In vivo study of the effect of antiviral acyclic nucleotide phosphonate (R)-9-[2-(phosphonomethoxy) propyl]adenine (PMPA, tenofovir) and its prodrug tenofovir disoproxil fumarate on rat microsomal cytochrome P450

Title:

In vivo study of the effect of antiviral acyclic nucleotide phosphonate (R)-9-[2-(phosphonomethoxy) propyl]adenine (PMPA, tenofovir) and its prodrug tenofovir disoproxil fumarate on rat microsomal cytochrome P450

Creator:

Eva Anzenbacherová, Pavel Anzenbacher, Zdeněk Zídek, Evžen Buchar, Eva Kmoníčková, Petr Potměšil, Nekvindová, J., Veinlichová, A., and Antonín Holý

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:a58544cd-81f6-470e-8da9-1258e9a2b5c6
uuid:a58544cd-81f6-470e-8da9-1258e9a2b5c6
issn:0862-8408

Subject:

Biochemie. Molekulární biologie. Biofyzika, fyziologie, cytochromy, physiology, cytochromes, tenofovir, (R)-9-[2-(phosphonomethoxy) propyl]adenine (PMPA), cytochrome P450, CYP2E1, CYP1A2, 2, and 577

Type:

article, články, model:article, and TEXT

Format:

print, bez média, and svazek

Description:

The total content of rat liver microsomal cytochrome P450 (CYP) significantly decreased after repeated i.p. administration of the antiviral agent tenofovir ((R)-9-[2-(phosphonomethoxy)propyl] adenine) and tenofovir disoproxil at a daily dose 25 mg/kg, although the content of liver microsomal protein did not change. The decrease of the CYP content was accompanied by concomitant increase of the amount of inactive CYP form, cytochrome P420. This effect was confirmed by a parallel study of the activities of selected CYP forms, CYP2E1 (p-nitrophenol hydroxylation) and CYP1A2 (7-ethoxyresorufin deethylation). The activity (expressed relatively to the protein content) of both CYP forms decreased significantly following the decrease of the total CYP. On the other hand, the CYP2E1 activity expressed relatively to the decreasing total CYP content remained unchanged. However, CYP1A2 activity also decreased when calculated relatively to the total native CYP content indicating lower stability of this form. Semiquantitative RT-PCR showed no significant changes in expression of major rat liver microsomal CYP forms after tenofovir treatment. In conclusion, repeated administration of tenofovir in higher doses led to significant decrease of the relative proportion of active liver microsomal CYPs accompanied by a conversion of these enzymes to the inactive form (CYP420) maintaining the sum of CYP proteins unchanged., E. Anzenbacherová, P. Anzenbacher, Z. Zídek, E. Buchar, E. Kmoníčková, P. Potměšil, J. Nekvindová, A. Veinlichová, A. Holý., and Obsahuje bibliografii a bibliografické odkazy

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2008 Volume:57 | Number:5

Harvested from:

CDK

Metadata only:

false