In-vitro studies of aluminium-induced toxicity on kidney proximal tubular cells.
The toxicity of aluminium (Al) to various cells is well described. However, little is known about its effect on kidney cells, which can be exposed to relatively high concentrations. In this study, the effect of aluminium as the citrate complex in concentrations up to 100 microM/l was investigated using a monolayer cell culture of kidney proximal tubular cells (PTC). Aluminium was found to be slightly toxic; at 100 microM/l the PTCs lost viability by 15, 20 and 24% after incubation for 24, 48 and 72 h, respectively. Viability was significantly reduced (P<0.001) after 48 h incubation with aluminium concentrations of 25, 50, 75 and 100 microM/l compared with controls. Lactate dehydrogenase (LDH) release was significantly increased (P<0.001) with 100 microM/l Al to 44.67+/-1.76 and 50.33+/-0.88 compared with controls 24+/-1.00 and 28.33 2.34 U/l after 24 and 48 h incubation, respectively, indicating damage to the plasma membrane. However, N-acetyl-beta-D-glucosaminidase (NAG) release in the medium of cells exposed to aluminium showed no difference from control values (P>0.1). Glucose consumption in aluminium-exposed cells at 100 microM/l was slightly, but not significantly (P=0.14), increased during 48 h incubation. Electron micrographs of cells exposed to aluminium at 100 microM/l showed a slight reduction in microvilli density and the cell tight junctions were not as clear compared with the control cells. Pretreatment with protective agents glutathione and tiopronin partly restored the viability of kidney proximal tubular cells to control values, whereas vitamin C and/or cysteine showed no effect. This study indicates that aluminium may show toxicity to kidney cells in culture. Several sites on the cell, i.e. microvilli, membrane and the cell junction, seem to be affected, however the mechanism(s) of damage remain unclear.
Sargazi
M
M
Department of Clinical Chemistry, Duncan Building, 4th Floor, The University of Liverpool, Prescot St., Liverpool L69 3GA, UK. mrsr@liverpool.ac.uk
Roberts
N B
NB
Shenkin
A
A
D000118:Acetylglucosaminidase / Q000378:metabolism; D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D005947:Glucose / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008854:Microscopy, Electron; D013552:Swine; D013997:Time Factors
D000535:Aluminum; D007770:L-Lactate Dehydrogenase; D000118:Acetylglucosaminidase; D005947:Glucose