Aluminum Accumulation In Tissues Research Articles

Importance of kidney function and duration of exposure on aluminum accumulation in mature rats

The objective of this study was to examine the impact of reduced renal function and duration of aluminum exposure on aluminum accumulation in tissues. Rats received a unilateral nephrectomy or sham operation at 9 months of age and were fed either 0.4 or 37.6 μmole Al/g diet for 6 or 9 months. The modest accumulation of aluminum in tissues was greater in tibia and liver after 9 versus 6 months of aluminum exposure and among rats with one rather than two kidneys. About 35% of variation in tibia aluminum concentrations could be predicted on the basis of creatinine clearance and about 19% of the variation in liver aluminum concentrations could be explained on the basis of aluminum load and urinary creatinine excretion. These data support the hypothesis that modest reductions in kidney function can result in somewhat elevated bone and liver aluminum retention. But renal function, per se, is not the primary determinant of tissue aluminum concentrations in mature rats.

The effects of calcium deficiency on aluminum accumulation in the tissues of rats treated by oral aluminum administration

We carried out this investigation to elucidate the effect of calcium (Ca) deficiency (Ca (-)) on aluminum (Al) accumulation in tissues of rats treated by oral Al administration. Thirty-two four-week-old rats (65g) were divided into two groups; a normal (N) diet group and a Ca (-) diet group. The N diet group was fed the N diet for 45 consecutive days, and then divided into four groups. Group (G)-1 rats were fed normal diet (N) for 9 days, G-2, G-3 and G-4 rats were fed an Al-overloaded N diet (1mg Al/g diet) for 3, 6 or 9 days, respectively. The Ca (-) diet group was fed Ca (-) diet for 45 consecutive days, and then divided into four groups. G-5 rats were fed the Ca (-) diet for 9 consecutive days, G-6, G-7 and G8 rats were fed an Al-overloaded Ca (-) diet for 3, 6 or 9 days. We studied the accumulation of Al in Ca- deficient rats fed Al (Ca (-) + Al) for 3, 6, and 9 days, comparing that of the normal- diet rats fed Al (N + Al) for the same period. The Al concentration in the small intestine increased on the third day after Al, and then decreased to the normal level on the 6th day in both N + Al and Ca (-) + Al rats. However, that of the Ca (-) + Al rats increased significantly compared to N + Al rats on the 9th day.(ABSTRACT TRUNCATED AT 250 WORDS)

Parenteral Drug Products Containing Aluminum as an Ingredient or a Contaminant: Response to Food and Drug Administration Notice of Intent and Request for Information

Aluminum remains a significant contaminant of total parenteral nutrition (TPN) solutions and may be elevated in bone, urine, and plasma of infants receiving TPN. Aluminum accumulation in tissues of uremic patients and adult TPN patients has been associated with low-turnover bone disease. Furthermore, aluminum has also been linked with encephalopathy and anemia in uremic patients and with hepatic cholestasis in experimental animals. Because of the toxic effects of aluminum, the Food and Drug Administration (FDA) recently published a notice of intent to set an upper limit of 25 micrograms/L for aluminum in large-volume parenterals and to require manufacturers of small-volume parenterals, such as calcium and phosphate salts, to measure aluminum content and note this content on the package label. The ASCN/A.S.P.E.N. Working Group on Standards for Aluminum Content of Parenteral Nutrition Solutions supports these intentions and further urges the FDA to require that cumulative aluminum intake in terms of safe, unsafe, and toxic quantities of aluminum per kilogram be made known to physicians and pharmacists preparing the TPN solutions, to ensure that manufacturers use appropriate control procedures in aluminum measurements, and to employ a standard unit of aluminum measurement.

Mineral Metabolism of Rats Fed Moderate Levels of Various Aluminum Compounds for Short Periods of Time

The effects of ingesting moderate levels of aluminum (5–272 µg Al/g diet) were assessed in two short-term (18-d) studies with rats. Rats were fed diets that contained no added aluminum or aluminum lactate, aluminum palmitate, aluminum phosphate or aluminum hydroxide in either reagent grade or dessicated gel forms. The average concentrations of aluminum in the tibias of rats fed 261–272 µg Al/g diet were 13.0–15.6 µg Al/g fresh weight, while those of control animals were 1.0–1.9 µg Al/g fresh weight. Rats fed aluminum accumulated less aluminum in their kidneys and brains than in their tibias. In study 1, animals fed aluminum hydroxide tended to accumulate more aluminum in tissues, i.e., brain, than animals fed the other aluminum compounds. In study 2 the type of aluminum hydroxide fed did not affect the accumulation of aluminum in tissues but rats fed 206 µg Al/g diet accumulated less aluminum in their tibias and more aluminum in their kidneys than rats fed 261 and 268 µg Al/g diet. Ingestion of these moderate doses of aluminum had no effects on tissue levels of calcium, magnesium and iron of rats and had only small effects on tissue levels of phosphorus, zinc and copper.

Water content of aluminum, dialysis dementia, and osteomalacia.

In the presence of normal renal function, a high concentration of aluminum in drinking water has been implicated as a factor in the etiology of a neurological syndrome in one specific geographical area. The role of aluminum as a toxic agent in other neurological disorders, where renal function is normal, is controversial. Aluminum is absorbed from the gastrointestinal tract and is normally excreted by the kidneys in the urine. In patients with chronic renal failure, aluminum appears to be of proven toxicological importance. In these patients the accumulation of aluminum in tissues causes an encephalopathy (dialysis encephalopathy or dialysis dementia), a specific form of metabolic bone disease (osteomalacic dialysis osteodystrophy), and an anemia and also plays an etiological role in some of the other complications associated with end-stage chronic renal disease. A failure in the normal renal excretory mechanism accounts for the tissue accumulation in chronic renal failure. The majority of chronic renal failure patients who develop aluminum toxicity are on long-term treatment with either hemo- or peritoneal dialysis; some patients develop toxicity who are only on treatment with aluminum-containing phosphate-binding agents. Aluminum in the dialysate appears to be the major source of the metal in chronic renal failure patients who develop aluminum toxicity. The aluminum content of the dialysate depends primarily on the content of the water with which it is prepared; there may be some contribution from the chemicals used in the concentrate which is added to the water. Some domestic tap-water supplies contain aluminum in high concentration, either naturally or because aluminum has been added as a flocculant in the purification process.(ABSTRACT TRUNCATED AT 250 WORDS)