NDLI: Tolbutamide hydroxylation by hepatic microsomes from Atlantic salmon (Salmo salar L.)

Content Provider	Springer Nature Link
Author	Vestergren, AnnaLotta Schiller Zlabek, Vladimir Pickova, Jana Zamaratskaia, Galia
Copyright Year	2012
Abstract	Metabolic transformations of two substrates for human cytochrome P450 (CYP450) 2C9, tolbutamide and diclofenac, were investigated in hepatic microsomes from Atlantic salmon (Salmo salar L.). Tolbutamide hydroxylation followed Michaelis–Menten kinetics. Mean apparent Michaelis–Menten constant (K$_{m}$) and maximum reaction velocity (V$_{max}$) values for 4-hydroxytolbutamide (TBOH) formation were 0.09 ± 0.031 mM and 49.5 ± 6.03 pmol/min/mg, respectively. Addition of sulfaphenazole, an inhibitor for mammalian CYP2C9, in a range from 1 to 200 μM decreased formation of TBOH in a concentration-dependent manner, but not to 50%. Neither fluconazole, an inhibitor of human CYP2C9, nor ketoconazole, inhibitor of CYP1A and CYP3A in fish, affected TBOH formation. In contrast ellipticine, an inhibitor of CYP1A in fish inhibited TBOH formation with the IC$_{50}$ value of 12.1 μM. The rate of TBOH formation was competitively inhibited by 100 μM of sesamin in the incubations, but the degree of inhibition did not increase with increased sesamin concentration. Ethoxyresorufin hydroxylase (EROD) activity was inhibited by tolbutamide in a non-competitive manner (inhibition constant K$_{i}$ = 218 μM). Our data suggest that tolbutamide is metabolized by salmon microsomes with formation of TBOH. CYP1A might be involved in this reaction as suggested by decreased TBOH formation in the presence of ellipticine and decreased EROD activity in the presence of tolbutamide. Incubation of diclofenac with the microsomes yielded no metabolite formation, suggesting that salmon does not possess diclofenac-metabolizing activity.
Starting Page	6867
Ending Page	6873
Page Count	7
File Format	PDF
ISSN	03014851
Journal	Molecular Biology Reports
Volume Number	39
Issue Number	6
e-ISSN	15734978
Language	English
Publisher	Springer Netherlands
Publisher Date	2012-02-05
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Tolbutamide 4-hydroxytolbutamide Diclofenac Fish Hepatic microsomes EROD Animal Anatomy / Morphology / Histology Animal Biochemistry
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

In vitro inhibition of 7-ethoxyresorufin-O-deethylase (EROD) and p-nitrophenol hydroxylase (PNPH) activities by sesamin in hepatic microsomes from two fish species

Effective size of an Atlantic salmon (Salmo salar L.) metapopulation in Northern Spain

An extended panel of single nucleotide polymorphisms in Atlantic salmon (Salmo salar L.) mitochondrial DNA

Seawater tolerance in Atlantic salmon, Salmo salar L., brown trout, Salmo trutta L., and S. salar × S. trutta hybrids smolt

Para-nitrophenol hydroxylation by fish liver microsomes: kinetics and effect of selective cytochrome P450 inhibitors

A moving light stimulus elicits a sustained swimming response in farmed Atlantic salmon, Salmo salar L.

Minor lipid metabolic perturbations in the liver of Atlantic salmon (Salmo salar L.) caused by suboptimal dietary content of nutrients from fish oil

Absorption of glucose, amino acids, and dipeptides by the intestines of Atlantic salmon (Salmo salar L.)

Effect of temperature and diet on wound healing in Atlantic salmon (Salmo salar L.)

Tolbutamide hydroxylation by hepatic microsomes from Atlantic salmon (Salmo salar L.)

Similar Documents

In vitro inhibition of 7-ethoxyresorufin-O-deethylase (EROD) and p-nitrophenol hydroxylase (PNPH) activities by sesamin in hepatic microsomes from two fish species

Effective size of an Atlantic salmon (Salmo salar L.) metapopulation in Northern Spain

An extended panel of single nucleotide polymorphisms in Atlantic salmon (Salmo salar L.) mitochondrial DNA

Seawater tolerance in Atlantic salmon, Salmo salar L., brown trout, Salmo trutta L., and S. salar × S. trutta hybrids smolt

Para-nitrophenol hydroxylation by fish liver microsomes: kinetics and effect of selective cytochrome P450 inhibitors

A moving light stimulus elicits a sustained swimming response in farmed Atlantic salmon, Salmo salar L.

Minor lipid metabolic perturbations in the liver of Atlantic salmon (Salmo salar L.) caused by suboptimal dietary content of nutrients from fish oil

Absorption of glucose, amino acids, and dipeptides by the intestines of Atlantic salmon (Salmo salar L.)

Effect of temperature and diet on wound healing in Atlantic salmon (Salmo salar L.)

Tolbutamide hydroxylation by hepatic microsomes from Atlantic salmon (Salmo salar L.)