Novel insights into famotidine as a GSK-3ß inhibitor: An explorative study in aluminium chloride-induced Alzheimer's disease rat model.

Alzheimer's disease (AD), a chronic neurodegenerative disease, presents a substantial global health challenge. This study explored the potential therapeutic role of famotidine, a histamine (H2) receptor antagonist, as a glycogen synthase kinase-3ß (GSK-3ß) inhibitor in the context of AD induced by aluminium chloride (AlCl3) in a rat model. The intricate relationship between GSK-3ß dysregulation and AD pathogenesis, particularly in amyloid-ß (Aß) production, formed the basis for investigating famotidine's efficacy. Molecular modelling revealed famotidine's efficient binding to GSK-3ß, suggesting inhibitory potential. In behavioural assessments, famotidine-treated groups exhibited dose-dependent improvements in Morris Water Maze, Novel Object Recognition, and Y-Maze tests, comparable to the standard Rivastigmine tartrate group. Biochemical analyses showed that famotidine inhibits acetylcholinesterase, decreases lipid peroxidation, increases antioxidant activity, and mitigates oxidative stress. Moreover, famotidine significantly lowered the levels of GSK-3ß, IL-6, and Aß(1-42). The neuroprotective effects of famotidine were further supported by histopathological analysis. This comprehensive investigation underscores famotidine's potential as a GSK-3ß inhibitor, providing insights into its therapeutic impact on AD induced by AlCl3. The study offers a promising avenue for repurposing famotidine due to its established safety profile and widespread availability, highlighting its potential in addressing the formidable challenge of AD.

Chronic aluminium chloride exposure induces redox imbalance, metabolic distress, DNA damage, and histopathologic alterations in Wistar rat liver.

Aluminium, a ubiquitous environmental toxicant, is distinguished for eliciting a broad range of physiological, biochemical, and behavioural alterations in laboratory animals and humans. The present work was conducted to study the functional and structural changes induced by aluminium in rat liver. Twenty five adult male Wistar rats (150-200 g) were randomly divided into five groups; control group and four Al-treated groups viz: Al 1 (25 mg AlCl3/kg b.wt), Al 2 (35 mg AlCl3/kg b.wt), Al 3 (45 mg AlCl3/kg b.wt), and Al 4 (55 mg AlCl3/kg b.wt). Rats in the aluminium-treated groups were administered AlCl3 for 30 days through oral gavage. Aluminium significantly increased the serum levels of liver function markers (ALT, AST, and ALP), phospholipids, and cholesterol. The activities of hepatocyte membrane (ALP, GGT, and LAP) and carbohydrate metabolic (G6P, F16BP, HK, LDH, MDH, ME, and G6PDH) enzymes were significantly altered by AlCl3 administration. Prolonged Al exposure induced oxidative stress in the liver, as evident by significant hepatocellular DNA damage, increased lipid peroxidation, and decreased non-enzymatic and enzymatic antioxidants. The toxic effects observed in this study were AlCl3 dose-dependent. Histopathological examination of liver sections revealed enlargement of sinusoidal spaces, derangement of the hepatic chord, loss of discrete hepatic cell boundaries, congestion of hepatic sinusoids, and degeneration of hepatocytes in Al-intoxicated rats. In conclusion, aluminium causes severe hepatotoxicity by inhibiting the hepatocyte membrane enzymes and disrupting the liver's energy metabolism and antioxidant defence.

