Abstract
Pyrazole, a potent inhibitor of alcohol dehydrogenase, was found to be a potent inducer of the activity of low (iKm) dimethylnitrosamine demethylase (DMN-d). One injection of pyrazole (200 mg/kg body wt) to weanling Wistar rats changed the microsomal DMN demethylase activity by 1.7, 1.9 and 2.5 times the control values at 6, 12 and 24 hr after the injection respectively. Pyrazole administration reduced arylhydrocarbon hydroxylase (AHH) activity. When animals were injected with pyrazole (200 mg/kg body wt) for 1, 2, 3 or 4 consecutive days, the values for DMN-d activity were 277, 297, 306 and 319% of the control values. The corresponding values for AHH were 91, 67, 57 and 45% for l, 2, 3 and 4 injections respectively. Pyrazole-induced DMN-d activity was NADPH dependent and was inhibited by CO; n-butanol gave a 50% inhibition at a concentration of 2 × 10-3 M. The corresponding value for metyrapone was 1 × 10-2 M. Cytochrome P-450 was slightly increased by pyrazole and its CO-complex gave an absorption maximum around 451 nm. When the microsomal proteins were separated using sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis, a large increase in a band at about 51,000 daltons was found in the liver microsomes of pyrazole-treated animals.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1245-1249 |
| Number of pages | 5 |
| Journal | Biochemical Pharmacology |
| Volume | 31 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 1 1982 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology
Cite this
Induction of microsomal dimethylnitrosamine demethylase by pyrazole. / Evarts, Ritva P.; Haliday, Emily; Negishi, Masahiko; Hjelmeland, Leonard M.
In: Biochemical Pharmacology, Vol. 31, No. 7, 01.04.1982, p. 1245-1249.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Induction of microsomal dimethylnitrosamine demethylase by pyrazole
AU - Evarts, Ritva P.
AU - Haliday, Emily
AU - Negishi, Masahiko
AU - Hjelmeland, Leonard M
PY - 1982/4/1
Y1 - 1982/4/1
N2 - Pyrazole, a potent inhibitor of alcohol dehydrogenase, was found to be a potent inducer of the activity of low (iKm) dimethylnitrosamine demethylase (DMN-d). One injection of pyrazole (200 mg/kg body wt) to weanling Wistar rats changed the microsomal DMN demethylase activity by 1.7, 1.9 and 2.5 times the control values at 6, 12 and 24 hr after the injection respectively. Pyrazole administration reduced arylhydrocarbon hydroxylase (AHH) activity. When animals were injected with pyrazole (200 mg/kg body wt) for 1, 2, 3 or 4 consecutive days, the values for DMN-d activity were 277, 297, 306 and 319% of the control values. The corresponding values for AHH were 91, 67, 57 and 45% for l, 2, 3 and 4 injections respectively. Pyrazole-induced DMN-d activity was NADPH dependent and was inhibited by CO; n-butanol gave a 50% inhibition at a concentration of 2 × 10-3 M. The corresponding value for metyrapone was 1 × 10-2 M. Cytochrome P-450 was slightly increased by pyrazole and its CO-complex gave an absorption maximum around 451 nm. When the microsomal proteins were separated using sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis, a large increase in a band at about 51,000 daltons was found in the liver microsomes of pyrazole-treated animals.
AB - Pyrazole, a potent inhibitor of alcohol dehydrogenase, was found to be a potent inducer of the activity of low (iKm) dimethylnitrosamine demethylase (DMN-d). One injection of pyrazole (200 mg/kg body wt) to weanling Wistar rats changed the microsomal DMN demethylase activity by 1.7, 1.9 and 2.5 times the control values at 6, 12 and 24 hr after the injection respectively. Pyrazole administration reduced arylhydrocarbon hydroxylase (AHH) activity. When animals were injected with pyrazole (200 mg/kg body wt) for 1, 2, 3 or 4 consecutive days, the values for DMN-d activity were 277, 297, 306 and 319% of the control values. The corresponding values for AHH were 91, 67, 57 and 45% for l, 2, 3 and 4 injections respectively. Pyrazole-induced DMN-d activity was NADPH dependent and was inhibited by CO; n-butanol gave a 50% inhibition at a concentration of 2 × 10-3 M. The corresponding value for metyrapone was 1 × 10-2 M. Cytochrome P-450 was slightly increased by pyrazole and its CO-complex gave an absorption maximum around 451 nm. When the microsomal proteins were separated using sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis, a large increase in a band at about 51,000 daltons was found in the liver microsomes of pyrazole-treated animals.
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UR - http://www.scopus.com/inward/citedby.url?scp=0020028287&partnerID=8YFLogxK
U2 - 10.1016/0006-2952(82)90011-9
DO - 10.1016/0006-2952(82)90011-9
M3 - Article
C2 - 7092919
AN - SCOPUS:0020028287
VL - 31
SP - 1245
EP - 1249
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 7
ER -