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العنوان
Possible protective role of Green tea extract and Vitamin E against Aluminum induced Nephrotoxicity and Neurotoxicity in Rats./
المؤلف
Mohamed Anwer Mohamed
هيئة الاعداد
باحث / محمد أنور محمد نعمان
مشرف / رندة حسين عبدالهادى
مناقش / عبد الوهاب عبد الكريم داوود
مناقش / محمد عبد العظيم خلف
الموضوع
Forensic Medicine and Clinical Toxicology.
تاريخ النشر
2017.
عدد الصفحات
135 p. ;
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
علم الأمراض والطب الشرعي
الناشر
تاريخ الإجازة
24/9/2017
مكان الإجازة
جامعة أسيوط - كلية الطب - Department of Forensic Medicine and Clinical Toxicology
الفهرس
Only 14 pages are availabe for public view

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from 182

Abstract

Summary and Conclusion
Aluminum, is the third most abundant element and the most common metal in the earth’s crust, it’s one of the most major pollutant of increasing use in our society as a result of the high rate of global industrialization and consequent pollution.
Human exposure occurs either by occupational exposure, food, air, water or drugs. Inhalation and ingestion are the major routes of exposure. Aluminum is a cumulative toxin that has a long half-life, it is mainly accumulated in lung, brain, kidney and bone.
In the present work, the effect of simultaneous administration of either vitamin E or green tea singly or in combination on the prevention of chronic aluminum toxicity on brain and kidney was studied.
Sixty four male rats were used weighing about (150±20gm). The rats were divided into two main groups. The first group served as a control group which divided in four subgroups received a daily saline, Vit E, green tea or Vit E and green tea, and the other group served as treatment group which divided into four subgroups received a daily intraperitoneal injection of aluminum, aluminum + vitamin E, aluminum + green tea or aluminum + vitamin E + green tea. The saline, vitamin E and green tea were given orally.
After 12 week the memory tests were done (novel object recognition test, passive avoidance test and Morris water maze test). Three months later the rats were sacrificed; blood, kidney and brain sample were collected. Biochemical analysis for oxidative stress indices (lipid peroxide and nitric oxide), antioxidant ( reduced glutathione) and aluminum concentration in brain and kidney were determined. Histopathological examination of kidney and brain tissues by light microscope was done. Changes in the body weight of all groups during the experimental period were observed.
Statistical analysis of the results was as follows:
The kidney was affected more than the brain as evidenced by more aluminum concentration in the kidney (74.6±7μg/g) while aluminum concentration in the brain (cerebellum and hippocampus) was (13.5± 0.4 and 9.2 ± 0.4ug/g) respectively.
The rats treated with aluminum showed the presence of kidney dysfunction as evidenced by an increase in the serum urea (76.0 ± 4.6 mg/dl) and serum creatinine (3.2 ± 0.2mg/dl).
The rats treated with aluminum showed the presence of brain dysfunction as evidenced by memory tests, there was decrease of discrimination index of novel object recognition test at 5min, 2h and 24 h (-0.7± 0.1, -0.5± 0.1and-0.3± 0.1) respectively, also there was decrease of step latency of passive avoidance test after 24h (147.5±7.7 s) and there was increase of escape latency of Morris water maze test on test phase at 24h and 30min (76.9±4.1 and 37.1±1.0 s) respectively.
There was an increase in the serum oxidative stress indices (lipid peroxide and nitric acid) (111.8±2.7 and 68.7±1.1um/l) respectively, and decrease in the serum antioxidants (reduced glutathione) (30.9±0.7um/l).

