FTIR Assessment of the Effect of <Emphasis Type="Italic">Ginkgo biloba</Emphasis> Leave Extract (EGb 761) on Mammalian Retina

Ginkgo biloba extract has been therapeutically used for several decades to increase peripheral and cerebral blood flow as well as for the treatment of dementia. The extract contains multiple compounds such as flavonoids and terpenoids that are thought to contribute to its neuroprotective and vasotropic effects. In this study, we investigated the effect of prolonged administration of EGb 761, up to 10 weeks, on mammalian retina using Fourier transform infrared spectroscopy (FTIR). Two main groups were involved in this study: the normal group (n = 10); and EGb-administrated group (n = 50) that received—orally—a dose of 40 mg/kg/day EGb 761. The results demonstrated that EGb administration was associated with different beneficial effects on the retinal constituents especially the underlying amide I protein secondary structure components as well as the NH-OH region. It concluded that the optimum daily administration period of EGb (40 mg/kg) for ophthalmic applications that targeting the retina ranges from 5 to 8 weeks.     

Effect of a short- and long-term treatment with Ginkgo biloba extract on amyloid precursor protein levels in a transgenic mouse model relevant to Alzheimer's disease

Several clinical trials have reported beneficial effects of the Ginkgo biloba extract EGb761 in the prevention and therapy of cognitive disorders including Alzheimer’s disease (AD). The aim of the present long-term feeding trial was to study the impact of dietary EGb761 on Amyloid precursor protein (APP) metabolism in mice transgenic for human APP (Tg2576). Tg2576 mice were fed diets with and without EGb761 (300 mg/kg diet) for 1 and 16 months, respectively. Long-term treatment (16 months) with EGb761 significantly lowered human APP protein levels by ∼50% as compared to controls in the cortex but not in the hippocampus. However, APP levels were not affected by EGb761 in young mice. Current data indicate that APP seems to be an important molecular target of EGb761 in relation to the duration of the Ginkgo biloba treatment and/or the age of the animals. Potential neuroprotective properties of EGb761 may be, at least partly, related to its APP lowering activity.     

The importance of scavenging reactive oxygen species in anti‐aging medicine

In a pilot study, we had reported on the beneficial effects of Ginkgo biloba (EGb 761) on arteriosclerotic nanoplaque formation and size in cardiovascular high‐risk patients who had undergone an aortocoronary bypass operation. Briefly, nanoplaque formation and size, the ratio oxLDL/LDL, and the highly atherothrombotic lipoprotein(a) concentration were substantially reduced, while superoxide dismutase activity and the blood concentration of the vasodilating substances cAMP and cGMP were upregulated. Since the arteriosclerosis prophylactic and well‐aging promotive impact of Ginkgo extract has been proven in this pilot study, we wanted to confirm these beneficial effects through a second observational clinical trial. The measurable variables formerly used were additionally supplemented by a wide, novel biomarker spectrum, through which the latest parameters and markers of plaque stability and progression, oxidative stress, and inflammation were available. In eleven patients with metabolic syndrome in the initial stage, the reduction of arteriosclerotic nanoplaque formation amounted to 14.3±2.9% (p<0.0077) and of nanoplaque size to 23.4±3.7% (p<0.0004), respectively, after 2‐months of treatment with Ginkgo biloba extract. Additionally, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were upregulated by 19.6±10.0% (p<0.0785) and 11.6±2.3% (p<0.001), respectively, the quotient oxLDL/LDL lowered by 21.0±4.3% (p<0.002), and lipoprotein(a) concentration decreased by 26.3±4.8% (p<0.001) in the patients' blood. The concentration of cAMP and cGMP was augmented by 43.5±12.0% (p<0.001) and 32.9±10.4% (p<0.001), respectively. Surprisingly, we found a lowering of the serum Ca²⁺ concentration by 5.4±1.6% (p<0.0076) from 2.37±0.03 to 2.24±0.04 mmol/L (p<0.0069). Apart from an additional vasodilatory effect, the lowered extracellular Ca²⁺ concentration affects nanoplaque formation restrictively, since this is a Ca²⁺ driven process. Furthermore, we could show a favourable development of the biomarkers 8‐iso‐PGF_2α, oxLDL/LDL, SOD, GPx (oxidative stress), hs‐CRP, MPO, TNFα, TGFβ₁ (inflammatory status) and MMP‐9 (plaque stability). The markers selected here are suited to provide a comprehensive risk profile for the prevention of arteriosclerosis. Finally, a multiple regression analysis reveals a basis for a mechanistic explanation of nanoplaque reduction under Ginkgo treatment. The arteriosclerosis inhibiting effect is due to an attenuation of the risk factors oxLDL/LDL, Lp(a), and [Ca²⁺]_o as well as to a significant increase in the vasodilator cAMP and cGMP concentration. Thus, Ginkgo with its pleiotropic effects should be assigned a fixed rank among the anti‐aging medical therapeutics as a prophylactic measure, especially in patients with early‐stage metabolic syndrome.     

