Plasmodium berghei (ANKA): infection induces CYP2A5 and 2E1 while depressing other CYP isoforms in the mouse liver |
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Authors: | De-Oliveira Ana C A X Da-Matta Anndressa C Paumgartten Francisco J R |
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Affiliation: | Laboratory of Environmental Toxicology, Department of Biological Sciences, National School of Public Health, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil. ana.oliveira@ensp.fiocruz.br |
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Abstract: | It has been reported that malaria infection impairs hepatic drug clearance and causes a down-regulation of CYP-mediated monooxygenase activities in rodents and humans. In the present study, we investigated the effects of Plasmodium berghei infection on the activity of liver monooxygenases in female DBA/2 and C57BL/6 mice. In both mouse strains, P. berghei infection decreased activities mediated by CYP1A (EROD: DBA/2 65.3%, C57BL/6 44.7%) and 2B (BROD: DBA/2 64.3%, C57BL/6 49.8%) subfamily isoforms and increased activities mediated by 2A5 (COH: DBA/2 182.4%, C57BL/6 148.5%) and 2E1 (PNPH: DBA/2 177.8%, C57BL/6 128.5%) isoforms as compared to non-infected controls. Since malaria infection also produced an increase in ALT (273.1%) and AST (354.1%) activities in the blood serum, our findings are consistent with the view that CYP2A5 activity is induced by liver injury. An almost generalized depression of CYP-mediated activities has been found with numerous infections and inflammatory stimuli but an induction of CYP2A5 had been previously noted only in some viral hepatitis and trematode (liver fluke) infections. |
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Keywords: | ALT, alanine aminotransferase AST, aspartate aminotransferase BROD, benzyloxi-resorufin-O-debenzylase COH, coumarin-7-hydroxylase CYP, cytochrome P450 EROD, ethoxyresorufin-O-deethylase LPS, lipopolysaccharide Monooxygenases NO, nitric oxide iNOS, inducible nitric oxide synthase MAL, malaria-infected mice CON, non-infected control mice PNPH, p-nitrophenol-hydroxylase Pharmacokinetics Plasmodium berghei (ANKA) Xenobiotic metabolism SEM, standard error of the mean |
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