Importance of T-cell-dependent inflammatory reactions in the decline of microsomal cytochrome P450 concentration in the livers of rats infected with Fasciola hepatica.
The concentration of cytochrome P450, measured spectrophotometrically in microsomal preparations from the livers of rats infected with 30 metacercariae of Fasciola hepatica, declined by approximately 50% at 3 weeks post-infection. Treatment of infected rats with the anti-inflammatory agent dexamethasone (2 mg/kg at 48 h intervals for 8 days prior to assay) abolished the decline in P450 content. Assay of P450 in infected congenitally athymic (nude) rats showed normal levels. These results demonstrate that the T-cell-dependent inflammatory response in the liver of the host is a necessary factor in the development of the decline in hepatic P450, which is known to compromise the metabolism of certain drugs in infected hosts.
Topfer
F
F
Division of Biochemistry and Molecular Biology, School of Life Sciences, Australian National University, Canberra, Australia.
Lenton
L M
LM
Bygrave
F L
FL
Behm
C A
CA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005211:Fascioliasis / Q000201:enzymology / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology* / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011923:Rats, Nude; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000276:immunology*
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System