Ethanolic Extract of Xylopia aethiopica Attenuated Aluminum-Induced Ovarian Toxicity in Adult Female Wistar Rats.

OBJECTIVE: Aluminum is a widely used metal in homes and industries. Xylopia aethiopica is an important medicinal plant with antioxidant properties. The objective of this study is to investigate the ameliorative potential of Xylopia aethiopica on aluminum-induced ovarian toxicity in Wistar rat. METHODS: Twenty-five rats were randomized into five groups with five rats per group. Group 1 received only distilled water; Group 2: received 150mg/kg of aluminum chloride; Group 3: received 150mg/kg aluminum chloride with 100/kg Xylopia aethiopica seed extracts; Group 4: received 150mg/kg aluminum chloride with 50 mg/kg Xylopia aethiopica seed extracts, and Group 5: received 150mg/kg aluminum chloride with 50mg/Kg zinc sulphate. For twenty-one days, all administrations were done orally. The rats were then sacrificed following chloroform anesthesia. The ovaries were harvested for histological examination. RESULTS: The data were analyzed on IBM SPSS software version 21 and the differences in mean values were considered significant at p<0.05. Xylopia aethiopica extracts significantly (p<0.05) reversed the detrimental effects of aluminum chloride on luteinizing hormone, follicle stimulating hormone, progesterone and estradiol. The histological analysis of the ovaries showed a significant improvement in rats treated with Xylopia aethiopica extract and zinc sulphate. However, Xylopia aethiopica was more effective in a dose-dependent manner. CONCLUSIONS: This study suggests that Xylopia aethiopica has ameliorative potential on aluminum-induced toxicity in the ovaries of adult female Wistar Rats.

Asiatic acid attenuates aluminium chloride-induced behavioral changes, neuronal loss and astrocyte activation in rats.

Aluminium (Al) is a potent neurotoxic metal known to cause neurodegeneration. Al exposure causes oxidative stress by accumulation of reactive oxygen species, followed by the activation of neuronal cell death in the brain. Asiatic acid (AA), the major bioactive compound of Centella asiatica (a medicinal plant), act as multifunctional drug as well as an antioxidant. Thus, the present study aimed to investigate the potential neuroprotective effect of AA against Al neurotoxicity. Rats were orally administered aluminium chloride (AlCl3; 100 mg/kg b. wt.) dissolved in distilled water for 8 weeks or AA (75 mg/kg b. wt.) in combination with AlCl3. The results showed that AlCl3-intoxication causes significant impairment of memory, enhances anxiety-like behavior, acetyl cholinesterase (AChE) activity, malondialdehydes (MDA) level, and concomitant decrease in the activities of superoxide dismutase (SOD) and catalase (CAT) in the cortex and hippocampus regions of rat brain. In addition, AlCl3-intoxication enhanced neuronal loss and reactive astrogliosis in both regions. However, co-administration of AA with AlCl3 significantly attenuated the behavioral alterations, restored SOD and CAT activities, while reduced AChE activity and MDA content. Further, the study demonstrated that AA attenuates neuronal loss and reactive astrogliosis in rat brain. In conclusion, the study suggests that AA protects rat brain from Al neurotoxicity by inhibiting oxidative stress, neuronal loss and reactive astrogliosis.

Differential neuroprotective effect of curcuminoid formulations in aluminum chloride-induced Alzheimer's disease.

