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Many drugs and xenobiotics are lipophilic and they should be transformed into more polar water soluble compounds to be excreted. Cimetidine inhibits cytochrome P450. The aim of this study was to investigate the preventive and/or reversal action of cimetidine on cytochrome P450 induction and other metabolic alterations provoked by the carcinogen p-dimethylaminoazobenzene. A group of male CFI mice received a standard laboratory diet and another group was placed on dietary p-dimethylaminoazobenzene (0.5% w w-1). After 40 days of treatment, animals of both groups received p-dimethylaminoazobenzene and two weekly doses of cimetidine (120 mg kg-1, i.p.) during a following period of 35 days. Cimetidine prevented and reversed δ-aminolevulinate synthetase induction and cytochrome P450 enhancement provoked by p-dimethylaminoazobenzene. However, cimetidine did not restore haem oxygenase activity decreased by p-dimethylaminoazobenzene. Enhancement in glutathione S-transferase activity provoked by p-dimethylaminoazobenzene, persisted in those animals then treated with cimetidine. This drug did not modify either increased lipid peroxidation or diminution of the natural antioxidant defence system (inferred by catalase activity) induced by p-dimethylaminoazobenzene. In conclusion, although cimetidine treatment partially prevented and reversed cytochrome P450 induction, and alteration on haem metabolism provoked by p-dimethylaminoazobenzene AB, it did not reverse liver damage or lipid peroxidation. These results further support our hypothesis on the necessary existence of a multiple biochemical pathway disturbance for the onset of hepatocarcinogenesis initiation. © 2002 Cancer Research UK.


Documento: Artículo
Título:Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation
Autor:Caballero, F.; Gerez, E.; Batlle, A.; Vazquez, E.
Filiación:Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP) (CONICET - FCEN, UBA), Ciudad Universitaria, Pabellón II, 2do piso, C1428EHA Buenos Aires, Argentina
Palabras clave:Cimetidine; Cytochrome P450; Haem metabolism; Hepatocarcinogenesis; Oxidative stress; P-dimethylaminoazobenzene; 4 dimethylaminoazobenzene; 5 aminolevulinate synthase; catalase; cimetidine; cytochrome P450; glutathione transferase; heme; heme oxygenase; malonaldehyde; thiobarbituric acid reactive substance; xenobiotic agent; animal experiment; animal model; animal tissue; article; controlled study; enzyme induction; enzyme inhibition; lipid peroxidation; liver cancer; liver carcinogenesis; liver injury; male; mouse; nonhuman; oxidative stress; priority journal; 5-Aminolevulinate Synthetase; Animals; Body Weight; Carcinogens; Catalase; Cimetidine; Cytochrome P-450 Enzyme System; Enzyme Inhibitors; Glutathione Transferase; Heme; Liver Neoplasms, Experimental; Male; Mice; p-Dimethylaminoazobenzene; Thiobarbituric Acid Reactive Substances
Página de inicio:630
Página de fin:635
Título revista:British Journal of Cancer
Título revista abreviado:Br. J. Cancer
CAS:5-Aminolevulinate Synthetase, EC; Carcinogens; Catalase, EC; Cimetidine, 51481-61-9; Cytochrome P-450 Enzyme System, 9035-51-2; Enzyme Inhibitors; Glutathione Transferase, EC; Heme, 14875-96-8; p-Dimethylaminoazobenzene, 60-11-7; Thiobarbituric Acid Reactive Substances


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---------- APA ----------
Caballero, F., Gerez, E., Batlle, A. & Vazquez, E. (2002) . Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation. British Journal of Cancer, 86(4), 630-635.
---------- CHICAGO ----------
Caballero, F., Gerez, E., Batlle, A., Vazquez, E. "Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation" . British Journal of Cancer 86, no. 4 (2002) : 630-635.
---------- MLA ----------
Caballero, F., Gerez, E., Batlle, A., Vazquez, E. "Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation" . British Journal of Cancer, vol. 86, no. 4, 2002, pp. 630-635.
---------- VANCOUVER ----------
Caballero, F., Gerez, E., Batlle, A., Vazquez, E. Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation. Br. J. Cancer. 2002;86(4):630-635.