Artículo

Noriega, G.O.; Ossola, J.O.; Tomaro, M.L.; Batlle, A.M.delC. "Effect of acetaminophen on heme metabolism in rat liver" (2000) International Journal of Biochemistry and Cell Biology. 32(9):983-991
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Abstract:

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.

Registro:

Documento: Artículo
Título:Effect of acetaminophen on heme metabolism in rat liver
Autor:Noriega, G.O.; Ossola, J.O.; Tomaro, M.L.; Batlle, A.M.delC.
Filiación:Centro De Investigaciones Sobre Porfirinas Y Porfirias (CIPYP), CONICET-Facultad De Ciencias Exactas Y Naturales, Universidad De Buenos Aires, Buenos Aires, Argentina
Departamento De Química Biológica, Facultad De Farmacia Y Bioquímica, Universidad De Buenos Aires, Junín 956, Buenos Aires 1113, Argentina
Palabras clave: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
Año:2000
Volumen:32
Número:9
Página de inicio:983
Página de fin:991
DOI: http://dx.doi.org/10.1016/S1357-2725(00)00040-6
Título revista:International Journal of Biochemistry and Cell Biology
Título revista abreviado:Int. J. Biochem. Cell Biol.
ISSN:13572725
CODEN:IJBBF
CAS:5-Aminolevulinate Synthetase, EC 2.3.1.37; Acetaminophen, 103-90-2; Bilirubin, 635-65-4; Heme, 14875-96-8; Porphobilinogen Synthase, EC 4.2.1.24; S-Adenosylmethionine, 29908-03-0
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13572725_v32_n9_p983_Noriega

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Citas:

---------- APA ----------
Noriega, G.O., Ossola, J.O., Tomaro, M.L. & Batlle, A.M.delC. (2000) . Effect of acetaminophen on heme metabolism in rat liver. International Journal of Biochemistry and Cell Biology, 32(9), 983-991.
http://dx.doi.org/10.1016/S1357-2725(00)00040-6
---------- CHICAGO ----------
Noriega, G.O., Ossola, J.O., Tomaro, M.L., Batlle, A.M.delC. "Effect of acetaminophen on heme metabolism in rat liver" . International Journal of Biochemistry and Cell Biology 32, no. 9 (2000) : 983-991.
http://dx.doi.org/10.1016/S1357-2725(00)00040-6
---------- MLA ----------
Noriega, G.O., Ossola, J.O., Tomaro, M.L., Batlle, A.M.delC. "Effect of acetaminophen on heme metabolism in rat liver" . International Journal of Biochemistry and Cell Biology, vol. 32, no. 9, 2000, pp. 983-991.
http://dx.doi.org/10.1016/S1357-2725(00)00040-6
---------- VANCOUVER ----------
Noriega, G.O., Ossola, J.O., Tomaro, M.L., Batlle, A.M.delC. Effect of acetaminophen on heme metabolism in rat liver. Int. J. Biochem. Cell Biol. 2000;32(9):983-991.
http://dx.doi.org/10.1016/S1357-2725(00)00040-6