Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats

Background and Aims. Both paracetamol (PA) and phenacetin (PH) are analgesic and antipyretic agents. Part of phenacetin therapeutic activity is attributed to its metabolism into paracetamol. Paracetamol causes direct hepatic oxidative stress damage. The present study aimed to investigate the possibl...

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Main Authors: Tahia H. Saleem, Nagwa Abo El-Maali, Mohammed H. Hassan, Nahed A. Mohamed, Nashwa A. M. Mostafa, Emaad Abdel-Kahaar, Azza S. Tammam
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:International Journal of Hepatology
Online Access:http://dx.doi.org/10.1155/2018/7603437
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author Tahia H. Saleem
Nagwa Abo El-Maali
Mohammed H. Hassan
Nahed A. Mohamed
Nashwa A. M. Mostafa
Emaad Abdel-Kahaar
Azza S. Tammam
author_facet Tahia H. Saleem
Nagwa Abo El-Maali
Mohammed H. Hassan
Nahed A. Mohamed
Nashwa A. M. Mostafa
Emaad Abdel-Kahaar
Azza S. Tammam
author_sort Tahia H. Saleem
collection DOAJ
description Background and Aims. Both paracetamol (PA) and phenacetin (PH) are analgesic and antipyretic agents. Part of phenacetin therapeutic activity is attributed to its metabolism into paracetamol. Paracetamol causes direct hepatic oxidative stress damage. The present study aimed to investigate the possible damaging effects of both PA and PH, when used in therapeutic doses, on rat liver and to compare the antioxidant and hepatoprotective effects of N-acetylcysteine (NAC), N-acetyl-methionine (NAM), and N-acetylglucosamine (NAG) against PA- or PH-induced hepatic damage. Methods. 90 male Wistar albino rats (120-140 gm) were undertaken, categorized randomly into 9 groups of 10 rats each, and administered by gavage for 2 weeks with DMSO 1% (controls), PA, PA+NAC, PA+NAM, PA+NAG, PH, PH+NAC, PH+NAM, and PH+NAG. Biochemical assays of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), total thiols, and alpha-fetoprotein (AFP) in liver homogenates and serum assays of ALT, AST, 8-hydroxy guanine (8-OH-Gua), and AFP were done. Also histopathological examinations of liver tissues in various groups were done. Results. PA and PH cause significant increase in hepatic levels of MDA, NO, and AFP and serum ALT, AST, and 8-OH-Gua levels, with significant decrease in hepatic GSH and total thiols. NAG and NAC significantly improve the PA- and PH-induced hepatic and blood, biochemical, and histopathological disturbances, respectively. Conclusions. Both PA and PH induce oxidative stress in rat liver within their therapeutic doses. NAG and NAC in pharmacological doses can antagonize the oxidative damaging effect of both PA and PH.
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spelling doaj-art-73a8b78bfa204d07b17de25ea9926ee52025-02-03T05:53:32ZengWileyInternational Journal of Hepatology2090-34482090-34562018-01-01201810.1155/2018/76034377603437Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in RatsTahia H. Saleem0Nagwa Abo El-Maali1Mohammed H. Hassan2Nahed A. Mohamed3Nashwa A. M. Mostafa4Emaad Abdel-Kahaar5Azza S. Tammam6Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, EgyptDepartment of Chemistry, Faculty of Science, Assiut University, Assiut, EgyptDepartment of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, EgyptDepartment of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, EgyptDepartment of Histology, Faculty of Medicine, Assiut University, Assiut, EgyptDepartment of Medical Pharmacology, Faculty of Medicine, South Valley University, Qena, EgyptDepartment of Chemistry, Faculty of Science, Assiut University, Assiut, EgyptBackground and Aims. Both paracetamol (PA) and phenacetin (PH) are analgesic and antipyretic agents. Part of phenacetin therapeutic activity is attributed to its metabolism into paracetamol. Paracetamol causes direct hepatic oxidative stress damage. The present study aimed to investigate the possible damaging effects of both PA and PH, when used in therapeutic doses, on rat liver and to compare the antioxidant and hepatoprotective effects of N-acetylcysteine (NAC), N-acetyl-methionine (NAM), and N-acetylglucosamine (NAG) against PA- or PH-induced hepatic damage. Methods. 90 male Wistar albino rats (120-140 gm) were undertaken, categorized randomly into 9 groups of 10 rats each, and administered by gavage for 2 weeks with DMSO 1% (controls), PA, PA+NAC, PA+NAM, PA+NAG, PH, PH+NAC, PH+NAM, and PH+NAG. Biochemical assays of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), total thiols, and alpha-fetoprotein (AFP) in liver homogenates and serum assays of ALT, AST, 8-hydroxy guanine (8-OH-Gua), and AFP were done. Also histopathological examinations of liver tissues in various groups were done. Results. PA and PH cause significant increase in hepatic levels of MDA, NO, and AFP and serum ALT, AST, and 8-OH-Gua levels, with significant decrease in hepatic GSH and total thiols. NAG and NAC significantly improve the PA- and PH-induced hepatic and blood, biochemical, and histopathological disturbances, respectively. Conclusions. Both PA and PH induce oxidative stress in rat liver within their therapeutic doses. NAG and NAC in pharmacological doses can antagonize the oxidative damaging effect of both PA and PH.http://dx.doi.org/10.1155/2018/7603437
spellingShingle Tahia H. Saleem
Nagwa Abo El-Maali
Mohammed H. Hassan
Nahed A. Mohamed
Nashwa A. M. Mostafa
Emaad Abdel-Kahaar
Azza S. Tammam
Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats
International Journal of Hepatology
title Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats
title_full Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats
title_fullStr Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats
title_full_unstemmed Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats
title_short Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats
title_sort comparative protective effects of n acetylcysteine n acetyl methionine and n acetyl glucosamine against paracetamol and phenacetin therapeutic doses induced hepatotoxicity in rats
url http://dx.doi.org/10.1155/2018/7603437
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