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العنوان
Neuroprotective effect of Ginkgo biloba extract on aluminium-induced neurotoxicity in rats\
الناشر
Ain Shams university.
المؤلف
Abdel Hady,Rasha Abdel Hady Mohamed.
هيئة الاعداد
مشرف / Amira Mohammed Elsheikh
مشرف / Amani Emam Khalifa
مشرف / Amira Mohammed Elsheikh
باحث / Rasha Abdel Hady Mohamed Abdel Hady
الموضوع
Ginkgo biloba. aluminium-induced neurotoxicity Rats.
تاريخ النشر
2011
عدد الصفحات
p.:225
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
العلوم الصيدلية
تاريخ الإجازة
1/1/2011
مكان الإجازة
اتحاد مكتبات الجامعات المصرية - Pharmacology and Toxicology
الفهرس
Only 14 pages are availabe for public view

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Abstract

On the other hand, treatment with Ginkgo biloba extract did not induce any histopathological alterations in any brain regions of treated rats. These results are in agreement with many previous studies (Takuma et al., 2007;Burda et al., 2009). These studies have also documented the absence of any histopathologies following Ginkgo biloba treatment. Moreover, concomitant treatment with Ginkgo biloba extract of aluminium-administered rats ameliorated most of the histopathological findings. Examination of brain sections of rats received both Ginkgo biloba extract and aluminium lactate has showed only mild oedema in meninges and gliosis but no brain fissures, endothelial cell swelling, nor blood capillaries congestions were recorded. These results are in accordance with Gong et al. (2006) who have also reported the ability of Ginkgo biloba extract to diminish histopathologies induced by aluminium toxicity.
The ability of Ginkgo biloba extract to ameliorate aluminium-induced histopathological alterations coud be a result of diverse portofolio of factors including:
1. Free radical scavenging and anti-oxidant properties (Altiok et al., 2006;Huang et al., 2007).
2. Protection against beta-amyloid induced synaptic dysfunction and neuronal cell death (Vitolo et al., 2009).
3. Direct down regulation of GFAP on both protein and mRNA levels (Zou et al., 2007).
4. Neuroprotective effect mediated via induction of heme oxygenase type 1 which enhances the reperfusion of ischemic brain injury (Saleem et al., 2008).
5. Protection against dopaminergic induced neurotoxicity (Rojas et al., 2008).
6. Enhancement of hippocampal neurogenesis and phosphorylation of cAMP response element binding protein (Tchantchou et al., 2007).
7. Ginkgo biloba extract treatment protects the neurons from excitotoxicity induced by over-activated N-methyl D-aspartate receptors and focal cerebral ischemia, which can be explained by the mild blocking effect of Ginkgo biloba extract on N-methyl D-aspartate receptors (Xiao et al., 2006).
8. Protective Effects on Mitochondrial Function (Shi et al., 2010a).
9. Anti-apoptotic activity since flavonoid fraction of Ginkgo biloba extract may be partly responsible for its anti-apoptotic properties (DeFeudis, 2002).
10. Anti-inflammatory effect (Chan et al., 2007).
Eventually, it can be concluded that Ginkgo biloba extract can effectively and extensively counteract aluminium-induced neurotoxicity in rats. The neuroprotection was evidenced by several findings including the ability of Ginkgo biloba extract to ameliorate most of neurodegeneration and histopathological alterations reported in aluminium-intoxicated rats. The recorded neuroprotective effect of Ginkgo biloba extract could be mediated through its anti-oxidant properties and free radical scavenging effect. It is noteworthy to mention that Ginkgo biloba extract also could protect neurons through restoration of brain normal content of GSH. Enhancement of hippocampal neurogenesis and protection of the neurons from excitotoxicity are also possible mechanisms. Furthermore, the observed neuroprotection was supported by improved rats’ performance in tha passive avoidance task as well as normalization of most of the disturbed biochemical parameters. Our results highlights the role of the natural remedy Ginkgo biloba extract in minimizing the serious neurological complication due to aluminium-intoxication, which could be a possible solution for this very serious and potential complication of aluminium exposure.
