Malaria downmodulates mRNA expression and catalytic activities of CYP1A2, 2E1 and 3A11 in mouse liver.
It has been reported that malaria reduces cytochrome-P450 (CYP) content and monooxygenase activities in the mammalian host liver. The mechanism by which malaria modulates CYP activities, however, remains unclear. In this study we found that activities of ethoxy- and benzyloxy-resorufin-O-dealkylases, p-nitrophenol-hydroxylase and erythromycin-N-demethylase (mediated by CYP1A, 2B, 2E1 and 3A, respectively) were depressed, while uridine-glucuronosyl-transferase (a phase 2 enzyme) was unaltered in liver microsomes of Plasmodium berghei-infected (parasitemia >20%) male Swiss Webster mice. Prolongation of midazolam sleeping time and a slower clearance of chlorzoxazone were also noted in infected mice. Reductions of hepatic levels of CYP1A2, 2E1 and 3A11 mRNAs indicated that malaria downregulated these CYP-mediated activities at a pre-translational level.
Carvalho
Renato Sampaio
RS
Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Friedrich
Karen
K
De-Oliveira
Ana C A X
AC
Suarez-Kurtz
Guilherme
G
Paumgartten
Francisco J R
FJ
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism*; D055162:Biocatalysis; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008288:Malaria; D008297:Male; D051379:Mice; D010962:Plasmodium berghei / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D012333:RNA, Messenger; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A