3-Acetyl coumarin alleviate neuroinflammatory responses and oxidative stress in aluminum chloride-induced Alzheimer's disease rat model.

Alzheimer's disease (AD) is a neurodegenerative disorder that impairs mental ability and interrupts cognitive function. Heavy metal exposure like aluminum chloride is associated with neurotoxicity linked to neuro-inflammation, oxidative stress, accumulation of amyloid plaques, phosphorylation of tau proteins associated with AD like symptoms. The objective of the present investigation was to assess the effect 3-acetyl coumarin (3AC) in a rat model of AD. Preliminary screening was performed with SWISS ADME to check for the bioavailability of 3-AC and likeness score which proved favorable. 3-AC docked against Caspase 3, NF-κß and tau protein kinase I exhibited good binding energies. Male rats were divided into six groups (n = 5). AlCl3 (100 mg/kg BW) was administered for 28 days before starting treatment to induce AD. Normal control rats received vehicle. Treatment groups received 10, 20 and 30 mg/kg 3-AC for 28 days. Rivastigmine (2 mg/kg) was the standard. Behavioral tests (EPM, MWM) were performed at 7-day intervals throughout study period. Rats showed improved spatial memory and learning in treatment groups during behavioral tests. Rats were euthanized on day 28. Inflammatory markers (IL-1ß, IL-16 and TNFα) exhibited significant improvement (p < 0.001) in treated rats. Oxidative stress enzymes (SOD, CAT, GSH, MDA) were restored. Caspase3 and NF-κß quantified through qRT-PCR also decreased significantly (p < 0.001) when compared to disease control group. Levels of acetyl cholinesterase, dopamine and noradrenaline were also restored in treated rats significantly (p < 0.001). 3-AC treatment restored neuroprotection probably because of anti-inflammatory, anti-oxidant and anti-cholinesterase potential; hence, this can be considered a promising therapeutic potential alternative.

The effect of three additives on properties of mineral trioxide aggregate cements: a systematic review and meta-analysis of in vitro studies.

BACKGROUND: Several efforts have been made to improve mechanical and biological properties of calcium silicate-based cements through changes in chemical composition of the materials. This study aimed to investigate the physical (including setting time and compressive strength) and chemical (including calcium ion release, pH level) properties as well as changes in cytotoxicity of mineral trioxide aggregate (MTA) after the addition of 3 substances including CaCl2, Na2HPO4, and propylene glycol (PG). METHODS: The systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Electronic searches were performed on PubMed, Embase, and Scopus databases, spanning from 1993 to October 2023 in addition to manual searches. Relevant laboratory studies were included. The quality of the included studies was assessed using modified ARRIVE criteria. Meta-analyses were performed by RevMan statistical software. RESULTS: From the total of 267 studies, 24 articles were included in this review. The results of the meta-analysis indicated that addition of PG increased final setting time and Ca2+ ion release. Addition of Na2HPO4 did not change pH and cytotoxicity but reduced the final setting time. Incorporation of 5% CaCl2 reduced the setting time but did not alter the cytotoxicity of the cement. However, addition of 10% CaCl2 reduced cell viability, setting time, and compressive strength. CONCLUSION: Inclusion of 2.5% wt. Na2HPO4 and 5% CaCl2 in MTA can be advisable for enhancing the physical, chemical, and cytotoxic characteristics of the admixture. Conversely, caution is advised against incorporating elevated concentrations of PG due to its retarding effect. TRIAL REGISTRATION: PROSPERO registration number: CRD42021253707.

Rutin, Puerarin and Silymarin Regulated Aluminum-Induced Imbalance of Neurotransmitters and Metal Elements in Brain of Rats.

