Regional accumulation of aluminium in the rat brain is affected by dietary vitamin E.

The regional accumulation of aluminium in the brain of male albino Wistar rats was investigated following 4 weeks of administration by intraperitoneal injection of aluminium lactate (10mg aluminium/kg body weight). The consequences of concomitant dietary vitamin E (5, 15, or 20 mg vitamin E/g of food) were also studied. Rat brains were dissected into functional regions, for the measurement of aluminium and markers of oxidative stress. Plasma aluminium levels were increased in all groups of animals receiving aluminium lactate (p < 0.01), and these levels were significantly reduced in rats receiving concomitant vitamin E (p < 0.05). In the group of rats receiving aluminium alone, levels of brain tissue aluminium were increased in all regions of brain examined (p< 0.01). Brain tissue aluminium levels were reduced by concomitant dietary vitamin E. Catalase and reduced glutathione levels were both reduced in several regions of brain in animals treated with aluminium (p < 0.05). Aluminium treatment was not associated with a significant increase in reactive oxygen species (ROS) generation (p > 0.05), although ROS production was attenuated by dietary vitamin E (p < 0.05) in some regions.     

Region specific increase in the antioxidant enzymes and lipid peroxidation products in the brain of rats exposed to lead

The objective of this study is to determine the effect of lead (pb) on antioxidant enzymes and lipid peroxidation products in different regions of rat brain. Wistar male rats were treated with lead acetate (500 ppm) through drinking water for a period of 8 weeks. Control animals were maintained on sodium acetate. Treated and control rats were sacrificed at intervals of 1st, 4th and 8th week and the whole brains were dissected on ice into four regions namely the cerebellum, the hippocampus, the frontal cortex and the brain stem. Antioxidant enzymes namely catalase and superoxide dismutase in all the four regions of brain were determined. In addition, lipid peroxidation products were also estimated. The results indicated a gradual increase in the activity of antioxidant enzymes in different regions of the brain and this response was time-dependent. However, the increase was more in the cerebellum and the hippocampus compared to other regions of the brain. The lipid peroxidation products also showed a similar trend suggesting increased effect of lead in these two regions of the brain. The data indicated a region-specific oxidative stress in the brain exposed to lead.     

Effect of aluminium phosphide exposure on kinetic properties of cytochrome oxidase and mitochondrial energy metabolism in rat brain

This study involves the effect of aluminium phosphide exposure on the kinetic characteristics of cytochrome oxidase and the mitochondrial respiratory chain function in rat brain. Mitochondrial preparations from both control and aluminium phosphide-treated rats demonstrated significant decrease in the maximal activity of cytochrome oxidase (approximately 50%) when expressed per unit membrane protein and on a turnover number basis (nmol/min/nmol haem a). The results indicated that there was a decrease in the catalytic efficiency of the active oxidase molecules on aluminium phosphide treatment. Arrhenius plot characteristics differ for cytochrome oxidase activity in mitochondria isolated from treated and control rats, in the break point of the biphasic plot which was shifted to a higher temperature. The decreased activity of cytochrome oxidase along with altered NADH and succinic dehydrogenase activities might have contributed towards a significant decline in state 3 and state 4 respiration. These alterations in the electron transport chain complexes in turn affected the ATP synthesis rate adversely in the mitochondria, isolated from treated rats. The data reflect the interaction of aluminium phosphide with redox chain components leading to the impairment of the electron transfer along the respiratory chain.     

Chronic exposure to aluminium impairs the glutamate-nitric oxide-cyclic GMP pathway in the rat in vivo.

Aluminium is neurotoxic and is considered a possible etiologic factor in Alzheimer's disease, dialysis syndrome and other neurological disorders. The molecular mechanism of aluminium-induced impairment of neurological functions remains unclear. We showed that aluminium impairs the glutamate-nitric oxide-cGMP pathway in cultured neurons. The aim of this work was to assess by in vivo brain microdialysis whether chronic administration of aluminium in the drinking water (2.5% aluminium sulfate) also impairs the glutamate-nitric oxide-cGMP pathway in the cerebellum of rats in vivo. Chronic exposure to aluminium reduced NMDA-induced increase of extracellular cGMP by ca 50%. The increase in extracellular cGMP induced by the nitric oxide generating agent S-nitroso-N-acetylpenicillamine was higher (240%) in rats treated with aluminium than in controls. Immunoblotting experiments showed that aluminium reduced the cerebellar content of calmodulin and nitric oxide synthase by 34 and 15%, respectively. Basal activity of soluble guanylate cyclase was decreased by 66% in aluminium-treated rats, while the activity after stimulation with S-nitroso-N-acetylpenicillamine was similar to controls. Basal cGMP in the cerebellar extracellular space was decreased by 50% in aluminium-treated rats. These results indicate that chronic exposure to aluminium reduces the basal activity of guanylate cyclase and impairs the glutamate-nitric oxide-cGMP pathway in the animal in vivo.     

