Open Access Peer-reviewed

Evaluation of Acetaminophen Effect on Oxidative Stressed Mice by Peroxide Hydrogen

BENKHASSI Zoubair1, LAHLOU Fatima Azzahra1,, HMIMID Fouzia1, LOUTFI Mohammed1, BENAJI Brahim2, BOURHIM Noureddine1

1Biochemistry and Molecular Biology laboratory, Ain Chock Faculty of Science Hassan II University, Casablanca, Morocco

2Microbiology pharmacology Biotechnology and Environment laboratory, Ain Chock Faculty of Science Hassan II University, Casablanca, Morocco

American Journal of Biomedical Research. 2013, 1(4), 75-79. DOI: 10.12691/ajbr-1-4-2
Published online: August 25, 2017


Acetaminophen (Paracetamol) is among the most commonly used analgesic and antipyretic drugs worldwide, it’s often, but anomalously, classified as non-steroidal anti-inflammatory drugs (NSAIDs) in textbooks of pharmacology . This study aims to evaluate if paracetamol has an antioxidant effect, relative to its analgesic antipyretic and weak anti-inflammatory activities, or it possesses a cytotoxic potential. Oxidative stress was induced by intraperetoneal injection of peroxide hydrogen (H2O2), and then a comparative study is made concerning the activities of the antioxidant enzymes SOD, CAT, and GR as well as lipid peroxidation levels in liver. An increase in SOD, CAT, GR activity and lipid peroxidation in mice treated with H2O2 accompanied by paracetamol; compared to the group treated by vitamin C + H2O2 showed that acetaminophen doesn’t show any antioxidant effect. Moreover this study has suggested that acetaminophen induced cytotoxicity in liver mediated by increased oxidative stress and altered redox metabolism.


