AlCl3 Treatment Research Articles

Ameliorative effects of probiotics in AlCl3-induced mouse model of Alzheimer's disease.

In recent years, gut microbiome alterations have been linked with complex underlying mechanisms of neurodegenerative disorders including Alzheimer's disease (AD). The gut microbiota modulates gut brain axis by facilitating development of hypothalamic-pituitary-adrenal axis and synthesis of neuromodulators. The study was designed to unravel the effect of combined consumption of probiotics; Lactobacillus rhamnosus GG (LGG®) and Bifidobacterium BB-12 (BB-12®) (1 × 109CFU) on AlCl3-induced AD mouse model in comparison with potent acetylcholine esterase inhibitor drug for AD, donepezil. Mice were randomly allocated to six different study groups (n = 8). Behavioral tests were conducted to assess effect of AlCl3 (300mg/kg) and probiotics treatment on cognition and anxiety through Morris Water Maze (MWM), Novel Object Recognition (NOR), Elevated Plus Maze (EPM), and Y-maze. The results indicated that the combined probiotic treatment significantly (p < 0.0001) reduced anxiety-like behavior post AlCl3 exposure. The AlCl3 + LGG® and BB-12®-treated group showed significantly improved spatial (p < 0.0001) and recognition memory (p < 0.0001) in comparison to AlCl3-treated group. The expression status of inflammatory cytokines (TNF-α and IL-1β) was also normalized upon treatment with LGG® and BB-12® post AlCl3 exposure. Our findings indicated that the probiotics LGG® and BB-12® have strong potential to overcome neuroinflammatory imbalance, cognitive deficits and anxiety-like behavior, therefore can be considered as a combination therapy for AD through modulation of gut brain axis. KEY POINTS: • Bifidobacterium BB-12 and Lactobacillus rhamnosus GG were fed to AlCl3-induced Alzheimer's disease mice. • This combination of probiotics had remarkable ameliorating effects on anxiety, neuroinflammation and cognitive deficits. • These effects may suggest that combined consumption of these probiotics instigate potential mitigation of AD associated consequences through gut brain axis modulation.

Melatonin promotes Al3+ compartmentalization via H+ transport and ion gradients in Malus hupehensis.

Soil acidification in apple (Malus domestica) orchards results in the release of rhizotoxic aluminum ions (Al3+) into soil. Melatonin (MT) participates in plant responses to abiotic stress; however, its role in AlCl3 stress in apple remains unknown. In this study, root application of MT (1 μM) substantially alleviated AlCl3 stress (300 μM) in Pingyi Tiancha (Malus hupehensis), which was reflected by higher fresh and dry weight, increased photosynthetic capacity, and longer and more roots compared with plants that did not receive MT treatment. MT functioned mainly by regulating vacuolar H+/Al3+ exchange and maintaining H+ homeostasis in the cytoplasm under AlCl3 stress. Transcriptome deep sequencing analysis identified the transcription factor gene SENSITIVE TO PROTON RHIZOTOXICITY 1 (MdSTOP1) was induced by both AlCl3 and MT treatments. Overexpressing MdSTOP1 in apple increased AlCl3 tolerance by enhancing vacuolar H+/Al3+ exchange and H+ efflux to the apoplast. We identified 2 transporter genes, ALUMINUM SENSITIVE 3 (MdALS3) and SODIUM HYDROGEN EXCHANGER 2 (MdNHX2), as downstream targets of MdSTOP1. MdSTOP1 interacted with the transcription factor NAM ATAF and CUC 2 (MdNAC2) to induce MdALS3 expression, which reduced Al toxicity by transferring Al3+ from the cytoplasm to the vacuole. Furthermore, MdSTOP1 and MdNAC2 coregulated MdNHX2 expression to increase H+ efflux from the vacuole to the cytoplasm to promote Al3+ compartmentalization and maintain cation balance in the vacuole. Taken together, our findings reveal an MT-STOP1 + NAC2-NHX2/ALS3-vacuolar H+/Al3+ exchange model for the alleviation of AlCl3 stress in apple, laying a foundation for practical applications of MT in agriculture.

