Cytotoxicity of dilutions of bioceramic materials in stem cells of human exfoliated deciduous teeth.

OBJECTIVE: Several materials have been developed to preserve pulp vitality. They should have ideal cytocompatibility characteristics to promote the activity of stem cells of human exfoliated deciduous teeth (SHED) and thus heal pulp tissue. OBJECTIVE: To evaluate the cytotoxicity of different dilutions of bioceramic material extracts in SHED. METHODOLOGY: SHED were immersed in αMEM + the material extract according to the following experimental groups: Group 1 (G1) -BBio membrane, Group 2 (G2) - Bio-C Repair, Group 3 (G3) - MTA Repair HP, Group 4 (G4) - TheraCal LC, and Group 5 (G5) - Biodentine. Positive and negative control groups were maintained respectively in αMEM + 10% FBS and Milli-Q Water. The methods to analyze cell viability and proliferation involved MTT and Alamar Blue assays at 24, 48, and 72H after the contact of the SHED with bioceramic extracts at 1:1 and 1:2 dilutions. Data were analyzed by the three-way ANOVA, followed by Tukey's test (p<0.05). RESULTS: At 1:1 dilution, SHED in contact with the MTA HP Repair extract showed statistically higher cell viability than the other experimental groups and the negative control (p<0.05), except for TheraCal LC (p> 0.05). At 1:2 dilution, BBio Membrane and Bio-C showed statistically higher values in intra- and intergroup comparisons (p<0.05). BBio Membrane, Bio-C Repair, and Biodentine extracts at 1:1 dilution showed greater cytotoxicity than 1:2 dilution in all periods (p<0.05). CONCLUSION: MTA HP Repair showed the lowest cytotoxicity even at a 1:1 dilution. At a 1:2 dilution, the SHED in contact with the BBio membrane extract showed high cell viability. Thus, the BBio membrane would be a new non-cytotoxic biomaterial for SHED. Results offer possibilities of biomaterials that can be indicated for use in clinical regenerative procedures of the dentin-pulp complex.

Evaluation of the Protective Effects of Lugol's Solution in Rats Poisoned with Aluminum Phosphide (Rice Tablets).

Aluminum phosphide (AlP) is the main component of rice tablets (a pesticide), which produces phosphine gas (PH3) when exposed to stomach acid. The most important symptoms of PH3 toxicity include, lethargy, tachycardia, hypotension, and cardiac shock. It was shown that Iodine can chemically react with PH3, and the purpose of this study is to investigate the protective effects of Lugol solution in poisoning with rice tablets. Five doses (12, 15, 21, 23, and 25 mg/kg) of AlP were selected, for calculating its lethal dose (LD50). Then, the rats were divided into 4 groups: AlP, Lugol, AlP + Lugol, and Almond oil (as a control). After 4 h, the blood pressure and electrocardiogram (ECG) were recorded, and blood samples were obtained for biochemical tests, then liver, lung, kidney, heart, and brain tissues were removed for histopathological examination. The results of the blood pressure showed no significant changes (P > 0.05). In ECG, the PR interval showed a significant decrease in the AlP + Lugol group (P < 0.05). In biochemical tests, LDH, Ca2+, Creatinine, ALP, Mg2+, and K+ represented significant decreases in AlP + Lugol compared to the AlP group (P < 0.05). Also, the administration of Lugol's solution to AlP-poisoned rats resulted in a significant decrease in malondialdehyde levels and a significant increase in catalase activity (P < 0.05). Histopathological evaluation indicates that Lugol improves changes in the lungs, kidneys, brain, and heart. Our results showed that the Lugol solution could reduce tissue damage and oxidative stress in AlP-poisoned rats. We assume that the positive effects of Lugol on pulmonary and cardiac tissues are due to its ability to react directly with PH3.

Mitotherapy with Fresh Isolated Cardiac Mitochondria Via Injection Into Blood Reduces Aluminum Phosphide-Induced Mortality and Protects Cardiac Tissue Against Oxidative Stress and Mitochondrial Damages.