Tannins-enriched fraction of TeMac™ protects against aluminum chloride induced Alzheimer's disease-like pathology by modulating aberrant insulin resistance and alleviating oxidative stress in diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease is the most common neurodegenerative disease with therapeutic limitations. Insulin resistance plays a role in the progression of Alzheimer's disease. Therapies that modulate insulin secretion and signaling, as well as oxidative stress in the brain are now being investigated for their potential role in the prevention of Alzheimer's disease (AD). Terminalia macroptera (Combretaceae) is a plant that different parts have been used traditionally for the treatment of metabolic and neurological conditions. Previous study has indicated that the crude extract exhibit anti-diabetic property. In addition, the plant is a rich source of tannins, phenolic acids, flavonoids, triterpenes. However, there is no study on its protective effect against biochemical alterations of AD in diabetic rats. AIM OF THE STUDY: The present research study investigated the neuroprotective effects of TeMac™ on Alzheimer-like pathology induced by aluminum chloride (AlCl3) in diabetic rats. METHODS: A phytochemical analysis of TeMac™ was carried out to quantify tannins. The potential effect of the tannins-enriched fraction (TEF) of TeMac™ to prevent the formation of senile plaques was conducted by its ability to inhibit the activities of ß-secretase (EC 3.4.23.46), monoamine oxidase A (EC 1.4.3.4) and the fibrillation of Aß. A diabetic model was induced from female Wistar rats by a single intraperitoneal injection of streptozotocin (STZ, 35 mg/kg BW). After that, the blood glucose level was measured to confirm the induction of diabetes. Three days after induction, animals received AlCl3 (75 mg/kg BW) alone (AD control) or concomitantly with 400 mg/kg BW of TEF of TeMac™ or 5 mg/kg BW Daonil by daily gavage for 42 days. At the end of the experiment, rats were sacrificed, blood and brains were collected. The levels of amyloid fibrils, glucose, albumin and the activities of DPP4, ß-secretase and phosphatase, and markers of oxidative stress in the brain were assessed. RESULTS: TEF of TeMac™ displays a potential ability to inhibit the activities of ß-secretase, monoamine oxidase, and Aß fibrillation. Treatment with TEF of TeMac™ significantly inhibited DPP4 and BACE1 activities and reduced brain glucose and amyloid fibril levels, and improved cerebral albumin levels and modulated oxidative stress markers. CONCLUSION: Our findings indicate that TEF of TeMac™ prevents Alzheimer's-type pathology linked to insulin resistance in rats. TEF of TeMac™ may be a potential drug candidate for the treatment of diabetes-associated cognitive impairment.

Pre-clinical protective potentials of Carica papaya constituents in experimentally induced anemia.

OBJECTIVE: Anemia is a pathological condition characterized by reduced oxygen bioavailability and/or changes in hematological parameters. This study investigated the anti-anemic activities of Carica papaya (CP) phytoconstituents in aluminium-chloride-induced anemic rats. METHOD: Twenty-seven rats were randomized into nine groups of three rats as follows; group 1 was the normal (non-induced) group, 2-9 were anemic rats administered 1 mL distilled water, standard drug (3 mg/kg body weight (bw) ferrous sulphate), 100, 300 and 500 mg/kg bw of crude methanolic extract of CP (CMECP) of the leaf and 100, 300 and 500 mg/kg bw of CMECP of the seed respectively in the first stage of the study. In the second stage, thirty-three rats were randomized into eleven groups of three rats as follows; group 1 was the normal group, 2-11 were anemic rats treated with 1 mL distilled water, standard drug, 75 mg/kg bw, 150 mg/kg of alkaloid fraction of CP seed, 75 mg/kg bw, 150 mg/kg bw of flavonoid fraction of CP seed, 75 mg/kg bw and 150 mg/kg of alkaloid fraction of CP leaf, 75 mg/kg bw and 150 mg/kg bw of flavonoid fraction of CP leaf respectively. RESULTS: Treatment of anemic rats with CP extracts and fractions of the seed and leaf significantly reversed the hematological parameters and body weight of anemic rats in a dose independent fashion. The CMECP leaf at 100 and 500 mg/kg gave PCV of 42.50±0.50 and 47.00±0.50, while the seed gave 49.50±0.50 and 42.50±0.50 respectively after 2 weeks of treatment. However, the alkaloid and flavonoid fraction of CP presented better anti-anemic properties probably due to constituents' synergism. CONCLUSION: This study concluded that CP possesses phytoconstituents which potentiates it as a safe anti-anemic drug candidate.

In silico pharmacokinetic and therapeutic evaluation of Musa acuminata peels against aluminium chloride-induced hepatotoxicity in adult BALB/c mice.

