ABSTRACT
The study of the effect of oral administration of aluminium chloride on the
Hippocampus of wistar rats was carried out in order to ascertain whether the small
daily amount of aluminium that gain access to the body produce any accumulation
damage to the hippocampus and if there is any association between drinking water
containing aluminium and brain damage. This investigation was carried out using 50
female adult wistar rats. The animals were divided into five groups; 10 rats per group.
Stock solution of aluminium chloride was prepared (2g/l or 2mg/ml).Different
concentrations of aluminium was administered to different groups orally. Group I was
control, while Groups II– V were given 2.3mg/kg(0.4mg),5.7mg/kg(1mg),11.4mg/kg
(2mg),and17.1mg/kg (3mg) respectively with an average weight of between 150-200g
for duration of twelve (12) weeks. Blood was collected from the tails of the rats for
haematological indices. The animals were sacrificed using chloroform and then the
brain tissues were fixed immediately in Bouin’s fluid. The hippocampus sections
were processed through the routine tissue processor. The stained samples were
examined by means of light microscope for histological changes. Histological
examination showed clumping of cell neurons, or reduced pyramidal cells and scanty
neurofibrillary tangle which was an indication of neurodegeneration in the treated
groups and which may suggest or tend to link accumulation of aluminium on brain
cells to incidence or aetiology of Alzheimer’s disease .The haematological results
showed that the differences in parked cell volume, white blood cell and neutrophils
of the control and experimental groups were statistically significant at P<0.05. The
increase in PCV, neutrophil and WBC observed in this study could be as a result of
the destruction of the hippocampal cells due to oral administration of aluminium
chloride. It was however, concluded that the oral administration of aluminium
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chloride could induce brain damage which may possibly impair memory and learning
as seen in Alzheimer disease.
TABLE OF CONTENTS
CONTENT PAGE
TITLE PAGE ……………………………………………………………………………………………. I
APPRECIATION …………………………………………………………………………………….. II
DECLARATION …………………………………………………………………………………….. III
CERTIFICATION …………………………………………………………………………………… IV
ACKNOWLEDGEMENT …………………………. ERROR! BOOKMARK NOT DEFINED.
TABLE OF CONTENTS ………………………………………………………………………… VIII
LIST OF TABLES ……………………………………………………………………………………. X
LIST OF PLATES ………………………………………………………………………………….. XII
ABSTRACT …………………………………………………………………………………………. XIII
CHAPTER 1 ……………………………………………………………………………………………… 1
INTRODUCTION ……………………………………………………………………………………. 1
1.1 Significance of the Study ………………………………………………………………. 4
1.2 Objectives of the Study Include the Following ………………………………….. 4
CHAPTER 2 ……………………………………………………………………………………………… 5
LITERATURE REVIEW …………………………………………………………………………… 5
2.1 Dietary and other sources of Aluminium Intake ………………………………… 8
2.2 Water as a Source of Aluminium ……………………………………………………. 8
2.3 Food Additive as a Source of Aluminium ………………………………………… 9
2.4 Unprocessed Foods as Source of Aluminium ………………………………….. 10
2.5 Packaging and Utensils as Sources of Aluminium……………………………. 11
2.6 Pharmaceutical Products as Sources of Aluminium …………………………. 12
2.7 Infant Formulae …………………………………………………………………………. 13
2.8 Bioavailability of Aluminium ………………………………………………………. 13
2.9 Epidemiology of Alzheimer’s Diseases in Relation to Aluminium ……… 15
2.10 Relationship between Alzheimer’s Disease and Aluminium in Drinking
Water ………………………………………………………………………………………. 17
2.11 Aluminium and Pathogenesis of Alzheimer’s disease (AD) ………………. 20
2.12 Alzheimer’s Disease …………………………………………………………………… 28
2.13 Plaques and Tangles-the Pathology of AD ……………………………………… 29
CHAPTER 3 ……………………………………………………………………………………………. 31
MATERIAL AND METHODS …………………………………………………………………. 31
3.1 Experimental Groups ……………………………………………………………………… 31
3.2 Experimental Procedure ………………………………………………………………….. 32
3.3 Tissues Preparation for Microscopic Examination ……………………………….. 33
3.4 Statistical Analysis …………………………………………………………………….. 34
CHAPTER 4 ……………………………………………………………………………………………. 35
RESULTS …………………………………………………………………………………………….. 35
4.1 Haemotological Indices ………………………………………………………………. 35
4.2 Microscopic Examination of Tissues …………………………………………….. 39
CHAPTER 5 ……………………………………………………………………………………………. 50
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DISCUSSION ……………………………………………………………………………………….. 50
CHAPTER 6 ……………………………………………………………………………………………. 53
SUMMARY, CONCLUSION AND RECOMMENDATION …………………………. 53
6.1 Summary and Conclusion ……………………………………………………………. 53
6.2 Recommendation ……………………………………………………………………….. 54
REFERENCES ………………………………………………………………………………………. 55
APPENDIX I …………………………………………………………………………………………. 65
APPENDIX II ………………………………………………………………………………………… 66
APPENDIX III ………………………………………………………………………………………. 67
APPENDIX IV ………………………………………………………………………………………. 68
CHAPTER ONE
INTRODUCTION
Aluminium is present in small amounts in mammalian tissues; research studies to
establish its specific positive functional effect to the mammalian body is yet to be
ascertained (Beavon, 2004). However, its neurotoxic effect on living organisms is
becoming clear, aluminium being implicated as interfering with a variety of cellular
metabolic processes in the nervous system and in other systems (Parkinson et al.,
1981). Although molecular mechanisms by which aluminium exerts its neurotoxicity
remain to be established, several pieces of evidence suggest that Aluminium can
interfere with cellular metabolism in terms of biological stimulation, inhibition, or
metal accumulation and compartmentation (Zatta et al., 1991).