The hallmark of aluminum phosphide (AlP) poisoning is heart failure in victims which is associated with reactive oxygen species (ROS), mitochondrial dysfunction, oxidative stress, alteration in antioxidant defense system and depletion of ATP in cardiomyocytes. In the present study, we hypothesized that the injection of isolated mitochondria into blood or mitochondrial transplantation can likely create a primary target for phosphine released from AlP and inhibit AlP-induced mortality and cardiotoxicity in rat. Male, Wistar, healthy and adult rats were randomly divided into 5 groups as control, AlP (12.5 mg/kg, orally), AlP + mitochondria (125 µg/kg), AlP + mitochondria (250 µg/kg) and mitochondria (250 µg/kg) alone. Functional and intact mitochondria isolated from rat heart and transplantation was carried out via tail vein, 30 min after exposure to AlP. Survival rate, histopathological alterations, cardiac biochemical markers, oxidative stress and mitochondrial toxicity parameters were monitored and analyzed during 30 days. We found that injection of healthy mitochondria into blood at concentrations of 125 and 250 125 µg/ml significantly increased the survival of rats up to 40% and 56.25% respectively, during 30 days. Moreover, we observed that mitochondria injection into blood decreased histopathological damages, cardiac biochemical markers, oxidative stress and mitochondrial toxicity parameters. To our knowledge, the current study is the first report in the literature that demonstrated good therapeutic effects of mitochondrial transplantation in AlP-induced mortality and cardiotoxicity. The findings of the present study suggests that injection of exogenous mitochondria into blood could be an effective therapeutic strategy in treating AlP poisoning.

Apoptotic effects of biodentine, calcium-enriched mixture (CEM) cement, ferric sulfate, and mineral trioxide aggregate (MTA) on human mesenchymal stem cells isolated from the human pulp of exfoliated deciduous teeth.

BACKGROUND: Preservation of primary teeth in children is highly important. Pulpotomy is a commonly performed treatment procedure for primary teeth with extensive caries. Thus, biocompatibility of pulpotomy agents is highly important. Biodentine, calcium enriched mixture (CEM) cement, ferric sulfate, and mineral trioxide aggregate (MTA) Angelus are commonly used for this purpose. Thus, this study aimed to assess the apoptotic effects of Biodentine, CEM cement, ferric sulfate, and MTA on stem cells isolated from the human pulp of exfoliated deciduous teeth. METHODS: In this in-vitro, experimental study, stem cells isolated from the human pulp of exfoliated deciduous teeth were exposed to three different concentrations of Biodentine, CEM cement, ferric sulfate, and MTA for different time periods. The cytotoxicity of the materials was evaluated by flow cytometry using the annexin propidium iodide (PI) kit. Data were analyzed by ANOVA and Tukey's test at P<0.05 level of significance. RESULTS: All four tested materials induced significantly greater apoptosis compared with the control group. The difference in cell apoptosis caused by the first concentration of ferric sulfate and MTA was not significant at 24 hours. In other comparisons, the cytotoxicity of ferric sulfate was significantly lower than that of other materials. Biodentine showed higher cytotoxicity than MTA at first; but this difference faded over time. The cytotoxicity of CEM cement was comparable to that of MTA. The highest cell viability was noted at 24 hours in presence of the minimum concentration of ferric sulfate. The lowest cell viability was noted at 72 hours in presence of the maximum concentration of CEM cement. CONCLUSIONS: In comparison with other materials, ferric sulfate showed minimum cytotoxicity; the cytotoxicity of the three cements was comparable. It appears that the concentration of ferric sulfate and the composition of cements are responsible for different levels of cytotoxicity.

Evaluation of the protective effect of coenzyme Q10 on hepatotoxicity caused by acute phosphine poisoning.

Background: Aluminum phosphide (AlP) poisoning is prevalent in numerous countries, resulting in high mortality rates. Phosphine gas, the primary agent responsible for AlP poisoning, exerts detrimental effects on various organs, notably the heart, liver and kidneys. Numerous studies have documented the advantageous impact of Coenzyme Q10 (CoQ10) in mitigating hepatic injuries. The objective of this investigation is to explore the potential protective efficacy of CoQ10 against hepatic toxicity arising from AlP poisoning. Method: The study encompassed distinct groups receiving almond oil, normal saline, exclusive CoQ10 (at a dosage of 100 mg/kg), AlP at 12 mg/kg; LD50 (lethal dose for 50%), and four groups subjected to AlP along with CoQ10 administration (post-AlP gavage). CoQ10 was administered at 10, 50, and 100 mg/kg doses via Intraparietal (ip) injections. After 24 h, liver tissue specimens were scrutinized for mitochondrial complex activities, oxidative stress parameters, and apoptosis as well as biomarkers such as aspartate transaminase (AST) and alanine transaminase (ALT). Results: AlP induced a significant decrease in the activity of mitochondrial complexes I and IV, as well as a reduction in catalase activity, Ferric Reducing Antioxidant Power (FRAP), and Thiol levels. Additionally, AlP significantly elevated oxidative stress levels, indicated by elevated reactive oxygen species (ROS) production, and resulted in the increment of hepatic biomarkers such as AST and ALT. Administration of CoQ10 led to a substantial improvement in the aforementioned biochemical markers. Furthermore, phosphine exposure resulted in a significant reduction in viable hepatocytes and an increase in apoptosis. Co-treatment with CoQ10 exhibited a dose-dependent reversal of these observed alterations. Conclusion: CoQ10 preserved mitochondrial function, consequently mitigating oxidative damage. This preventive action impeded the progression of heart cells toward apoptosis.