East Africa (Musa spp.), notably Musa acuminata, "Matooke" a staple and economically important food in the region. Here, 12 selected M. acuminata peels extract (MAPE) bioactive compounds were studied for hepatoprotective potentials in aluminium chloride-induced hepatoxicity in adult BALB/c mice. GC-MS analysis was used to identify active components of MAPE. In silico estimation of the pharmacokinetic, the GCMS-identified compounds' toxicity profile and molecular docking were compared with the standard (Simvastatin) drug. Hepatotoxicity was induced using aluminium-chloride treated with MAPE, followed by biochemical and histopathological examination. Twelve bioactive compounds 2,2-Dichloroacetophenone (72870), Cyclooctasiloxane 18993663), 7-Hydroxy-6,9a-dimethyl-3-methylene-decahydro-azuleno[4,5-b]furan-2,9-dione (534579), all-trans-alpha-Carotene (4369188), Cyclononasiloxane (53438479), 3-Chloro-5-(4-methoxyphenyl)-6,7a-dimethyl-5,6,7,7a-tetrahydro-4H-furo[2,3-c]pyridin-2-one (536708), Pivalic acid (6417), 10,13-Octadecadienoic acid (54284936), Ethyl Linoleate (5282184), Oleic acid (5363269), Tirucallol (101257), Obtusifoliol (65252) were identified by GC-MS. Of these, seven were successfully docked with the target proteins. The compounds possess drug likeness potentials that do not inhibits CYP450 isoforms biotransformation. All the docked compounds were chemoprotective to AMES toxicity, hERGI, hERGII and hepatotoxicity. The animal model reveals MAPE protective effect on liver marker's function while the histological studies show regeneration of the disoriented layers of bile ducts and ameliorate the cellular/histoarchitecture of the hepatic cells induced by AlCl3. The findings indicate that MAPE improved liver functions and ameliorated the hepatic cells' cellular or histoarchitecture induced by AlCl3. Further studies are necessary to elucidate the mechanism action and toxicological evaluation of MAPE's chronic or intermittent use to ascertain its safety in whole organism systems.

Safeguarding Neuronal Integrity: Unveiling Possible Role of NFκB in the Neuroprotective Efficacy of Andrographolide Contrary to Aluminium Chloride-induced Neurotoxicity and Associated Spatial Memory Impairments in Rats.

OBJECTIVE: The current study was structured to evaluate the neuroprotective properties of andrographolide in the context of aluminum chloride (AlCl3)-induced neurotoxicity, along with its concurrent impact on spatial memory impairment in Wistar rats. The present investigation elucidated the biochemical and neurobehavioral outcomes of andrographolide treatment in rats, emphasizing the areas of the brain associated with memory, i.e., the cortex and the hippocampus. MATERIALS AND METHODS: Prolonged dosing of AlCl3 (7 mg/kg) intraperitoneally for 10 days exhibited a substantial enhancement in the values of oxidative stress markers associated with a reduction in the concentrations of antioxidant enzymes within the brain. The selection of andrographolide doses (1, 2, and 3 mg/kg) was grounded in precedent safety and toxicity investigations, with subsequent oral administration. The evaluation of behavioral parameters, specifically spatial memory, was conducted through the utilization of the Radial Eight Arm Maze (RAM) test. On the concluding day of the experiment, the assessment encompassed biochemical parameter analysis and histological scrutiny of the brain tissue. RESULTS: The oral dosing of andrographolide at 1, 2, and 3 mg/kg, in conjunction with AlCl3, effectively mitigated the behavioral deficits induced by aluminum exposure. Notably, a significant suppression of NFκB was uncovered in the rats treated with andrographolide. Furthermore, histopathological examinations of the cortex and hippocampus of rat brains provided corroborative evidence, demonstrating that andrographolide substantially alleviated the toxic impact of AlCl3, thereby maintaining the typical histoarchitectural arrangement of these regions. CONCLUSION: These findings collectively suggest that andrographolide holds the potential to counteract memory impairment instigated by aluminum toxicity, accomplished through the modulation of NFκB activity and the amelioration of the adverse consequences of AlCl3 exposure.

Treatment of effluents from Food Services Establishment (FSEs) by physico-chemical processes: a case study for Trinidad & Tobago.

