Malaria downmodulates mRNA expression and catalytic activities of CYP1A2, 2E1 and 3A11 in mouse liver

• Published in: European journal of pharmacology Vol. 616; no. 1; pp. 265 - 269
• Main Authors: Carvalho, Renato Sampaio, Friedrich, Karen, De-Oliveira, Ana C.A.X., Suarez-Kurtz, Guilherme, Paumgartten, Francisco J.R.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.08.2009; Elsevier
• Subjects: Animals; Aryl Hydrocarbon Hydroxylases - genetics; Aryl Hydrocarbon Hydroxylases - metabolism; Biocatalysis; Biological and medical sciences; Cytochrome 450; Cytochrome P-450 CYP1A2 - genetics; Cytochrome P-450 CYP1A2 - metabolism; Cytochrome P-450 CYP2E1 - genetics; Cytochrome P-450 CYP2E1 - metabolism; Cytochrome P-450 CYP3A - genetics; Cytochrome P-450 CYP3A - metabolism; Down-Regulation; Drug metabolism; Gene Expression Regulation, Enzymologic; Human protozoal diseases; Humans; Infectious diseases; Liver - enzymology; Liver - metabolism; Malaria; Male; Medical sciences; Mice; Parasitic diseases; Pharmacokinetics; Pharmacology. Drug treatments; Plasmodium; Plasmodium berghei; Plasmodium berghei - physiology; Protozoal diseases; Rats; RNA, Messenger - genetics; RNA, Messenger - metabolism; Drug metabolism; Plasmodium berghei; Malaria; Cytochrome 450; Pharmacokinetics; Drug; Protozoa; Apicomplexa; Protozoal disease; Digestive system; Enzyme; Isozyme; Cytochrome P450; Liver; Rodentia; Parasitosis; Gene expression; Metabolism; Infection; Vertebrata; Mammalia; Mouse; Animal
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2009.05.030

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.