Mitochondria,oxidative stress and aging

In the eighties, Miquel and Fleming suggested that mitochondria play a key role in cellular aging. Mitochondria, and specially mitochondrial DNA (mtDNA), are major targets of free radical attack. At present, it is well established that mitochondrial deficits accumulate upon aging due to oxidative damage. Thus, oxidative lesions to mtDNA accumulate with age in human and rodent tissues. Furthermore, levels of oxidative damage to mtDNA are several times higher than those of nuclear DNA. Mitochondrial size increases whereas mitochondrial membrane potential decreases with age in brain and liver.

Recently, we have shown that treatment with certain antioxidants, such as sulphur-containing antioxidants, vitamins C and E or the Ginkgo biloba extract EGb 761, protects against the age-associated oxidative damage to mtDNA and oxidation of mitochondrial glutathione. Moreover, the extract EGb 761 also prevents changes in mitochondrial morphology and function associated with aging of the brain and liver. Thus, mitochondrial aging may be prevented by antioxidants. Furthermore, late onset administration of certain antioxidants is also able to prevent the impairment in physiological performance, particularly motor co-ordination, that occurs upon aging.     

High Levels of Cadmium and Lead in Seminal Fluid and Blood of Smoking Men are Associated with High Oxidative Stress and Damage in Infertile Subjects

We measured the levels of malondialdehyde (MDA), protein carbonyls, glutathione S-transferase (GST) and reducte glutathione (GSH) in seminal plasma and spermatozoa from 95 subjects including 50 infertile patients to evaluate the association between oxidative stress and damage and the components of the anti-oxidant defenses in seminal plasma and spermatozoa of infertile subjects and concentrations of cadmium (Cd) and lead (Pb) in the blood and seminal plasma because of tobacco smoke exposure. The reactive oxygen species (ROS) in spermatozoa were also evaluated by luminol (5-amino-2,3-dihydro-1,4-phthalazinedione)-enhanced chemiluminescence assay. The sperm count, motility, and morphology in the smokers infertile group were found to be lower than those in the fertile male group and nonsmokers infertile group (p < 0.001). Concentrations of Cd, Pb, MDA, protein carbonyls, and ROS levels in the smokers infertile group were significantly higher than those in the fertile male and nonsmokers infertile male groups (p < 0.001). However, GSH levels and GST activities were decreased in the smokers infertile male group than those in the fertile male and nonsmokers infertile male groups (p < 0.001). The results indicate that smoking could affect semen quality and oxidative lipid and protein damage in human spermatozoa. From Pearson correlation analysis, positive correlations were demonstrated between the seminal plasma Cd and seminal plasma protein carbonyls and between seminal plasma Pb and spermatozoa ROS levels in smokers of the subfertile group, while there was a significant positive correlation between blood Cd and ROS levels in smokers of the fertile group. There was also a significant negative correlation of the Cd level of the blood and GSH levels of the sperm and seminal plasma. These findings suggest that cigarette smoking enhances the levels of Cd and Pb in seminal plasma and blood and the extent of oxidative damage associated with a decrease in components of the anti-oxidant defenses in the sperm of infertile males.     