Neuro-protective and Neuro-curative effect of Vernonia Amygdalina in rat model of neurodegenerative disease

BackgroundIn this study, we assessed the protective potential of Vernonia amygdalina methanolic extract on aluminum chloride- induced neurotoxicity damage in Wistar rats. MethodologyForty Adult female Wistar rats weighing (109 ± 16 g) were randomly divided into four (4) groups (A-D, of 10 rats respectively). Group A rats served as the normal control (treated with 5 mL/kg normal saline) for 28 days, Group B rats received 0.43 mL/kg Aluminum chloride (AlCL3) via oropharyngeal cannula for 14 days and 1.31 mL of Vernonia amygdalina extract after AlCL3 treatment for 14days, Group C rats received 1.31 mL of Vernonia amygdalina (VA) extract for 14 days and 0.43 mL/kg AlCL3 after VA treatment for 14 days, D rats received only 0.43 mL/kg Aluminum chloride (AlCL3) via oropharyngeal cannula for 14 days. The rats were sacrificed, and the hippocampus processed using Haematoxylin and Eosin (H&E) and Cresyl fast violet. ResultsResults showed a significant (P ≤ 0.05) increase in body weight of groups B-D rats when compared to group A rats. Histological examinations showed clumpy of cell neurons, condensed pyramidal cells, necrotic and vascular edema and scanty neurofibrillary tangle which was an indication of neurodegeneration in the other groups when compared to the control group. Conclusionthat the oral administration of aluminum chloride could induce brain damage which may impair memory and learning as seen in Alzheimer disease and can be ameliorated with Vernonia Amygdalina leaf extract.

The therapeutic effect of Zhenbao pills on behavioral changes in zebrafish caused by aluminum chloride

Zhenbao pill (ZBP) is a type of traditional Mongolian medicine that contains 241 ingredients such as flavonoids, anthraquinones, triterpenoids, sterols, and Calculus bovis, which are mainly used for treating neurological diseases in clinical practice. In this study, we established an Alzheimer’s disease (AD)-mimetic symptomatic zebrafish model by AlCl3 treatment and investigated the therapeutic effect of ZBP on the AD-mimetic zebrafish model. The results revealed that AlCl3 treatment led to behavioral impairment, induced apoptotic cell (body) in the brain, increased acetylcholinesterase (AChE) activity, and decreased the ACh content in zebrafish. After treatment with ZBP, 16 μg/mL ZBP could alleviate the behavioral disorder of zebrafish larvae. This effect was found superior to the effect of the cholinesterase inhibitor donepezil hydrochloride. The analysis of transcriptomics data revealed that ZBP mainly acted on apoptosis, the p53 signaling pathway, and the enrichment of the AChE-associated pathway. Furthermore, the overexpression of AChE RNA produced similar AD-mimetic disorders, whereas AChE-gene knockdown (AChE-MO) decreased the AChE activity and alleviated the AD-mimetic symptoms. These results suggested that ZBP is a potential cholinergic-enhancing drug, which can be used for the treatment of AD in the future.

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.

Comparative study of aluminum speciation on brain-type creatine kinase: Enzyme kinetic, molecular docking, cellular experiment, and mouse model study

