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PHYSIOLOGICAL CONSEQUENCES OF EARLY NEONATAL GROWTH RETARDATION: EFFECTS OF A-DIFLUOROMETHYLORNITHINE ON RENAL GROWTH AND FUNCTION IN THE RAT
Citation:
Gray, J. AND R. Kavlock. PHYSIOLOGICAL CONSEQUENCES OF EARLY NEONATAL GROWTH RETARDATION: EFFECTS OF A-DIFLUOROMETHYLORNITHINE ON RENAL GROWTH AND FUNCTION IN THE RAT. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-91/015 (NTIS PB91183517), 1991.
Description:
The physiological consequences of early neonatal growth retardation in the kidney are investigated using DFMO (a-difluoromethylornithine), a specific irreversible inhibitor of ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines. e administered 500 eg/kg/day DFMO, or saline to Sprague-Dawley rat pups from the day of birth through postnatal day (PD) 6 and evaluated renal function on PD 4, 7, 10, and 13 using tests of basal renal clearance and urinary concentrating ability. Kidney weights and gross pathology were also obtained. n PD 39, serum chemistries and organ weights were determined. n a second experiment, we evaluated concentrating ability on PD 7-10, and basal renal function, concentrating ability, diuretic response, serum chemistries and organ weights on PD 132-14O. FMO selectively inhibited renal growth, but did not inhibit glomerular and tubular functional maturation. n fact, the rates of filtration and reabsorption (per g renal tissue), and concentrating ability were increased in treated pups. hese changes were associated with long-term effects on renal function, including uresia, glucosuria, and male-specific concentrating deficits in adulthood. everal hypotheses can be developed concerning the physiological mechanisms underlying these changes (e.g. altered renal urea metabolism), which in turn say reflect either a direct role of ODC in the regulation of saturation or secondary consequences of inhibition of ODC. n conclusion, the renal growth retardation induced by neonatal administration of DFMO was associated with an apparent precocious saturation of function in the early postnatal period and dysfunction in adulthood, thus demonstrating that the physiological consequences of growth retardation are not always obvious and predictable, and must be evaluated on a case by case basis.