Comparative analysis of telomeric restriction fragment lengths in different tissues of <Emphasis Type="Italic">Ginkgo biloba</Emphasis> trees of different age

Ginkgo trees of four different ages were selected as experimental material. Telomeric restriction fragment (TRF) lengths, as an indicator of telomere length, were determined for different tissues by Southern hybridization analysis. Statistical analysis was performed to compare two aspects of TRF length. By determining TRF lengths for different tissues for each age, a latent tendency was found. TRF length varied from short to long in these tissues in the order microspore < embryonal callus < leaf < branchlet. TRF lengths for leaf tissue and branchlet tissue were dissimilar for female and male mature trees, although this difference between TRF lengths for the two sexes was not statistically significant. Evaluation of TRF lengths for each tissue for trees of all four ages revealed TRF lengths increased with age to some extent. Different rates of change were found for leaf tissue and for branchlet tissue, although tendencies to increase were not linear for either. Finally, a simple mathematical model was formulated to describe the relationship between telomere length and age for Ginkgo biloba L.     

<Emphasis Type="Italic">Ginkgo biloba</Emphasis> extract (EGb761) and FK506 preserve energy metabolites in the striatum during focal cerebral ischemia and reperfusion in gerbils monitored by microdialysis

Cell death after cerebral ischemia is mediated by the accumulation of excitatory amino acids, calcium influx into cells and the generation of free radicals. The aim of this study was to evaluate changes in energy-related metabolites in the striatum of gerbils subjected to focal cerebral ischemia after pretreatment withGinkgo biloba extract (EGb761), a well-known antioxidant, and FK506, a calcium-dependent phosphatase calcineurin inhibitor. Ischemia was induced by occlusion of the right common carotid artery and the right middle cerebral artery for 60 min. A microdialysis probe was inserted into the right striatum to monitor extracellular glucose, lactate and pyruvate levels. This study showed decreases in glucose (10% of the baseline), pyruvate (20% of the baseline) and lactate (60% of the baseline), and a 5-fold increase in the lactate to pyruvate ratio during ischemia in the control group. Both EGb761 treatment and the combination (EGb761 and FK506) therapy significantly preserved glucose (50% of the baseline) and pyruvate (60% of the baseline) levels during ischemia. The marked increase in the lactate to pyruvate ratio was not observed in the combination group. These results suggest that preservation of cellular energy metabolism during cerebral ischemia and after restoration with reperfusion may contribute to the neuroprotective effects of EGb761 and FK506.     

Buffalo (<Emphasis Type="Italic">Bubalus bubalis</Emphasis>) Epiphyseal Proteins Counteract Arsenic-Induced Oxidative Stress in Brain,Heart, and Liver of Female Rats

Arsenic (As) toxicity through induction of oxidative stress is a well-known mechanism of organ toxicity. To address this problem, buffalo epiphyseal proteins (BEP, at 100 μg/kg BW, i.p. for 28 days) were administered intraperitoneally to female Wistar rats exposed to As (100 ppm sodium arsenite via drinking water for 28 days). Arsenic exposure resulted in marked elevation in lipid peroxidation in brain, cardiac, and hepatic tissues, whereas significant (p < 0.05) adverse change in catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, and reduced glutathione level were observed in cardiac, hepatic, and brain tissues of As-administered animals. BEP significantly (p < 0.05) counteracted all the adverse changes in antioxidant defense system brought about by As administration. Based on these results, we consider BEP as a potent antioxidant to be used for protection from arsenic-induced oxidative stress related damage of vital organs.     

