Effect of acetaminophen on heme metabolism in rat liver

Background and aims: Acetaminophen (APAP) or paracetamol is a hepatotoxic drug through mechanisms involving oxidative stress. To know whether mammalian cells possess inducible pathways for antioxidant defense, we have to study the relationship between heme metabolism and oxidative stress. Methods: f...

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Autores principales:	Noriega, Guillermo Osvaldo, Batlle, Alcira María del Carmen
Publicado:	2000
Materias:	Acetaminophen Bilirubin Heme metabolism Oxidative stress S-adenosyl-L-methionine 5 aminolevulinate synthase bilirubin catalase glutathione glutathione peroxidase heme oxygenase malonaldehyde paracetamol porphobilinogen synthase s adenosylmethionine animal experiment antioxidant activity article controlled study enzyme activity female lipid peroxidation liver metabolism liver toxicity nonhuman oxidative stress rat 5-Aminolevulinate Synthetase Animals Female Heme Injections, Intraperitoneal Lipid Peroxidation Liver Oxidative Stress Porphobilinogen Synthase Rats Rats, Wistar S-Adenosylmethionine Animalia Mammalia Rattus norvegicus
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13572725_v32_n9_p983_Noriega http://hdl.handle.net/20.500.12110/paper_13572725_v32_n9_p983_Noriega
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_13572725_v32_n9_p983_Noriega2023-06-08T16:11:16Z Effect of acetaminophen on heme metabolism in rat liver Noriega, Guillermo Osvaldo Batlle, Alcira María del Carmen Acetaminophen Bilirubin Heme metabolism Oxidative stress S-adenosyl-L-methionine 5 aminolevulinate synthase bilirubin catalase glutathione glutathione peroxidase heme oxygenase malonaldehyde paracetamol porphobilinogen synthase s adenosylmethionine animal experiment antioxidant activity article controlled study enzyme activity female lipid peroxidation liver metabolism liver toxicity nonhuman oxidative stress rat 5-Aminolevulinate Synthetase Acetaminophen Animals Bilirubin Female Heme Injections, Intraperitoneal Lipid Peroxidation Liver Oxidative Stress Porphobilinogen Synthase Rats Rats, Wistar S-Adenosylmethionine Animalia Mammalia Rattus norvegicus Background and aims: Acetaminophen (APAP) or paracetamol is a hepatotoxic drug through mechanisms involving oxidative stress. To know whether mammalian cells possess inducible pathways for antioxidant defense, we have to study the relationship between heme metabolism and oxidative stress. Methods: fasted female Wistar rats received a single injection of APAP (3.3 mmol kg-1 body weight) and then were killed at different times. Heme oxygenase-1 (HO), δ-aminolevulinic acid (ALA) synthase, ALA dehydratase, and porphobilinogenase activities, lipid peroxidation, GSH, catalase and glutathione peroxidase, were measured in liver homogenates. The antioxidant properties of bilirubin and S-adenosyl-L-methionine were also evaluated. Results: APAP increased lipid peroxidation (115% ± 6; S.E.M., n = 12 over control values) 1 h after treatment. GSH reached a minimum at 3 h (38% ± 5) increasing thereafter. At the same time antioxidant enzymes reached minimum values (catalase, 5.6 ± 0.4 pmol mg-1 protein, glutathione peroxidase, 0.101 ± 0.006 U mg-1 protein). HO induction was observed 6 h after treatment reaching a maximum value of 2.56 ± 0.12 U mg-1 protein 15 h after injection. ALA synthase (ALA-S) induction occurred after enhancement of HO, reaching a maximum at 18 h (three-fold the control). ALA dehydratase activity was first inhibited (31 ± 3%) showing a profile similar to that of GSH, while porphobilinogenase activity was not modified along the whole period of the assay. Administration of bilirubin (5 μmol kg-1 body weight) or S-adenosyl L-methionine (46 μmol kg-1 body weight) 2 h before APAP treatment entirely prevented the increase in malondialdehyde (MDA) content, the decrease in GSH levels as well as HO and ALA-S induction. Conclusion: This study shows that oxidative stress produced by APAP leads to increase in ALA-S and HO activities, indicating that toxic doses of APAP affect both heme biosynthesis and degradation. (C) 2000 Elsevier Science Ltd. Fil:Noriega, G.O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Batlle, A.M.delC. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2000 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13572725_v32_n9_p983_Noriega http://hdl.handle.net/20.500.12110/paper_13572725_v32_n9_p983_Noriega
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Acetaminophen Bilirubin Heme metabolism Oxidative stress S-adenosyl-L-methionine 5 aminolevulinate synthase bilirubin catalase glutathione glutathione peroxidase heme oxygenase malonaldehyde paracetamol porphobilinogen synthase s adenosylmethionine animal experiment antioxidant activity article controlled study enzyme activity female lipid peroxidation liver metabolism liver toxicity nonhuman oxidative stress rat 5-Aminolevulinate Synthetase Acetaminophen Animals Bilirubin Female Heme Injections, Intraperitoneal Lipid Peroxidation Liver Oxidative Stress Porphobilinogen Synthase Rats Rats, Wistar S-Adenosylmethionine Animalia Mammalia Rattus norvegicus
