Hepatic cytochrome P-450 system in experimental hepatosplenic schistosomiasis. Presence of an artifact in spectrophotometric analysis.
Several recent reports suggesting that the liver microsomal cytochrome P-450 system is impaired in Schistosoma mansoni infections in mice prompted a detailed investigation of the hepatic cytochrome P-450 system in murine schistosomiasis. Mice were prepared with three levels of Schistosoma mansoni infection and studied 8, 12 and 14 weeks post-exposure. Histological sections of the liver confirmed prominent granuloma formation and portal fibrosis which was dose and time dependent. Cytochrome P-450 levels appeared reduced grossly in microsomes from homogenates of infected livers, but accurate quantitation was complicated by the presence of a prominent peak at 422 nm. Ethylmorphine N-demethylase activity also appeared to be reduced in all infected animals, reaching a maximum decrease at 14 weeks of 44% of control values in the most heavily infected mice. NADPH-cytochrome c reductase activity and cytochrome b5 levels were similarly reduced. Utilization of techniques to separate hepatocytes from granulomatous material in infected livers eliminated the 422 nm peak and reversed several of the findings made with whole-liver derived microsomes. Cytochrome P-450 levels were reduced modestly (30%) at 8 weeks in the most heavily infected mice but returned to normal values by 14 weeks. Specific ethylmorphine N-demethylase activity of isolated hepatocytes was increased at 8 weeks with a return to normal by 14 weeks. Isolated granulomata were incriminated as one possible source of the 422 nm pigment in whole-liver derived microsomes but appeared unlikely to account fully for this finding. Thus, this investigation concluded that the cytochrome P-450 system is altered by experimental murine hepatosplenic schistosomiasis, but such alterations are subtle in nature and unlikely to contribute in major fashion to the observed changes in drug disposition.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006099:Granuloma / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000201:enzymology*; D013053:Spectrophotometry
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C020130:ethylmorphine O-deethylase; D009251:NADPH-Ferrihemoprotein Reductase