BACKGROUND: Effluents from Food Services Establishments (FSEs) contain primarily Fats, Oil and Grease (FOG) which severely impact on sewers and the environment when released in high concentrations. In Trinidad & Tobago, it is estimated that approximately 231,304 kg/day of unaccounted for FOG bearing wastewaters from FSEs, are released into the environment with no viable treatment in the country. This research explored the optimization of physico-chemical processes for the treatment of FOGs for subsequent release into sewers. RESULTS: Bench-scale studies analysed the characteristics of FSE's effluents from three popular sources, conducted the treatment of these effluents using Jar Tests, and subsequently confirm results via a pilot plant study. Characterization showed the mean concentration of the parameters examined to be; FOG (511 mg/l ± 116 mg/l), Suspended Solids (446 mg/l ± 146 mg/l), Chemical Oxygen Demand (2229 mg/l ± 963 mg/l) and pH (6 ± 0.3). Jar Tests were conducted using Poly-aluminium Chloride (PACl) as coagulant, anionic and cationic polyelectrolytes as flocculant aids with suitable pH adjustments of samples to determine the isoelectric point for the coagulant. Effluent results showed FOG removal levels of 99.9% and final effluent concentration of 0.17 mg/l. This was attained using PACl concentration of 250 mg/l, a 0.1% low cationic polyelectrolyte (CP 1154) at 4 mg/l with the pH of sample adjusted to 8. The pilot plant achieved a 97.4% removal of FOG (residual of 16.8 mg/l) using the same coagulant dosing, and pH value, but increasing the strength of the flocculant aid to 0.1% medium cationic (CP1156) at 5 mg/l. CONCLUSION: Experimentation showed high concentrations of emulsified FOG can be efficiently removed to levels below the permissible requirements (20 mg/l) for entry into sewer systems in Trinidad and Tobago using coagulation, flocculation and sedimentation techniques. Pilot scale study also revealed that a higher strength and/or dose of the cationic polyelectrolyte and increased times in primary and final tanks were required to attain the desired results as in the bench level study, where equipment limitations in the flocculation tank were faced. This is in alignment with theory where factors critical for agglomeration is equipment type and density charge. It is, concluded that the optimum combination of chemicals and the respective dosages attained at the bench level study should prove effective should the right equipment be made available.

Enhanced Neuroprotective Synergy of Atorvastatin and Magnesium L-Threonate in a Rat Model of Alzheimer's Disease Induced by Aluminum Chloride.

INTRODUCTION: Alzheimer's disease (AD) is a widespread neurodegenerative condition with complex causes and a significant global impact, particularly among the elderly. This brief introduction emphasizes AD's hallmark features and the urgent public health concern it poses, with numbers on the rise. It also highlights the potential of statins and magnesium L-threonate as a combined therapeutic approach to prevent AD and mitigate its underlying pathological features. The study's goal is to shed light on these promising interventions in a rat model induced by aluminum chloride (AlCl3). MATERIALS AND METHODS: A total of 30 aged female Wistar rats were divided into five groups (n=6/group). The vehicle control group received normal saline orally (p.o.).The model control group received AlCl3(4.2 mg/kg/day intraperitoneal (i.p.)). The standard-treated group received rivastigmine (1 mg/kg/day p.o.), and the atorvastatin-treated and atorvastatin with magnesium L-threonate-treated groups received atorvastatin (20 mg/kg/day p.o.) and atorvastatin (20 mg/kg/day) with magnesium L-threonate (604 mg/kg/day p.o.), respectively. Cognitive functions such as radial arm maze, elevated plus maze (EPM), passive shock avoidance test, and open-field test (OFT) were performed at weekly intervals up to 28 days. After completion of the study on the 29th day, all animals were sacrificed, and the brain was used for estimation of AchE enzyme activity, oxidative stress parameters, and histopathological analysis. RESULT: At the end of the fourth week, administration of atorvastatin and atorvastatin with magnesium L-threonate resulted in a decreased average time taken to reach the correct arm, reduced transfer latency (TL) in the EPM, shortened latency to reach the shock-free zone (SFZ), and an increase in rearing and counts by locomotion activity in the OFT. It also demonstrated improved anti-cholinesterase activity and suppressed oxidative stress, as indicated by a decrease in nitric oxide (NO) levels and an increase in superoxide dismutase (SOD) and catalase levels. Additionally, it led to reductions in brain changes observed in histopathological analysis. CONCLUSION: Atorvastatin with magnesium L-threonate provides a better beneficial protective effect against AD than atorvastatin alone. This combination can be a first choice for patients who are already taking atorvastatin in the early stages of AD.

Simvastatin attenuates aluminium chloride-induced neurobehavioral impairments through activation of TGF-ß1/ SMAD2 and GSK3ß/ß-catenin signalling pathways.

Alzheimer's disease (AD) is a neurodegenerative disease characterised by the presence of ß-amyloid plaques and acetylcholine depletion leading to neurobehavioral defects. AD was contributed also with downregulation of TGF-ß1/SMAD2 and GSK3ß/ß-catenin pathways. Simvastatin (SMV) improved memory function experimentally and clinically. Hence, this study aimed to investigate the mechanistic role of SMV against aluminium chloride (AlCl3) induced neurobehavioral impairments. AD was induced by AlCl3 (50 mg/kg) for 6 weeks. Mice received Simvastatin (10 or 20 mg/kg) or Donepezil (3 mg/kg) for 6 weeks after that the histopathological, immunohistochemical and biochemical test were examined. Treatment with SMV improved the memory deterioration induced by AlCl3 with significant recovery of the histopathological changes. This was concomitant with the decrease of AChE and Aß (1-42). SMV provides its neuroprotective effect through upregulating the protein expression of ß-catenin, TGF-ß1 and downregulating the expression of GSK3ß, TLR4 and p-SMAD2.

