[Disulfiram and butylhydroxyanisole induction of glutathione-S- and UDP glucuronosyltransferase activities in the liver and its role in preventing the toxic action of diethylnitrosamine in rats].
Pretreatment of Wistar male rats with disulfiram (DSF, 500 mg/kg, three times, orally) or butylhydroxyanisole (BHA, 400 mg/kg, three times, orally) was shown to protect animals completely against intoxication with diethylnitrosamine (DENA) in the dose equal to LD50 (280 mg/kg, once, orally). DSF and BHA were also found to produce a significant modification of the 2nd stage of metabolism of xenobiotics: to induce the activity of cytosol and microsomal glutathione-S-transferases (GST) (by 1.7 and 2 times, 2.3 and 3.1 times, respectively), the content of glutathione (by 1.6 and 2.3 times), the activity of UDP glucuronosyltransferase (UDP-GT) (by 2 and 3.2 times) but to decrease the activity of sulfotransferase (by 22 and 35%). Administration of DENA decreased the activity of GST, UDP-GT and the content of glutathione, however they remain significantly higher than the corresponding parameters in intact animals. It is concluded that the protective action of DSF and BHA is related greatly to the induction of the systems of conjugation with glutathione and UDP-glucuronic acid.
Kalinina
E V
EV
Spiridonova
S M
SM
Saprin
A N
AN
Berezov
T T
TT
D000818:Animals; D002083:Butylated Hydroxyanisole / Q000494:pharmacology* / Q000627:therapeutic use; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004052:Diethylnitrosamine / Q000506:poisoning / Q000633:toxicity*; D004221:Disulfiram / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000096:biosynthesis*; D005982:Glutathione Transferase / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains
D002083:Butylated Hydroxyanisole; D004052:Diethylnitrosamine; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D004221:Disulfiram
Induktsiia disul'firamom i butilgidroksianizolom aktivnosti glutation-S- i UDF-gliukuronoziltransferaz v pecheni i ee rol' v predotvrashchenii toksicheskogo deĭstviia diétilnitrozamina u krys.