Aluminium was found to possess neurotoxic properties; this neurotoxicity was mainly mediated via its pro-oxidant properties as well as its capability to induce/ exacerbate oxidative stress followed by enhanced lipid peroxidation. In addition, aluminium was demonstrated to cause remarkable dysfunction in several neurotransmitters, increased amyloid deposition, altered energy metabolism, impaired calcium homeostasis, aggreveated inflammatory response as well. Therefore, aluminium induced brain dysfunction could be due to any of these mechanisms or the interaction between all of them. This reported neurotoxicity and brain dysfunction of aluminium were manifested as significant impairment of memory as well as remarkable deterioration in learning ability of aluminium-intoxicated members.
Herein, the purpose of this study was to evaluate the neuroprotective effect of Ginkgo biloba extract in modulating or antagonizing the toxic effect resulting from daily treatment with aluminium via establishment of a valid animal model sufficiently and accurately able to identify the efficiency of the neuroprotective treatment. This aim was studied via investigating
• Pharmacological changes in aluminium content in brain and five diffrent regions of the brain of control rats and experimental ones. Also, aluminium serum level was estimated.
• Biochemical changes in brain of control rats and experimental ones.
• Histopathological changes in certain brain regions of control rats and experimental ones.
• Psychopharmacological changes due to aluminium toxicity using open field test and passive avoidance test.
Results of this thesis could be summarized as follows:
 Effect of aluminium lactate treatment on the investigated parameters:
1) Intraperitoneal administration of aluminium lactate at a dose of 10 mg/kg for 4 weeks induced prominent histopathological changes in cephalic tissue of aluminium-treated rats. These histopathological findings include:
A- Diffuse gliosis in the cerebrum with swelling in the endothelial cells lining the congested blood capillaries.
B- Neuronal degeneration was observed in the cells of the hippocampus associated with focal hyalinosis with plaques formation in the cerebrum.
C- There were oedema and congestion in the brain fissures associated with haemorrhage in the choroid plexus.
D- The medulla oblongata showed focal gliosis with congestion in the blood capillaries.
2) Administration of aluminium lactate at a dose of 10 mg/kg intraperitoneally daily for 28 days caused a marked increase in aluminium level in serum. In addition significant elevations in aluminium content were observed in whole brain either/or in all selected brain regions (hippocampus, cortex, T+H, C+M, P+M) following aluminium treatment. Aluminium showed a maximum accumulation in hippocampus.
3) Daily treatment with aluminium lactate induced remarkable increase in AChE activity of aluminium-treated rats compared to control ones.
4) Aluminium lactate administartion i.p daily for 28 days caused marked increase in brain content of MDA, GSSG as well as depletion of brain GSH content.
5) Daily administration of aluminium lactate i.p led to non-statistically significant changes in all of the psychopharacological parameters (latency period, number of ambulations, rearing, grooming) during performance in the open field test.
6) Treament with aluminium lactate i.p daily for 28 days induced marked deterioration in memory of aluminium-treated rats tested in passive avoidance task that was evidenced by shorter duration required by rats to remember not to enter the dark compartment where they were exposed to electric foot shocks.
 Effect of Ginkgo biloba extract on aluminium-induced neurotoxicity:
Daily intragastric administration of Ginkgo biloba extract at a dose of 200 mg/kg in rats exposed to aluminium toxicity
1) Has markedly ameliorated most of the histopathological findings reported in aluminium-treated rats.
2) Had no effect on neither serum aluminium level, nor whole brain aluminium content, nor brain regional distribution of aluminium.
3) Normalized brain AChE activity.
4) Achieved a protective effect against aluminium-induced oxidative damage that was associated with remarkable decrease in the oxidative stress biomarkers (MDA, GSSG) as well as the preservation of GSH content in brain.
5) Caused non significant change in all measured psychopharmacological parameters using open field test.
6) Significantly ameliorated the memory impairment in the passive avoidance task in rats chronically exposed to aluminium that is evdinced by marked prolongation of step through latency.
In conclusion, this in vivo study provides evidence that Ginkgo biloba extract significantly protected rats from neurotoxic effects of aluminium lactate as evidenced by minimal histopathological damage of brain, restoration of normal brain AChE activity, lowered oxidative stress biomarkers, normalization of brain anti-oxidants content, and prolongation of step through latency in passive avoidance test. As aluminium-induced neurotoxicity is often unavoidable; our results open a window for prevention of this devastating neurological complication by administration of the versatile herbal medicine Ginkgo biloba extract, which might hopefully be the answer to this serious neurotoxicity induced by aluminium. Further clinical studies are needed to provide further support of this conclusion and to investigate the ability to use that portfolio of therapy in human.