Hepatic mixed-function oxidase activity in mice infected with Trypanosoma brucei gambiense or treated with trypanocides.
Three days after mice were inoculated with Trypanosoma brucei gambiense, total hepatic cytochrome P-450 levels were decreased 14% from control values, while the specific mixed-function oxidase activity (per nmole of cytochrome P-450) was inhibited almost 40% in infected animals. Furthermore, drugs used to treat trypanosomiasis (Suramin and Melarsoprol B) are themselves potent in vitro inhibitors of hepatic mixed-function oxidase activity. These two trypanocides also produced a decrease in mixed-function oxidations and an increase in pentobarbital sleeping time when administered intraperitoneally in vivo. These results demonstrate that mice with trypanosomiasis or undergoing trypanosome chemotherapy have a significantly impaired capacity to metabolize foreign compounds.
D000818:Animals; D001152:Arsenicals / Q000627:therapeutic use*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008549:Melarsoprol / Q000627:therapeutic use*; D051379:Mice; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D010424:Pentobarbital / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects; D013498:Suramin / Q000627:therapeutic use*; D014346:Trypanosoma brucei brucei; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000201:enzymology*
D001152:Arsenicals; D013498:Suramin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D010424:Pentobarbital; D008549:Melarsoprol