title: Pathological role of aminolevulinate in uremic patients.
abstract: Previous reports have demonstrated that δ-aminolevulinate (ALA) can promote iron release from horse spleen ferritin under conditions of high serum ALA levels in uremia; therefore, we speculated that the accumulated ALA in uremic patients would stimulate iron release from ferritin, resulting in accelerated oxidative stress and uremic complications. We measured the plasma ALA of uremic patients and examined the ALA-induced iron release from human ferritin. The participants consisted of 30 hemodialysis patients and 14 healthy subjects. Plasma malondialdehyde was measured as a surrogate marker of lipid peroxidation. The plasma exchange effluent from two patients who had undergone plasma exchange (for the treatment of systemic lupus erythematosus and acute myeloblastic leukemia) was collected and treated to obtain the human ferritin-rich fraction. Iron release from ferritin was examined using bathophenanthroline sulfate. The influence of antioxidants and different pH levels on iron release were investigated. Plasma ALA and malondialdehyde concentration in the hemodialysis patient was significantly higher than that in healthy subjects. ALA was positively correlated with malondialdehyde. The abundance of iron release was dependent on the ALA concentration and incubation time. Iron release at the high pH of 7.6 was decreased compared with that at pH 7.4. Citrate increased iron release at pH 7.4, but citrate-stimulated iron release was totally abolished at pH 7.6. Our study suggests that ALA accumulation may have a role to play in certain complications in uremic patients, such as oxidative stress, by releasing iron from ferritin.
authors.affiliation: Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Hyogo, Japan. cherry39@hyo-med.ac.jp
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hasuike
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nonoguchi
authors.forename: Masanori
authors.initials: M
authors.lastname: Tokuyama
authors.forename: Reiko
authors.initials: R
authors.lastname: Hata
authors.forename: Rie
authors.initials: R
authors.lastname: Kitamura
authors.forename: Kahori
authors.initials: K
authors.lastname: Hori
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nanami
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Otaki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kuragano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakanishi
mesh_terms: D000622:Aminolevulinic Acid / Q000097:blood*; D000975:Antioxidants; D005260:Female; D005293:Ferritins / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D006435:Renal Dialysis; D014511:Uremia
chemical_list: D000975:Antioxidants; D000622:Aminolevulinic Acid; D005293:Ferritins; D007501:Iron