The objectives of this project ar:1) to assess the practical effects of variations in 3 dietary factors (Fe, Ca, citrate) on Al retention; 2) to determine the importance of age, duration of A1 exposure & renal function on A1 metabolism & to assess the extent to which these physiological factors modify interactions of the dietary factors with A1; & 3) to develop a more sensitive model for studying A1 metabolism. In the first series of studies (1,1a,1b) we will develop a """"""""desferoxamine test"""""""" & determine whether the changes in serum A1 in response to an infusion of desferoxamine can be used to monitor the total body load or an exchangeable pool of A1. Then the response of rats (tissue A1, response to desferoxamine test, urine A1) to chronic ingestion & to repeated injection of 5 different levels of A1 will be compared. In the second series of studies (2,2a,3,3a) renal function of rats will be reduced by surgery to approximate the impairment that might occur with aging. We will monitor kidney function, absorption and tissue levels of A1, Ca, Mg & Fe & the t1/2 of A1 in tissues. In Study 4 duration of exposure to dietary A1 (2 mo or 1 year) and age of rats (approximately 9 mo or 21 mo) on absorption, urinary excretion & tissue levels of A1, Ca, Mg & Fe on t1/2 of A1 in tissues will be determined. The relative importance of changes in kidney function and bone resorption ion A1 retention in these aging rats will be assessed statistically. In the last series of studies (5,5a,5b,6,6a,7) the effects of variations in intake of Fe, Ca & citrate on absorption, urinary excretion & tissue levels of A1, Fe & Ca and on t1/2 of A1 tissues will be assessed using animal models that we've developed in previous studies to maximize sensitivity. We will also evaluate the use of Ga-67 as a marker for A1 in a variety of situations. In the assessment of effects of dietary Ca on A1 retention, we will evaluate the effect of confounding factors such as poor growth and reduced food intake when calcium intake is very low and nephrocalcinosis when calcium intake is high.