Non-specifically binding of aluminum to various substances in the organism can result in toxicity. The accumulation of large amounts of aluminum can cause an imbalance in metal homeostasis and interfere with the synthesis and release of neurotransmitters. Flavonoids have strong metal chelating activity, which can reduce damage to the central nervous system. The purpose of this study was to investigate the protective effect of three representative flavonoids, rutin, puerarin and silymarin, on the brain toxicity induced by long-term exposure to aluminum trichloride (AlCl3). Sixty-four Wistar rats were randomly divided into eight groups (n = 8). The rats in six intervention groups were given 100 or 200 mg/kg BW/day of three different flavonoids for four weeks after a 4-week exposure to 281.40 mg/kg BW/day AlCl3·6H2O, while the rats in the AlCl3-toxicity and control groups were given the vehicle after the period of AlCl3 exposure. The results showed that rutin, puerarin, and silymarin could increase the concentrations of magnesium, iron, and zinc in the brains of the rats. Moreover, the intake of these three flavonoids regulated the homeostasis of amino acid neurotransmitters and adjusted the concentrations of monoamine neurotransmitters to normal levels. Taken together, our data suggest that rutin, puerarin, and silymarin could ameliorate AlCl3-induced brain toxicity in the rats by regulating imbalance of metal elements and neurotransmitters in the brains of rats.

Comparison of cytotoxic and apoptosis-inducing effects of MTA, propolis, and propolis-MTA on immature dental pulp stem cells.

BACKGROUND: Pulpotomy is a treatment option for the preservation of pulp vitality in primary teeth with extensive caries. Propolis is a natural resinous substance with optimal antimicrobial, anti-inflammatory, and immune-regulatory properties. Thus, this study aimed to compare the cytotoxic and apoptosis-inducing effects of mineral trioxide aggregate (MTA), propolis, and MTA-propolis on immature dental pulp stem cells (IDPSCs). METHODS: In this in vitro, experimental study, primary IDPSCs were exposed to propolis, MTA, and MTA-propolis for 24 and 72-h. The cytotoxicity and apoptosis-inducing effects were evaluated using the methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Data were analyzed using ANOVA and Tukey's test at 0.05 level of significance. RESULTS: The cytotoxicity of MTA and MTA-propolis was higher than that of propolis alone at both 24/48 h. In addition, all tested concentrations showed higher biocompatibility at 72-h compared with 24-h (P < 0.0001). In the assessment of apoptosis, propolis-MTA showed higher cell viability compared with other materials (P < 0.0001). CONCLUSION: Propolis-MTA showed higher biocompatibility than MTA. Addition of propolis to MTA improved cell proliferation in the first 24-h. Also, the cytotoxicity of propolis was lower than other materials in the first 24-h. Thus, propolis may serve as a promising pulp capping agent given that its other properties are approved.

Neuroprotective effects of a combination of Boswellia papyrifera and Syzygium aromaticum on AlCl3 induced Alzheimer's disease in male albino rat.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by hippocampal, and cortical neuron deterioration, oxidative stress, and severe cognitive dysfunction. Aluminum is a neurotoxin inducer for cognitive impairments associated with AD. The treatment approaches for AD are unsatisfactory. Boswellia papyrifera and Syzygium aromaticum are known for their pharmacological assets, including antioxidant activity. Therefore, the current study explored the possible mitigating effects of a combination of Boswellia papyrifera and Syzygium aromaticum against aluminum chloride (AlCl3) induced AD. The AD model was established using AlCl3 (100 mg/kg), and the rats were orally administrated with Boswellia papyrifera or Syzygium aromaticum or a combination of them daily for 8 weeks. The Y-maze test was used to test cognition in the rats, while acetylcholinesterase (AChE) and oxidative stress markers were estimated in homogenates of the cerebral cortex and hippocampus. Also, the histopathological examination of the cortex and hippocampus were investigated. The results revealed that administration of either B. papyrifera or S. aromaticum extracts significantly improved the cognitive functions of AD rats, enhanced AChE levels, increased oxidative enzymes levels, including SOD and GSH, and reduced MDA levels in homogenates of the cerebral cortex and hippocampus and confirmed by improvement in histological examination. However, using a combination therapy gave better results compared to a single treatment. In conclusion, the present study provided primary evidence for using a combination of B. papyrifera and S. aromaticum to treat cognitive dysfunction associated with AlCl3 Induced AD by improving the AChE levels and modulating oxidative stress in the brain.