Copper Intoxication; Antioxidant Defenses and Oxidative Damage in Rat Brain

Copper (Cu) is an integral part of many important enzymes involved in a number of vital biological processes. Even though Cu is essential to life, it can become toxic to cells, at elevated tissue concentrations. Oxidative damage due to Cu has been reported in recent studies in various tissues. In this study, we aimed to determine the effect of excess Cu on oxidative and anti-oxidative substances in brain tissue in a rat model. Sixteen male Wistar albino rats were divided into two groups: the control group, which was given normal tap water, and the experimental group, which received water containing Cu in a dose of 1 g/l. All rats were sacrificed at the end of 4 wk, under ether anesthesia. Cu concentration in the liver and in plasma alanine aminotransferase (ALT) and aspartate transaminase (AST) activities were determined. There were multiparameter changes with significant ALT and AST activity elevation and increased liver Cu concentration. In brain tissue, Cu concentration, superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels and glutathione (GSH) concentrations were determined. Brain Cu concentration was significantly higher in rats receiving excess Cu, compared with control rats (p < 0.05). Our results showed that SOD activities and GSH levels in brain tissue of the Cu-intoxicated animals were significantly lower than in the control group (p < 0.01 and p < 0,001, respectively). The brain MDA levels were found to be significantly higher in the experimental group than in the control group (p < 0.001). The present results indicate that excessive Cu accumulation in the brain depressed SOD activities and GSH levels and resulted in high MDA levels in brain homogenate due to the lipid peroxidation induced by the Cu overload.     

Change of season-specific telomere lengths in <Emphasis Type="Italic">Ginkgo biloba</Emphasis> L.

Telomeres have lately received considerable attention in the development of tree species. Normal somatic cells have limited replicative capacity and telomeres get shorten with each round of DNA replication. For broad-leaved tree species, to determine what changes happen to their somatic cells in its annual development cycle, an exhaustive research on different ages of gingko trees telomere length changes was carried out. Analysis of changes in leaf telomere lengths in the annual development cycle of Ginkgo biloba L. showed no significant changes (P > 0.05) from April to August, but a dramatic decrease in September and October (P < 0.05). Statistical analyses showed that TRF length of males and females are equal, the p values of the three age groups comparison were all bigger than 0.05. The results showed that specific apoptotic changes occur in the annual development cycle of Ginkgo biloba L.     

General microflora,arbuscular mycorrhizal colonization and occurrence of endophytes in the rhizosphere of two age groups of <Emphasis Type="Italic">Ginkgo biloba</Emphasis> L.of Indian Central Himalaya

The populations of the general microflora (bacteria, actinomycetes and fungi) in the rhizosphere and their corresponding non-rhizosphere soil samples of Ginkgo biloba L. of two age groups (Group A, <25 years-young trees; Group B, >60 years-old trees) growing under a temperate location of Indian Himalayan Region (IHR) have been determined. Observations were also made for the diversity, distribution and colonization of arbuscular mycorrhizal (AM) fungi and occurrence of endophytes in roots of G. biloba. The population of general microflora was found to be higher in the rhizosphere of Group B trees, more clearly reflected in terms of rhizosphere: soil (R:S) ratios. Contrary to this, per cent colonization and spore densities of AM fungi were higher in the rhizosphere of Group A trees as compared to the rhizosphere of Group B. AM fungal colonization was observed mostly in form of loose coils. All the spores detected, belonged to the genus Glomus with five different types. Presence of endophytes (both bacteria and fungi) was observed in the cortical cells of G. biloba roots, more profound in case of Group B trees. Data suggest that, while the species of Glomus dominated the rhizosphere of G. biloba, an inverse correlation exist between the colonization of general microflora and the colonization of AM fungi including endophytes.     

Specific memory effects of Ginkgo biloba extract EGb 761 in middle-aged healthy volunteers

Introduction

Recent reviews showed that Ginkgo biloba extract EGb 761¹ is effective to enhance performance in patients with cognitive impairment (e.g., dementia). The aim of this study was to investigate the effects of EGb 761 on memory and the specificity of such effects on distinct memory functions in middle-aged healthy volunteers.