spellingShingle	Acetaminophen Bilirubin Heme metabolism Oxidative stress S-adenosyl-L-methionine 5 aminolevulinate synthase bilirubin catalase glutathione glutathione peroxidase heme oxygenase malonaldehyde paracetamol porphobilinogen synthase s adenosylmethionine animal experiment antioxidant activity article controlled study enzyme activity female lipid peroxidation liver metabolism liver toxicity nonhuman oxidative stress rat 5-Aminolevulinate Synthetase Acetaminophen Animals Bilirubin Female Heme Injections, Intraperitoneal Lipid Peroxidation Liver Oxidative Stress Porphobilinogen Synthase Rats Rats, Wistar S-Adenosylmethionine Animalia Mammalia Rattus norvegicus Noriega, Guillermo Osvaldo Batlle, Alcira María del Carmen Effect of acetaminophen on heme metabolism in rat liver
topic_facet	Acetaminophen Bilirubin Heme metabolism Oxidative stress S-adenosyl-L-methionine 5 aminolevulinate synthase bilirubin catalase glutathione glutathione peroxidase heme oxygenase malonaldehyde paracetamol porphobilinogen synthase s adenosylmethionine animal experiment antioxidant activity article controlled study enzyme activity female lipid peroxidation liver metabolism liver toxicity nonhuman oxidative stress rat 5-Aminolevulinate Synthetase Acetaminophen Animals Bilirubin Female Heme Injections, Intraperitoneal Lipid Peroxidation Liver Oxidative Stress Porphobilinogen Synthase Rats Rats, Wistar S-Adenosylmethionine Animalia Mammalia Rattus norvegicus
description	Background and aims: Acetaminophen (APAP) or paracetamol is a hepatotoxic drug through mechanisms involving oxidative stress. To know whether mammalian cells possess inducible pathways for antioxidant defense, we have to study the relationship between heme metabolism and oxidative stress. Methods: fasted female Wistar rats received a single injection of APAP (3.3 mmol kg-1 body weight) and then were killed at different times. Heme oxygenase-1 (HO), δ-aminolevulinic acid (ALA) synthase, ALA dehydratase, and porphobilinogenase activities, lipid peroxidation, GSH, catalase and glutathione peroxidase, were measured in liver homogenates. The antioxidant properties of bilirubin and S-adenosyl-L-methionine were also evaluated. Results: APAP increased lipid peroxidation (115% ± 6; S.E.M., n = 12 over control values) 1 h after treatment. GSH reached a minimum at 3 h (38% ± 5) increasing thereafter. At the same time antioxidant enzymes reached minimum values (catalase, 5.6 ± 0.4 pmol mg-1 protein, glutathione peroxidase, 0.101 ± 0.006 U mg-1 protein). HO induction was observed 6 h after treatment reaching a maximum value of 2.56 ± 0.12 U mg-1 protein 15 h after injection. ALA synthase (ALA-S) induction occurred after enhancement of HO, reaching a maximum at 18 h (three-fold the control). ALA dehydratase activity was first inhibited (31 ± 3%) showing a profile similar to that of GSH, while porphobilinogenase activity was not modified along the whole period of the assay. Administration of bilirubin (5 μmol kg-1 body weight) or S-adenosyl L-methionine (46 μmol kg-1 body weight) 2 h before APAP treatment entirely prevented the increase in malondialdehyde (MDA) content, the decrease in GSH levels as well as HO and ALA-S induction. Conclusion: This study shows that oxidative stress produced by APAP leads to increase in ALA-S and HO activities, indicating that toxic doses of APAP affect both heme biosynthesis and degradation. (C) 2000 Elsevier Science Ltd.
author	Noriega, Guillermo Osvaldo Batlle, Alcira María del Carmen
author_facet	Noriega, Guillermo Osvaldo Batlle, Alcira María del Carmen
author_sort	Noriega, Guillermo Osvaldo
title	Effect of acetaminophen on heme metabolism in rat liver
title_short	Effect of acetaminophen on heme metabolism in rat liver
title_full	Effect of acetaminophen on heme metabolism in rat liver
title_fullStr	Effect of acetaminophen on heme metabolism in rat liver
title_full_unstemmed	Effect of acetaminophen on heme metabolism in rat liver
title_sort	effect of acetaminophen on heme metabolism in rat liver
publishDate	2000
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13572725_v32_n9_p983_Noriega http://hdl.handle.net/20.500.12110/paper_13572725_v32_n9_p983_Noriega
work_keys_str_mv	AT noriegaguillermoosvaldo effectofacetaminophenonhememetabolisminratliver AT batllealciramariadelcarmen effectofacetaminophenonhememetabolisminratliver
_version_	1768543670944923648

Effect of acetaminophen on heme metabolism in rat liver

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