Vitamin K2 protects against aluminium chloride-mediated neurodegeneration.

Recent studies have shown that, coupled with other environmental factors, aluminium exposure may lead to neurodegeneration resulting in cognitive impairment resembling Alzheimer's disease. Menaquinone, a form of vitamin K2, aids in maintaining healthy bones and avoids coronary calcification. It also has anti-inflammatory and antioxidant properties. Here, we study the neuroprotective effects of vitamin K2 (MK-7) using the animal model of Alzheimer's disease (AD). Aluminium chloride (AlCl3; 100 mg/kg for 3 weeks orally) was administered to Swiss albino mice to induce neurodegeneration and Vitamin K2 (100 g/kg for 3 weeks orally) was applied as treatment. This was followed by behavioural studies to determine memory changes. The behavioural observations correlated with proinflammatory, oxidative, and brain histopathological changes in AlCl3-treated animals with or without vitamin K2 treatment. AlCl3 administration led to memory decline which was partially restored in Vitamin K2 treated animals. Myeloperoxidase levels in the brain increased due to AlCl3-mediated inflammation, which Vitamin K2 prevented. The acetylcholine esterase and oxidative stress markers induced by AlCl3 were reversed by Vitamin K2. Also, Vitamin K2 helps to restore hippocampal BDNF levels and reduced the amyloid ß accumulation in AlCl3-administered animals. Additionally, Vitamin K2 protected the hippocampal neurons against AlCl3-mediated damage as observed in histopathological studies. We conclude that Vitamin K2 could partially reverse AlCl3-mediated cognitive decline. It increases acetylcholine and BDNF levels while reducing oxidative stress, neuroinflammation, and ß-amyloid deposition, thus protecting the hippocampal neurons from AlCl3-mediated damage.

Exploring research gaps and trends in the management of acute phosphide poisoning: a systematic review.

Metal phosphides are highly toxic pesticides that result in high morbidities and mortalities worldwide. This systematic review included 350 studies that fulfilled the eligibility criteria. There were significant rising trends of studies on acute aluminum phosphide (AlP) and zinc phosphide (Zn3P2) poisoning (p-values = <.001), pointing to an increased number of phosphide-intoxicated patients. Acute AlP poisoning studies represented 81%, 89.3%, and 97.7% of all descriptive, analytical, and experimental interventional studies included in this review, respectively. High AlP poisoning mortality explains great research interest in AlP poisoning. Thus, after 2016, nearly half (49.7%) of studies on acute AlP poisoning were issued. Also, 78.82% of experimental interventional studies on AlP poisoning were published after 2016. The trends of in-vitro, animal, and clinical studies on AlP poisoning significantly increased with p-values equal to .021, <.001, and <.001, respectively. Seventy-nine treatment modalities for acute AlP poisoning were pooled from 124 studies; 39 management-related case reports, 12 in-vitro studies, 39 animal studies, and 34 clinical studies. All therapeutic modalities were summarized to formulate an integrated and comprehensive overview. For clinicians, therapeutic modalities significantly decreased mortality of acute AlP poisoning in clinical trials included extracorporeal membrane oxygenation (ECMO), N-acetyl cysteine (NAC), vitamin E, glucose-insulin-potassium (GIK) infusion, fresh packed RBCs infusion, and GIT decontamination using oils. However, meta-analyses are needed to provide solid evidence regarding their efficacies. To date, there is no effective antidote nor evidence-based standardized protocol for managing acute AlP poisoning. This article outlined the potential research gaps in phosphide poisoning that might promote and direct future medical research in this context.

Cytotoxicity, biocompatibility and osteoinductive profile of an MTA-hydrogel-based cement: An in vitro and animal study.