Influence of Zinc on the Biokinetics of 65Zn in Brain and Whole Body and Its Bio-distribution in Aluminium-Intoxicated Rats

The present study was designed to understand the influence of zinc (Zn) if any, on the biokinetics of ⁶⁵Zn in brain as well as whole body and its bio-distribution following aluminium (Al) treatment to rats. Male Sprague–Dawley rats weighing 140–160 g were divided into four different groups viz: normal control, aluminium treated (100 mg/kg b.wt./day via oral gavage), zinc treated (227 mg/L in drinking water) and combined aluminium and zinc treated. All the treatments were carried out for a total duration of 8 weeks. Al treatment showed a significant increase in fast component (Tb₁) but revealed a significant decrease in slow component (Tb₂) of biological half-life in brain as well as in whole body. However, Zn supplementation to Al-treated rats reversed the trend in both brain and whole body, which indicates a significant decrease in Tb₁ component while the Tb₂ component was significantly increased. Further, Al treatment showed an increased percent uptake value of ⁶⁵Zn in cerebrum, cerebellum, heart, liver and lungs whereas a decrease in uptake was found only in blood. On the other hand, there was a significant decline in ⁶⁵Zn activity in nuclear and mitochondrial fractions of brain of Al-treated rats. However, Zn treatment reversed the altered ⁶⁵Zn uptake values in different organs as well as in various subcellular fractions. The study demonstrates that Zn shall prove to be effective in regulating the biokinetics of ⁶⁵Zn in brain and whole body and its distribution at the tissue and subcellular levels in Al-treated rats.     

Effect of aluminum on the blood-brain barrier permeability during nitric oxide-blockade-induced chronic hypertension in rats

We examined the effect of aluminum on the permeability of the blood-brain barrier (BBB) during nitric oxide-blockade-induced chronic hypertension in rats. Animals were given the inhibitor of nitric oxide synthase, l-NAME (N ^ω-nitro-l-arginine methyl ester), for 4 wk to induce chronic hypertension. Two groups of rats were given an intraperitoneal injection of aluminum chloride. The integrity of the BBB was assessed by a quantitative measurement for Evans blue (EB) dye. The arterial blood pressure in l-NAME- and l-NAME plus aluminum-treated animals was significantly elevated from 115±2.8 and 110±1.7 mm Hg to 174±5.2 and 175±4.8 mm Hg, respectively (p<0.01). The EB dye content in the brain regions of the rats in the l-NAME group was increased, but there was no statistical significance compared to the saline group. The extravasation of EB dye was significantly increased in the brain regions of the animals treated with aluminum compared to the rats treated with saline (p<0.05). A significantly higher EB dye content in the brain regions was observed in the l-NAME plus aluminium group compared to l-NAME, aluminum, and saline groups (p<0.01). These findings indicate that exposure to a high level of aluminum leads to an additional increase in BBB permeability where nitric oxide-blockade-induced chronic hypertension potentiates the effect of aluminum to enhance BBB permeability to EB dye.     

Myelin Deficits Produced by Early Postnatal Exposure to Inorganic Lead or Triethyltin Are Persistent