Evaluating the possible genotoxicity of nanoaluminum incorporated in human vaccines and the potential protective role of nanocurcumin: an in vivo study.

For nearly 90 years, aluminum (Al) salts have been utilized as vaccination adjuvants. Nevertheless, there is a risk of adverse effects associated with the amount of nanoaluminum used in various national pediatric immunization regimens. This study aimed to investigate the possible genotoxic effects of nanoaluminum incorporated in human vaccines on the brains of newborn albino rats and whether nanocurcumin has a potential protective effect against this toxicity. Fifty newborn albino rats were randomly assigned to 5 groups, with 10 in each group. Groups 1 and 2 received "high" and "low" Al injections corresponding to either the American or Scandinavian pediatric immunization schedules, respectively, as opposed to the control rats (group 5) that received saline injections. Groups 3 and 4 received the same regimens as groups 1 and 2 in addition to oral nanocurcumin. The expression of both the cell breakdown gene tumor protein (P53) and the cell stress gene uncoupling protein 2 (UCP2) was significantly greater in groups 1 and 2 than in group 5. Groups 1 and 2 exhibited severe DNA fragmentation, which was observed as DNA laddering. Nanocurcumin significantly reduced the expression of the P53 and UCP2 genes in groups 3 and 4, with very low or undetectable DNA laddering in both groups. Vaccination with nanoaluminum adjuvants can cause genotoxic effects, which can be mediated by the inflammatory response and oxidative stress, and nanocurcumin can protect against these toxic effects through the modulation of oxidative stress regulators and gene expression.

Leaching and cytotoxicity of bismuth oxide in ProRoot MTA - A laboratory investigation.

AIM: The present study examined the leaching and cytotoxicity of bismuth from ProRoot MTA and aimed to identify whether bismuth leaching was affected by the cement base and the immersion regime used. METHODOLOGY: The leaching profile of bismuth was examined from ProRoot MTA and compared with hydroxyapatite containing 20% bismuth oxide as well as hydroxyapatite and tricalcium silicate to investigate whether bismuth release changed depending on the cement base. Bismuth leaching was determined after 30 and 180 days of ageing immersed in Dulbecco's modified Eagle's medium (DMEM) using mass spectroscopy (ICP-MS). The media were either unchanged or regularly replenished. The pH, surface microstructure and phase changes of aged materials were assessed. Wistar rat femoral bone marrow stromal cells (BMSCs) and cutaneous fibroblasts were isolated, cultured and seeded for cell counting (trypan blue live/dead) after exposure to non-aged, 30- and 180-days-aged samples in regularly replenished DMEM. Aged DMEM in contact with materials was also used to culture BMSCs to investigate the effect of material leachates on the cells. Gene expression analysis was also carried out after direct exposure of cells to non-aged materials. Differences between groups were statistically tested at a significance level of 5%. RESULTS: All materials exhibited alterations after immersion in DMEM and this increased with longer exposure times. The bismuth leached from ProRoot MTA as detected by ICP-MS. Aged ProRoot MTA samples exhibited a black discolouration and surface calcium carbonate deposition. ProRoot MTA influenced cell counts after direct exposure and its 180-days leachates reduced BMSC viability. After direct BMSC contact with non-aged ProRoot MTA an upregulation of metallothionein (MT1 and MT2A) expression and down-regulation of collagen-1a (Col-1a) and bone sialoprotein (BSP) expression was identified. CONCLUSIONS: Bismuth leaching was observed throughout 180-days observation period from all materials containing bismuth oxide. This negatively influenced cell viability and gene expression associated with bismuth exposure. This is the first study to report that metallothionein gene expression was influenced by exposure to ProRoot MTA.

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.

Modulating oxidative stress, apoptosis, and mitochondrial dysfunctions on cardiotoxicity induced by aluminum phosphide pesticide using resveratrol.

