title: Effects of the induction of hepatic microsomal metabolism on the toxicity of cyclophosphamide.
abstract: Cyclophosphamide (CP) administration to rats in a single i.p. dose (200 mg kg-1), while producing urinary bladder toxicity and 30-40% depression of the hepatic microsomal mixed function oxidase (MFO), failed to produce any depression of MFO activities in extrahepatic tissues such as lung, kidney and intestine. Phenobarbital pretreatment of the rats, which is known to enhance hepatic microsomal activation of CP, protected against CP-induced urinary bladder toxicity and the depression of hepatic MFO activities. This protection appears to be, at least in part, related to phenobarbital induction of hepatic cytochrome P-450 isozyme(s) that metabolizes CP to a new metabolite tentatively identified as didechlorodihydroxycyclophosphamide.
mesh_terms: D000818:Animals; D003520:Cyclophosphamide / Q000378:metabolism / Q000633:toxicity*; D004347:Drug Interactions; D007422:Intestines / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D001745:Urinary Bladder Diseases / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D003520:Cyclophosphamide; D006899:Mixed Function Oxygenases; D010634:Phenobarbital