Response of mouse liver coumarin 7-hydroxylase activity to hepatotoxins: Dependence on strain and agent and comparison to other monooxygenases

Pellinen, P., Stenback, F., Rautio, A., Pelkonen, O., Lang, M. and Pasanen, M. (1993) Response of mouse liver coumarin 7-hydroxylase activity to hepatotoxins: Dependence on strain and agent and comparison to other monooxygenases. Naunyn-Schmiedeberg's Archives of Pharmacology, 348 4: 435-443.

Author Pellinen, P.
Stenback, F.
Rautio, A.
Pelkonen, O.
Lang, M.
Pasanen, M.
Title Response of mouse liver coumarin 7-hydroxylase activity to hepatotoxins: Dependence on strain and agent and comparison to other monooxygenases
Journal name Naunyn-Schmiedeberg's Archives of Pharmacology   Check publisher's open access policy
ISSN 0028-1298
1432-1912
Publication date 1993-10
Sub-type Article (original research)
Volume 348
Issue 4
Start page 435
End page 443
Total pages 9
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Abstract Acute effects of a single intraperitoneal dose of allyl alcohol (AA, 64 mg/kg), dimethylnitrosamine (DMNA, 30 mg/kg), hexachlorobutadiene (HCBD, 50 mg/kg), carbon tetrachloride (CCl4, 24 mg/kg), cocaine (60 mg/kg) and pyrazole (300 mg/kg) on the hepatic histology and monooxygenases in DBA/2 and C57Bl/6 strains of mice were investigated. All substances caused histologically verified injury to the liver, which varied in appearance and severity-depending on the compound and the mouse strain. Responses of P450-catalyzed reactions were highly dependent on the toxin and varied between different monooxygenase (MO) reactions and two mouse strains. In DBA/2 strain, coumarin 7-hydroxylase (COH) activity was increased from 3- to 5-fold by pyrazole, cocaine, HCBD and CCl4. With respect to P450 content and other MO activities, no changes or even decreases were generally observed. Some exceptions to this rule were found: HCBD significantly increased T15αOH, PROD and EROD activities in C57Bl/6 mice, whereas cocaine-caused a significant stimulation of T15α OH and PROD in DBA/2 mice, it is concluded that i) different hepatoxins cause different types of liver injury and responses of the monooxygenase complex ('hepatotoxinspecific finger prints'), ii) although DBA/2 and C57Bl/6 mice responded rather similarly to hepatotoxins, also with respect to P450 content and most MO activities, they displayed a profound difference in the behaviour of COH activity, and iii) within the P450 superfamily, the regulation of COH activity seems to be rather unique, also when compared to its structurally close enzyme, testosterone 15α-hydroxylase.
Keyword Coumarin
P450COH
drug metabolism
Hepatoxicity
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
 
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Created: Mon, 30 Nov 2009, 15:07:24 EST