The agricultural fumigant pesticide aluminum phosphide (AlP) is cardiotoxic. Water causes AlP to emit phosphine gas, a cardiac toxin that affects heart function and causes cardiogenic shock. AlP poisoning's high fatality rate is due to cardiotoxicity. This study examines how resveratrol reduces oxidative stress, mitochondrial activity, and apoptosis in human cardiac myocyte (HCM) cells. After determining the optimal doses of resveratrol using the MTT test, HCM cells were subjected to a 24-h treatment of resveratrol following exposure to AlP (2.36 µM). The levels of reactive oxygen species (ROS), superoxide dismutase (SOD) activity, mitochondrial swelling, mitochondrial cytochrome c release, and mitochondrial membrane potential (MMP) in HCM cells were investigated. Also, the expression of Bax and Bcl-2, caspace-3 activity, and apoptosis were assessed. The present investigation revealed that AlP substantially increased the level of ROS and decreased SOD activation, which were significantly modulated by resveratrol in a dose-dependent manner. Moreover, AlP induced an elevation of mitochondrial swelling, cytochrome c release, and MMP collapse. Co-administration of resveratrol significantly reduced above mitochondrial markers. AlP also significantly upregulated BAX and downregulated Bcl-2 expression, elevated caspace-3 activity, and apoptosis. Resveratrol co-administration was able to meaningfully modulate the mentioned parameters and finally reduce apoptosis. In conclusion, resveratrol, via its pleotropic properties, significantly demonstrated cytoprotective effects on HCM cytotoxicity induced by AlP.

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.

Neurotoxicity Profiling of Aluminum Salt-Based Nanoparticles as Adjuvants for Therapeutic Cancer Vaccine.

Therapeutic vaccines containing aluminum adjuvants have been widely used in the treatment of tumors due to their powerful immune-enhancing effects. However, the neurotoxicity of aluminum adjuvants with different physicochemical properties has not been completely elucidated. In this study, a library of engineered aluminum oxyhydroxide (EAO) and aluminum hydroxyphosphate (EAHP) nanoparticles was synthesized to determine their neurotoxicity in vitro. It was demonstrated that the surface charge of EAHPs and size of EAOs did not affect the cytotoxicity in N9, bEnd.3, and HT22 cells; however, soluble aluminum ions trigger the cytotoxicity in three different cell lines. Moreover, soluble aluminum ions induce apoptosis in N9 cells, and further mechanistic studies demonstrated that this apoptosis was mediated by mitochondrial reactive oxygen species generation and mitochondrial membrane potential loss. This study identifies the safety profile of aluminum-containing salts adjuvants in the nervous system during therapeutic vaccine use, and provides novel design strategies for their safer applications. SIGNIFICANCE STATEMENT: In this study, it was demonstrated that engineered aluminum oxyhydroxide and aluminum hydroxyphosphate nanoparticles did not induce cytotoxicity in N9, bEnd.3, and HT22 cells. In comparation, soluble aluminum ions triggered significant cytotoxicity in three different cell lines, indicating that the form in which aluminum is presenting may play a crucial role in its safety. Moreover, apoptosis induced by soluble aluminum ions was dependent on mitochondrial damage. This study confirms the safety of engineered aluminum adjuvants in vaccine formulations.

Protective effect of resveratrol and tannic acid combination on aluminium chloride induced neurotoxicity in rats.

OBJECTIVE: Alzheimer's disease is a progressive neurodegenerative disease and one of the most common causes of dementia. Despite recent advancements, there exists an unmet need for a suitable therapeutic option. This study aimed to evaluate the protective effects of the combination of resveratrol (20 mg/kg/day p.o.) and tannic acid (50 mg/kg/day p.o.) to reduce aluminium trichloride-induced Alzheimer's disease in rats. METHODS: Wistar rats weighing 150-200g were administered with aluminium chloride (100 mg/kg/day p.o.) for 90 days to induce neurodegeneration and Alzheimer's disease. Neurobehavioral changes were assessed using novel object recognition test, elevated plus maze test, and Morris water maze test. Histopathological studies were performed using H&E stain and Congo Red stains to check amyloid deposits. Further oxidative stress was measured in brain tissue. RESULTS: Aluminium trichloride treated negative control group showed cognitive impairment in the Morris water maze test, novel object recognition test, and elevated plus maze test. Further, the negative control group showed significant oxidative stress, increase amyloid deposits, and severe histological changes. Treatment with the combination of resveratrol and tannic acid showed significant attenuation in cognitive impairment. The oxidative stress markers and amyloid plaque levels were significantly attenuated with the treatment. CONCLUSION: The present study indicates the beneficial effects of resveratrol-tannic acid combination in AlCl3 induced neurotoxicity in rats.

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.