Methods

A total of 188 healthy subjects aged 45-56 years were randomised to receive EGb 761 (240 mg once daily) or placebo for 6 weeks. Outcome measures were the change in memory performance in a demanding standardised free recall paradigm (list of appointments) and a less demanding standardised recognition test (driving-route). Based on previous findings we predicted superiority of EGb 761 in recall testing. Specificity in effects was assessed by separating immediate vs. delayed and quantitative vs. qualitative free recall measures.

Results

After 6 weeks, EGb 761-treated subjects improved significantly in quantity of recall, i.e., the number of correctly recalled appointments (drug-placebo differences: p = 0.038 for immediate and p = 0.008 for delayed recall). Effects on qualitative recall performance (ratio of false to correct items) were similar (drug-placebo differences: p = 0.092 for immediate and p = 0.010 for delayed recall). No superiority of Ginkgo was evident in another everyday memory test which asked for recognition of a driving route (drug-placebo differences: p > 0.10). The incidence of adverse events was low and not significantly different between treatment groups.

Discussion

EGb 761 (240 mg once daily) improves free recall of appointments in middle-aged healthy volunteers, which requires high demands on self-initiated retrieval of learned material. This function is known to be sensitive to normal aging, i.e., reduced in healthy middle-aged subjects. No effects are seen in a less demanding everyday memory task which does not tap this critical function. This ties in with previous studies which found specific patterns of benefit from EGb 761 in demanding cognitive tasks.     

Reproductive and developmental toxicity of the Ginkgo biloba special extract EGb 761® in mice

Extracts from leaves of Ginkgo biloba are among the most widely used and best investigated phytopharmaceuticals worldwide. Almost all clinical trials and the majority of preclinical studies have been performed with a specifically defined extract (EGb 761^®) standardized to contain confined concentrations of active ingredients and limited quantities of potentially harmful substances. Besides pharmaceutical grade extracts poorly characterized Ginkgo preparations are now increasingly appearing on the market as nutraceuticals. While the safety of EGb 761^® has been evaluated in an extensive set of toxicology studies, adverse effects of Ginkgo extracts of non-pharmaceutical quality on reproductive functions in mice have been reported in several publications in recent years. As this species has not previously been used in reproductive toxicity studies with EGb 761^®, the present investigation was conducted to examine the influence of EGb 761^® (100, 350 and 1225 mg/kg/day) on embryo-fetal development in mice during the critical period of organogenesis. During external and internal inspection of the fetuses as well as examination of skeletal and soft tissues no embryotoxic properties were noted. In particular, the incidence of malformations, variations or retardations was not increased and the general condition of dams was not influenced. Thus, the no-observed-effect level (NOEL) was above 1225 mg/kg/day for the dams and the fetuses.     

Molecular cloning, characterization and expression of atpA and atpB genes from Ginkgo biloba

The chloroplast ATP synthase (ATPase) utilizes the energy of a transmembrane electrochemical proton gradient to drive the synthesis of ATP from ADP and phosphate. The chloroplast ATPase α and β subunits are the essential components of multisubunit protein complex. In this paper, the full-length cDNA and genomic DNA of ATPase α (designated as GbatpA) and β (designated as GbatpB) subunit genes were isolated from Ginkgo biloba. The GbatpA and GbatpB genes were both intronless. The coding regions of GbatpA and GbatpB were 1530 bp and 1497 bp long, respectively, and their deduced amino acid sequences showed high degrees of identity to those of other plant ATPase α and β proteins, respectively. The expression analysis by RT-PCR revealed that GbatpA and GbatpB both expressed in tissue-specific manners in G. biloba and might involve in leaf development. The recombinant GbATPB protein was successfully expressed in E. coli strain using pET28a vector with ATPase activity as three times high as the control, and the results showed that the molecular weight of the recombinant protein was about 54 kDa, a size that was in agreement with that predicted by bioinformatics analysis. This study provides useful information for further studying on overall structure, function and regulation of the chloroplast ATPase in G. biloba, the so-called “living fossil” plant as one of the oldest gymnosperm species. These authors contributed equally to this work     

