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Changes in the expression of cytochrome P450 isozymes and related carcinogen metabolizing enzyme activities in Schistosoma mansoni-infected mice

Published online by Cambridge University Press:  12 April 2024

S.A. Sheweita ,
J. Mubark ,
M.J. Doenhoff ,
M.H. Mostafa ,
G.P. Margison ,
P.J. O'Connor  and
R.H. Elder
S.A. Sheweita*
Affiliation:
Department of Bioscience and Technology, Institute of Graduate Studies and Research, Alexandria University, 163 Horreya Ave., PO Box 832, Alexandria, Egypt
J. Mubark
Affiliation:
School of Biological Sciences, University of Wales, Bangor, UK
M.J. Doenhoff
Affiliation:
School of Biological Sciences, University of Wales, Bangor, UK
M.H. Mostafa
Affiliation:
Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Egypt
G.P. Margison
Affiliation:
CRC Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK
P.J. O'Connor
Affiliation:
CRC Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK
R.H. Elder
Affiliation:
CRC Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK
*
*Fax: (203) 428 5792 Email: [email protected]
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Abstract

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Mixed-function oxidase enzymes metabolize most xenobiotic agents. Western blotting was used to investigate the effect of Schistosoma mansoni infection on the expression of various cytochrome P450 (CYP) isozymes and specific enzyme assays to study related metabolic functions in mouse liver microsomes. Male BK-TO mice were infected with 200 cercariae per mouse and their livers were assayed at 6, 15, 30 and 45 days post-infection (p.i.) and compared with appropriately matched controls. The expression of each of the CYP isozymes (1A1, 2B1/2, 2C6, and 4A) was either unaffected or transiently increased up to 30 days post-infection. By 45 days, a significant loss of signal was observed, particularly for CYP 1A1 and 2B1/2 where no signal could be detected. Evidence supporting these findings was obtained from enzyme assays specific for particular CYP isozymes. The activity of ethoxyresorufin O-deethylase (CYP 1A1) was reduced by 97% and that of pentoxyresorufin O-depentylase (CYP 2B1/2) by 96% at 45 days p.i. Similarly, the activity of ethoxycoumarin hydroxylase was progressively reduced over the period under study. It is believed that N-nitrosamines are activated principally by N-nitrosodimethylamine N-demethylase I which was significantly increased at both 30 and 45 days p.i. To further investigate metabolic competency following S. mansoni infection, the in vitro binding of benzo(a)pyrene metabolites to DNA was measured, using isolated liver microsomes to activate benzo(a)pyrene. Benzo(a)pyrene-DNA adduct formation was markedly increased at 6, 15 and 30 days with a maximum at 15 days, but decreased at 45 days p.i. It was concluded that S. mansoni infection changes the expression of different CYP isozymes and also the activity of phase I drug-metabolizing enzymes at different periods of infection and may thus change the liver's capacity to activate or detoxify many endogenous and exogenous compounds. Such alterations may also change the therapeutic actions of drugs that are primarily metabolized by the P450 system, when administered to patients with schistosomiasis.

Type
Review Article
Information
Journal of Helminthology , Volume 76 , Issue 1 , March 2002 , pp. 71 - 78
Copyright
Copyright © Cambridge University Press 2002

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