Abstract: Long-Evans rat pups were exposed to either inorganic lead (400 mg Pb as lead acetate/kg body weight/day) or triethyltin sulfate (1.0 mg/kg body weight/day), by gastric intubation, from 2 days through 29 days of age. The rats were then weaned and placed on standard lab chow ad libitum. At 30 days of age, leadtreated rats exhibited statistically significant decreases in body and brain weights (22% and 17%, respectively), and the concentration of forebrain myelin was significantly reduced, by 21% relative to the 4.9 mg myelin protein/g brain in control rats. Although these animals recovered from the body weight deficits after several months, the deficits in brain weight and myelin concentration were still present at 120 days of age. This suggests that the lead-induced myelin deficits were permanent. Lead levels in brain, which were maximal at 30 days of age when the treatment was terminated, decreased more slowly than in other organs and were still 30% of maximal levels at 120 days of age. Triethyltin-treated animals also had significantly decreased body and brain weights (20% and 11%, respectively) at 30 days of age, and an even more severe reduction in forebrain myelin concentration (33%). These animals also regained a normal body weight by 120 days of age, but again the deficits in brain weight and myelin concentration persisted. Tin levels in brain and other organs had decreased to control levels by 60 days of age. Animals malnourished by maternal deprivation to match the body weights of the treated animals had myelin deficits that were less severe than those in the treated animals at 30 days of age (approximately 11% less than controls); however, these myelin deficits also persisted throughout the subsequent 90-day recovery period examined. The apparent lack of recovery from CNS myelin deficits produced by neonatal exposure to different heavy metals or to malnutrition reemphasizes the vulnerability of the developing nervous system to a wide range of metabolic insults.     

Prevention of post-ischemic brain lipid conjugated diene production and neurological injury by hydroxyethyl starch-conjugated deferoxamine.

Hydroxyethyl starch conjugated deferoxamine (DFO) was administered to rats following resuscitation from 6.5 min cardiac arrest (CA) in an attempt to prevent the iron-catalyzed production of oxygen free radicals which may lead to neurologic injury and ultimately death following restoration of spontaneous circulation (ROSC). Brain conjugated dienes were analyzed spectrophotometrically 4 and 24 hr following ROSC, and were found to be significantly elevated when compared to non-ischemic controls. Hydroxyethyl starch-DFO treated rats demonstrated no increased conjugated diene production at either period. Neurologic injury was significantly less in drug treated rats surviving 24 or 72 hours when compared to controls. While mortality was similar in drug treated or control rats for the first 24 hours following ROSC, delayed mortality (days 1-10) was significantly less in drug treated animals, presumably as a result of neurologic protection afforded by post-ischemic drug administration. Administration of DFO conjugated to hydroxyethyl starch appears to modulate the neurologic injury which occurs during brain ischemia and reperfusion.     

Antioxidant effects of Emblica officinalis and Zingiber officinalis on arsenic and lead induced toxicity on Albino rats

It is of interest to document the effect of Emblica officinalis (E. officinalis) and Zingiber officinalae (Z. officinalae) leaf extract on reactive oxygen species, antioxidant potential changes in arsenic and lead-induced toxicity in male rats. We used 8 groups of adult male Wistar rats with 1 control group for this study. The animals were divided into Group I: Control and Group II: Lead and sodium arsenite induced rats (animals were induced for metal toxicity by the combined administration of arsenic (13.8 mg/ kg body weight) and lead (116.4 mg/kg body weight). These doses were administered by gastric intubation during 14 consecutive days using known standard procedures. Arsenic and lead induced rats treated with ethanolic extract of Emblica officinalis (60 mg/kg body weight/day, orally for 45 days) are group III rats. Group IV animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis (120 mg/kg body weight/day for 45 days). Group V animals are arsenic and lead induced rats treated orally with ethanolic extracts of Z. officinalae (60 mg/kg body weight/day for 45 days). Group VI animals are arsenic and lead induced rats orally treated with ethanolic extracts of Zingiber officinalis (120 mg/kg body weight/day for 45 days). Group VII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (60 + 60 mg/kg body weight/day for 45 days). Group VIII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day, orally for 45 days). Normal Control animals were treated orally with ethanolic extracts of E. officinalis (120mg/kg body weight) + Z. officinalae (120mg/kg body weight) for 45 days. The control and experimental animals were then subjected to analysis for oxidative stress markers such as H2O2, *OH, and lipid peroxidation (LPO), antioxidant enzymes in addition to liver and kidney function markers. Results: Arsenic and lead induced rats showed a significant increase in the levels of reactive oxygen species (H2O2, OH* and LPO) with concomitant alterations in the renal and liver tissues. However, enzymic and non-enzymic antioxidant levels were decreased. Nevertheless, an oral effective dose of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day increased the antioxidant enzymes and retrieved the altered levels of ROS and LPO that were induced by arsenic and lead. Thus, we show that E. officinalis and Z. officinalae leaf extract exhibits nephroprotective and hepatoprotective role through the restoration of reactive oxygen species and antioxidant enzymes in the kidney and liver tissue of Arsenic and Lead-induced nephrotoxicity and hepatotoxicity in rats. Hence, E. officinalis and Z. officinalae leaf extract are potential therapeutic options for the treatment of metal toxicity-induced kidney and liver diseases.     