Antidepressant-like effect of a Ginkgo biloba extract (EGb761) in the mouse forced swimming test: role of oxidative stress

EGb761 is a well-defined mixture of active compounds extracted from Ginkgo biloba leaves. This extract is used clinically due to its neuroprotective effects, exerted probably via its potent antioxidant or free radical scavenger action. Previous studies suggest that oxidative stress, via free radical production, may play an important role in depression and animal models for depression-like behavior. Preclinical studies have suggested that antioxidants may have antidepressants properties. The aim of this study was to investigate the antidepressant-like of EGb761 due to its antioxidant role against oxidative stress induced in the forced swimming test, the most widely used preclinical model for assessing antidepressant-like behavior. Male BALB/c mice were pretreated with EGb761 (10 mg/kg, ip) daily for 17 days followed by the forced swimming test and spontaneous locomotor activity. Animals were sacrificed to evaluate lipid peroxidation, different antioxidant enzyme activities, serotonin and dopamine content in midbrain, hippocampus and prefrontal cortex. EGb761 significantly decreased the immobility time (39%) in the forced swimming test. This antidepressant-like effect of EGb761 was associated with a reduction in lipid peroxidation and superoxide radical production (indicated by a downregulation of Mn-superoxide dismutase activity), both of which are indicators of oxidative stress. The protective effect of EGb761 is not related to excitatory or inhibitory effects in locomotor activity, and was also associated with the modulation of serotonergic and dopaminergic neurotransmission. It is suggested that EGb761 produces an antidepressant-like effect, and that an antioxidant effect against oxidative stress may be partly responsible for its observed neuroprotective effects.     

Influence of chromium-enriched yeast on blood glucose and insulin variables, blood lipids, and markers of oxidative stress in subjects with type 2 diabetes mellitus

The aim of this study was to determine the effect of chromium (Cr)-enriched yeast on blood glucose and insulin variables, blood lipids, and blood markers of oxidative stress in persons with type 2 diabetes mellitus (median duration: 3.0 yr). Thirty-six subjects (9 men, 27 women; mean age: 61.3 yr; mean body mass index: 34.33 kg/m²) were supplemented with 400 μg Cr/d as Cr-enriched yeast (n=19) or placebo (n=17) for 12 wk in a randomized, double-blind study. The most interesting results were obtained by comparison of the change in the placebo group to the change in the Cr group. The Cr group showed a significantly greater increase in serum Cr compared to the placebo group (p<0.05). Supplementation with Cr-enriched yeast was associated with a significant decrease in fasting serum glucose compared to placebo (p<0.01). Blood markers of oxidative stress glutathione peroxidase activity and levels of reduced glutathione were essentially unchanged in the Cr group after 12 wk, but decreased significantly in the placebo group (p<0.05, p<0.01, respectively), Serum HbA_1c and glycated protein (fructosamine) were essentially unchanged in the Cr group, whereas HbA_1c tended to increase in the placebo group (from 6.94% to 7.11%). Fasting serum insulin decreased in both groups, with a greater tendency in the Cr group (−16.5% vs −9.5%). These data suggest that supplementation of well-controlled type 2 diabetics with Cr-enriched yeast is safe and can result in improvements in blood glucose variables and oxidative stress.     

The Analog of Ginkgo biloba Extract 761 is a Protective Factor of Cognitive Impairment Induced by Chronic Fluorosis

Ginkgo biloba extract EGb761 is widely used to treat patients with learning and memory impairment in Alzheimer’s disease and Parkinson’s disease in China. However, it is not yet clear whether the analog of EGb761 (EGb) has a protective effect on the learning and memory damage induced by chronic fluorosis. In this study, 30 Wistar rats were randomly divided into three groups: a control group, a sodium fluoride (NaF) + EGb group, and a NaF group. The rats were administered 0.5 ml water containing NaF (100 mg/l) and EGb (120 mg/kg) per day via gavage. After 3 months, the rats’ capacity for learning and memory was tested using a Y-maze. Damage to hippocampal neurons was evaluated by histological examination of the CA3 area. Superoxide dismutase (SOD) activity and the levels of glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured. Furthermore, the expression levels of Bcl-2 and Bax and the levels of cleaved Caspase3 in the hippocampus were evaluated by RT-PCR and Western blotting. The results showed that EGb could improve learning and memory abilities, enhance the activities of SOD and GSH-Px, attenuate the level of MDA, upregulate the ratio of Bcl-2/Bax, and downregulate the level of cleaved Caspase3.     