Brain-type Creatine kinase (CK-BB), which has a high affinity for Aluminum (Al), and its abnormality is closely related to neurodegenerative diseases. In this study, the comparative effect of Al speciation on the bioactivity of CK-BB has been studied by the inhibition kinetics method, molecular docking, cellular experiment, and mouse model study. Results showed that the half-inhibitory concentration of AlCl3 was 0.67 mM, while Al(mal)3 was 3.81 mM. Fluorescence spectra showed that Al(mal)3 had a more substantial effect on the endogenous fluorescence of CK-BB than AlCl3. Molecular docking showed that AlCl3 was closer to the active site of CK-BB. C6 cells were used to explore the enzyme activity and intracellular distribution of CK-BB by AlCl3 or Al(mal)3. AlCl3 treatment may directly affect CK-BB activity and cause insufficient local ATP supply in cells which affected the formation of F-actin and cell morphology. The change in the hydrophobicity of CK-BB induced by Al(mal)3 affected the movement of CK-BB, which subsequently activated thecytochrome C (Cyt C)/Caspase 9/Caspase 3 pathway. Similar results have been found in vivo experiments. This study demonstrated that interaction between Al and CK-BB might be related to the process of Al-induced energy metabolism disorders, in which the Al speciation revealed differentiated toxicity mechanisms.

GmWRKY21, a Soybean WRKY Transcription Factor Gene, Enhances the Tolerance to Aluminum Stress in Arabidopsis thaliana.

The WRKY transcription factors (TFs) are one of the largest families of TFs in plants and play multiple roles in plant growth and development and stress response. In this study, GmWRKY21 encoding a WRKY transcription factor was functionally characterized in Arabidopsis and soybean. The GmWRKY21 protein containing a highly conserved WRKY domain and a C2H2 zinc-finger structure is located in the nucleus and has the characteristics of transcriptional activation ability. The GmWRKY21 gene presented a constitutive expression pattern rich in the roots, leaves, and flowers of soybean with over 6-fold of relative expression levels and could be substantially induced by aluminum stress. As compared to the control, overexpression of GmWRKY21 in Arabidopsis increased the root growth of seedlings in transgenic lines under the AlCl3 concentrations of 25, 50, and 100 μM with higher proline and lower MDA accumulation. The results of quantitative real-time polymerase chain reaction (qRT-PCR) showed that the marker genes relative to aluminum stress including ALMT, ALS3, MATE, and STOP1 were induced in GmWRKY21 transgenic plants under AlCl3 treatment. The stress-related genes, such as KIN1, COR15A, COR15B, COR47, GLOS3, and RD29A, were also upregulated in GmWRKY21 transgenic Arabidopsis under aluminum stress. Similarly, stress-related genes, such as GmCOR47, GmDREB2A, GmMYB84, GmKIN1, GmGST1, and GmLEA, were upregulated in hair roots of GmWRKY21 transgenic plants. In summary, these results suggested that the GmWRKY21 transcription factor may promote the tolerance to aluminum stress mediated by the pathways regulating the expression of the acidic aluminum stress-responsive genes and abiotic stress-responsive genes.

GsMYB7 encoding a R2R3-type MYB transcription factor enhances the tolerance to aluminum stress in soybean (Glycine max L.)

BackgroundMYB transcription factor (TF) is one of the largest families of TFs in plants and play essential roles in plant growth and development, and is involved in responses to biological and abiotic stress. However, there are few reports on GsMYB7 gene in soybean under aluminum acid stress, and its regulatory mechanism remains unclear.ResultsThe GsMYB7 protein is localized in the nucleus and has transcriptional activation ability. Quantitative real-time PCR (qRT-PCR) results showed that GsMYB7 held a constitutive expression pattern rich in roots. When AlCl3 concentration was 25 µM, the total root surface area (SA) of GsMYB7 transgenic lines were 34.97% higher than that of wild-type Huachun 6 (HC6). While the accumulation of Al3+ in root tip of transgenic plants after aluminum treatment was 17.39% lower than that of wild-type. RNA-sequencing analysis indicated that over 1181 genes were regulated by GsMYB7 and aluminum stress. Among all the regulated genes, the expression levels of glutathione peroxidase, protein kinase, cytochrome and other genes in the transgenic lines were significantly higher than those in wild type by acidic aluminum stress. The bioinformatics and qRT-PCR results showed that 9 candidate genes were induced under the treatments of acidic aluminum stress which were indirectly and/or directly regulated by GsMYB7. After AlCl3 treatments, the transcripts of these genes in GsMYB7 transgenic seedlings were significantly higher than those of wide-type HC6.ConclusionsThe results suggested that GsMYB7 may enhance soybean tolerance to acidic aluminum stress by regulating the downstream genes.

