Effect of a single high dose and repeated small doses of dianhydrogalactitol (DAG; NSC-132313) on rat intestinal mucosa.
The influence of the treatment schedule of dianhydrogalactitol on its effect on the activity of mucosal enzymes in rat intestine was studied. The effect of a single high dose (10 mg/kg) was compared with that of repeated small doses (4 x 2.5 mg/kg) given at daily intervals. At 48 h after a single high dose the activities of thymidine kinase, which is a marker of dividing crypt cells, and of alkaline phosphatase, sucrase, maltase, xanthine oxidase, which are markers of mature enterocytes, were strongly depressed. Even 96 h after the treatment low enzyme activities could be observed. Repeated small doses caused milder enzyme inhibition and almost total recovery had occurred by 96 h after administration of the last dose. The results indicate that fractionation of drug administration can reduce the toxic side-effects on the intestinal mucosa and might be partly responsible for the higher therapeutic index of such schedules in experimental tumor models.
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors; D000818:Animals; D003961:Dianhydrogalactitol / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005087:Glucan 1,4-alpha-Glucosidase / Q000037:antagonists & inhibitors; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology*; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013393:Sucrase / Q000037:antagonists & inhibitors; D013402:Sugar Alcohols / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D013402:Sugar Alcohols; D003961:Dianhydrogalactitol; D014969:Xanthine Oxidase; D013937:Thymidine Kinase; D000469:Alkaline Phosphatase; D005087:Glucan 1,4-alpha-Glucosidase; D013393:Sucrase