title: Effect of chronic accumulation of aluminum on renal function, cortical renal oxidative stress and cortical renal organic anion transport in rats.
abstract: The aim of the present work was to study the nephrotoxicity of aluminum lactate administered for 3 months (0.57 mg/100 g bodyweight aluminum, i.p., three times per week) to male Wistar rats. Renal function was studied after 6 weeks of treatment (urine was obtained from rats in metabolic cages) and at the end of the treatment using clearance techniques. Another group of rats was used as kidneys donors at the end of treatment. The renal cortex was separated and homogenized to determine glutathione (GSH) level, glutathione S-transferase (GST) activity and lipid peroxidation (LPO) level. Renal cortex slices were also used to study the p-aminohippuric acid (PAH) accumulation during steady-state conditions and the kinetics of uptake process. Clearance results, at the end of the treatment, indicated that renal functions in treated-rats were not different from those measured in control rats, although the renal concentration parameters differ when they were measured in treated rats after 24 h of food and water deprivation. Balances of water and sodium were also modified at both 1.5 and 3 months of treatment. The activity of alkaline phosphatase (AP) relative to inulin excreted in urine was significantly impaired: controls 2.2+/-0.6 IUI/mg, Al-treated 5.1+/-0.5 IU/mg, P<0.05. These data indicated that proximal tubular cells were loosing apical brush border membranes. Data obtained in cortex homogenates indicated that both GSH and GST activity were significantly decreased, and a significant increase of LPO was noted simultaneously in Al-treated rats. Renal accumulation of PAH, estimated as slice-to-medium ratio, decreased significantly in the Al-treated rats: control rats 3.06+/-0.02 ( n=12), Al-treated rats 2.26+/-0.04 ( n=12), P<0.0001. The maximal rate of uptake was also diminished in treated rats, while the apparent affinity remained unchanged. All these results indicate that aluminum accumulation in renal tissue affects cellular metabolism, promotes oxidative stress and induces alterations in renal tubular PAH transport, together with an impairment in sodium and water balance only detected under conditions of water deprivation, without other evident changes in glomerular filtration rate or other global functions measured by clearance techniques at least at this time of chronic toxicity.
authors.affiliation: Fisiología Humana, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Paraje El Pozo (3000), Santa Fe, Argentina.
authors.forename: Stella T
authors.initials: ST
authors.lastname: Mahieu
authors.forename: Marisa
authors.initials: M
authors.lastname: Gionotti
authors.forename: Néstor
authors.initials: N
authors.lastname: Millen
authors.forename: María Mónica
authors.initials: MM
authors.lastname: Elías
mesh_terms: D000535:Aluminum / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D007672:Kidney Cortex / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D027361:Organic Anion Transporters / Q000378:metabolism*; D009994:Osmolar Concentration; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014882:Water-Electrolyte Balance / Q000187:drug effects; D010130:p-Aminohippuric Acid / Q000378:metabolism
chemical_list: D027361:Organic Anion Transporters; D008627:Mercuric Chloride; D000535:Aluminum; D005982:Glutathione Transferase; D005978:Glutathione; D010130:p-Aminohippuric Acid