Assessment of Anti-Alzheimer Pursuit of Jambolan Fruit Extract and/or Choline against AlCl3 Toxicity in Rats.

Jambolan fruit extract and choline were investigated for Aluminum tri chloride (AlCl3)-induced Alzheimer's disease in rats. Thirty-six male "Sprague Dawley" rats weighing (150 ± 10 g) were allocated into six groups; the first group was fed a baseline diet and served as a negative control. Alzheimer's disease (AD) was induced in Group 2 rats by oral administration of AlCl3 (17 mg/kg body weight) dissolved in distilled water (served as a positive control). Rats in Group 3 were orally supplemented concomitantly with both 500 mg/kg BW of an ethanolic extract of jambolan fruit once daily for 28 days and AlCl3 (17 mg/kg body weight). Group 4: Rivastigmine (RIVA) aqueous infusion (0.3 mg/kg BW/day) was given orally to rats as a reference drug concomitantly with oral supplementation of AlCl3 (17 mg/kg body weight) for 28 days. Group 5 rats were orally treated with choline (1.1 g/kg) concomitantly with oral supplementation of AlCl3 (17 mg/kg body weight). Group 6 was given 500 mg/kg of jambolan fruit ethanolic extract and 1.1 g/kg of choline orally to test for additive effects concurrently with oral supplementation of AlCl3 (17 mg/kg bw) for 28 days. Body weight gain, feed intake, feed efficiency ratio, and relative brain, liver, kidney, and spleen weight were calculated after the trial. Brain tissue assessment was analyzed for antioxidant/oxidant markers, biochemical analysis in blood serum, a phenolic compound in Jambolan fruits extracted by high-performance liquid chromatography (HPLC), and histopathology of the brain. The results showed that Jambolan fruit extract and choline chloride improved brain functions, histopathology, and antioxidant enzyme activity compared with the positive group. In conclusion, administering jambolan fruit extract and choline can lower the toxic impacts of aluminum chloride on the brain.

Neuro-amelioration of Ficus lyrata (fiddle-leaf fig) extract conjugated with selenium nanoparticles against aluminium toxicity in rat brain: relevance to neurotransmitters, oxidative, inflammatory, and apoptotic events.

Aluminium is a non-essential metal, and its accumulation in the brain is linked with potent neurotoxic action and the development of many neurological diseases. This investigation, therefore, intended to examine the antagonistic efficacy of Ficus lyrata (fiddle-leaf fig) extract (FLE) conjugated with selenium nanoparticles (FLE-SeNPs) against aluminium chloride (AlCl3)-induced hippocampal injury in rats. Rats were allocated to five groups: control, FLE, AlCl3 (100 mg/kg), AlCl3 + FLE (100 mg/kg), and AlCl3 + FLE-SeNPs (0.5 mg/kg). All agents were administered orally every day for 42 days. The result revealed that pre-treated rats with FLE-SeNPs showed markedly lower acetylcholinesterase and Na+/K+-ATPase activities in the hippocampus than those in AlCl3 group. Additionally, FLE-SeNPs counteracted the oxidant stress-mediated by AlCl3 by increasing superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents in rat hippocampus. Besides, the formulated nanoparticles decreased the hippocampal malondialdehyde, carbonyl protein, and nitric oxide levels of AlCl3-exposed animals. Furthermore, FLE-SeNPs attenuated neural tissue inflammation, as demonstrated by decreased interleukin-1 beta, interleukin-6, nuclear factor kappa B, and glial fibrillary acidic protein. Remarkable anti-apoptotic action was exerted by FLE-SeNPs by increasing B cell lymphoma 2 and decreasing caspase-3 and Bcl-2-associated-X protein in AlCl3-exposed rats. The abovementioned results correlated well with the hippocampal histopathological findings. Given these results, SeNPs synthesized with FLE imparted a remarkable neuroprotective action against AlCl3-induced neurotoxicity by reversing oxidative damage, neuronal inflammation, and apoptosis in exposed rats.