AlCl3 induced learning and memory deficit in zebrafish

Aluminium is a metal known to cause neurotoxicity in the brain, by promoting neurodegeneration and affecting memory and cognitive ability. AlCl3 has been reported to enhance reactive oxygen species (ROS) and inflammatory markers which are further responsible for the degeneration of neurons. AlCl3 exposure to zebrafish causes behavioral, biochemical, and neurochemical changes in the brain. In our study, Zebrafish were exposed to AlCl3 at three different doses (50 µg/L, 100 µg/L, and 200 µg/L) for four consecutive days. On days 1st and 4th, a novel diving test was performed to check anxiety in zebrafish. T - maze and novel object recognition test were used to check the memory on days 3rd and 4th with the help of ANY-maze software. On the last day (4th day), zebrafishes were sacrificed and whole brains were used to perform the biochemical, neurotransmitters, histopathological, and immunohistochemistry analysis. Our study revealed that AlCl3 exposure significantly decreased the total distance traveled, and the number of entries in the top zone and increased the time spent in the bottom zone, checked through the novel diving test. In the T maze test, AlCl3 treated zebrafish showed significantly increased transfer latency to the favorable zone and time spent, and the number of entries to the unfavorable zone. The exploration time with the novel object was reduced significantly after AlCl3 treatment. Moreover, reduced glutathione (GSH) and superoxide dismutase (SOD) levels were significantly reduced in AlCl3 treated zebrafish whereas malondialdehyde (MDA) level was found to be increased, indicating high oxidative stress. The neurotransmitters level was also disturbed indicated by the significantly decreased GABA, dopamine, noradrenaline, and Serotonin levels and increased glutamate level in the brain of zebrafish treated with AlCl3. Moreover, histopathological and immunohistochemistry study shows a markedly increased number of pyknotic neurons and reduced the expression of Nrf2 in the zebrafish brain after AlCl3 exposure. These findings suggest that AlCl3 significantly causes behavioral, biochemical, neurotransmitters, morphological, and molecular changes in zebrafish, ultimately causing AD.

AlCl3 treatment: Tailoring band alignment and enhancing performance for Cu2Cd0.4Zn0.6SnS4 solar cells

In this study, we proposed a low-cost and non-toxic AlCl3 solution treatment for tailoring the band alignment to passivate the defects at grain boundaries (GBs) of Cu2Cd0.4Zn0.6SnS4 (CCZTS) solar cells. With the treatment, much reduced leakage currents at GBs of the CCZTS film were demonstrated through CP-AFM measurements. In addition, we found the conduction band offset turns from downward to upward and valance band offset turns from upward to downward after the treatment. This type of band alignment can deplete both electron and hole and reduce the recombination at GBs, which is responsible for the reduced leakage current at GBs. Consequently, the CCZTS solar cell performance was improved with fill factor from 65% up to 71% and efficiency up to 11.10%. Our work not only provides a new and effective passivation method for high efficiency CCZTS solar cells, but also demonstrates a new direction for optimizing the solar cells performance with band alignment engineering.

GmWRKY81 Encoding a WRKY Transcription Factor Enhances Aluminum Tolerance in Soybean.