AIM: This study aimed to evaluate the cytotoxicity, biocompatibility and osteoinductive profile of a mineral trioxide aggregate (MTA)-hydrogel-based material (MTA Flow) in comparison with MTA Angelus. METHODOLOGY: Cell viability was evaluated in human periodontal ligament stem cells (hPDLSCs) using the methyl-thiazol-tetrazolium (MTT) colourimetric assay. Polyethylene tubes containing the tested materials and empty polyethylene tubes (control) were implanted in the subcutaneous tissue of Wistar rats. Cellular (lymphocyte infiltration) and extracellular events (ECM; collagen fibres) were analysed in histological sections. Immunohistochemical (collagen I, osteopontin, bone sialoprotein, bone morphogenetic protein4) analyses were also performed. RESULTS: At 24, 48 and 72 h, all tested groups showed cell viability similar to control (p > .05). Regarding biocompatibility, all groups showed similar cellular events represented by a slight inflammatory reaction characterized by hyperaemia and a mild lymphocytic inflammatory infiltrate. The analysis of lymphocytes during the time showed a decrease in these cells in the control group and a significant interaction between MTA Angelus and control (p < .001), with MTA Angelus showing a more extensive inflammatory infiltrate. Regarding fibres, an increase in content was observed in all groups during the experimental time (7, 30 and 60 days), however, no difference was detected among the experimental groups (p = .063). After 60 days, the immunoexpression of bone matrix proteins in the MTA Flow group was similar to or higher than that observed in the MTA Angelus and in the control group. CONCLUSIONS: MTA Flow showed a non-cytotoxic behaviour, biocompatibility and ability to stimulate tissue mineralization.

Cytotoxicity and genotoxicity of Bio-C Repair, Endosequence BC Root Repair, MTA Angelus and MTA Repair HP.

The aim was to evaluate in vitro cytotoxicity and genotoxicity of Bio-C Repair (BCR), compared to Endosequence BC Root Repair (ERRM), MTA Angelus (MTA-Ang), and MTA Repair HP (MTA-HP). MC3T3 osteoblastic cells were exposed to extracts of the repairing bioceramic cements. After 1, 3, and 7 days, cytotoxicity and genotoxicity were evaluated by MTT and Micronucleus tests, respectively. Cells not exposed to biomaterials were used as a negative control. Data were compared using ANOVA two-way, followed by the Tukey Test (α=5%). MTA-Ang and MTA-HP showed no difference in relation to control regarding cytotoxicity in any experimental times. BCR and ERRM reduced cell viability after 3 and 7 days (p<0.05); however, the reduction caused by BCR was less than that caused by ERRM. Considering the micronucleus formation, all biomaterials caused an increase after 3 and 7 days (p<0.05), being greater for the BCR and ERRM groups. It can be concluded that BCR is non-cytotoxic in osteoblastic cells, as well as MTA-Ang e MTA Repair HP. BCR and ERRM showed greater genotoxicity than others tested biomaterials.

Trihydroxy piperlongumine protects aluminium induced neurotoxicity in zebrafish: Behavioral and biochemical approach.

Aluminium (Al) is proven to be a potent environmental neurotoxin involved in progressive neurodegeneration. Al primarily induces oxidative stress by free radical generation in the brain, followed by neuronal apoptosis. Antioxidants are promising therapeutic options for Al toxicity. Piperlongumine is traditionally long known for its medicinal properties. Therefore, the present study has been designed to explore the antioxidant role of trihydroxy piperlongumine (THPL) against Al-induced neurotoxicity in the zebrafish model. Zebrafish exposed to AlCl3 exhibited higher oxidative stress and altered locomotion. Adult fish displayed anxiety comorbid with depression phenotype. THPL increases antioxidant enzyme activity by quenching Al-induced free radicals and lipid peroxidation, thus minimizing oxidative damage in the brain. THPL rescues behavior deficits and improves anxiety-like phenotype in adult fish. Histological alterations caused by Al were also attenuated on administration with THPL. Results of the study demonstrate the neuroprotective role of THPL against Al-induced oxidative damage and anxiety, which could be exploited as a psychopharmacological drug.