Alzheimer's disease (AD) is a slowly progressive brain degenerative disorder which gradually impairs memory, thinking, and ability to perform easy routine tasks. This degenerative disorder mainly targets the elderly people and has imposed an endemic burden on society. Hence, there is a crucial need to investigate the efficacious herbal pharmacotherapies that can effectively mitigate and prevent the pathological hallmarks of AD. The current study aims to explore the potential efficacy of curcuminoid-rich extract (CRE) and its ternary complex (TC). Experimental rodents were administered with AlCl3 (300 mg/kg) to induce AD and treated with rivastigmine, curcuminoid crude extract, CRE, and TC orally for three consecutive weeks. Neurobehavioral, biochemical, and histopathological studies were performed from the last week of the study period. The mRNA expression of different pathological biomarkers was estimated by RT-qPCR analysis. The results of the study suggested that CRE and TC significantly improved the behavioral, biochemical parameters and acetylcholinesterase inhibitory activity in treatment groups. Histological analysis was also carried out indicating that the neurodegenerative changes and neuronal loss were stabilized by CRE and TC supplementation. CRE and TC supplementation remarkably downregulated the interleukin-1α, tumor necrosis factor-α, interleukin-1ß, acetylcholinesterase, and ß-secretase pathological gene expression. Hence, it was concluded that CRE and TC may act as promising candidates in the prevention of AD via numerous underlying signaling pathways.

Melatonin and zinc supplements with physical and mental activities subside neurodegeneration and hepatorenal injury induced by aluminum chloride in rats: Inclusion of GSK-3ß-Wnt/ß-catenin signaling pathway.

Alzheimer's disease (AD) is an irreversible, progressive cognitive dysfunction. Inflammaging is the greatest common factor between AD and hepatorenal malfunction. This study aimed to use melatonin (MEL) and zinc sulfate (Zn) in addition to physical and mental activities (PMA) to ameliorate AlCl3-induced AD as well as investigate their impact on the associated hepatorenal impairment. METHODS: Seven groups of rats each received: saline (control group), AlCl3 (70 mg/kg, i.p.), PMA, either alone or with a combination of Mel (10 mg/kg, p.o) and/or Zn (16 mg/kg, p.o). Neurological deterioration was assessed after 5 weeks using behavioral tests, histopathological examination, and measurements of acetylcholinesterase (ACHE), brain monoamines, oxidative stress, and inflammatory markers, Amyloid precursor protein (APP), amyloid-ß (Aß), tau levels, and brain derived neurotrophic factor (BDNF). Moreover, the GSK-3ß-Wnt/ß-catenin signaling pathway was assessed. Additionally, oxidative stress and inflammatory markers were determined in liver and kidney tissues with concurrent evaluation of hepatic and renal functions. RESULTS: The histopathological examination revealed a cerebral cortex and hippocampus deterioration in the AD group with a decline in spatial learning and memory, besides a significant increase in AD markers in the brain and disturbance in GSK-3ß-Wnt/ß-catenin signaling. The AD group showed hepatorenal injuries supported by elevated oxidative stress and inflammatory markers. However, adding Mel and Zn to PMA significantly attenuated the neurodegeneration and enhanced hepatic and renal functions by ameliorating oxidant and inflammatory markers. CONCLUSIONS: Combining Mel and Zn supplements with PMA defends against AlCl3-induced AD by modulating GSK-3ß-Wnt/ß-catenin signaling and palliates the associated hepatorenal dysfunction.

Nutritional supplementation of gallic acid ameliorates Alzheimer-type hippocampal neurodegeneration and cognitive impairment induced by aluminum chloride exposure in adult Wistar rats.

Prolonged exposure to aluminum through occupational hazards or food/water intake has been linked to the occurrence of Alzheimer's disease (AD). This study aimed at investigating the neuroprotective effects of Gallic Acid (GA) against aluminum-chloride induced AD in adult Wistar rats. Twenty eight (28) adult Wistar rats were divided into four groups (n = 7). Group A received normal saline as placebo; Group B received 200 mg/kg bw of AlCl3 only; Group C received 100 mg/kg bw of GA only and group D received 100 mg/kg bw of GA and 200 mg/kg bw of AlCl3. At the end of the 60 days experiment, blood samples were collected to obtain serum for analysis and the brain was harvested. Neurobehavioural tests (Morris Water maze, Y-Maze), neurotransmitter levels, oxidative stress markers, serum electrolytes, antioxidant enzymes and histological assessment were carried out. There was a significant decrease in antioxidant enzymes (CAT, GSH and SOD), serum electrolyte (except K+) and neurotransmitter levels (except norepinephrine) with corresponding increase in stress markers (MDA, H2O2 and NO) among group B compared to control but was restored nearly to normal after GA administration. Neurobehavioral tests showed decreased spatial memory impairment and learning deficit in group B compared to control but was ameliorated with GA administration. Histological observation showed neurofibrillary tangles and amyloid plaques in the external granular layer of group B but protected by GA administration. Nutritional supplementation of GA preserve the morphological and physiological integrity of the hippocampus against environmental neurotoxins (AlCl3) by mopping up free radicals associated with oxidative stress induced AD.