Aluminum (Al) toxicity is an essential factor that adversely limits soybean (Glycine max (L.) Merr.) growth in acid soils. WRKY transcription factors play important roles in soybean responses to abiotic stresses. Here, GmWRKY81 was screened from genes that were differentially expressed under Al treatment in Al-tolerant soybean Baxi10 and Al-sensitive soybean Bendi2. We found that GmWRKY81 was significantly induced by 20 μM AlCl3 and upregulated by AlCl3 treatment for 2 h. In different tissues, the expression of GmWRKY81 was differentially induced. In 0–1 cm root tips, the expression of GmWRKY81 was induced to the highest level. The overexpression of GmWRKY81 in soybean resulted in higher relative root elongation, root weight, depth, root length, volume, number of root tips and peroxidase activity but lower root average diameter, malonaldehyde and H2O2 contents, indicating enhanced Al tolerance. Moreover, RNA-seq identified 205 upregulated and 108 downregulated genes in GmWRKY81 transgenic lines. Fifteen of these genes that were differentially expressed in both AlCl3-treated and GmWRKY81-overexpressing soybean had the W-box element, which can bind to the upstream-conserved WRKY domain. Overall, the combined functional analysis indicates that GmWRKY81 may improve soybean Al tolerance by regulating downstream genes participating in Al3+ transport, organic acid secretion and antioxidant reactions.

Boswellic acids ameliorate neurodegeneration induced by AlCl3: the implication of Wnt/β-catenin pathway

Alzheimer’s disease (AD) is a neurodegenerative disease (ND) that represents the principal cause of dementia. Effective treatment is still lacking. Without prevention, Alzheimer’s disease (AD) incidence is expected to triple within 30 years. The risk increases in highly polluted areas and is positively linked to chronic aluminum (Al) exposure. Canonical Wingless-Int (Wnt)/β-catenin pathway has been found to play a considerable role in ND pathogenesis. Resins of Boswellia serrata (frankincense) have been used traditionally for their psychoactive activity, in addition to their memory-boosting effects. Boswellic acids (BA) are pentacyclic triterpenes. They have antioxidant, anti-inflammatory, antinociceptive, and immunomodulatory activities. This study aimed to elucidate the role of the Wnt/β-catenin pathway in BA protective activity against aluminum-induced Alzheimer’s disease. For 6 weeks, rats were treated daily with AlCl3 (100 mg/kg/i.p.) either alone or with BA (125 or 250 mg/kg PO). Results indicated that BA significantly improved learning and memory impairments induced by AlCl3 treatment. Moreover, BA treatment significantly decreased acetylcholinesterase levels and reduced amyloid-beta (Aβ) expression. In addition, BA ameliorated the increased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), inhibited lipid peroxidation, and increased total antioxidants in the brain. Indeed, BA significantly suppressed AlCl3-induced decrease of brain-derived neurotrophic factor, pGSK-3β (Ser 9), and β-catenin. BA (250 mg/kg) showed a significant protective effect compared to a lower dose. The results conclude that BA administration modulated the expression of Wnt/β-catenin pathway-related parameters, contributing to BA’s role against Al-induced Alzheimer’s disease.Graphical abstractEffect of Boswellic acids on AlCl3-induced neurodegenerative changes. ChE cholinesterase, Ach acetylcholine, BDNF brain-derived neurotrophic factor, IL-1β interleukin-1β, TNF-α tumor necrosis factor-α

Aluminum chloride impaired spatial memory, but not senile plaques formation in the rat model of Alzheimer’s disease

Aluminum compounds can be easily found in the environment. Aluminum contamination is the environmental factor as one of the risk factors for Alzheimer's disease (AD). In the animal model, aluminum chloride (AlCl3) induces inflammation and oxidative stress. Inflammation and oxidative stress are important pathogenesis pathways in the AD. This study was conducted to determine whether AlCl3 can impair spatial memory and induce senile plaques formation. A total of 24 young adult Wistar rats were used in this study. The rats were divided into four groups; one control group and three AlCl3 treated groups with doses of 150 mg/kg, 300 mg/kg, and 600 mg/kg, respectively for 8 weeks. The spatial memory test was measured using Morris water maze and the histopathology was done by identification of senile plaques formation in the hippocampal tissue. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by Tukey's test for multiple comparisons. The level of statistical significance was set at a p value &lt; 0.05. This study showed that there are significant differences (p&lt;0,05) between the control group and all the AlCl3 treatment groups in the memory test, however, there is no change in the senile plaque’s expression in all groups. Administration of AlCl3 for 8 weeks can cause the impaired of spatial memory without senile plaques formation.