acetaminophen (paracetamol), peroxide hydrogen, oxidative stress
[1]  Brunton, L.L, Lazo, J.S, Parker, K.L, Buxton, I.L.O, Blumenthal, D, Analgesic-antipyretic and anti-inflammatory agents: pharmacotherapy of gout, Hardman J.G, Limbrid L.E (eds), Goodman and Gilman, The Pharmacological Basis of Therapeutics, New York, 2005.
[2]  Rang, H.P, Dale, M.M, Ritter, J.M, Moore, P, Pharmacology, Churchill Livingstone, London, 2006. PubMed
[3]  Botting, R.M, “Mechanism of action of acetaminophen: is there a cyclooxygenase 3?” Clin Infect Dis, 31.202-210.2000.
[4]  Ruepp, S.U., Tonge, R.P., Shaw, J., Wallis, N. and Pognan, F, “Genomics and proteomics analysis of acetaminophen toxicity in mouse liver”, Toxicol Sci, 65.135-150.2001.
[5]  Sumioka, I., Matsura, T. and Yamada, K, “Acetaminophen induced hepatotoxicity: Still an important issue”, Yonago Acta Med, 47.17-28.2004.
[6]  Aleksunes, L.M., Campion, S.N., Goedken, M.J. and Manautou, J.E, “Acquired resistance to acetaminophen hepatotoxicity is associated with induction of multidrug resistance-associated protein 4 (Mrp4) in proliferating hepatocytes”, Toxicol Sci, 104.261-273.2008.
[7]  Ghosh, J. and Myers, C.E, “Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells”, Proc Natl Acad Sci, 95.13182-13187.1998.
[8]  Yin, G.Y., Yin, Y.F. and He, X.F, “Effect of zhuchun pill on immunity and endocrine function of elderly with kidney-yang deficiency”, Chung Kuo Chung Hsi I Chieh Ho Tsa Chih, 15.601-603.1995.
[9]  Bae, Y.S., Kang, S.W., Seo, M.S., Baines, I.C., Tekle, E., Chock, P.B. and Rhee, S.G, “Epidermal growth factor (EGF)-induced generation of hydrogen peroxide”, J Biol Chem, 272.217-221.1997.
[10]  Lee, Y.J., Galoforo, S.S., Berns, C.M., Chen, J.C., Davis, B.H., Sim, J.E., Corry, P.M. and Spitz, D.R, “Glucose deprivation-induced cytotoxicity and alterations in mitogen-activated protein kinase activation are mediated by oxidative stress in multidrug-resistant human breast carcinoma cells”, J Biol Chem, 273.5294-5299.1998.
[11]  Percival, M., “Antioxidants”, Clin Nutr, 31.1-4.1998.
[12]  Young, I.S. and Woodside, J.V, “Antioxidants in health and disease”, J Clin Pathol, 54.176-186.2001.
[13]  Zentella de Pina, M., Sandoval-Montiel, A., Serrano-Alessandri, L., Montalvo-Jave, E., Zentella-Dehesa, A. and Pina, E, “Ethanol-mediated Oxidative Changes in Blood Lipids and Proteins Are Reversed by Aspirin-like Drugs”, Archi Med Res, 38.269-275.2006.
[14]  Lahlou, F.Z., Hmimid, F., Loutfi, M. and Bourhim, N, “Antioxidant response of Camellia sinensis and Rosmarinus officinalis aqueous extracts toward H2O2 stressed mice”, J Appl Pharm Sci, 2.70-76.2012.
[15]  Aebi, H., “Catalase in vivo”, Methods Enzymol, 105.121-126.1984.
[16]  Di Ilio, C., Polidoro, G., Arduini, A., Muccini, A. and Federici, G, “Glutathione peroxidase, Glutathione reductase, gluthatione S-transferase and gamma_glutamyl transpeptidase activities in the human early pregnancy placenta”, Biochem Med, 29.143-148. 1983.
[17]  Paoletti, F., Aldinucci, D., Mocali, A. and Carparrini, A, “A sensitive spectrophotometric method for the determination of superoxide dismutase in tissue extracts”, Anal Biochem, 154.526-541.1986.
[18]  Samokyszyn, V.M. and Marnett, L.J, “Inhibition of liver microsomal lipid peroxidation by 13-cis-retinoic acid”, Free Radic Biol Med, 8.491-496.1990.
[19]  Bradford, M., “A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding”, Anal Biochem, 72.248-254.1976.
[20]  Agency for Toxic Substances and Disease Registry (ATSDR), Tox FAQs TM for Hydrogen Peroxide. U.S Department of Health and Human Services, Public Health Service, April 2002.
[21]  European Commission Joint Research Centre (ECJRC), European Union Risk Assessment Report, Hydrogen peroxide. 2nd Priority List, Volume.38. Report by the European Commission Joint Research Centre, Luxembourg, 2003.
[22]  Liebmann, J., Fisher, J., Lipschultz, C., Kuno, R. and Kaufman, D.C, “Enhanced glutathione peroxidase expression protects cells from hydroperoxides but not from radiation or doxorubicin”, Cancer Res, 55.4465-4470.1995.
[23]  Gonzalez-Flecha, B. and Demple, B, “Metabolic sources of hydrogen peroxide in aerobically growing Escherichia coli”, J Biol Chem, 179.13681-13687.1995.
[24]  Brown, S.M., Howell, M.L., Vasil, M.L., Anderson, A.J. and Hassett, D.J, “Cloning and characterization of the katB gene of Pseudomonas aeruginosa encoding a hydrogen peroxide-inducible catalase: purification of katB, cellular localization, and demonstration that it is essential for optimal resistance to hydrogen peroxide”, J Bacteriol, 177. 6536-6544.1995.
[25]  Nielsen, F., Mikkelsen, B.B., Nielsen, J.B., Andersen, H.R. and Grandjean, P, “Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors”, Clin Chem, 43.1209-1214.1997.
[26]  Niedernhofer, L.J., Daniels, J.S., Rouzer, C.A., Greene, R.E. and Marnett, L.J, “Malondialdehyde a product of lipid peroxidation, is mutagenic in human cells”, J Biol Chem, 278.31426-31433.2003.
[27]  Tian, W.N., Braunstein, L.D., Apse, K., Pang, J., Rose, M., Tian, X. and Stanton, R.C, “Importance of glucose-6-phospahate dehydrogenase activity in cell death”, Am J Physiol, 276.1121-1131.1999.
[28]  Leopold, J.A. and Loscalzo, J, “Cyclic strain modulates resistance to oxidant stress by increasing G6PDH expression in smooth muscle cells”, Am J Physiol, 279.2477-2485.2000.
[29]  Bierl, C., Voetsch, B., Jin, R.C., Handy, D.E. and Loscalzo, J, “Determinants of human plasma glutathione peroxidase (GPx-3) expression”, J Biol Chem, 10.107-122.2004.
[30]  Dahlin, D.C., Miwa, G.T., Lu, A.Y.H. and Nelson, S.D, “N-Acetylp- benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen”, Proc Natl Acad Sci, 81.1327-1331.1984.
[31]  Nordblom, G.D. and Coon, M.J, “Hydrogen peroxide formation and stoichiometry of hydroxylation reactions catalyzed by highly purified liver microsomal cytochrome P-450”, Arch Biochem Biophys, 180.343-347.1977.
[32]  Kuthan, H., Tsuji, H., Graf, H. and Ullrich, V, “Generation of superoxide anion as a source of hydrogen peroxide in a reconstituted monooxygenase system”, FEBS Lett, 91.343-345.1978.
[33]  De Vries, J., “Hepatotoxic metabolic activation of paracetamol and its derivatives phenacetin and benorilate: oxygenation or electron transfer?” Biochem Pharmacol, 30 .399-402.1981.