Chelation of lead during co-exposure to ethanol

Efficacy of calcium disodium EDTA, D-penicillamine (DPA), 2,3 dimercaptosuccinic acid (DMSA), and alpha-mercapto-beta-(2-furyl) acrylic acid (MFA) to reduce the body burden of lead and restore the altered biochemical variables in lead or lead + ethanol administered rats was investigated. The investigation was aimed to suggest suitable prophylaxis of lead intoxication prevalent among workers co-exposed to lead and alcohol ingestion. Administration of lead (10 mg/kg, oral, once daily for 8 weeks) produced a significant inhibition in the activity of blood delta-aminolevulinic acid dehydratase (ALAD), elevation in the blood zinc protoporphyrin (ZPP) and urinary elimination of lead and delta-aminolevulinic acid (ALA). Lead contents of blood, liver, kidney and brain were also significantly higher than the normal control. The above changes were more marked in animals co-exposed to lead + ethanol (20% in drinking water) compared to lead alone. All the chelators were effective in increasing the urinary lead elimination, reducing the above biochemical alterations and lead contents of tissues. The order of effectiveness being DMSA greater than Calcium disodium EDTA greater than DPA greater than MFA. However, the protection was more noticeable in animals treated with lead alone than with lead and ethanol.     

Effect of lead with vitamin E, C, or Spirulina on malondialdehyde, conjugated dienes and hydroperoxides in rats

Lead (100 ppm) was given in doubly deionised water for 30 days to one group of rats. The other groups received lead along with exogenous antioxidants like vitamin E (50 IU/kg), vitamin C (800 mg/kg) or Spirulina (1500 mg/kg) in food for a similar period. Levels of lipid peroxidation products such as malondialdehyde, conjugated diene and hydroperoxide were measured in liver, lung and kidney of treated rats. In lead treated animals there was a significant increase in the levels of these lipid peroxidative products. Administration of exogenous antioxidants in the lead treated animals reduced the levels of malondialdehyde, conjugated diene and hydroperoxide. It indicated that vitamin E, vitamin C and Spirulina had significant (P < 0.001) antioxidant activity thereby protecting the animals from lead induced toxicity.     

Brain oxidative stress and selective behaviour of aluminium in specific areas of rat brain: potential effects in a 6-OHDA-induced model of Parkinson's disease

The ability of aluminium to affect the oxidant status of specific areas of the brain (cerebellum, ventral midbrain, cortex, hippocampus, striatum) was investigated in rats intraperitoneally treated with aluminium chloride (10 mg Al³⁺/kg/day) for 10 days. The potential of aluminium to act as an etiological factor in Parkinson's disease (PD) was assessed by studying its ability to increase oxidative stress in ventral midbrain and striatum and the striatal dopaminergic neurodegeneration induced by 6-hydroxydopamine in an experimental model of PD. The results showed that aluminium caused an increase in oxidative stress (TBARS, protein carbonyl content, and protein thiol content) for most of the brain regions studied, which was accompanied by a decrease in the activity of some antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase). However, studies in vitro confirmed the inability of aluminium to affect the activity of those enzymes. The reported effects exhibited a regional-selective behaviour for all the cerebral structures studied. Aluminium also enhanced the ability of 6-hydroxydopamine to cause oxidative stress and neurodegeneration in the dopaminergic system, which confirms its potential as a risk factor in the development of PD.     