Aluminium Chloride according to Wells (1963), is used as a catalyst in the process of
Friedel crafts(dye making process).According to him,it has an electron deficient
molecule forming only 3 bonds and has no lone pairs. The catalyst acts as an electron
acceptor for a lone pair on the halide atom. It is widely used in other manufacturing of
petrochemicals such as alkylbenzene, ethylbenzene, alkylarylkertone, ethylchloride
(Greenwood, 1990). It is also used in the manufacturing pharmaceuticals, dyes
intermediates and other organic chemicals such as anthraquinone, phthalocyanines,
acetophenone, buytl rubber, phenylethyl alcohols (Lide, 1996). It is used as a nucleus
inhibitor in the production of titanium dioxide (West, 1999).
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Aluminium Chloride is also used in the production of aluminium, in the metallurgical
industry and as a flux in aluminium smelting, in production of rubber, lubricants and
wood preservatives and in cosmetics as an astringent; active ingredient in
antiperspirants (Cotton et al., 1999).
Aluminium chloride is an effective antiperspirant that is applied to the skin to control
severe excessive sweating (hyperhidrosis) that works by blocking the sweat glands
and causes the pressure of fluid within the glands to rise to the point where it shuts off
sweat production (Net Doctor, 2004). The antiperspirant is applied before going to
bed at night and should be washed off in the morning. It should not be reapplied
during the day. Overtime, sweating will stop during the day and the number of times
you apply the antiperspirant at night can be reduced. Aluminium has a wide variety of
uses which include aircraft production, utensils, apparatus and electrical conductors.
The coarse powder is used in aluminothermic (thermite process): the fine powder as
flashlight in photography, in explosives, fireworks and in aluminium paint; for
absorbing gases in manufacturing of steel (Net Doctor, 2004).
Frank (2006),describing Aluminum toxicity in U.S.A.stated that “from the earliest
days of food regulation, the use of alum (aluminum sulphate) in foods has been
condemned. It is universally acknowledged as a poison in all countries. If the Bureau
of chemistry, U.S.A. had been permitted to enforce the law, no food product in the
country would have any trace of any aluminium. No soft drink would contain
caffeine: no bleached floor would be in interstate commerce. Our food and drugs
would be wholly without adulteration and the health of our people would be vastly
improved and their life greatly extended”.
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Dr. Wiley in U.S.A vehemently resisted crime against food laws, was the prime
mover behind the original pure food law and Director of Food and Drug
Administration (FDA) in 1929, and resigned in disgust in 1912 over exceptions
granted to the law and lack of enforcement particularly on aluminium where
aluminium has been exempted from testing for safety by the FDA under a convoluted
logic wherein it is classified as GRAS (Generally Regarded as Safe). It has never been
tested by the FDA on its safety and there are no restrictions whatever on the amount
or use of Aluminium (Wiley, 1975).Frank also noted that 4 ppm of aluminium in
human blood can cause it to inhibit learning (Frank, 2006.)
The functions of certain learning and memories have been associated with different
areas of the brain like the hippocampus prefrontal cortex and cerebellum.
Hippocampus is associated with memory of new words, faces, places and event.
Cerebellum has been associated with the memory of learning new skills like playing
an instrument etc while the prefrontal cortex is linked with retention of mental image
and delayed response (Brodal, 1992).
Williams (1992), opines that aluminium compounds have been used for 30 years to
control phosphate levels in patients undergoing haemodialysis. The toxic effect
arising from the absorption and accumulation of aluminium have well been
documented and include a progressive encephalopathy which eventually leads to
dementia (Williams, 1992). Aluminium compounds are also the major cause of
damage to fish gill epithelia and plant root membrane in the acidic conditions
produced by “acid rain” (Tam and Williams, 1986). Although aluminium is known to
be a neurotoxin which affects many neurochemicals reactions, the details of the
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biochemistry underlying cell damage and death are largely matters of conjecture
(Mclachlan et al., 1991b). Aluminium has also been implicated as a toxic agent in
aetiology of Alzheimer’s disease and parkinsonism-dementia (Hewitt et al., 1990). It
is argued that glutamate and aspartate complexes of Aluminium (Al3+) play roles in
Alzheimer’s diseases and other Aluminium related conditions (Deloncle and Guillard,
1990).
1.1 Significance of the Study
This study becomes important in order to ascertain whether the small daily amount of
aluminum chloride that gains access to the body produce any accumulated damage to
brain tissues (hippocampus) of wistar rats.
1.2 Objectives of the Study Include the Following
a. To determine the relationship between drinking water containing Aluminium
chloride and hippocampus damage of wistar rats by looking for histological
changes in the hippocampus.
b. To compare the haematological indices of the treated and control of wistar
rats.
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