GsERF1 enhances Arabidopsis thaliana aluminum tolerance through an ethylene-mediated pathway

Ethylene response factor (ERF) transcription factors constitute a subfamily of the AP2/ERF superfamily in plants and play multiple roles in plant growth and development as well as in stress responses. In this study, the GsERF1 gene from the wild soybean BW69 line (an Al-resistant Glycine soja line) was rapidly induced in response to aluminum stress. Quantitative real-time PCR (qRT–PCR) analysis showed that the GsERF1 gene maintained a constitutive expression pattern and was induced in soybean in response to aluminum stress, with increased amounts of transcripts detected in the roots. The putative GsERF1 protein, which contains an AP2 domain, was located in the nucleus and maintained transactivation activity. In addition, under AlCl3 treatment, GsERF1 overexpression increased the relative growth rate of the roots of Arabidopsis and weakened the hematoxylin staining of hairy roots. Ethylene synthesis-related genes such as ACS4, ACS5 and ACS6 were upregulated in GsERF1 transgenic lines compared with the wild type under AlCl3 treatment. Furthermore, the expression levels of stress/ABA-responsive marker genes, including ABI1, ABI2, ABI4, ABI5 and RD29B, in the GsERF1 transgenic lines were affected by AlCl3 treatment, unlike those in the wild type. Taken together, the results indicated that overexpression of GsERF1 may enhance aluminum tolerance of Arabidopsis through an ethylene-mediated pathway and/or ABA signaling pathway, the findings of which lay a foundation for breeding soybean plants tolerant to aluminum stress.

The effects of aqueous leaf extract of Portulaca oleracea on haemato-biochemical and histopathological changes induced by sub-chronic aluminium toxicity in male wistar rats

BackgroundPurslane has wide acceptability as a potherb in Central Europe, Asia, and Mediterranean region, it is very used in traditional Chinese medicine (TCM) to treat fever, dysentery, diarrhea, carbuncles, eczema, and to remove toxic substances. Our study aimed to investigate the impact of purslan on physiological and biochemical alterations induced by AlCl3 intoxication in rats. MethodologyFifteen males albino Wistar rats were randomly divided into 3 groups (n = 5); healthy rats (Control), AlCl3 (200 mg/kg b.w) treated rats and AlCl3 (200 mg/kg b.w) rats treated with aqueous extract of P. oleracea (400 mg/kg b.w). AlCl3 treatments were given to rats orally for 70 days and purslan extract for 21 days. Various parameters as hematological, biochemical, oxidative stress markers and liver histopathology were estimated. In-vitro study of plant, some quantitative parameters was analyzed using standard protocols. ResultsIn vitro phytochemical test results revealed that purslane contains most of the principal active molecules, especially flavonoids and phenolic compounds. In vivo results, the AlCl3 group showed an alteration in the antioxidant defend system by increasing the MDA level and decreasing the GSH levels, GST and SOD activities compared to control. Furthermore, the hematological parameters revealed that AlCl3 induce an inflammation in rats by significant raise (P<0.01) of WBC, Monocyte, LYM and platelet (P<0.001) levels with a significant perturbation in lipid profile and biochemical parameters. In the other hand, histopathological analysis recorded a deep modification in liver tissues of AlCl3 rats group compared to control. However, the treatment of AlCl3 rats by purslan ensured a partial amelioration and correction of the previous parameters. ConclusionWe conclude that the use of purslane seems to be the powerful limited of AlCl3 toxicity development, which opening the new horizons for the use of phytotherapy in medical approach.