Genotoxic impact of aluminum-containing nanomaterials in human intestinal and hepatic cells.

Exposure of consumers to aluminum-containing nanomaterials (Al NMs) is an area of concern for public health agencies. As the available data on the genotoxicity of Al2O3 and Al0 NMs are inconclusive or rare, the present study investigated their in vitro genotoxic potential in intestinal and liver cell models, and compared with the ionic form AlCl3. Intestinal Caco-2 and hepatic HepaRG cells were exposed to Al0 and Al2O3 NMs (0.03 to 80 µg/cm2). Cytotoxicity, oxidative stress and apoptosis were measured using High Content Analysis. Genotoxicity was investigated through γH2AX labelling, the alkaline comet and micronucleus assays. Moreover, oxidative DNA damage and carcinogenic properties were assessed using the Fpg-modified comet assay and the cell transforming assay in Bhas 42 cells respectively. The three forms of Al did not induce chromosomal damage. However, although no production of oxidative stress was detected, Al2O3 NMs induced oxidative DNA damage in Caco-2 cells but not likely related to ion release in the cell media. Considerable DNA damage was observed with Al0 NMs in both cell lines in the comet assay, likely due to interference with these NMs. No genotoxic effects were observed with AlCl3. None of the Al compounds induced cytotoxicity, apoptosis, γH2AX or cell transformation.

Pomegranate juice moderates anxiety- and depression-like behaviors in AlCl3-treated male mice.

PURPOSE: Aluminum trichloride (AlCl3) exposure was proven to encourage some behavioral deficits and eventually induces anxiety and depression in rodents animals. Therefore, this experiment aimed to scout about the effects of pomegranate juice on anxiety- and depression-like behaviors caused by AlCl3 in male mice. METHODS: Six groups of male mice were administrated orally for 35 days by PJ and AlCl3. The control group (G-I) received tap water, while the PJ groups (G-II and G-III) were treated with 20 % and 40 % PJ, respectively. The AlCl3 group (G-IV) was treated with 400 mg/kg/day of AlCl3, and the last two groups (G-V and G-VI) were treated with AlCl3 and 20 % PJ or 40 % PJ, respectively. Then, the open-field (O-F), elevated plus maze (EPM), tail suspension (TS), forced swimming (FS), and light/dark box (L/DB) tests were applied for anxiety- and depression-like behavior studies. In addition, neurotransmitters and oxidative parameters in the brain were evaluated. The plasma cortisol was measured at the end of the experiment. RESULTS: Behavioral analyses showed that PJ inhibited AlCl3-induced depressive and anxiogenic effects in the O-F, EPM, TS, FS, L/DB tests. In addition, neurochemical results indicated that PJ at 20 % concentration minimized the AlCl3 toxicity on dopamine (DOP), serotonin (SER), and acetylcholinesterase (AChE) levels in the for-brain of male mice. Moreover, PJ moderated the AlCl3 effects by decreasing the level of thiobarbituric acid reactive substances (TBARS), and enhancing catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST) and glutathione (GSH) activities. The plasma cortisol increased in male mice treated with AlCl3 and in a group treated with a high dose of PJ. CONCLUSION: Our results proposed that the anxiety- and depression-like behaviors induced by AlCl3 exposure in male mice can be ameliorated by PJ treatment, probably through the inhibition of oxidative damage and minimizing the changes in neurotransmitters and hormonal activity.