Neuroprotective Effect of Quercetin and Memantine against AlCl3-Induced Neurotoxicity in Albino Wistar Rats.

Recent evidences indicate that there is a substantial increase in worldwide cases of dementia. Alzheimer's disease is the leading cause of dementia and may contribute to 60-70% of cases. Quercetin is a unique bioflavonoid that has numerous therapeutic benefits such as anti-allergy, anti-ulcer, anti-inflammatory, anti-hypertensive, anti-cancer, immuno-modulatory, anti-infective, antioxidant, acetylcholinesterase inhibitory activity, neuroprotective effects, etc. In the present study, we evaluated the neuroprotective effect of orally administered quercetin with memantine in albino Wistar rats after inducing neurotoxicity through AlCl3 (100 mg/kg, p.o.). Chronic administration of AlCl3 resulted in poor retention of memory and significant oxidative damage. Various behavioral parameters, such as locomotor activity, Morris water maze, elevated plus maze, and passive avoidance test, were assessed on days 21 and 42 of the study. The animals were euthanatized following the completion of the last behavioral assessment. Various oxidative stress parameters were assessed to know the extent of oxidative damage to brain tissue. Quercetin with memantine has shown significant improvement in behavioral studies, inhibition of AChE activity, and reduction in oxidative stress parameters. Histopathological studies assessed for cortex and hippocampus using hematoxylin and eosin (H&E), and Congo red stain demonstrated a reduction in amyloid-ß plaque formation after treatment of quercetin with memantine. Immunohistochemistry showed that quercetin with memantine treatment also improved the expression of brain-derived neurotrophic factor (BDNF) and inhibited amyloid-ß plaque formation. The present study results demonstrated protective effects of treatment of quercetin with memantine in the neurotoxicity linked to aluminum chloride in albino Wistar rats.

Ameliorative Effect of Palm Oil in Aluminum Lactate Induced Biochemical and Histological Implications in Rat Brain.

α-Tocotrienol is one of the major constituents of palm oil. It is a well-known antioxidant and cholesterol-lowering neuroprotectant. To prevent the initiation of Alzheimer's like symptoms, much attention has been shifted to the major role played by antioxidants. Previous epidemiological reports correlate the increasing incidence of developing Alzheimer's disease (AD), to the aluminum (Al) content in drinking water. Al, being a ubiquitous element, has a long history of being particularly reactive towards multiple aspects of neurobiology. So, the current study examines the effect of Al-induced behavioral, biochemical, and histopathological changes in rat brain; and the ameliorative effect of palm oil in reducing the resulting neurotoxicity. The experimental design consisted of 4 groups: control group which received rodent chow diet and water ad libitum; Al group received aluminum lactate (50 mg/kg bw); Al + palm oil group was administered with Al (50 mg/kg bw) and palm oil (60 mg/kg bw); and palm oil group received palm oil (60 mg/kg bw). Al was given by oral gavage once daily for 6 weeks and palm oil was administered intraperitoneally. After 6 weeks of supplementation, Al + palm oil group showed significantly lower malondialdehyde (MDA) content, but higher superoxide dismutase (SOD), catalase (CAT), GST, and GPx activity as compared to Al group. Al group has significantly higher level of MDA content, but lower SOD, CAT, GST, and GPx activity as compared to control group. In conclusion, this study suggested that palm oil was effective in preventing the Al-induced brain damage in rats.

Preparation and Multitarget Anti-AD Activity Study of Chondroitin Sulfate Lithium in AD Mice Induced by Combination of D-Gal/AlCl3.