Reversal of an aluminium induced alteration in redox status in different regions of rat brain by administration of centrophenoxine

Aluminium is one of the most studied neurotoxin, and its effects on nervous system are both structural and functional, involving various regions of brain. Aluminium toxicity is known to have multiple mechanisms of action in the central nervous system. Affinity of aluminium for thiol substrates is considered a possible molecular mechanism involved in aluminium neurotoxicity. The reduced glutathione (GSH) is especially important for cellular defence against aluminium toxicity. This study pertains to the modulatory action of Centrophenoxine on GSH status in aluminium exposed different brain regions of the female rats. Aluminium was administered orally at a dose of 40 mg/Kg. b.wt. /day for a period of eight weeks whereas, Centrophenoxine was administered intraperitoneally at a dose of 100 mg/Kg b.wt./day for a period of six weeks. The study was carried out in different regions of brain namely Cerebrum, Cerebellum, Medulla Oblongata and Hypothalamus. Animals exposed to aluminum, registered a significant decrease in the levels of reduced glutathione, and oxidized glutathione as well as in the activity of glutathione reductase in all the different regions studied when compared to normal control animals. Post-treatment with Centrophenoxine, showed a significant improvement in the thiol levels in different regions. Centrophenoxine when administered alone also had a profound effect on the levels of reduced glutathione as well as on the activity of glutathione reductase. From the present results, it can be stated that Centrophenoxine administration, as a thiol-antioxidant, arrests the aluminium induced cellular damage by improving the thiol status in brain regions.     

Regional alterations in calcium homeostasis in the primate brain following chronic aluminium exposure

The present study investigates the possible effects of chronic aluminium exposure on the various aspects of calcium homeostasis in the primate central nervous system. Aluminium administration caused a marked decline in the activity of Ca2+ ATPase in the monkey brain. The total calcium content was also significantly raised following aluminium exposure. Concomittant to the increase in the calcium content, the levels of lipid peroxidation were also augmented in the aluminium treated animals, thereby further accentuating the aluminium induced neuronal damage. In addition, aluminium had an inhibitory effect on the depolarization induced 45Ca2+ uptake via the voltage operated channels. The results presented herein, indicate that the toxic effects of aluminium could be mediated through modifications in the intracellular calcium homeostasis with resultant altered neuronal function.     

Chelation in metal intoxication. XXIII: Effect of N-(2-mercaptopropionyl) glycine on lead or lead and ethanol intoxicated rats

Efficacy of N-(2-mercaptopropionyl) glycine to reduce the body burden of lead and restore the altered biochemical parameters in lead or lead and ethanol intoxicated rats was investigated. The investigation was aimed to suggest suitable prophylaxis of lead poisoning prevalent among workers in lead industry who may also be exposed to ethanol. The rats were given lead (10 mg/kg, p.o.) or lead and ethanol (10% v/v in drinking water) daily for 8 weeks. Following exposure period a single dose of N-(2-mercaptopropionyl) glycine (0.3 mmole/kg, intraperitoneal) was given daily for 4 days. The chelator was effective in enhancing the urinary and faecal excretion of lead, reducing the concentration of lead in liver and kidney and lowering the excretion of delta-aminolevulinic acid in lead treated rats. However, the protection was more noticeable in animals treated with lead alone than with lead and ethanol.     

Lead induced alterations in nitrite and nitrate levels in different regions of the rat brain

Nitric oxide (NO) is a free radical synthesized by nitric oxide synthase (NOS) during the conversion of l-arginine to citrulline. Lead (Pb) affects neuronal functioning in the rat brain. Nitric oxide, a neuronal messenger has a short half life and converts immediately into nitrite and nitrate. The present study is designed to determine lead-induced alterations in NO production by measuring nitrite and nitrate in the cerebellum, the hippocampus, the frontal cortex and the brain stem of the rat brain. Male Sprague–Dawley rats were treated with lead acetate (5 and 15 mg/kg body wt.) by intraperitoneal injection. The control and experimental rats were sacrificed at the end of 7 and 14 days after treatment and different regions of the brain were isolated. Nitrite and nitrate (NOx) levels were estimated by the chemiluminescent method using the NOA 280 (Sievers). The data suggested dose-dependent and region-specific responses to lead. Both treatments of lead reduced NOx levels in the cerebellum and the hippocampus. However, the frontal cortex and the brain stem responded differently to Pb exposure. NOx levels in the frontal cortex were significantly increased in rats treated with low and high doses of Pb for 7 days but not in rats treated for 14 days, whereas in the brain stem, NOx levels were increased in a dose- and time-dependent manner. Although, the response was time-dependent, the variation between 7- and 14-day treatment was not clearly delineated. These results provide additional evidence that Pb exposure alters NO-production in rat brain leading to neuronal dysfunction.     