Combination of docosahexaenoic acid and Ginko biloba extract improves cognitive function and hippocampal tissue damages in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by a progressive loss of memory and other cognitive functions among elder people. Nowadays, natural antioxidants have been used to recover the quality of life for those with AD. In this study, we investigated, for the first time, the combined effect of docosahexaenoic acid (DHA) and Ginkgo bilobastandardized extract (EGb761) on AD mice. AD was induced in adult male albino mice with AlCl3 (20 mg/kg b.w, i.g.) and D-galactose (D-gal; 120 mg/kg, i.p.) for 90 days. 30 days after induction, mice were treated with DHA (200 mg/kg b.w., i.g.) and EGb761 (200 mg/kg b.w., i.g.) for two months. Our data revealed that the dual treatment of DHA and EGb761 significantly improved cognitive memory and spatial learning abilities in AD-induced mice. The drug treatments preserved the hippocampal CA3 architecture and restored neuronal ultrastructural alterations. Expression of protein phosphatase 2A (PP2A), the most implicated protein phosphatase in AD neurodegeneration, was highly upregulated in the CA3 hippocampus of AD mice treated with DHA and EGb761. Intriguingly, TNF-α expression was significantly reduced in the same group. In conclusion, our findings proved that the combined effect of DHA and EGb761 tended to be potent against the neurodegenerative effect of AlCl3 and D-gal. The applied treatment enhanced neuronal survival and cognitive functions via upregulation of PP2A and restoration of TNF-α expression.

Aluminum chloride-induced amyloid ß accumulation and endoplasmic reticulum stress in rat brain are averted by melatonin.

Accumulation of aluminium (Al) in the brain is known to be a toxic insult that result in neurodegenerative diseases and melatonin is known to have neuroprotective role. The present study was designed to investigate the neuroprotective effects of melatonin for aluminium chloride (AlCl3)-induced neurotoxicity in rats. Twelve-week old male Wistar rats were orally received 175 mg/kg AlCl3 with or without 5 mg/kg melatonin intraperitoneal pretreatment. Group 3 intraperitoneally recieved 5 mg/kg melatonin and group 4 rats were orally treated with saline solution for 8 weeks. A series of behavioral tests, biochemical analysis and expression of AD-associated proteins in the brain were determined after 7 weeks of all treatments. Our results indicated that AlCl3 treatment tends to induce memory and cognitive impairment. However, melatonin treatment attenuated amyloid beta (Aß) (1-42) level by decreasing ß-secretase, augmented low-density lipoprotein receptor-related protein 1, and neprilysin protein expression. Moreover, AlCl3 -induced endoplasmic reticulum (ER) stress and oxidative stress was attenuated by melatonin supplementation. In conclusion, these findings demonstrate a protective role of melatonin against Aß peptide accumulation, ER stress and oxidative stress in the AlCl3 -treated AD model. Hence, the melatonin supplement might be an alternative way to alleviate the development of AD.

Nephroprotective role of bromelain against oxidative injury induced by aluminium in rats.

The present study was designed to investigate the nephroprotective effect of bromelain against oxidative stress stimulated by aluminium chloride in rats. Rats were grouped as follows; group one was used as control while groups 2, 3 and 4 were treated orally with bromelain (250 mg/kg, daily), aluminium chloride (AlCl3; 34 mg/kg BW, every other day) and bromelain plus AlCl3 for 30 days, respectively. Administration of AlCl3 caused a significant reduction in rats' body and kidney weights, and increased Al accumulation in kidney tissue. Also, AlCl3 treatment elevated thiobarbituric acid reactive substances, hydrogen peroxide, kidney functions biomarkers levels and lactate dehydrogenase activity. While enzymatic (SOD, CAT, GPx, GR, GST) and non-enzymatic (GSH) antioxidants, protein content, and alkaline phosphatase activity were significantly decreased. In addition, significant alterations in lipid and protein profiles were detected. Furthermore, histopathological and immunohistochemical variations were seen in kidney sections supporting the obtained biochemical changes. Otherwise, rats supplemented with bromelain singly declined lipid peroxidation and improved most of the studied parameters. Moreover, rats pretreated with bromelain followed by AlCl3 intoxication showed significant alleviation in lipid peroxidation, antioxidant status and biochemical indices with respect to AlCl3 treated group. Conclusively, bromelain has beneficial protective effects and has the capability to counteract the toxic influence of AlCl3. So, bromelain might represent a novel approach in the therapy of metal toxicity because of its antioxidant and chelating properties.

Methylphenidate and Rosmarinus officinalis improves cognition and regulates inflammation and synaptic gene expression in AlCl3-induced neurotoxicity mouse model.

Methylphenidate (MPH), a psychotropic medication is commonly used for children with attention deficit hyperactivity disorder (ADHD). In this study we elucidated the neuroprotective and anti-inflammatory effects of MPH and Rosmarinus officinalis (rosemary) extract, an ancient aromatic herb with several applications in traditional medicine. Briefly, six groups of mice (n = 8 each group), were specified for the study and behavioral analysis was performed to analyze spatial memory followed by histological assessment and gene expression analysis of synaptic (Syn I, II and III) and inflammatory markers (IL-6, TNFα and GFAP) via qRT-PCR, in an AlCl3-induced mouse model for neurotoxicity. The behavioral analysis demonstrated significant cognitive decline, memory defects and altered gene expression in AlCl3-treated group. Rosemary extract significantly decreased the expression of inflammatory and synaptic markers to the similar levels as that of MPH. The present findings suggested the neuroprotective potential of Rosmarinus officinalis extract. However, further characterization of its anti-inflammatory and neuroprotective properties and MPH is required to strategize future treatments for several neurological and neurodegenerative disorders, including Alzheimer's disease.

Bergamot essential oil attenuate aluminum-induced anxiety-like behavior through antioxidation, anti-inflammatory and GABA regulation in rats.

A large number of studies showed that aluminum (Al) has potential neurotoxicity to human and animal bodies. Al-treated animals showed anxiety-like behavior, oxidative stress, neuroinflammation and γ-aminobutyric acid (GABA) changes. Bergamot essential oil (BEO) is a kind of well-known plant extract from the fresh fruit of bergamot. Previous studies suggested that BEO improved mood and relieved symptoms of stress-induced anxiety. This study was designed to study the effects of BEO on anxiety-like behavior, oxidative stress, neuroinflammation and GABA system in aluminum trichloride (AlCl3) treated rats. Results showed that AlCl3 exposure induced anxiety-like behavior in the elevated plus maze and the open field test. Moreover, AlCl3 exposure decreased the level of GABA and the activity of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in the hippocampus (HP) and the frontal cortex (FC). In addition, AlCl3 exposure increased the levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the levels of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the HP and the FC. To the contrary, co-administration of BEO and AlCl3 improved the anxiety-like behavior, GABA system, oxidative stress and neuroinflammation. These results indicated that BEO can alleviate the anxiety-like behavior of AlCl3-exposed rats through the combined action of antioxidant, anti-inflammatory and GABA regulation.

Flavonoids ameliorate aluminum chloride-induced learning and memory impairments via suppression of apoptosis and oxidative stress in rats.

The study was to investigate the effects of flavonoids (rutin, puerarin, and silymarin) on learning and memory function in rats exposed to aluminum chloride (AlCl3). Wistar rats were administered flavonoids at a dose of 100 mg/(kg·bw)/day or 200 mg/(kg·bw)/day after exposed to 281.40 mg/(kg·bw)/day AlCl3·6H2O. The results of Morris water maze suggested that rutin and puerarin increased the frequency of crossing the platform and swimming time spent in the target quadrant of AlCl3-induced rats significantly. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay indicated that three flavonoids could alleviate apoptosis of hippocampal neurons induced by AlCl3. Real time-PCR and western blot suggested that rutin, puerarin and 100 mg/(kg·bw)/day silymarin could decrease the AlCl3-induced high expression of Bcl-2 associated X protein (Bax) mRNA and protein in hippocampus, but the expression of B cell lymphoma/leukemia-2 (Bcl-2) mRNA and protein was not significantly different among groups. Flavonoids could up regulate the low expression of autophagy related proteins (Beclin 1 (Bcl-2-interacting protein with a coiled-coil domain 1) and LC3 (microtubule-associated protein 1 light chain 3)) caused by AlCl3 exposure. Flavonoids could also adjust the change in adenosine triphosphatase, superoxide dismutase, glutathione peroxidase and malondialdehyde induced by intake of AlCl3. The results of inductively coupled plasma atomic emission spectroscopy (ICP-AES) suggested that flavonoids could effectively reduce the high Al level in brain and serum of AlCl3 exposed rats. In conclusion, three flavonoids may improve learning and memory function by inhibiting excessive apoptosis and oxidative stress in AlCl3 exposed rats.

Transcriptome alterations and genotoxic influences in zebrafish larvae after exposure to dissolved aluminum and aluminum oxide nanoparticles.

Manufactured nanoparticles (NPs) can potentially cause negative effects on molecular (proteins and nucleic acids), subcellular, cellular, tissue, organ, and organism due to their unusual physicochemical characteristics. Ionizable NPs in water (e.g., Al2O3-NPs) may create toxic effects on aquatic animals. The present research determined the influences of Al2O3-NPs and appropriate concentrations of ionizing Al(III) using water-soluble AlCl3 in zebrafish larvae (72 h post-fertilization, Danio rerio) by analyzing transcriptional alterations of stress-associated genes (rad51, p53, mt2) with quantitative real-time PCR (qRT-PCR). In addition, genotoxic effects of Al(III) and Al2O3-NPs were evaluated. The lethal concentrations that cause death of 50% (LC50) of zebrafish larvae when exposed to 0-50 mg/l Al(III) and 0-500 mg/l Al2O3-NPs were 3.26 ± 0.38 and 130.19 ± 5.59 mg/l, respectively, for 96 h. A concentration-dependent increase was observed in the genotoxicity in cells of larvae exposed to Al(III) and Al2O3-NPs for 96 h. DNA damage was more severe in larvae exposed to Al(III) (41.0% tail) than that of Al2O3-NPs (21.8% tail). A complex induction of stress-associated genes was observed in fish and this induction was not directly related to the concentrations of Al(III) and Al2O3-NPs, although a significant induction was detected in mt2 gene of larvae exposed to Al(III) and Al2O3-NPs relative to control group. The induction levels of mt2 were 4.13 ± 0.1 and 2.13 ± 0.1-fold change (mean ± S.E.M.) in larvae at 15 mg/l of Al(III) and 100 mg/l of Al2O3-NP concentrations, respectively.

Ginsenoside Rg1 ameliorates the cognitive deficits in D-galactose and AlCl3-induced aging mice by restoring FGF2-Akt and BDNF-TrkB signaling axis to inhibit apoptosis.

Ginsenoside Rg1 is the main active ingredient of Panax ginseng with the activity of neuroprotective, antioxidant and strengthening the immune system. Therefore, we hypothesized that Rg1 may afford anti-aging effects although the mechanism remains to be elucidated. In this study, chemically induced aging mice were established by consecutive administration of D-galactose and AlCl3. We found that Rg1 effectively ameliorates spatial learning and memory deficits in aging mice demonstrated by their improved performance in step down avoidance tests and Morris water maze experiments. Rg1 restored aging-induced decline of FGF2 and BDNF, reactivated TrkB/Akt signaling pathways in the hippocampus and prefrontal cortex to inhibit apoptosis, for the expression of anti-apoptotic protein Bcl-2 and apoptosis promoting enzyme cleaved-Caspase3 were antagonistically restored. Therefore, these results established the anti-aging effects of Rg1, and FGF2, BDNF and associated signaling pathways might be promising targets. Our data may provide a new avenue to the pharmacological research and diet therapeutic role of ethnic products such as Rg1 in anti-aging and aging associated diseases.

Tyrosol prevents AlCl3 induced male reproductive damage by suppressing apoptosis and activating the Nrf-2/HO-1 pathway.

Aluminium is a ubiquitous element that occurs naturally in the soil making human exposure to it is unavoidable. Tyrosol is present in olive oil and is known to have antioxidant effects. Therefore, the present study explores the toxic effects of aluminium chloride (AlCl3 ) and evaluates the possible protection by tyrosol in male rats. Testicular injury was induced by the administration of AlCl3 (34 mg kg-1  day-1 ). Rats were treated with either tyrosol (20 mg kg-1 day-1 ) or AlCl3 (34 mg kg-1 day-1 ). The experiment lasted for 10 weeks. Biochemical, histopathological and protein expression profiles were determined to decipher the role of tyrosol in protecting the cellular damage. Further, histomorphometric analyses of testes showed deranged architecture along with other noted abnormalities. AlCl3 group rats' testes showed decreased GSH levels, CAT activities, Nrf-2, HO-1, bcl-2 expressions and sperm motility whereas increased caspase-3 expressions, MDA levels, abnormal and dead/live sperm ratio. However, tyrosol treatment attenuated these changes. The present results demonstrate the beneficial role of tyrosol treatment in AlCl3 induced testicular toxicity alterations of rat.

Assessment of the Protective Effect of Lepidium sativum against Aluminum-Induced Liver and Kidney Effects in Albino Rat.

BACKGROUND AND OBJECTIVES: Environmental pollution with the different Aluminum (Al) containing compounds has been increased. Liver and kidney are two vital organs targeted by Al accumulation. The aim of this study was to assess the possible protective and curative effects of Lepidium sativum Linn (LS) against Al-induced impairment of liver and kidney in albino rat and to explore the mechanism behind this effect. MATERIALS AND METHODS: This experimental animal-based study included fifty albino rats divided into five groups, the control, LS-treated (20 mg/kg), AlCl3-treated (10 mg/kg), AlCl3 then LS, and AlCl3 plus LS-treated, simultaneously for 8 weeks. At the end of the experiment, hepatic and renal functions as well as the biomarkers of antioxidants activities were assessed in the serum. Both liver and kidney were dissected out and histopathologically examined. RESULTS: This study showed that administration of AlCl3 caused a significant (p<0.05) reduction in rats body weight. It significantly increased serum AST, ALT, ALP, bilirubin, urea, and creatinine levels and decreased total protein and albumin. AlCl3 significantly reduced enzymatic (catalase), nonenzymatic (reduced glutathione), and ferric reducing antioxidant power (FRAP) in the serum. Histopathologically, it induced necrosis and degeneration of hepatocytes, glomeruli, and renal tubules. Administration of LS after or along with AlCl3 significantly restored the serum biomarkers of liver and kidney functions to their near-normal levels and had the ability to overcome Al-induced oxidative stress and preserved, to some extent, the normal hepatic and renal structure. The coadministration of LS had a superior effect in alleviating Al-induced changes. CONCLUSION: Exposure to AlCl3 induced a set of functional and structural changes in the liver and kidney of rats evident through both biochemical and histopathological assessment. The antioxidant activity of LS seeds mediated a protective and curative effect of LS against such changes. Further study through a rigorous clinical trial to prove LS activity on human is recommended.

Neuroprotective evaluation of Tribulus terrestris L. in aluminum chloride induced Alzheimer's disease.

Tribulus terrestris (T.T) is enriched with steroidal saponins and flavonoids which have neuroprotective effect. The study was aimed to explore the potential of T.T methanol extract (T.T ME) for anti-Alzheirmer activity along with its safety evaluation. Plant was characterized by physicochemical, phytochemical and GCMS analyses whereas acute oral toxicity (OECD 425) was performed for safety evaluation. AlCl3 induced Alzheimer's disease rat model was used for anti-Alzheirmer activity. T.T ME was given orally at 100, 300 and 1000 mg/kg doses for 21 days and behavioral parameters were observed on 22nd study day. Physicochemical parameters were in permissible limits. GCMS analysis showed eight different compounds and benzene dicarboxylic acid showed maximum % peak area (64.19). No mortality was noted in acute toxicity study. Behavioral studies showed highly significant (p<0.001) improvement in T.T ME treated groups. Antioxidant enzymes and acetylcholinesterase levels were significantly (p<0.05) improved on treatment with T.T ME. Histopathological analysis indicated that neurofibrillary tangles were significantly improved in T.T ME treated groups. Biochemical and behavioral results suggested that T.T contained lead compounds which are effective in the treatment of Alzheimer disease.

Aluminum in liver cells - the element species matters.

Aluminum (Al) can be ingested from food and released from packaging and can reach key organs involved in human metabolism, including the liver via systemic distribution. Recent studies discuss the occurrence of chemically distinct Al-species and their interconversion by contact with biological fluids. These Al species can vary with regard to their intestinal uptake, systemic transport, and therefore could have species-specific effects on different organs and tissues. This work aims to assess the in vitro hepatotoxic hazard potential of three different relevant Al species: soluble AlCl3 and two nanoparticulate Al species were applied, representing for the first time an investigation of metallic nanoparticles besides to mineral bound γ-Al2O3 on hepatic cell lines. To investigate the uptake and toxicological properties of the Al species, we used two different human hepatic cell lines: HepG2 and differentiated HepaRG cells. Cellular uptake was determined by different methods including light microscopy, transmission electron microscopy, side-scatter analysis, and elemental analysis. Oxidative stress, mitochondrial dysfunction, cell death mechanisms, and DNA damage were monitored as cellular parameters. While cellular uptake into hepatic cell lines occurred predominantly in the particle form, only ionic AlCl3 caused cellular effects. Since it is known, that Al species can convert one into another, and mechanisms including 'trojan-horse'-like uptake can lead to an Al accumulation in the cells. This could result in the slow release of Al ions, for which reason further hazard cannot be excluded. Therefore, individual investigation of the different Al species is necessary to assess the toxicological potential of Al particles.

Centella asiatica Protects d-Galactose/AlCl3 Mediated Alzheimer's Disease-Like Rats via PP2A/GSK-3ß Signaling Pathway in Their Hippocampus.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder more prevalent among the elderly population. AD is characterised clinically by a progressive decline in cognitive functions and pathologically by the presence of neurofibrillary tangles (NFTs), deposition of beta-amyloid (Aß) plaque and synaptic dysfunction in the brain. Centella asiatica (CA) is a valuable herb being used widely in African, Ayurvedic, and Chinese traditional medicine to reverse cognitive impairment and to enhance cognitive functions. This study aimed to evaluate the effectiveness of CA in preventing d-galactose/aluminium chloride (d-gal/AlCl3) induced AD-like pathologies and the underlying mechanisms of action were further investigated for the first time. Results showed that co-administration of CA to d-gal/AlCl3 induced AD-like rat models significantly increased the levels of protein phosphatase 2 (PP2A) and decreased the levels of glycogen synthase kinase-3 beta (GSK-3ß). It was further observed that, CA increased the expression of mRNA of Bcl-2, while there was minimal effect on the expression of caspase 3 mRNA. The results also showed that, CA prevented morphological aberrations in the connus ammonis 3 (CA 3) sub-region of the rat's hippocampus. The results clearly demonstrated for the first time that CA could alleviate d-gal/AlCl3 induced AD-like pathologies in rats via inhibition of hyperphosphorylated tau (P-tau) bio-synthetic proteins, anti-apoptosis and maintenance of cytoarchitecture.