Life Cycle Assessment of a system for the extraction and transformation of Waste Water Treatment Sludge (WWTS)-derived lipids into biodiesel.

In recent years, the demand for biofuels has been growing exponentially, as has the interest in biodiesel produced from organic matrices. Particularly interesting, due to its economic and environmental advantages, is the use of the lipids present in sewage sludge as a raw material for the synthesis of biodiesel. The possible processes of this biodiesel synthesis, starting from lipid matter, are represented by the conventional process with sulfuric acid, by the process with aluminium chloride hexahydrate and by processes that use solid catalysts such as those consisting of mixed metal oxides, functionalized halloysites, mesoporous perovskite and functionalized silicas. In literature there are numerous Life Cycle Assessment (LCA) studies concerning biodiesel production systems, but not many studies consider processes that start from sewage sludge and that use solid catalysts. In addition, no LCA studies were reported on solid acid catalysts nor on those based on mixed metal oxides which present some precious advantages, over the homogeneous analogous ones, such as higher recyclability, prevention of foams and corrosion phenomena, and an easier separation and purification of biodiesel product. This research work reports the results of a comparative LCA study applied to a system that uses a solvent free pilot plant for the extraction and transformation of lipids from sewage sludge via seven different scenarios that differ in the type of catalyst used. The biodiesel synthesis scenario using aluminium chloride hexahydrate as catalyst has the best environmental profile. Biodiesel synthesis scenarios using solid catalysts are worse due to higher methanol consumption which requires higher electricity consumption. The worst scenario is the one using functionalized halloysites. Further future developments of the research require the passage from the pilot scale to the industrial scale in order to obtain environmental results to be used for a more reliable comparison with the literature data.

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.

Flavonoid-enrich extract of Autranella congolensis (Sapotaceae) protects against aluminium chloride-mediated Alzheimer's disease-like oxidative stress in rat through the antioxidant properties.

Oxidative stress (OS) is well established as a major event in Alzheimer's disease (AD) pathology. One of the mostly-researched classes of antioxidants to manage with overwhelming OS include flavonoids. This study was aimed to investigate the protective effect of A. congolensis extract (HEEAC) on AlCl3-mediated AD-like OS and assess the contribution of its antioxidant flavonoid contents. Female Wistar (250-300 g) rats received orally 50 mg/Kg bw of AlCl3, followed one hour later by doses (150 or 300 mg/kg) of HEEAC or vitamin E at 100 mg/kg daily for eight consecutive weeks. OS related biomarkers were evaluated at the end of treatment. To assess the contribution of flavonoid contents to its activity, HEEAC was fractioned using solvent of varying polarities. Flavonoid-rich extracts obtained were tested for their antioxidant capacity. AlCl3 administration significantly lowered antioxidant enzymes (catalase, glutathione peroxidase) and aconitase levels, reduced total thiol and thiol protein levels and increased lipid peroxidation and protein oxidation levels in brain. When co-administrated with HEEAC at 150 mg/kg, all of these OS related biomarkers were significantly moderated. The efficacity of the extract was significantly higher than vitamin E. Flavonoid-rich fractions extracted mainly n-butanol fraction show strong antioxidant activity, which can be considered as the major antioxidant fraction of this plant. HEEAC protect brain cells against oxidative damage induced by AlCl3, specifically through the strong antioxidant property of its n-butanol flavonoid-rich fraction, which may be a promising agent for preventing oxidative damage in AD.

Exposure of aluminium to C6 glioma cells modulates molecular and functional neurotoxic markers.

The risk of aluminium exposure to humans is very high as it may get into the human body through excessive dietary contaminants, inhalation of fine particulate matter, or through parenteral routes as a vaccine adjuvant and so forth. The increased level of aluminium in brain tissue has been shown to be associated with several neurodegenerative and neurotoxic adverse effects, including AD. However, the exact mechanism of aluminium-induced neurotoxicity is still unclear. Therefore, our study aimed to investigate the mechanism of neurotoxic and neurodegenerative effects through in vitro exposure of aluminium in rat glioma C6 cell line. The findings of our study have indicated that aluminium chloride exposure may lead to alteration in acetylcholine levels, increased oxidative imbalance and induction of molecular structural and functional markers of neuronal inflammation. This study also demonstrated that aluminium exposure may lead to the induction of caspase-3 along with apoptotic cell death and a significant increase in amyloid-beta and hyperphosphorylated tau levels in C6 cells. Thus, this study may provide a mechanistic understanding of the regulation of neuroinflammatory and neurodegenerative biomarkers due to aluminium exposure.

