title: Aluminium-induced injury to kidney proximal tubular cells: Effects on markers of oxidative damage.
abstract: Aluminium (Al)-induced injury to various cells including brain and bone is well described. We have previously shown that Al initiated damage to kidney cells in culture assessed by loss of cell viability, enzyme release and damage to cell brush borders. However, little is known about the mechanism(s) of these effects, we therefore investigated whether lipid peroxidation and/or sulphydryl depletion, i.e. cellular glutathione (GSH) depletion, could be part of this process(es). Monolayers of porcine kidney proximal tubular cells (PTC), LLC-PK1, were either exposed to 100 micromol/L Al as a citrate complex or cis-platin (cis-Pt) or mercury (Hg) as damage mediating controls (positive), or no added metals (negative control). Malondialdehyde (MDA), a marker of lipid peroxidation, cellular GSH as the intracellular sulphydryl compound, heat shock protein 70 (Hsp70), glutathione peroxidase (GPx) as a reactive oxygen species scavenger enzyme and cellular uptake of Al were assessed. MDA increased significantly (p = 0.03) more than two-fold in the cell lysate after PTCs were exposed to Al for 48 h. In Al-treated PTC, the GSH content of the cell lysate increased to 1.042 +/- 0.080 mmol/L compared with the 0.80 +/- 0.1.64 mmol/L control value. The Hsp70 content of the cells showed no significant change for Al (6.5% vs. 4.4% control value) and GPx activity increased slightly from 0.41 to 0.45 mU/mg protein. Treatment with cis-Pt and Hg also resulted in a significant increase in MDA and Hsp70 and reduction in cellular GSH and GPx activity. The low cellular Al uptake as well as some inherent insensitivity related to the cell type might be contributory factors for the small effect of Al on kidney cells and markers of oxidative damage.
authors.affiliation: Department of Clinical Biochemistry & Metabolic Medicine, Royal Liverpool University Hospital, The University of Liverpool, Prescot Street, Liverpool L7 8XP, UK. mrsr@liverpool.ac.uk
authors.forename: Mansour
authors.initials: M
authors.lastname: Sargazi
authors.forename: Alan
authors.initials: A
authors.lastname: Shenkin
authors.forename: Norman B
authors.initials: NB
authors.lastname: Roberts
mesh_terms: D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D015415:Biomarkers / Q000378:metabolism*; D002945:Cisplatin / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism; D008628:Mercury / Q000633:toxicity; D013552:Swine
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; D008315:Malondialdehyde; D000535:Aluminum; D005979:Glutathione Peroxidase; D008628:Mercury; D005978:Glutathione; D002945:Cisplatin