The functional state of the xenobiotic metabolizing system in rat liver following chronic administration of diethylnitrosamine or its precursors.
The effect of chronic administration of 0.002% N-nitrosodiethylamine (DENA), 0.002% diethylamine (DEA) and 0.0005% sodium nitrite (SN) on the functional state of the xenobiotic metabolizing system in rat liver was investigated. Administration of DEA and DENA increased concentration of cytochromes P-450 and b5. SN did not affect the enzymes of the monooxygenase system. Coadministration of DEA and SN maximally increased the concentration of cytochrome P-450. It is not possible to explain the phenomenon of combined administration of SN and DEA by simple summation of the effects caused by them separately. The activity of microsomal glutathione S-transferase did not change when DEA and SN were given together, yet increased when they were administered separately. The maximum increase of the total activity of cytosol glutathione S-transferases was observed following DENA. In all four experimental groups a decrease of isoenzyme 5-5 activity was observed. Investigation of Se-independent glutathione peroxidase activity showed the multivariance of response of the glutathione S-transferase family to the compounds studied. The concentration of hepatic free SH-groups increased following administration of DENA and decreased dramatically when SN and DEA were coadministered. When they were given separately the concentration remained at control level.
Semak
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Department of Biochemistry, Belarussion State University, Minsk.
Pikulev
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AT
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004048:Diethylamines / Q000494:pharmacology; D004052:Diethylnitrosamine / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D012977:Sodium Nitrite / Q000494:pharmacology; D015262:Xenobiotics / Q000378:metabolism*
D000477:Alkylating Agents; D004048:Diethylamines; D015262:Xenobiotics; D004052:Diethylnitrosamine; D003577:Cytochrome P-450 Enzyme System; C034281:diethylamine; D005982:Glutathione Transferase; D012977:Sodium Nitrite