 628-635.
12.
Plewka A., Czekaj P., Kamiński M., et. al.: Circadian changes of cytochrome P450-dependent monooxygenase system in the rat liver. Pol J Pharmacol Pharm 1992; 44: 655-661.
13.
Czekaj P., Plewka A., Kamiński M., et. al.: Daily and circadian rhythms in the activity of mixed function oxidases Res 1994;.
14.
Dallner G.: Isolation of rough and smooth microsomes – general. Methods Enzymol 1974; 32: 191-215.
15.
Estabrook R. W., Werringloer J.: The measurement of difference Methods Enzymol 1978; 52: 212-220.
16.
Hodges T. K., Leonard R. T.: Purification of a plasma membrane- bound adenosine triphosphatase from plant roots. Methods Enzymol 1974; 32: 392-406.
17.
Lowry O. H., Rosebrough N. J, Farr A. L., et. al.: Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-275.
18.
Bruckner J. V., Davis B. D. Blancato J. N.: Metabolism, toxicity, and carcinogenecity of trichloroethylene. Crit Rev Toxicol 1989; 20: 31-50.
19.
Anand S. S., Mumtaz M. M., Mehendale H. M.: Dosedependent liver regeneration in chloroform, trichloroethylene and allil alcohol ternary mixture hepatotoxicity in rats. Arch Toxicol 2005; 79: 671-682.
20.
Wang R. S., Nakajima T., Tsuruta H., et. al.: Effect of exposure to four organic solvents on hepatic cytochrome P450 isozymes in rat. Chem Biol Interact.. 1996; 99: 239-252.
21.
Kalsi S. S., Wood M. D., Waring S. W., et. al.: Does cytochrome P450 liver isoenzyme induction increase the risk of liver toxicity after paracetamol overdose. Open Access Emergency Medicine 2011; 3: 69–76.
22.
Bernauer U., Birner G., Dekant W., et. al.: Biotransformation of trichloroethene: dose-dependent excretion of 2,2,2- trichloro-metabolites and mercapturic acids in rats and humans after inhalation. Arch Toxicol 1996; 70: 338-346.
23.
Kaneko T., Wang P. Y., Sato A.: Assessment of the health effects of trichloroethylene. Ind Health 1997; 35: 301-324.
24.
Jollow D. J., Bruckner J. V., McMillan D. C., et. al.: Trichloroethylene risk assessment: A review and commentary. Crit RevToxicol 2009; 39: 782-797.
25.
Nakajima T., Wang R.-S., Elovaara E., et. al.: A comparative study on the contribution of cytochrome P450 isozymes to metabolism of benzene, toluene and trichloroethylene in rat liver. Biochem Pharmacol 199; 243: 251-257.
26.
Ramdhan D. H., Kamijima M., Yamada N., et. al.: Molecular mechanism of trichloroethylene-induced hepatotoxicity mediated by CYP2E1. Toxicol Appl Pharmacol 2008; 231: 300-307.
27.
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.
28.
Okino T., Nakajima T., Nakano M.: Morphological and biochemical analyses of trichloroethylene hepatotoxicity: Differences in ethanol– and phenobarbital-pretreatred rats. Toxicol Appl Pharmacol 1991; 108, 379-389.
29.
Plewka A., Zielińska-Psuja B., Kowalówka-Zawieja J., et. al.: Influence of acetaminophen and trichloroethylene on liver cytochrome P450-dependent monooxygenase system. Acta Biochim Pol 2000; 47: 1129-1136.
30.
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.
31.
Laine J. E., Auriola S., Pasanen M., et. al.: Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes. Xenobiotica.. 2009; 39: 11-21.
32.
Fakurazi S., Hairuszah I., Nanthini U.: Moringa oleifera Lam prevents acetaminophen induced liver injury through restoration of glutathione level. Food Chem Toxicol 2008; 46: 2611-2615.
33.
Dart R. C., Bailey E.: Does therapeutic use of acetaminophen cause acute liver failure? Pharmacotherapy 2007; 27: 1219-1230.
34.
Ogino K., Hobara T., Kobayashi H., et. al.: Lipid peroxidation induced by trichloroethylene in rat liver. Bull Environ Contam Toxicol 1991; 46: 417-421.
35.
Chiu W. A., Okino M. S., Lipscomb J. C., et. al.: Issues in the pharmacokinetics of trichloroethylene and its metabolites. Environ Health Perspect 2006; 114: 1450-1456.
36.
Clewell H. J., Andersen M. E.: Applying mode-of-action and pharmacokinetic considerations in contemporary cancer risk assessments: an example with trichloroethylene. Crit Rev Toxicol 2004; 34: 385-445.
| eISSN: | 2084-6312 |
| ISSN: | 1505-7054 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
