INTRODUCTION:

Environmental pollution is the presence of a pollutant in environment such as air, water and food which may be poisonous or toxic and will cause harm to living things. The excessive amount of pollutants such as heavy metals are often due to human actions, resulting from either agricultural or industrial production or deliberate misuse (1).

Lead (Pb) is ubiquitous and one of the earliest metals discovered by the human race (2). Unique properties of lead, like softness, high malleability, low melting point and resistance to corrosion, have resulted in its widespread usage in different industries like automobiles, ceramics, plastics. This has led to a manifold rise in the occurrence of free lead in biological systems (3). Lead is one of the toxic metals, it is dangerous to most human body organ if exposure exceed to lerable levels.

It primarily affects the central nervous system, hematopoietic, hepatic and renal system (4), and also causes anemia, immunotoxicity and toxicity to the reproductive organs (5).

Aluminium (Al) is the most abundant metal on earth that constitutes 8.13 % of the crust, may enter the human body through food, drinking water, and Al-containing drugs.Al is highly reactive and does not exist as a free metal in nature, and is found in combination with oxygen, fluorine, chloride and other elements in soil, rocks and clays (6). Al metal is used in the manufacturing of automotive aircraft, alloys, cooking utensils, decorations, highway signs, food packaging, dental crowns, antacid drugs, food additives, toothpaste (7). However, it is not essential for life. Owing to its specific chemical properties, aluminum inhibits more than 200 biologically important functions and causes various adverse effects. The toxicity of Al is directly linked to its bioavailability (8). Al is known as a neurotoxin that can cause diseases such as Alzheimer disease, dialysis dementia, Parkinsonism, and amyotropic lateral sclerosis. In addition to its neurotoxicity, Al affects other body structures like the skeletal system, brain tissue, bone, liver and kidney (9). Al accumulation in kidney promotes degeneration in renal tubular cells, inducing nephrotoxicity. Salts of aluminium may bind to DNA, RNA; inhibit such enzymes as hexokinase, acid and alkaline phosphatases, and phosphooxydase (10).

MATERIALS AND METHODS:

Forty five adult male albino rats of the Wistar strain were used in this study, 5–6 months of age and250±50 gm weighing. Animals were housed in plastic cages with standard conditions under controlled temperature (24-26 'C) and lighting (12 hours light/12 hours dark). Water and food were available ad labium.

After the period of acclimation, animals were divided into three equal groups (15 rats in each group) as follows:- Group 1: rats were treated with normal saline (0.9% NaCl) and considered as control group. Group 2:that given lead acetate concentration of 60 mg/kg of body weight per day. Group 3: which givenaluminium chloride concentration of 70 mg/kg of body weight per day. The duration of the daily oral gavage administration during the experiments lasts for 30 day.

At the end of the experiments, all animals were sacrificed by decapitation. The brains were removed after dissection and exposure of skull from foramen magnum posteriorly, olfactory bulbs and cerebellum were dissected and the brain were removed gently from the skull and rinsed in isotonic saline.

For brain tissues, 50 mg of tissue were homogenized in1 ml HCl (0.01N) with EDTA (1mM) and sodium metabisulfite (4mM). Under this condition, DA is positively charged and has the optimized solubility. The homogenate was centrifuged at 15000g at 4⁰C for 15 min (11), and the supernatant was collected for measuring DA concentration by enzyme linked immunosorbent assay (ELISA) technique using kitpurchased from )ABO, Switzerland( Co.,

brain was homogenizedto give 10% (w/v) homogenate in icecold medium containing 50 mMTris-HCl and300 mM sucrose at pH: 7.415.The homogenatewas centrifuged at 3000 rpm for 10 min in coolingcentrifuge at 4⁰C. (12), The supernatant (10%) wascollected for measuring acetylcholine (Ach) concentration by ELISA technique using kit purchased from )ABO, Switzerland( Co.

Statistical analysis:

ANOVA analysis and LSD test were used according to (SPSS version 18) program to find the means for all treatments (13).

RESULTS AND DISCUSSION:

The results showed a significant decrease (P<0.05) in the level of dopamine in the brain in each treated group as compared to the control group (Table 1).

lead induces a reduction in the catecholaminergic transmission, either by an inhibition of the synthesis of dopamine and its release, or by an inhibition of the postsynaptic D2 receptors (14). other researchers showed that intoxication with lead induces a reduction in the metabolites of dopamine (DOPAC, and homovanillic acid) in the nigrostriatal and mesolimbic systems (15).

lead can attack the synaptic neurotransmission in two ways: by depressing the Ca-KC1-evoked release of GABA, dopamine and by a selective stimulation of a spontaneous release of GABA and dopamine (16).

The other researchers indicate that chronic Pb2+ intoxication induces an oxidative stress in rat brainand increases in lipid peroxide level in the liver and brain (17).

Studies have demonstrated that aluminum blocks BH4 synthesis in vitro, Since BH4 is the co-enzyme for tyrosine hydroxylase, this enzymeplays an essential role in of dopamine synthesis pathway (18), it could be possible that inhibit the synthesis of dopamine. Another possible mechanism could be through the inhibitory effect of aluminum on calcium influx into synaptosomes, and inhibit the release of dopamine because calcium as a secondary messenger plays a critical role in release of dopamine (19).

In addition, it has been exhibited that aluminum interacts with transferrin, and it led to decreasethe intake of iron through the surface receptors of oligodendrocytes, Since tyrosine hydroxylase is a metal enzyme containing iron (20), reduction in iron intake could interfere the activity of enzyme and inhibit the dopamine production .

Also these results were showed a significant increase (P <0.05) in the level of acetylcholine in the brain in each treated group as compared to the control group (Table 1).

Another Results revealed that aluminum and lead treatment leading to a significant reduction in brain content and activity of acetylcholinesterase (AChE), This enzyme plays an essential role in catalyzing the hydrolysis of acetylcholine and rapidly terminates cholinergic neurotransmission (21,7), it could be possible that increase in the level of acetylcholine in brain.

Effect of the acetylcholine according the present results showed significant increasing in acetylcholine treatment animals in comparative with control and this high level elevated according the repeat of dose because of in the normal midbrain, there is a balance between dopamine and acetylcholine the loss of dopamine tilts the balance toward too much acetylcholine, which alsocontributes to motor symptoms so thatdopamine depletion blocks auto inhibition of acetylcholine release through muscarinic auto receptors, leading to excessive acetylcholine release which eventually prunes spines of the indirect-pathway projection neurons of the striatum and thus interrupts information transfer from motor command centers in the cerebral cortex (22).

Table 1: The effects of lead and aluminum on dopamine and acetylcholine in rat brain

Parameter Groups	Dopamine	Acetylcholine
C	22.5 ± 0.3 a	37.1 ± 0.1 c
G1	9 ± 0.5 b	50.5 ± 0.7 b
G2	7.6 ± 0.2 b	59.2 ± 0.5 a

Values represent means ± SE.

Similar Letters represent no significant differences between the groups at (P<0.05).

Different letters represent significant differences between the groups at (P<0.05).

CONCLUSIONS:

The results showed thatlead and aluminiumhad a inhibitory role in brain function, which led to a decrease in dopamine levels .Exposure tolead and aluminium led to increased oxidative stress in brain resulting in increased levels ofacetylcholine in the brain.

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Received on 28.09.2017 Modified on 08.11.2017

Research J. Pharm. and Tech 2018; 11(5):2055-2057.

DOI: 10.5958/0974-360X.2018.00381.5