Impairment of bone formation with aluminum and ferric nitrilotriacetate complexes.
The deleterious effects of aluminum(AL) and iron(Fe) on bone formation were studied in the presence of nitrilotriacetate (NTA) as a chelator. Both Al-NTA (1.0-1.5 mg Al/kg/day, n = 12)- and ferric nitrilotriacetate (Fe-NTA) (2.0 mg/kg/day, n = 4)-treated Wistar rats showed renal insufficiency blood urea nitrogen [BUN] levels of 25 +/- 8.8-20 +/- 0.7 compared to 12 +/- 0.7-11 +/- 0.4 mg/dl), osteomalacia with a relative osteoid volume of 31.5 +/- 5.6-13.2 +/- 2.4 compared to 4.6 +/- 1.8-0.83 +/- 0.12%, and bone growth retardation (3.1 +/- 0-3.0 +/- 0.2 compared to 3.4 +/- 0-3.3 +/- 0.1 cm) in 24 control rats. Dietary vitamin E(VE) supplementation prevented the Fe-NTA-induced impairment, but not the Al-NTA toxicity. Aluminum was deposited at the interface between osteoid and mineralized bone, while Fe was deposited in the osteoblasts and osteoclasts. There seems to be a positive correlation between hypophosphatemia and osteomalacia but carboxy-terminal parathyroid hormone (C-PTH) and calcium (Ca) levels in the serum were not related to the degree of osteomalacia. Administration of Al-NTA results in more bone Al deposition than that of aluminum chloride (AlCl3) (450 +/- 40 compared to 211 +/- 18 mg/kg fat-free dry weight). The Fe-NTA bone change is related to VE-preventable cellular injury, being consistent with the notion that Fe-NTA toxicity is caused by lipid peroxidation. Al-NTA can be used as an animal model of renal osteodystrophy. Osteodystrophy by Al in chronic renal failure may be mediated by the intrinsic chelator or chelating substance(s) retained in the body fluid due to renal insufficiency.
Ebina
Y
Y
Department of Pathology, Faculty of Medicine, Kyoto University, Japan.
Okada
S
S
Hamazaki
S
S
Toda
Y
Y
Midorikawa
O
O
D000535:Aluminum / Q000032:analysis; D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002614:Chelating Agents / Q000378:metabolism / Q000494:pharmacology; D004032:Diet; D005290:Ferric Compounds / Q000494:pharmacology* / Q000633:toxicity; D007674:Kidney Diseases / Q000378:metabolism; D008297:Male; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology
D002614:Chelating Agents; D005290:Ferric Compounds; D010281:Parathyroid Hormone; D014810:Vitamin E; D000535:Aluminum; D009571:Nitrilotriacetic Acid; D002118:Calcium; C020326:ferric nitrilotriacetate