Exposure to aluminium chloride during the peripuberal period induces prostate damage in male rats.

Aluminium (Al) is an important metal, but it can be toxic including for prostate tissue. This study aimed to evaluate whether exposure to aluminium chloride (AlCl3) during the peripubertal period affects ventral prostate development in rats. Male Wistar rats (30 days old) were distributed into three experimental groups: control (sterile 0.9% saline solution), AL7 (7 mg AlCl3/kg) and AL34 (34 mg AlCl3/kg). Animals were treated intraperitoneally from postnatal day (PND) 36-66 (peripubertal period). At PND67, the animals were anaesthetized and euthanized. Blood was collected for testosterone levels. The ventral prostate (VP) was removed, weighed and processed for histochemistry and immunohistochemistry to detect androgen (AR) and Ki67. Stereological and histopathological analyses, mast cell counts, and determinations of myeloperoxidase (MPO) and N-acetyl glycosidase (NAG) activity and IL-6 levels were performed. The AL34 group presented a reduction in body weight and increase in MPO activity compared to the other groups. In both the AL7 and AL34 groups, there was reorganization of the prostatic tissue compartments. There was no significant difference in prostate weight, number of granulated or degranulated mast cells, or testosterone levels. In conclusion, the exposure to aluminium chloride during the peripubertal period impairs the prostatic development.

Spermine protects aluminium chloride and iron-induced neurotoxicity in rat model of Alzheimer's disease via attenuation of tau phosphorylation, Amyloid-ß (1-42) and NF-κB pathway.

Alzheimer's disease (AD) is the most prevalent type of dementia, characterized by a gradual decline in cognitive and memory functions of the aged peoples. Long-term exposure to heavy metals (aluminium and iron) cause neurotoxicity by amyloid plaques accumulation, tau phosphorylation, increased oxidative stress, neuroinflammation, and cholinergic neurons degeneration, contributes to the development of AD-like symptoms. The present research work is designed to investigate the neuroprotective effect of spermine in aluminium chloride (AlCl3), and iron (Fe) induced AD-like symptoms in rats. Rats were administered of AlCl3 (100 mg/kg p.o.) alone and in combination with iron (120 µg/g, p.o.) for 28 days. Spermine (5 and 10 mg/kg) through intraperitoneal (i.p.) route was given for 14 days. The recognition and spatial memory impairment were tasted using Morris water maze (MWM), actophotometer, and Novel Object Recognition test (NORT). All the rats were sacrificed on day 29, brains were isolated, and tissue homogenate was used for neuroinflammatory, biochemical, neurotransmitters, metals concentration, and nuclear factor-kappa B (NF-κB) analysis. In the present study, AlCl3 and iron administration elevated oxidative stress, cytokines release, dysbalanced neurotransmitters concentration, and biochemical changes. Rats treated with spermine dose-dependently improved the recognition and spatial memory, attenuated proinflammatory cytokine release, and restored neurotransmitters concentration and antioxidant enzymes. Spermine also mitigated the increased beta-amyloid (Aß42), with downregulation of tau phosphorylation. Furthermore, spermine augmented the hippocampal levels of B cell leukaemia/lymphoma-2 (Bcl-2), diminished nuclear factor-kappa B (NF-κB) and caspase-3 (casp-3) expression. Moreover, spermine exhibited the neuroprotective effect through anti-inflammatory, antioxidant, neurotransmitters restoration, anti-apoptotic Aß42 concentration.

WIN55,212-2 Attenuates Cognitive Impairments in AlCl3 + d-Galactose-Induced Alzheimer's Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress.