Previous studies have demonstrated that both CS and LiCl possess anti-Alzheimer's disease (AD) activities. We prepared chondroitin sulfate-Li (CS-Li) and investigated its effect on AD and explored the possible mechanisms both in vitro and in vivo. We found that CS-Li could inhibit amyloid ß (Aß) aggregation and protect SH-SY5Y cells from Aß 1-42-induced cytotoxicity in vitro. In D-gal and AlCl3-induced AD mouse model, CS-Li improves the spatial learning and memory abilities of AD mice, reverses the nuclear pyknosis and cell edema, and increases the survival rate of neurons in hippocampus of mice. Moreover, CS-Li significantly increased the levels of GSH-Px, Na+/K+-ATPase, and ChAT and decreased the levels of MDA and AchE in AD mice. Western blot results demonstrated that CS-Li could decrease the hyperphosphorylation of tau (Ser396/Ser404) by regulating the expression of p-GSK-3ß (Ser9) and PP2A and inhibit the expression of proinflammatory factors through inhibiting NF-κB nuclear translocation by activating the MAPK signaling pathways. In a word, CS-Li can delay AD development through multitarget processes, including Aß aggregation inhibition, oxidative stress damage, tau hyperphosphorylation, and inflammatory response, thereby improves learning and memory abilities.

Global Proteomic Profile of Aluminum-Induced Hippocampal Impairments in Rats: Are Low Doses of Aluminum Really Safe?

Hippocampus is the brain area where aluminum (Al) accumulates in abundance and is widely associated with learning and memory. In the present study, we evaluate behavioral, tissue, and proteomic changes in the hippocampus of Wistar rats caused by exposure to doses that mimic human consumption of aluminum chloride (AlCl3) in urban areas. For this, male Wistar rats were divided into two groups: Control (distilled water) and AlCl3 (8.3 mg/kg/day), both groups were exposed orally for 60 days. After the Al exposure protocol, cognitive functions were assessed by the Water maze test, followed by a collection for analysis of the global proteomic profile of the hippocampus by mass spectrometry. Aside from proteomic analysis, we performed a histological analysis of the hippocampus, to the determination of cell body density by cresyl violet staining in Cornu Ammonis fields (CA) 1 and 3, and hilus regions. Our results indicated that exposure to low doses of aluminum chloride triggered a decreased cognitive performance in learning and memory, being associated with the deregulation of proteins expression, mainly those related to the regulation of the cytoskeleton, cellular metabolism, mitochondrial activity, redox regulation, nervous system regulation, and synaptic signaling, reduced cell body density in CA1, CA3, and hilus.

Physico-chemical properties of aluminum adjuvants in vaccines: Implications for toxicological evaluation.

Aluminum salts have been used as adjuvants in human vaccines since 1932. The most used adjuvants are Al oxyhydroxide (AlOOH) and Al hydroxyphosphate (AlOHPO4). Al adjuvants have different physico-chemical properties. The differences in these properties are not well documented and not considered by the Food and Drug Administration (FDA), though they can largely influence biological effects of the adjuvants which are particulate components. In this study, different physico-chemical properties including the shape, size and charge of particles have been evaluated under different conditions in three Al adjuvants containing-vaccines and two corresponding commercial adjuvants suspensions. The results showed that the two Al adjuvants have different shapes, sizes and charges but both form aggregates. In addition, a clear effect of dilution on the size of the aggregates was observed. Moreover, different sizes of Al particles were measured for both Al oxyhydroxide adjuvant alone or in the vaccine, at identical concentrations, displaying the impact of adsorbed proteins on the size of aggregates in the case of the vaccine. Taken together, this paper suggests the importance to evaluate, before any biological and especially toxicological impact study, the whole physico-chemical properties of Al particle without restricting to the sole evaluation of the injected concentration. Furthermore, any modification of these mentioned parameters during manipulation, before animal or cell exposure, should be considered. In a more global way, the fixed "safe dose" of Al adjuvants should be specific for each type of Al adjuvant independently or for a mix of the two compounds, due to their different properties.

Antimicrobial Action, Genotoxicity, and Morphological Analysis of Three Calcium Silicate-Based Cements.