Comparative study of aluminum (Al) speciation on apoptosis-promoting process in PC12 cells: Correlations between morphological characteristics and mitochondrial kinetic disorder

Aluminum contamination in environment is very serious and the central nervous system is the main target of aluminum toxicity. The neurotoxic of aluminum is closely related to its speciation. PC12 cells were taken as the cell model to compare the morphological characteristics and mitochondrial kinetic disorder of two speciation of aluminum compounds (AlCl3 and aluminum-maltolate (Al(mal)3)). When the concentration of AlCl3 was 3 mM, the intracellular aluminum ion content was 3.87 times that of the 0.5 mM Al(mal)3 treatment group. At the 3 mM AlCl3 treatment group, intracellular ion homeostasis was disrupted. Abnormally elevated Ca2+ levels inhibited protein kinase B (AKT) phosphorylation, resulting in impaired cell morphology. At the 0.5 mM Al(mal)3 treatment group, abnormally high levels of Ca2+ caused mitochondrial kinetic disorder, which led to impaired cellular energy metabolism. Al(mal)3 had shown more cytotoxic in PC12 than AlCl3 at the same concentration. AlCl3 tended to inhibit the phosphorylation of AKT and damages cell morphology. Al(mal)3 mainly affected mitochondrial kinetic disorder, which led to impaired cellular energy metabolism. These findings provided experimental evidence for in-depth research on aluminum-induced neurotoxicity.

Marine fungal metabolite butyrolactone I prevents cognitive deficits by relieving inflammation and intestinal microbiota imbalance on aluminum trichloride-injured zebrafish

BackgroundMounting evidences indicate that oxidative stress, neuroinflammation, and dysregulation of gut microbiota are related to neurodegenerative disorders (NDs). Butyrolactone I (BTL-I), a marine fungal metabolite, was previously reported as an in vitro neuroprotectant and inflammation inhibitor. However, little is known regarding its in vivo effects, whereas zebrafish (Danio rerio) could be used as a convenient in vivo model of toxicology and central nervous system (CNS) diseases.MethodsHere, we employed in vivo and in silico methods to investigate the anti-NDs potential of BTL-I. Specifically, we established a cognitive deficit model in zebrafish by intraperitoneal (i.p.) injection of aluminum trichloride (AlCl3) (21 μg) and assessed their behaviors in the T-maze test. The proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) as well as acetylcholinesterase (AChE) activity or glutathione (GSH) levels were assayed 24 h after AlCl3 injection. The intestinal flora variation of the zebrafish was investigated by 16S rDNA high-throughput analysis. The marine fungal metabolite, butyrolactone I (BTL-I), was used to modulate zebrafish cognitive deficits evoked by AlCl3 and evaluated about its effects on the above inflammatory, cholinergic, oxidative stress, and gut floral indicators. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of BTL-I were studied by the in silico tool ADMETlab.ResultsBTL-I dose-dependently ameliorated AlCl3-induced cognitive deficits in zebrafish. While AlCl3 treatment elevated the levels of central and peripheral proinflammatory cytokines, increased AChE activity, and lowered GSH in the brains of zebrafish, these effects, except GSH reduction, were reversed by 25–100 mg/kg BTL-I administration. Besides, 16S rDNA high-throughput sequencing of the intestinal flora of zebrafish showed that AlCl3 decreased Gram-positive bacteria and increased proinflammatory Gram-negative bacteria, while BTL-I contributed to maintaining the predominance of beneficial Gram-positive bacteria. Moreover, the in silico analysis indicated that BTL-I exhibits acceptable drug-likeness and ADMET profiles.ConclusionsThe present findings suggest that BTL-I is a potential therapeutic agent for preventing CNS deficits caused by inflammation, neurotoxicity, and gut flora imbalance.

Protective effects of hydroxy-α-sanshool from the pericarp of Zanthoxylum bungeanum Maxim. On D-galactose/AlCl3-induced Alzheimer's disease-like mice via Nrf2/HO-1 signaling pathways

