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Effect of a single high dose and repeated small doses of dianhydrogalactitol (DAG; NSC-132313) on rat intestinal mucosa

✍ Scribed by Judit Kralovánszky; Noémi Prajda; Sándor Kerpel-Fronius; Ferenc Gál; Zoltán Szentirmay

Book ID: 104684532
Publisher: Springer
Year: 1983
Tongue: English
Weight: 556 KB
Volume: 11
Category: Article
ISSN: 0344-5704
DOI: 10.1007/bf00254198

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✦ Synopsis

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.

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