Studies of the effects of cyclophosphamide, vincristine, and prednisone on some hepatic oxidations and conjugations.
The effects of low and high doses of three anticancer agents, cyclophosphamide, vincristine, and prednisone (given individually or in various combinations), on oxidative and conjugation pathways were studied in Sprague-Dawley male rats. Cyclophosphamide used alone at low doses decreased aniline hydroxylase and ethylmorphine demethylase activities by about 20% and at high doses produced a 30%-50% decrease in the specific activities of several microsomal mixed-function oxygenase activities, in the contents of cytochromes P-450 and b5, and in the magnitudes of type I and II drug-binding spectrum. The levels of microsomal glucouronidase, glucuronyl transferase, and sulfatase per gram of liver were also decreased (30%-50%) by the high dose of cyclophosphamide. The high dose of cyclophosphamide in conjunction with either vincristine or prednisone also produced a noticeable decrease in several activities tested; however, when cyclophosphamide was given at either low or high doses in combination with vincristine and prednisone, the activities tested were comparable to those seen in untreated controls. The mechanism of this protection is presently unknown. Vincristine, at both low and high doses, produced little effect on oxidative pathways; however, at low doses it caused a significant increase (80%) in the specific activity of hepatic microsomal sulfatase. This effect was also discernible when vincristine was given in combination with cyclophosphamide and prednisone. Other than producing a 15% decrease in liver weight and a 40% decrease in the specific activity of microsomal glucuronidase, the high dose of prednisone used had no effect on various activities tested. Results of these studies indicate a potential for drug interaction among anticancer agents and supportive drugs used in combination cancer chemotherapy.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects*; D003520:Cyclophosphamide / Q000494:pharmacology*; D003580:Cytochromes / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005966:Glucuronidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D011241:Prednisone / Q000494:pharmacology*; D051381:Rats; D013429:Sulfatases / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology*
D003580:Cytochromes; D014750:Vincristine; D003520:Cyclophosphamide; D006899:Mixed Function Oxygenases; D013429:Sulfatases; D005966:Glucuronidase; D011241:Prednisone