Hydroxy-α-sanshool (HAS) is an unsaturated fatty acid amide from Zanthoxylum bungeanum Maxim. with hypolipidemic, hypoglycemic, anti-inflammatory, and neurotrophic effects, etc. In this study, results indicated that HAS effectively ameliorated spontaneous locomotion deficit of mice induced by D-galactose (D-gal) and AlCl3 treatment in open field test. Results of Morris water maze test (MWM) showed that HAS significantly improved the spatial learning and memory ability of aging mice. Histopathological evaluations revealed that HAS markedly alleviated morphological changes and increased number of Nissl neurons in hippocampus of D-gal/AlCl3-induced Alzheimer's disease (AD)-like mice. HAS markedly reduced malondialdehyde (MDA) production, and increased the activity of antioxidative enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), showing an inhibitory effect on oxidative stress. Furthermore, HAS treatment obviously reversed the inhibitory expressions of mRNA and protein of HO-1 and Nrf2 in the hippocampus of AD mice, suggesting that neuroprotective effects of HAS against oxidative stress might be mediated by the Nrf2/HO-1 pathway. Meanwhile, HAS significantly inhibited neuronal apoptosis by decreasing mRNA and protein expressions of Cyt-c, Bax and Caspase 3, and increasing Bcl-2 expression in the hippocampus of AD mice. These results suggest that HAS have the potential to be developed as antioxidant drug for the prevention and early therapy of AD.

Acid soil tolerance of 28 soybean varieties in hydroponics and soil-based evaluation

Utilization of marginal soil plays important role in improving soybean production in Indonesia. Soybean breeding program targeting high yielding varieties and tolerant to acid soils is estimated to be more cost-effective and environmentally friendly approach in improving plant productivity on acid soil. The aim of this research was to study plant response under acid soil stress and to identify tolerant and sensitive genotype which might be useful for further breeding program. The experiment was conducted using 28 soybean varieties as genetic material. The experiment was carried out in two parts, including seedling evaluation in hydroponics and plant growth evaluation in polybag using acid soil. The first experiment was arranged in factorial randomized block design, consisting of genotype, pH, and AlCl3 treatment as the factors with 5 replications. The second experiment was conducted using randomized complete block design with 5 replications to identify the plant growth in different genotype and acid soil conditions. The results showed that the low pH and high Al inhibits seedlings root growth of soybean genotypes. The estimation of STI from root and shoot dry weight suggests Detam 1 as the most tolerant genotype followed by other varieties with lower level of tolerance. Plant response was different each genotype to both seedling evaluation in hydroponics and plant growth evaluation using acid soil.

Cultivar Differences in the Biochemical and Physiological Responses of Common Beans to Aluminum Stress.

Soil conditions leading to high levels of available aluminum are detrimental to plant growth, but data are limited on genotypic differences in tolerance to aluminum stress in some crops. The aim of this study was to examine the morphological, biochemical, and physiological changes in roots and shoots of 25 common bean (Phaseolus vulgaris L.) cultivars (Pinto market class) under aluminum (Al) treatment. Additionally, this study aimed to assess the range of responses amongst the common bean cultivars relative to their Al toxicity tolerance and sensitivity. Plants were grown hydroponically using a simplified nutrient solution with or without 20 µM AlCl3. Reactive oxygen species (ROS), activities of the antioxidant enzymes superoxide dismutase (SOD) and guaiacol peroxidase (POD), and malondialdehyde (MDA) concentration, an indicator of lipid peroxidation, were measured to establish the effects of Al treatment on the plants. In addition, growth parameters such as shoot and root dry weight, root-to-shoot ratio, root elongation, and root volume changes were also investigated. The cultivar effect was significant for all the measured parameters, except for shoot dry weight. Inhibition of the root and shoot dry weight for selected common bean cultivars shows that the response of common bean to Al stress is genotype-specific. Additionally, Al-induced root elongation inhibition and root volume changes varied among the cultivars. Most cultivars had significantly higher SOD activity (20 of 25 cultivars) and POD activity (12 cultivars) under AlCl3 treatment compared to the controls. A positive significant correlation was observed between MDA and ROS, showing that Al stress induced the accumulation of ROS along with an increase in lipid peroxidation. According to the results of this study, Arapaho and AC Island cultivars could potentially be used in the future production of common beans under Al stress. Therefore, these two cultivars could also be included in Al tolerance breeding programs.