This study is aimed at evaluating five mineral oxides (5MO), mineral trioxide aggregate repair high plasticity (MTA HP), and mineral trioxide aggregate (MTA) in relation to the antimicrobial action over Porphyromonas gingivalis, Porphyromonas endodontalis, Parvimonas micra, Fusobacterium nucleatum, and Prevotella intermedia; the genotoxicity over mouse macrophage (RAW 264.7) and osteoblast (Mg-63) cultures; and the morphological analysis using scanning electron microscopy (SEM) analysis (50 k and ×100 k). Sodium hypochlorite (NaOCl), calcium hydroxide, and saline solution were used as control groups in the different analysis. All data were submitted to a normality test and then analyzed with one-way ANOVA, Tukey, and Kruskal-Wallis and Dunn tests, considering α ≤ 0.05 significance level. It was found that over P. gingivalis and P. endodontalis, there was no a significant difference between the calcium silicate-based cements (CSC) and the control group of saline solution, and only 5MO was similar to the NaOCl group. However, over P. micra, all groups were effective and showed a statistically significant difference compared to the saline solution group. Conversely, none of the groups were effective over F. nucleatum and P. intermedia, except of the NaOCl group. There was a significant difference between 5MO and MTA groups in comparison with NaOCl and MTA HP over osteoblasts and macrophages after 24 hours. SEM images showed small irregular particles interspersed with some elongated needle-like particles and small irregular particles with some larger particles as well as elongated particles. It was concluded that 5MO, MTA, and MTA HP have effective antimicrobial action over P. micra. However, only 5MO is effective over P. gingivalis and P. endodontalis. Besides, 5MO and MTA are not genotoxic over mouse macrophage (RAW 264.7) and osteoblast (Mg-63) cultures.

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.

Chronic oral exposure of aluminum chloride in rat modulates molecular and functional neurotoxic markers relevant to Alzheimer's disease.

Aluminum is an environmentally abundant potential neurotoxic agent that may result in oxidative damage to a range of cellular biomarkers. The potential sources of aluminum accumulation in the body include drinking water, food, medicines, vaccines, and aluminum cookware utensils, etc. The accumulation of aluminum in the brain is reported to be associated with cholinergic dysfunction, oxidative stress and neuronal damage, which may ultimately cause Alzheimer's disease. Since chronic exposure to aluminum leads to its accumulation in the brain, so this study was done by a long-term (24 weeks) low dose (20 mg/kg) oral exposure of aluminum chloride in rats. In this chronic model, we have evaluated the major hallmarks of Alzheimer's disease including amyloid-beta (Aß1-42) and phosphorylated-tau (p231-tau) protein in brain tissue. Furthermore, we evaluated the level of acetyl cholinesterase activity, inflammatory cytokines such as TNF-α, IL-6 and IL-1ß, and oxidative stress biomarkers in the rat brain in this model. The neurobehavioral parameters were also assessed in animals by using spontaneous locomotor activity, passive avoidance, rotarod test and novel object recognition test to evaluate alteration in learning, memory and muscle co-ordination. We found that chronic oral exposure to aluminum chloride causes a significant increase in structural hallmarks such as Aß1-42 and p231-tau levels along with pro-inflammatory cytokines (TNF-α and IL-6), oxidative stress, and a decrease in antioxidant markers such as GSH and catalase in the brain tissue. These biomarkers significantly affected neurobehavioral parameters in animals. This study provides a mechanistic understanding of chronic aluminum-induced neuronal toxicity in the brain with relevance to Alzheimer's disease.

A case of aluminum phosphide poisoning managed successfully in Nepal: a case report / Un caso de intoxicación por fosfuro de aluminio manejado con éxito en Nepal: informe de un caso

Aluminum phosphide (ALP) is a highly toxic compound most commonly available as Celphos in Nepal. Suicidal ingestion is common in developing countries like Nepal as it is easily available and has a high mortality rate. Farmers to protect crops from rodents and pests use it. Here we present a case of a 24-year-old female with suicidal ingestion of one and a half-tablet of ALP presented with abdominal pain and vomiting. The patient developed metabolic acidosis, hyperkalemia, acute respiratory distress, and hypotension during the Intensive Care Unit stay. Supportive treatment with gastric lavage (coconut oil), intravenous magnesium sulfate, sodium-bicarbonate infusion, adequate vasopressor and close monitoring of hemodynamic parameters helped in the survival of the patient (AU)