The histopathological examination of the kidney showed distorted renal tubules and glomeruli with vacuolar degeneration of the epithelium in some renal tubules as well as intertubular infiltration with mononuclear cells.
The brain showed degenerated cerebral cortex neurons (pyramidal cells) with vacuolation and increased number of glial cells accompanied by cellular infiltration. The cerebellum of Al alone -treated rats showed irregular outlined nuclei with degeneration of purkinjee cells. Moreover, the hippocampus showed dark neurons with dark nuclei associated with vacuolation.
Aluminum treated rats also showed a decrease in the percentage of mean body weight change (4.9±8.6).
The use of the protective agent (vitamin E, green tea and combination of both) can ameliorate the chronic aluminum toxicity. They inhibit the oxidative stress and counteract the effect of aluminum on the antioxidants.
The least aluminum concentration was present in the kidney and brain (cerebellum and hippocampus) of rats treated with a combination of vitamin E and green tea (16.3 ± 0.4, 6.3 ± 0.6 and 4.6 ± 0.3um/l) compared to the group treated with vitamin E (23.9±1.5, 9.8 ± 0.2 and 5.2 ± 0.4um/l) or green tea (16.3 ± 0.4, 10.2 ±0.5 and 5.0 ±0.2um/l) alone.
The rats treated with vitamin E, green tea or a combination of both with aluminum showed improvement of kidney functions as evidenced by a decrease in the serum urea (54.1± 2.5, 54.5 ± 2.5 and 52.2 ± 3.1mg/dl ) and serum creatinine (2.3± 0.2, 2.0 ± 0.1 and 1.9 ± 0.2mg/dl ).
The rats treated with vitamin E, green tea or combination of both with aluminum showed improvement of brain functions as evidenced by improvement of memory tests there was increase of discrimination index of novel object recognition test at 5min (0.3±0.1, 0.4±0.1 and 0.5 ± 0.1 respectively), 2h (0.3±0.2, 0.1±0.1 and 0.5 ± 0.1 respectively) and 24 h (0.4±0.1, 0.1±0.1 and 0.6 ± 0.1 respectively). There was increase of step latency of passive avoidance test after 24h (202.5±9.7, 220.1± 11.7 and 236.3± 4.2 s) and there was a decrease of escape latency of Morris water maze test on the test phase at 24h (34.1±1.7, 33.8±1.8 and 32.4±1.8s) and 30min (28.5±1.0, 28.8±0.6 and 28.4±1.7 s) respectively.
The rats treated with vitamin E, green tea or a combination of both with aluminum showed an increase of serum reduced glutathione (49.9±1.8, 48.0±2.0 and 56.4±1.8 um/l) and decrease of lipid peroxide (44.7±3.1, 53.3±2.6 and 45.5±3.8 um/l) and nitrite (44.3±0.9, 47.2±1.0 and 44.6 ±0.9 um/l) respectively.
The rats treated with vitamin E, green tea or a combination of both with aluminum showed histopathological examination more or less similar to the control groups.
The rats treated with vitamin E, green tea or a combination of both with aluminum showed an increase in % of the body weight changes (22.0±6.0, 33.3±7.7 and 49.6±10.1) respectively.
In conclusion, aluminum induces neurotoxicity and nephrotoxicity via oxidative stress, increase free radical generation and aluminum deposition in tissue will lead to toxicity. The functions of certain learning and memory have been associated with different areas of the brain like the hippocampus and cerebellum. Aluminum treated group showed marked cell distortion. The green tea alone or in Combination with Vitamin E have a protective effect on Alzheimer’s disease Induced by Aluminum in Rats. In this way green tea and vitamin E have a neuroprotective effect which confirmed by biochemical, behavioral and histopathological examination. The combination treatment has more pronounced effects in minimizing the hazards of aluminum- induced toxicity. The behavioral and biochemical results of the present work are confirmed by the histological examinations of the brain regions and kidney in which administration of Vit E and green tea to model rats showed histologically intact hippocampus, cerebellum and kidney . Thus Vit E and green tea counteracts aluminum harmful effects not only by preventing free radical formation but also by favoring aluminum excretion.


Recommendations
Recommendations
1) Complete kidney functions profiles and memory assessment should be done to new workers exposed to aluminum to avoid any further deterioration in their condition on exposure to aluminum if there were diseased as they more susceptible to aluminum toxicity.
2) Workers exposed to aluminum must wear protective clothes, gloves and masks. They must learn the personal safety measures.
3) Workers involved in occupational exposure to aluminum must receive a combination of green tea and vitamin E.
4) Regular urine analysis, blood analysis, memory assessment and kidney function tests must be done to assess the kidney function status and memory. The concentration of aluminum in urine and body weight must be observed periodically.
5) Workers showing any signs of aluminum toxicity should avoid further exposure.
6) Further studies needed to assess the effectiveness of these protective agents against aluminum toxicity.