Prenatal alpha-difluoromethylornithine treatment: effects on postnatal renal growth and function in the rat

Teratology
J A GrayR J Kavlock

Abstract

DFMO (alpha-difluoromethylornithine) is a specific irreversible inhibitor of ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines, which in turn control macromolecule synthesis during cell proliferation. The current study was designed to investigate the effects of inhibition of ODC during discrete prenatal periods on renal growth and function. We administered 5 doses of 500 mg/kg DFMO or saline s.c. to timed pregnant Sprague-Dawley rats at 12 hr intervals beginning on gestation days (GD) 11, 14, or 17. Half the dams were killed on GD 20 for fetal morphological analyses and half were allowed to go to term. Renal function was assessed on postnatal days (PD) 3, 6, 10, and 14 by tests of basal renal clearance and urinary concentrating ability, and on PD 42-44 we measured serum chemistries. All three gestational treatment regimens resulted in postnatal deficits in general growth. Only in the GD 11-13 treatment group was there evidence of embryotoxicity and neonatal renal pathophysiology. Fetal weights and urogenital morphology were altered following GD 14-16 treatment and there were persistent deficits of renal growth. GD 17-19 treatment was associated only with transient postnatal deficits of renal growth. ...Continue Reading

References

Mar 1, 1986·The Biochemical Journal·A E Pegg
Apr 1, 1986·Teratology·R J KavlockB F Rehnberg
Sep 15, 1985·Experientia·W L Whitmore, T A Slotkin
Jan 1, 1981·Differentiation; Research in Biological Diversity·O Heby
Nov 1, 1982·The American Journal of Physiology·A E Pegg, P P McCann
Jan 1, 1982·Biology of the Neonate·R J Kavlock, J A Gray
Jan 1, 1983·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·T A SlotkinJ Bartolome

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Citations

Apr 1, 1992·The Journal of Experimental Zoology·K J Gawel-Thompson, R M Greene
Jan 1, 1992·Teratogenesis, Carcinogenesis, and Mutagenesis·A MantovaniF Maranghi
May 24, 2012·Obstetrics and Gynecology·Lauren W RothUNKNOWN Reproductive Medicine Network

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