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.

Melatonin Prevents Oxidative Stress in Ovariectomized Rats Treated with Aluminium

“…We found that Al induced in male rats an increment change (+40%) in lipid peroxidation (LPO) levels with an associated depletion of GSH and a reduction of activity of GSH-Px, glutathione-S-transferase and CAT [25]. These changes were restored after the administration of Mel [49].…”

“…The Al dose, the frequency and the route of administration were described previously [25,61]. Al-treated rats received an IP injection, three times per week for 12 weeks, of a sterile solution of Al (Merck) containing 2.7 g/L of Al and 26.7 g/L of anion lactate, pH 7 [0.575 mg Al/100 g of body weight (bw)].…”

“…We have detected that Al promotes oxidative stress and induces alterations in the renal tubular p-aminohippuric acid transport and renal tubular phosphate reabsorption, together with impairment in sodium and water balance [23][24][25]. We found decreased urinary concentrating ability in situations in which endogenous or exogenous plasma antidiuretic hormone was increased.…”

Effects of aluminum on phosphate metabolism in rats: a possible interaction with vitamin D3 renal production

“…The rats from the control group were injected with a sterile solution of sodium lactate containing 26.7 g/l of anion lactate during the same period and with the same frequency as treated rats. This protocol was used in a previous work to study renal function associated with chronic Al administration (Mahieu et al 2003). This treatment assures higher levels of Al in serum, intestine, kidney, and bones than in control animals.…”

“…Previous work from our laboratory indicated that this Al species used chronically for 3 months promoted a renal dysfunction without changes in the glomerular filtration rate (Mahieu et al 2003). The possible impact of the Al on the physiological changes of the metabolism of Pi and calcium (Ca) during the stage of the growth was also studied.…”