Neurotransmission and cognitive dysfunctions have been linked to old age disorders including Alzheimer's disease (AD). Aluminium is a known neurotoxic metal, whereas d-galactose (d-gal) has been established as a senescence agent. WIN55,212-2 (WIN), is a potent cannabinoid agonist which partially restores neurogenesis in aged rats. The current study aimed to explore the therapeutic potentials of WIN on Aluminium chloride (AlCl3) and d-gal-induced rat models with cognitive dysfunction. Healthy male albino Wistar rats weighing between 200-250 g were injected with d-gal 60 mg/kg intra peritoneally (i.p), while AlCl3 (200 mg/kg) was orally administered once daily for 10 consecutive weeks. Subsequently, from weeks 8-11 rats were co-administered with WIN (0.5, 1 and 2 mg/kg/day) and donepezil 1 mg/kg. The cognitive functions of the rats were assessed with a Morris water maze (MWM). Furthermore, oxidative stress biomarkers; malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and neurogenesis markers: Nestin and glial fibrillary acidic protein (GFAP) were also evaluated, as well as the histology of the hippocampus. The results revealed that rats exposed to AlCl3 and d-gal alone showed cognitive impairments and marked neuronal loss (p < 0.05) in their hippocampal conus ammonis 1 (CA1). Additionally, a significant decrease in the expressions of GFAP and Nestin was also observed, including increased levels of MDA and decreased levels of SOD and GSH. However, administration of WIN irrespective of the doses given reversed the cognitive impairments and the associated biochemical derangements. As there were increases in the levels SOD, GSH, Nestin and GFAP (p < 0.05), while a significant decrease in the levels of MDA was observed, besides attenuation of the aberrant cytoarchitecture of the rat's hippocampi. The biochemical profiles of the WIN-treated rats were normal. Thus, these findings offer possible scientific evidence of WIN being an effective candidate in the treatment of AD-related cognitive deficits.

Comparison of novel aluminium lactate versus aluminium chloride-based antiperspirant in excessive axillary perspiration: First prospective cohort study.

Aluminium chloride-based antiperspirants are an effective topical therapeutic option for mild to moderate states of excessive perspiration. Its use is primarily limited by the occurrence of skin irritation, especially in sensitive skin types. The objective of this study was to compare the antiperspirant efficacy and tolerability of a novel antiperspirant with 12.5% aluminium lactate, and a 12.5% aluminium chloride-based antiperspirant. This cohort study was conducted as a two-sided self-assessment comparison between both preparations in healthy volunteers to generate selfcare-related data. Almost half of the participants stated that aluminium chloride was more efficacious than aluminium lactate; 22% stated aluminium lactate was more efficacious than aluminium chloride; 28% observed no difference in the efficacy of both preparations (p = 0.04). However, 88% described greater tolerability with aluminium lactate (p < 0.0001). In this study, aluminium lactate showed significantly greater tolerability than aluminium chloride, although the latter tended to show slightly greater efficacy.

Allicin ameliorates aluminium- and copper-induced cognitive dysfunction in Wistar rats: relevance to neuro-inflammation, neurotransmitters and Aß(1-42) analysis.

Alzheimer's disease (AD) is a multifactorial neurological disorder associated with neuropathological and neurobehavioral changes, like cognition and memory loss. Pathological hallmarks of AD comprise oxidative stress, formation of insoluble ß-amyloid (Aß) plaques, intracellular neurofibrillary tangles constituted by hyperphosphorylated tau protein (P-tau), neurotransmitters dysbalanced (DA, NE, 5-HT, GABA and Glutamate) and metal deposition. Chronic exposure to metals like aluminium and copper causes accumulation of Aß plaques, promotes oxidative stress, neuro-inflammation, and degeneration of cholinergic neurons results in AD-like symptoms. In the present study, rats were administered with aluminium chloride (200 mg/kg p.o) and copper sulfate (0.5 mg/kg p.o) alone and in combination for 28 days. Allicin (10 and 20 mg/kg i.p) was administered from day 7 to day 28. Spatial and recognition memory impairment analysis was performed using Morris water maze, Probe trial, and Novel Object Recognition test. Animals were sacrificed on day 29, brain tissue was isolated, and its homogenate was used for biochemical (lipid peroxidation, nitrite, and glutathione), neuro-inflammatory (IL-1ß, IL-6 and TNF- α), neurotransmitters (DA, NE, 5-HT, GABA and Glutamate), Aß(1-42) level, Al concentration estimation, and Na+/K+-ATPase activity. In the present study, aluminium chloride and copper sulfate administration increased oxidative stress, inflammatory cytokines release, imbalanced neurotransmitters' concentration, and promoted ß-amyloid accumulation and Na+/K+-ATPase activity. Treatment with allicin dose-dependently attenuated these pathological events via restoration of antioxidants, neurotransmitters concentration, and inhibiting cytokine release and ß-amyloid accumulation. Moreover, allicin exhibited the neuroprotective effect through antioxidant, anti-inflammatory, neurotransmitters restoration, attenuation of neuro-inflammation and ß-amyloid-induced neurotoxicity.