Plasmodium berghei (ANKA): infection induces CYP2A5 and 2E1 while depressing other CYP isoforms in the mouse liver.
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.
De-Oliveira
Ana C A X
AC
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
Da-Matta
Anndressa C
AC
Paumgartten
Francisco J R
FJ
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D000072467:Cytochrome P450 Family 2; D015536:Down-Regulation; D004790:Enzyme Induction; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000469:parasitology / Q000473:pathology; D008288:Malaria / Q000201:enzymology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D018512:Parasitemia / Q000201:enzymology / Q000469:parasitology; D010962:Plasmodium berghei / Q000502:physiology*; D013154:Spleen / Q000473:pathology
D007527:Isoenzymes; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C585520:Cyp2a5 protein, mouse; D019363:Cytochrome P-450 CYP1A1; D065637:Cytochrome P-450 CYP2A6; D019362:Cytochrome P-450 CYP2B1; D000072467:Cytochrome P450 Family 2