The effect of Ginkgo biloba extract on 3-nitropropionic acid-induced neurotoxicity in rats

3-Nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase enzyme (SDH), induces neurodegeneration similar to that observed in Huntington’s disease (HD). Reduction of prepulse inhibition (PPI) of acoustic startle response, locomotor hypoactivity, bilateral striatal lesions as well as brain oxidative stress are major features of HD. The present study was designed to investigate neuroprotective effect of Ginkgo biloba extract (EGb 761) on 3-NP induced neurobehavioral changes and striatal lesions.Rats administered 3-NP (20 mg/kg, s.c.) for five consecutive days exhibited PPI deficits and locomotor hypoactivity whereas, pretreatment of animals with EGb 761 (100 mg/kg, i.p. for 15 days) ahead of and during the induction of HD by 3-NP (20 mg/kg for 5 days starting at day 8) ameliorated 3-NP-induced neurobehavioral deficits. Administration of 3-NP increased the level of striatal malondialdehyde (MDA). This effect was prevented in animals pre-treated with EGb 761. Changes in the level of apoptotic regulatory gene expressions, following 3-NP treatment, were demonstrated as both an up-regulation and a down-regulation of the expression levels of striatal Bax and Bcl-xl genes, respectively. In addition, an up-regulation of the expression level of striatal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was also observed. Pre-treatment with EGb 761 caused a down-regulation in striatal GAPDH and Bax together with an up-regulation of striatal Bcl-xl expression level as compared to the 3-NP treated group. Histochemical examination of striatal tissue showed that EGb 761 significantly prevented 3-NP induced inhibition of SDH activity. Histopathological examination further affirmed the neuroprotective effect of EGb 761 against 3-NP toxicity.Taken together, these results suggest that EGb 761 has a neuroprotective role in the current HD paradigm, which may be related to improvement of energy metabolism, antioxidant properties and antiapoptotic effects.     

The Protective and Antidotal Effects of Taurine on Hexavalent Chromium-Induced Oxidative Stress in Mice Liver Tissue

Acute exposure to hexavalent chromium [Cr(VI)] compounds can cause hepatotoxicity. Reactive intermediates and free radicals generated during reduction process may be responsible for Cr(VI) toxicity. In this study, the effects of pretreatment or posttreatment of taurine on Cr(VI)-induced oxidative stress and chromium accumulation in liver tissue of Swiss Albino mice were investigated. Single intraperitoneal (ip) potassium dichromate treatment (20 mgCr/kg), as Cr(VI) compound, significantly elevated the level of lipid peroxidation as compared with control group (p < 0.05). This was accompanied by significant decreases in nonprotein sulfhydryls (NPSHs) level, superoxide dismutase (SOD), and catalase (CAT) enzyme activities as well as a significant chromium accumulation in the tissue (p < 0.05). Taurine administration (1 g/kg, ip) before or after Cr(VI) exposure resulted in reduction of lipid peroxidation (p < 0.05) showed rebalancing effect on tissue NPSH levels either in pretreatment or in posttreatment (p < 0.05). Enzyme activities of SOD and CAT were restored by taurine pretreatment (p < 0.05), whereas posttreatment had less pronounced effects on these parameters. On the other hand, taurine treatment, before or after exposure, could exert only slight decreases in tissue Cr levels (p > 0.05). In view of the results, taurine seems to exert some beneficial effects against Cr(VI)-induced oxidative stress in liver tissue.