El fosfuro de aluminio (ALP) es un compuesto altamente tóxico más comúnmente disponible como Celphos en Nepal. La ingestión suicida es común en países en desarrollo como Nepal, ya que está fácilmente disponible, teniendo una alta tasa de mortalidad. Los agricultores lo utilizan para proteger los cultivos de roedores y plagas. Aquí presentamos el caso de una mujer de 24 años con ingesta suicida de una tableta y media de ALP que presentó dolor abdominal y vómitos. La paciente desarrolló acidosis metabólica, hiperpotasemia, dificultad respiratoria aguda e hipotensión durante su estancia en la Unidad de Cuidados Intensivos. El tratamiento de soporte con lavado gástrico (aceite de coco), sulfato de magnesio intravenoso, infusión de bicarbonato de sodio, vasopresor adecuado y monitoreo estrecho de los parámetros hemodinámicos ayudaron a la supervivencia del paciente (AU)

Intoxicación por fosfuro de aluminio / Aluminum phosphide poisoning

Resumen En la industria agrícola se ha implementado el uso de plaguicidas lo que ha aumentado la cantidad y calidad de los productos agrícolas en varios países en desarrollo, su objetivo es mejorar la calidad de vida y sustento de los consumidores, sin embargo, el uso inadecuado puede causar graves intoxicaciones tanto por ingestión accidental, ocupacional o ingestión con fines suicidas u homicidas, lo cual los hace un tema de relevancia médico legal. El fosfuro de aluminio es un rodenticida, insecticida y fumigante sólido usado como una sustancia ideal para la conservación de los granos, ya que es altamente tóxico contra los insectos que invaden los granos en todos sus estadios sin afectar como tal las semillas y su germinación, es un compuesto accesible y económico lo que hace que su uso con fines suicidas y homicidas sea elevado, ante la intoxicación con fosfuro de aluminio se han descritos síntomas bastante inespecíficos como lo son dolor en el epigastrio, vómitos, diarrea, mareos, disnea y en algunos casos acompañado de un olor a ajo que es característico de ésta intoxicación lo que aumenta la sospecha clínica. Se realizó una revisión bibliográfica en diferentes bases de datos, de los artículos publicados referentes al tema de los últimos doce años, con el objetivo de profundizar en las características del fosfuro de aluminio, su mecanismo de acción y toxicidad. Se concluye que es fundamental conocer los diferentes plaguicidas y sus efectos en la salud, principalmente de aquellos con una alta letalidad, que se podrían estar utilizando clandestinamente y que al ser sumamente económicos son de fácil acceso para emplearse con fines delictivos.

Abstract The agricultural industry has implemented the use of pesticides, which has increased the quantity and quality of agricultural products in several developing countries, its objective is to improve the quality of life and livelihood of consumers, however, improper use can cause serious intoxications both by accidental ingestion, occupational or ingestion for suicidal or homicidal purposes, which makes them an issue of medico-legal relevance. Aluminum phosphide is a rodenticide, insecticide and solid fumigant used as an ideal substance for the preservation of grains, since it is highly toxic against insects that invade the grains in all their stages without affecting the seeds and their germination, it is an accessible and economic compound which makes its use for suicidal and homicidal purposes high, In the face of aluminum phosphide poisoning, quite unspecific symptoms have been described, such as pain in the epigastrium, vomiting, diarrhea, dizziness, dyspnea and in some cases accompanied by a garlic odor which is characteristic of this poisoning, which increases clinical suspicion. A bibliographic review was conducted in different databases, of the articles published on the subject in the last twelve years, with the aim of deepening in the characteristics of aluminum phosphide, its mechanism of action and toxicity. It is concluded that it is essential to know the different pesticides and their effects on health, those with a high lethality, which could be used clandestinely and which, being extremely cheap, are easily accessible to be used for criminal purposes