Alterations of hepatic microsomal enzymes in the early phase of murine schistosomiasis.
Schistosoma mansoni has been reported to cause a downregulation of hepatic cytochrome P450 activities after granulomas are formed around worm eggs harbored in the mouse liver. Only a few studies, however, provided data on the activity of xenobiotic-biotransaformation enzymes in the early phase of S. mansoni infection. In this study, we evaluated the alterations of liver microsomal enzymes during early infection (post-infection days, PIDs, 15 and 30) when granulomas are not found in the mouse liver yet. Swiss Webster (SW) and DBA/2 mice of either sex were infected with 100 S. mansoni cercariae on postnatal day 10. Levels of total-CYPs and activities of alkoxyresorufin-O-dealkylases (EROD, MROD, PROD and BROD), N-nitrosodimethylamine-N-demethylase (NDMA-d), coumarin 7-hydroxylase (COH, DBA/2 only) and UDP-glucuronosyltransferase (UGT) were measured in liver microsomes from mice killed on PIDs 15 and 30. Age-matched (sham-infected) mice of the same sex and strain were used as controls. Neither total-CYP levels nor microsomal enzyme activities were altered in SW and DBA/2 mice on PID 15. On PID 30, total-CYP levels, and COH, PROD and UGT activities remained unaltered, while gender- and strain-specific minor changes of EROD, MROD, BROD and NDMA-d (i.e., increase in SW and reduction in DBA/2) were found. In conclusion, our results suggest that, contrasting to a consistent and almost generalized downregulation of CYPs in chronic schistosomiasis, alterations of hepatic CYPs in early (acute) infection are isoform and mouse's gender and strain specific.
Manhães-Rocha
Dayse A
DA
Laboratory of Environmental Toxicology, Department of Biological Sciences, National School of Public Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Conte
Fernando P
FP
Fidalgo-Neto
Antonio A
AA
De-Oliveira
Ana C A X
AC
Ribeiro-Pinto
Luis F
LF
Paumgartten
Francisco J R
FJ
D000208:Acute Disease; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008862:Microsomes, Liver / Q000201:enzymology* / Q000473:pathology; D012550:Schistosoma mansoni / Q000472:pathogenicity*; D012555:Schistosomiasis mansoni / Q000469:parasitology / Q000503:physiopathology*; D013997:Time Factors
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase