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.

Silicon attenuates aluminum toxicity in sugarcane plants by modifying growth, roots morphoanatomy, photosynthetic pigments, and gas exchange parameters.

Aluminum (Al) inhibits growth and limits plant productivity in acidic soils. An important strategy to increase Al tolerance is the use of silicon (Si) nutrition. Thus, the aim of this study was to evaluate the interactive role of Si in increasing the growth, physiological and morphoanatomy responses of sugarcane plants under Al toxicity. A 4 × 2 factorial scheme in a completely randomized design was used to study the impact of Si (2 mM) on attenuating Al toxicity (0, 10, 15 and 20 mg L-1, as Al2(SO4)3·18H2O) in sugarcane seedlings. After 45 days, Al toxicity affected sugarcane growth by increasing Al uptake and accumulation, modifying root growth, thickness, and morphoanatomy, and decreasing pigment content, gas exchange parameters, and the number of adaxial and abaxial stomata. However, Si attenuated Al toxicity in the sugarcane seedlings by limiting Al uptake and transport to the shoots, causing positive changes in root morphoanatomy, higher pigment content, improving gas exchange parameters, thereby increased growth. Furthermore, cultivar 'CTC9003' showed beneficial impacts from Si supplementation than 'CTC9002', especially under Al toxicity. The findings of this study suggest that Si plays a notable role in improving anatomical and physiological aspects, particularly the growth of sugarcane seedlings under Al toxicity.

Ethanol extract of Andrographis paniculata alleviates aluminum-induced neurotoxicity and cognitive impairment through regulating the p62-keap1-Nrf2 pathway.

BACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative and remains incurable. Aluminum is a potent neurotoxin associated with AD. The main pathological features of AD are extracellular amyloid-ß protein deposition and intracellular hyperphosphorylated Tau protein. A body of evidence suggest that oxidative stress and autophagy are involved in the pathogenesis of AD. Andrographis paniculata (AP) is a native plant with anti-inflammatory, anti-oxidative stress, and regulation of autophagy properties. AP significantly alleviated cognitive impairments, reduced Aß deposition and has neuroprotective effect. However, its effects on aluminum-induced AD model have not been studied much. In this study, we investigated whether AP protect against aluminum-induced neurotoxicity through regulation of p62-Kelch-like ECH-associated protein 1(Keap1)-Nuclear factor E2 related factor 2 (Nrf2) pathway and activation autophagy in vivo and in vitro. METHODS: UPLC-ESI-qTOF-MS/MS was used to identify the chemical constituents of AP ethanol extract. The mice with cognitive deficit were established by injecting aluminum chloride and D-galactose, and treated with either AP extract (200, 400, or 600 mg/kg/d) or andrographolide (2 mg/kg/2d).The spatial memory ability was detected by Morris water maze, HE staining were used to detect in brain tissue,Oxidative stress indexs and SOD activity in both serum and brain tissue were detected by kit.The expression of p62-Nrf2 pathway proteins were measured via western blotting. Furthermore, the neurotoxicity model was induced by aluminum maltolate (700 µM) in PC12 cells. Following AP and andrographolide treatment, the cell viability was detected. The relevant mRNA and protein expressions were detected in cells transfected with the p62 siRNA. RESULTS: The main active components of AP included andrographolide, neoandrographolide and deoxyandrographolide as identified. AP and andrographolide significantly improved the spatial memory ability of mice, attenuated pathological changes of hippocampal cells, reduced the level of malondialdehyde, and increased superoxide dismutase activity in serum or brain tissue as compared to model control. In addition, the Nrf2, p62 and LC3B-II proteins expression were increased, and p-Tau and Keap1 proteins were decreased in the hippocampus after AP and andrographolide treatment.Furthermore, AP increased aluminum maltolate-induced cell viability in PC12 cells. Silencing p62 could reverse the upregulation expression of Nrf2 and downregulation of Keap1 and Tau proteins induced by AP in aluminum maltolate-treated cells. CONCLUSIONS: AP had neuroprotective effects against aluminum -induced cognitive dysfunction or cytotoxicity, which was involved in the activation of the p62-keap1-Nrf2 pathway and may develop as therapeutic drugs for the treatment of AD. However, this study has certain limitations, further optimize the protocol or model and study the molecular mechanism of AP improving AD.

The transporter PHO84/NtPT1 is a target of aluminum to affect phosphorus absorption in Saccharomyces cerevisiae and Nicotiana tabacum L.

The molecular mechanism of aluminum toxicity in biological systems is not completely understood. Saccharomyces cerevisiae is one of the most used model organisms in the study of environmental metal toxicity. Using an unbiased metallomic approach in yeast, we found that aluminum treatment caused phosphorus deprivation, and the lack of phosphorus increased as the pH of the environment decreased compared to the control strain. By screening the phosphate signaling and response pathway (PHO pathway) in yeast with the synthetic lethality of a new phosphorus-restricted aluminum-sensitive gene, we observed that pho84Δ mutation conferred severe growth defect to aluminum under low-phosphorus conditions, and the addition of phosphate alleviated this sensitivity. Subsequently, the data showed that PHO84 determined the intracellular aluminum-induced phosphorus deficiency, and the expression of PHO84 was positively correlated with aluminum stress, which was mediated by phosphorus through the coordinated regulation of PHO4/PHO2. Moreover, aluminum reduced phosphorus absorption and inhibited tobacco plant growth in acidic media. In addition, the high-affinity phosphate transporter NtPT1 in tobacco exhibited similar effects to PHO84, and overexpression of NtPT1 conferred aluminum resistance in yeast cells. Taken together, positive feedback regulation of the PHO pathway centered on the high-affinity phosphate transporters is a highly conservative mechanism in response to aluminum toxicity. The results may provide a basis for aluminum-resistant microorganisms or plant engineering and acidic soil treatment.

Root microbiota confers rice resistance to aluminium toxicity and phosphorus deficiency in acidic soils.

Aluminium (Al) toxicity impedes crop growth in acidic soils and is considered the second largest abiotic stress after drought for crops worldwide. Despite remarkable progress in understanding Al resistance in plants, it is still unknown whether and how the soil microbiota confers Al resistance to crops. Here we found that a synthetic community composed of highly Al-resistant bacterial strains isolated from the rice rhizosphere increased rice yield by 26.36% in acidic fields. The synthetic community harvested rhizodeposited carbon for successful proliferation and mitigated soil acidification and Al toxicity through extracellular protonation. The functional coordination between plants and microbes offers a promising way to increase the usage of legacy phosphorus in topsoil. These findings highlight the potential of microbial tools for advancing sustainable agriculture in acidic soils.

Melatonin alleviates aluminum toxicity by regulating aluminum-responsive and nonresponsive pathways in hickory.

Aluminum (Al) toxicity is a significant constraint on agricultural productivity worldwide. Melatonin (MT) has been shown to alleviate Al toxicity in plants; however, the underlying mechanisms remain largely unknown. Here, we employed a combination of physiological and molecular biology techniques to examine the role of MT in mitigating Al toxicity of hickory. We found that MT decreased the contents of cell wall pectin, hemicellulose, Al, and Al-induced massive reactive oxygen species accumulation in the roots of hickory. Transcriptomic analysis revealed that MT may alleviate root tip Al stress by regulating Al-responsive and nonresponsive pathways. Co-expression regulatory network and dual-luciferase receptor assays revealed that transcription factors, CcC3H12 and CcAZF2, responded to MT and significantly activated the expression of two cell wall pectin-related genes, CcPME61 and CcGAE6, respectively. Further, yeast one-hybrid and electrophoretic mobility shift assay (EMSA) assays verified that CcC3H12 and CcAZF2 regulated CcPME61 and CcGAE6, respectively, by directly binding to their promoters. Overexpression of CcPME61 enhanced the Al sensitivity of Arabidopsis thaliana. Our results indicate that MT can improve Al tolerance of hickory via multiple pathways, which provides a new perspective for the study of the mechanism of MT in alleviating abiotic stress.

Clinical Outcomes of the Deleterious Effects of Aluminum on Neuro-Cognition, Inflammation, and Health: A Review.

Introduction: In the scenario of metal toxicity, aluminum (Al) stands out as a ubiquitous type of metal that can be combined with other elements and form different compounds. Al is widely used daily as an adjuvant in vaccines, antacids, food additives (as components of AI-containing food additives), skin care products, cosmetics, and kitchenware, and can be an element or contaminant present in our daily life. Objective: To present a review of the main deleterious effects of Al on human health. Methods: The search was carried out from September 2022 to February 2023 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases, using scientific articles from 2012 to 2023. The quality of the studies was based on the GRADE instrument, and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusions: A total of 115 files were search returned. Further, 95 articles were evaluated, and 44 were included in this review. Based on the results, measuring Al's relevance to health is essential in medicine. Several studies have demonstrated clinical outcomes and metabolic alterations with Al exposure. The tolerable weekly intake established by the European Food Safety Authority (EFSA) of 1 mg Al/kg body weight can be achieved through dietary exposure alone. Proven neurotoxicity in humans is the critical adverse effect of Al. A carcinogenic effect of Al has not been proven so far. Preventive medicine advocates that exposure to Al should be kept as low as possible. Chelating agents, such as calcium disodium ethylene diamine tetraacetic acid and deferoxamine, are options for acute poisoning, and monomethysilanetriol supplementation may be a long-term strategy with chelation potential. Further studies are needed to assess the impacts of Al on human health.

Selenium-rich yeast counteracts the inhibitory effect of nanoaluminum on the formation of porcine neutrophil extracellular traps.

Aluminum is widely used in daily life due to its excellent properties. However, aluminum exposure to the environment severely threatens animal and human health. Conversely, selenium (Se) contributes to maintaining the balance of the immune system. Neutrophils exert immune actions in several ways, including neutrophil extracellular traps (NETs) that localize and capture exogenous substances. Despite the recent investigations on the toxic effects of aluminum and its molecular mechanisms, the immunotoxicity of aluminum nanoparticles on pigs and the antagonistic effect of selenium on aluminum toxicity are poorly understood. Here, we treated porcine peripheral blood neutrophils with zymosan for 3 h to induce NETs formation. Then, we investigated the effect of nanoaluminum on NETs formation in pigs and its possible molecular mechanisms. Microscopy observations revealed that NETs formation was inhibited by nanoaluminum. Using a multifunctional microplate reader, the production of extracellular DNA and the burst of reactive oxygen species (ROS) in porcine neutrophils were inhibited by nanoaluminum. Western blot analyses showed that nanoaluminum caused changes in amounts of cellular selenoproteins. After Se supplementation, the production of porcine NETs, the burst of ROS, and selenoprotein levels were restored. This study indicated that nanoaluminum inhibited the zymosan-induced burst of ROS and release of NETs from porcine neutrophils, possibly through the selenoprotein signaling pathway. In contrast, Se supplementation reduced the toxic effects of nanoaluminum and restored NETs formation.

Deciphering Interactions between Phosphorus Status and Toxic Metal Exposure in Plants and Rhizospheres to Improve Crops Reared on Acid Soil.

Acid soils are characterized by deficiencies in essential nutrient elements, oftentimes phosphorus (P), along with toxicities of metal elements, such as aluminum (Al), manganese (Mn), and cadmium (Cd), each of which significantly limits crop production. In recent years, impressive progress has been made in revealing mechanisms underlying tolerance to high concentrations of Al, Mn, and Cd. Phosphorus is an essential nutrient element that can alleviate exposure to potentially toxic levels of Al, Mn, and Cd. In this review, recent advances in elucidating the genes responsible for the uptake, translocation, and redistribution of Al, Mn, and Cd in plants are first summarized, as are descriptions of the mechanisms conferring resistance to these toxicities. Then, literature highlights information on interactions of P nutrition with Al, Mn, and Cd toxicities, particularly possible mechanisms driving P alleviation of these toxicities, along with potential applications for crop improvement on acid soils. The roles of plant phosphate (Pi) signaling and associated gene regulatory networks relevant for coping with Al, Mn, and Cd toxicities, are also discussed. To develop varieties adapted to acid soils, future work needs to further decipher involved signaling pathways and key regulatory elements, including roles fulfilled by intracellular Pi signaling. The development of new strategies for remediation of acid soils should integrate the mechanisms of these interactions between limiting factors in acid soils.

Physiological and TMT-based quantitative proteomic responses of barley to aluminium stress under phosphorus-Piriformospora indica interaction.

Barley (Hordeum vulgare L.) is one of the most important cereal crop in the world, and is also the one being seriously affected by heavy metals, particularly aluminium (Al). Keeping in view the utility of barley as food, fodder and raw material for traditional beer brewing, the top-notch quality and higher production of this crop must be sustained. Phosphorus (P) has a quintessential role in plant growth with a potential to relieve symptoms caused by Al poisoning. Displaying a phytopromotive and stress alleviatory potential, Piriformospora indica (P. indica) can improve the stress tolerance in crops. Several studies have been conducted to evaluate the mechanism of Al translocation in a variety of crops including barley, however, the bio-remediative studies related to detoxification and/or sequestration of metals are scarce. Therefore, the current study was carried out to elucidate the tolerance mechanism of an Al-sensitive barley cultivar ZU9 following the colonization with P. indica and exogenous P supply by physio-biochemical, elemental, leaf ultrastructural and root proteome analyses. When compared to the Al alone treated counterparts, the Al + P + P.i treated plants exhibited 4.1-, 1.38-, 2.7 and 1.35-fold improved root and shoot fresh and dry weights, respectively. With the provision of additional phosphorus, the content of P in the root and shoot for Al + P + P.i group was reportedly higher (71.6% and 49.5%, respectively) as compared to the control group. Moreover, inoculation of P. indica combined with P improved barley leaves' cell arrangement and also maintained normal cell wall shape. The root protemics experiment was divided into three groups: Al, Al + P.i and Al + P + P.i. In total, 28, 598, and 823 differentially expressed proteins were found in Al + P.i vs. Al and Al + P + P.i vs. Al, and phenylpropanoid biosynthesis was the most prominently enriched pathway, which contributed significantly to the recuperating effects of P-P. indica interaction. Conslusively, it was found that the percentage of protein related to peroxidase was 70/359 (Al + P + P.i vs. Al) and 92/447 (Al + P + P.i vs. Al + P.i), respectively, which indicated that P. indica in combination with P might be involved in the regulation of peroxidases, increasing the adaptability of barley plants by enhanced reactive oxygen species (ROS) scavenging mechansism.

Magnesium alleviates aluminum-induced growth inhibition by enhancing antioxidant enzyme activity and carbon-nitrogen metabolism in apple seedlings.

Previous studies have determined that magnesium (Mg) in appropriate concentrations prevents plants from suffering from abiotic stress. To better understand the mechanism of Mg alleviation of aluminum (Al) stress in apple, we investigated the effect of Mg on plant growth, photosynthetic fluorescence, antioxidant system, and carbon (C) and nitrogen (N) metabolism of apple seedlings under Al toxicity (1.5 mmol/L) via a hydroponic experiment. Al stress induced the production of reactive oxygen in the leaves and roots and reduced the total dry weight (DW) by 52.37 % after 20 days of treatment relative to plants grown without Al, due to hindered photosynthesis and alterations in C and N metabolism. By contrast, total DW decreased by only 11.07 % in the Mg-treated plants under Al stress. Supplementation with 3.0 mmol/L Mg in the Al treatment decreased Al accumulation in the apple plants and reduced Al-induced oxidative damage by enhancing the activity of antioxidant enzymes (superoxide dismutase, catalase, and peroxidase) and reducing the production of H2O2 and malondialdehyde (MDA). Under Al stress, the Mg-treated plants showed a 46.17 % higher photosynthetic rate than the non-treated plants. Supplementation with Mg significantly increased the sucrose content by increasing sucrose synthase (SS) and sucrose-phosphate synthase (SPS) activities. Moreover, Mg facilitated the transport of 13C-carbohydrates from the leaves to roots. Regarding N metabolism, the nitrate reductase (NR), glutamine synthase (GS), and glutamate synthase (GOGAT) activities in the roots and leaves of the Mg-treated plants were significantly higher than those of the non-treated plants under Al stress. Compared with the non-treated plants under Al stress, the Mg-treated plants exhibited a significantly high level of NO3- and soluble protein content in the leaves, roots, and stems, but a low level of free amino acids. Furthermore, Mg significantly improved nitrogen accumulation and enhanced the transport of 15N from the roots to leaves. Overall, our results revealed that Mg alleviates Al-induced growth inhibition by enhancing antioxidant capacity and C-N metabolism in apple seedlings.

Ameliorative effects of bromelain on aluminum-induced Alzheimer's disease in rats through modulation of TXNIP pathway.

Alzheimer's disease (AD) is known as "type 3 diabetes". As thioredoxin binding protein (TXNIP) has been shown to be involved in brain insulin resistance, the present study evaluated the roles of TXNIP, phospho-insulin receptor substrate 1 (P-IRS-1), and phosphatidyl inositol-3 kinase (PI3K) in the pathogenesis of AD. The potential ameliorative effect of bromelain compared to donepezil was evaluated in an aluminum chloride (AlCl3)-induced AD in rats. Behavioral tests demonstrated similar improvements in exploratory activity, cognitive and spatial memory functions, anxiety, and depression levels between rats treated with bromelain and donepezil. Donepezil was superior to bromelain in improving locomotor activity. Histopathological examinations demonstrated neuronal degeneration in the AlCl3 group that was almost normalized by bromelain and donepezil. Moreover, there was deposition of amyloid plaques in the AlCl3 group that was improved by bromelain and donepezil. Acetylcholine esterase levels were significantly increased in rats treated with AlCl3 group and significantly decreased in rats treated with bromelain and donepezil. Furthermore, AlCl3 group showed a significantly increased TXNIP and P-IRS1 and a significantly reduced PI3K levels. These effects were ameliorated by bromelain and donepezil treatment. The present study demonstrates a previously unreported modulatory effect of bromelain on the TXNIP/P-IRS-1/PI3K axis in AD model.

Aluminum Supplementation Mediates the Changes in Tea Plant Growth and Metabolism in Response to Calcium Stress.

Tea plants are more sensitive to variations in calcium concentration compared to other plants, whereas a moderate aluminum concentration facilitates the growth and development of tea plants. Aluminum and calcium show a competitive interaction with respect to the uptake of elements, consequently exerting physiological effects on plants. To further explore these interactions, in this study, we used the solution culture method to treat tea plants with two calcium concentrations (0.8 mM and 5.6 mM) and three aluminum concentrations (0 mM, 0.4 mM, and 1 mM). We then determined the influence of the combined treatments on root growth and quality compound accumulation in the tissues by a combination of phenotype, gene expression, and metabolite analyses. Moderate aluminum supplementation (0.4 mM) alleviated the inhibition of root growth caused by high calcium stress. High calcium stress significantly inhibited the accumulation of most amino acids (e.g., Glutamic acid, Citulline, and Arginine) and organic acids (e.g., a-ketoglutaric acid) in the roots, stems, and leaves, whereas aluminum deficiency significantly increased most amino acids in the roots and leaves (except Serine, Alanine, and Phenylalanine in the roots and Ser in the leaves), with a more than two-fold increase in Arg and Lysine. High calcium stress also induced the accumulation of secondary metabolites such as epigallocatechin gallate and procyanidin in the roots, whereas aluminum supplementation significantly reduced the contents of flavonol glycosides such as quercetin, rutin, myricitrin, and kaempferitrin, as well as caffeine, regardless of calcium concentration. Aluminum supplementation reversed some of the changes in the contents of leaf metabolites induced by calcium stress (e.g., 4-dihydroquercetin, apigenin C-pentoside, phenethylamine, and caffeine). Overall, calcium stress caused severe growth inhibition and metabolic disorders in tea plants, which could be reversed by aluminum supplementation, particularly in maintaining the root tips and the accumulation of secondary metabolites. These results provide a theoretical basis for improving calcium-aluminum nutrient management to promote tea plant growth and quality.

The effect of aluminum treatment on metabolism in oil palm seedlings

Due to rainfall and high temperatures, the Amazonian soil undergoes changes in its source material and leaching of base cations. This results in deep, infertile, and acidic soil. Aluminum present in acidic soil impairs plant growth and development by inhibiting root formation, enzymatic reactions, absorption, transport, and nutrient utilization. This study aimed to evaluate the effects of aluminum dosage on the metabolism of the oil palm Elaeis guineensis Jacq. The study was conducted in a greenhouse at the Federal Rural University of Amazonia. The experimental design was randomized, with five replications, in which dosages of 0, 10, 20, 30, and 40 mg L-1 aluminum chloride (AlCl3.6H2O) were administered. Electrolyte leakage, nitrate, nitrate reductase, free ammonium, soluble amino acids, proline content, and soluble proteins were analyzed in the leaves and roots of the oil palm. The highest concentration of aluminum was found in the roots. AlCl3 treatment at 40 mg L-1 increased electrolyte leakage, nitrate, ammonium, and proline concentrations in the roots, and amino acid concentrations in both the leaves and roots. Furthermore, a decrease in nitrate reductase enzyme activity was observed in the roots. This study demonstrates that the oil palm has mechanisms of tolerance to aluminum toxicity.

Therapeutic and Preventive Effects of Piperine and its Combination with Curcumin as a Bioenhancer Against Aluminum-Induced Damage in the Astrocyte Cells.

Recently, studies conducted with astrocyte cells have drawn attention to neurodegeneration pathologies caused by aluminum exposure. In particular, investigating the potential of herbal therapeutic agents to prevent this effect of aluminum has gained importance. The purpose of this study was to investigate the therapeutic and preventive effects of piperine, curcumin, and the combination of these compounds on reactive primary astrocyte cells. In order to examine the preventive effect, certain concentrations of compounds were applied to the cells before the aluminum application, and to be able to determine the therapeutic effect, the compounds were examined after the aluminum application. The efficacy of the compounds was analyzed in terms of cell viability, apoptosis, necrosis, and cytokine release. In conclusion, the results of the study showed that the use of different concentrations of piperine, curcumin, and their combination had significantly higher % cell viability on aluminum-induced damage in astrocyte cells compared to the damaged control group. In addition, a decrease in the number of apoptotic and necrotic cells was observed in the same groups, which indicated that piperine increased curcumin activity. The decrease in the amount of IL-6 and TGF-ß cytokines also supported that piperine increased the effectiveness of curcumin. Considering all these results, it can be said that in terms of aluminum damage in astrocyte cells, the bioavailability-enhancing property of piperine on curcumin was shown for the first time in the literature. In line with these results, it is inevitable to carry out further studies.

Based on 16 S rRNA sequencing and metabonomics to reveal the new mechanism of aluminum potassium sulfate induced inflammation and abnormal lipid metabolism in mice.

More and more discoveries have been made about the chronic toxic effects of aluminum, but the specific mechanism of action remains unclear. In this study, we explored the perturbation of aluminum on intestinal microflora and its effects on host and microbial metabolites through a more realistic nutrient absorption model. The microorganisms Turicibacter, Lactobacillus murinus, Lactobacillus_reuteri and Bifidobacterium pseudolongum may be the main targets of the aluminum affecting microbiota. Lysine, proline, putrescine, serotonin and cholesterol may be important metabolites affected by aluminum ions after the interference of intestinal flora composition, leading to abnormal metabolism pathways of amino acids and lipids in the body, and thus promoting inflammation and lesion. The possible mechanisms of aluminum action on the body: (1) Affecting immune cell response, ROS generation and production of a series of pro-inflammatory factors to promote inflammation; (2) Through the disturbance of intestinal microbiota composition structure, change the abundance of metabolites, and then affect amino acid metabolism, lipid metabolism pathways. The joint analysis of multiple omics showed significant difference in microbiome abundance and metabolomics expression between high dose group and the control group.

Functional groups on wheat (Triticum aestivum) root surface affect aluminium transverse accumulation.

Plant root growth is inhibited markedly by aluminium (Al) even at micromolar concentration and Al is mainly accumulated in plant roots outer layer cell walls. But the underlying reason for this asymmetric transverse distribution is unknown. In this study, two wheat (Triticum aestivum L.) genotypes ET8 and ES8 differing in Al resistance were investigated by hydroculture. The Al-tolerant ET8 expressed a higher root elongation rate (RER) than Al-sensitive ES8 under Al stress. Morphological examination showed symptoms such as root surface ruptures were observed in ET8 and ES8, with ES8 being more obvious. The cation exchange capacity (CEC) values of root tips of ES8 under different Al concentrations are higher than those of ET8. The sensitive genotype ES8 accumulated more Al than ET8 in plant apical root tips as well as cell walls. Under 48 h Al exposure, the root cell wall pectin concentration was increased with a higher magnitude in ES8 than in ET8. The functional groups on ET8 and ES8 roots outer layer and inner cells were investigated by Fourier transform infrared spectrometry (FTIR) under Al stress. The FTIR spectra of selected examined areas showed that the characteristic absorption peaks were located at 1692, 2920, and 3380 cm-1. The outer layer cells had stronger peaks than inner cells at wavenumber 1680-1740 cm-1, indicating root outer layer cells contain more carboxyls in both ET8 and ES8. The results demonstrate that Al transverse distribution on plants apical root cross section is likely influenced by functional groups such as negatively charged carboxylic acid.

Conjugated linoleic acid downregulates Alzheimer's hallmarks in aluminum mouse model through an Nrf2-mediated adaptive response and increases brain glucose transporter levels.

Mitochondrial dysfunction, oxidative stress, inflammation and glucose dysmetabolism are pathological signs of Alzheimer's disease (AD). Dietary aluminum (Al) overload is often used to induce AD in rodents and trigger the onset of oxidative-stress hallmarks resembling those of the human disease. The Nuclear factor erythroid 2-related factor 2 (Nrf2), owing to its key role in redox homeostasis, mitochondrial function and inflammation, is a promising drug target for neurological disorders, but only a few data are available on its modulatory effects on glucose transporter expression levels. While it has been found that the protective effect of Conjugated linoleic acid (CLA) occurs through the activation of an Nrf2-mediated adaptive response, its beneficial effect on the considered pathological signs in the Al-induced model has not been established yet. Thirty-five male BalbC mice were divided into 5 groups: two Al-intoxicated groups were treated for 5 weeks with low or high Al doses (8 or 100 mg/kg/day in drinking water, respectively; L or H). Two groups of animals, orally supplemented with CLA (600 mg/kg bw/day) for 7 weeks (2 preliminary weeks plus the 5-week treatment with Al; CLA + L, CLA + H) were used to investigate its protective effect, while untreated mice were used as control (Cntr). We provide evidence that mitochondrial dysfunction, Nrf2 alteration, inflammation and Acetylcholinesterase (AChE) hyperactivation can occur even from L exposure. Interestingly, animal pre-treatment with an allometric CLA dose led to significant downregulation of the toxic effects elicited by L or H, likely through the activation of an adaptive response. In conclusion, CLA ability to increase the level of glucose transporters - along with its antioxidant and anti-inflammatory effect - expands the therapeutic targets of these molecules and comes out as an intriguing suitable candidate for the treatment of multifactorial disease.

Gene/environment interaction in the susceptibility of Crohn's disease patients to aluminum.

BACKGROUND & AIM: The key role of environmental factors in the pathogenesis of Inflammatory Bowel Diseases (IBD) is recognized. Aluminum is suspected to be a risk factor for IBD. However, mechanisms linking aluminum exposure to disease development are unknown. We examined the role of aluminum transport and subcellular localisation on human colon susceptibility to aluminum-induced inflammation. METHODS: Human colon biopsies isolated from Crohn's disease (CD) or control patients and Caco-2 cells were incubated with aluminum. The effects of aluminum were evaluated on cytokine secretion and transporter expression. The role of aluminum kinetics parameters was studied in Caco-2 using transport inhibitors and in human colon biopsies by assessing genetic polymorphisms of transporters. RESULTS: Aluminum exposure was shown to induce cytokine secretion in colon of CD but not healthy patients. In Caco-2 cells, aluminum internalisation was correlated with inflammatory status. In human colon, analysis of genetic polymorphisms and expression of ABCB1 and SLC26A3 transporters showed that their decreased activity was involved in aluminum-induced inflammation. CONCLUSIONS: We hypothesize that alteration in detoxifying response would lead to a deregulation of intestinal homeostasis and to the expression of IBD. Our study emphasizes the complexity of gene/environment interaction for aluminum adverse health effect, highlighting at risk populations or subtypes of patients. A better understanding of correlations between gene expression or SNP and xenobiotic kinetics parameters would shift the medical paradigm to more personalized disease management and treatment.

Blood pressure mediated the effects of cognitive function impairment related to aluminum exposure in Chinese aluminum smelting workers.

OBJECTIVES: The aim of this study is to investigate the effects that the Al on blood pressure and the effect of hypertension in aluminum-induced cognitive impairment in electrolytic aluminum worker. METHODS: The study was conducted 392 male aluminum electrolytic workers in an aluminum plant of China. The concentration of alumina dust in the air of the electrolytic aluminum workshop is 1.07 mg/m3-2.13 mg/m3. According to the Permissible concentration-Time Weighted Average of alumina dust is 4 mg/m3, which does not exceed the standard. The blood pressure of the workers was measured. The plasma aluminum concentration of workers was determined by ICP-MS (Inductively Coupled Plasma Mass Spectrometry). Cognitive functions were measured using MMSE (Mini-Mental State Examination), VFT (Verbal Fluency Test), ATIME (Average Reaction Time), FOM (Fuld Object Memory Evaluation), DST (Digit Span Test), CDT (Clock Drawing Test) scales. Modified Poisson regression was used to analyze the risk of hypertension and cognitive impairment with different plasma aluminum concentrations. Generalized linear regression model was used to analyze the relationship between aluminum and cognitive function, blood pressure and cognitive function. Causal Mediation Analysis was used to analyze the mediation effect of blood press in aluminum-induced cognitive impairment. RESULTS: Plasma aluminum appeared to be a risk factor for hypertension (PR (prevalence ratio) = 1.630, 95 %-CI (confidence interval): 1.103-2.407), systolic blood pressure (PR = 1.578, 95 %-CI: 1.038-2.399) and diastolic blood pressure (PR = 1.842, 95 %-CI: 1.153-2.944). And plasma aluminum increased by e-fold, the scores of MMSE and VFT decreased by 0.630 and 2.231 units respectively and the time of ATIME increased by 0.029 units. In addition, generalized linear regression model showed that blood press was negatively correlated with the scores of MMSE and VFT. Finally, causal Mediation Analysis showed that hypertension was a part of the mediating factors of aluminum-induced decline in MMSE score, and the mediating effects was 16.300 % (7.100 %, 33.200 %). In addition, hypertension was a part of the mediating factors of aluminum-induced decline in VFT score, and the mediating effects was 9.400 % (2.600 %, 29.000 %) CONCLUSION: Occupational aluminum exposure increases the risk of hypertension and cognitive impairment. And hypertension may be a mediating factor of cognitive impairment caused by aluminum exposure.