Flaxseed Oil as a Neuroprotective Agent on Lead Acetate-Induced Monoamineric Alterations and Neurotoxicity in Rats

Lead remains a considerable occupational and public health problem, which is known to cause a number of adverse effects in both man and animals. Here, the neuroprotective effect of flaxseed oil (1,000 mg/kg) on lead acetate (20 mg/kg) induced alternation in monoamines and brain oxidative stress was examined in rats. The levels of lead, dopamine (DA), norepinephrine (NE), serotonin (5-HT), lipid peroxidation, nitrite/nitrate (NO), and glutathione (GSH) were determined; also, the activity of acetylcholinesterase (AChE) and Na(+)-K(+)-ATPase were estimated on different brain regions of adult male albino rats. The level of lead was markedly elevated in different brain regions of rats. This leads to enhancement of lipid peroxidation and NO production in brain with concomitant reduction in AChE activity and GSH level. In addition, the levels of DA, NE, and 5-HT were decreased in the brain. These findings were associated with BAX over expression. Treatment of rats with flaxseed oil induced a marked improvement in most of the studied parameters as well as the immunohistochemistry features. These data indicated that dietary flaxseed oil provide protection against lead-induced oxidative stress and neurotoxic effects.     

Aluminium hydroxide uptake in the stomach and in the intestine of the rat: a histochemical study.

Using the histochemical stains aluminon, solochrome azurine and solochrome cyanine, intracellular binding of aluminium was examined in the mucosa of the stomach, duodenum, jejunum and ileum of adult rats. A first group of rats (n = 42) was sacrificed 1, 3, 6, 12, 24, 48 and 96 h after a single (300 mg x kg-1) oral administration of aluminium hydroxide. A second group of animals (n = 30) received daily the same dose of Al(OH)3 and was euthanatized after 3, 4, 5, 6 and 7 days of treatment. Aluminium deposits occurred only in the antral glands of the stomach and in rats treated for at least 3 days. The reactive deposits are located in the cytoplasm of the upper glandular cells and in the lumen of the antral glands. These results suggest that aluminium is absorbed through the antral mucosa and may be re-excreted through the glandular mucus flow into the digestive lumen where it will be absorbed again. We hypothesize that the metal could act as a delayed-effect drug.     

Pyruvate Metabolism in the Brain of Young Rats Intoxicated with Organic and Inorganic Lead

Abstract: The activities of lipoyl dehydrogenase, aspartate transaminase, and alanine transaminase, and levels of lactate were estimated in cerebral cortex, cerebellum, and brainstem of rats intoxicated acutely with tetraethyl lead and chronically with lead acetate. A significant inhibition of lipoyl dehydrogenase was observed in both groups of animals, whereas transaminase activities were increased in inorganic lead toxicity. Oxidative decarboxylation and anaplerosis of pyruvate was assessed in brain slices using [l-¹⁴C]pyruvate. Pyruvate dehydrogenase activity was decreased in both organic and inorganic lead toxicity, whereas labelling of aspartate and alanine was increased in inorganic lead toxicity. In studies in vitro , lead acetate showed a more significant effect than tetraethyl lead. The higher anaerobic metabolism in inorganic lead toxicity, as evidenced by increased anaerobic lactate production by brain slices, could either be an adaptive mechanism or be due to the delayed maturation of brain in the developing rat. Such a mechanism does not occur in acute organic lead toxicity, as the compound brings about massive and rapid degenerative changes in brain, resulting in convulsive seizures and death of the animals.     

Tissue distribution and urinary excretion of essential elements in rats orally exposed to aluminum chloride

The purpose of this study was to determine disorders in the metabolism of the essential elements (Ca, Fe, Cu, and Zn) in some tissues of rats, as well as to detect the dynamics of urinary excretion of these metals after oral administration of 20 mgAl/kg every day for 8 wk. The elements were determined in brain, kidneys, blood, and urine of the animals in 1st, 2nd, 3rd, 4th, and 8th wk after the exposure to AlCl₃. After the 1st wk of aluminium administration, we observed increase of Ca and a decrease of Fe in blood. In brain Ca, Fe, and Cu concentrations were significantly higher in Al-treated rats than in controls after 8-wk exposure. The concentration changes of the essential metals in the tissue were accompanied by increase of the Ca, Fe, and Zn urinary excretion. We assume that the increase in urinary excretion of Ca and the decrease of Fe in the blood may be sensitive indicators of oral aluminium administration.