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.

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.

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.

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.

Combination of donepezil and gallic acid improves antioxidant status and cholinesterases activity in aluminum chloride-induced neurotoxicity in Wistar rats.

The present study compared the effect of donepezil only and combination of donepezil and gallic acid on oxidative status and cholinesterase activity in the brain of Wistar rats administered AlCl3 for 60 days. Twenty-eight rats (180 - 200 g) were arbitrarily distributed into four groups of seven animals apiece. Group 1 served as normal control and received distilled water throughout the study. Group 2 animals received only AlCl3 throughout the study while animals in groups 3 and 4 were administered donepezil only (10 mg/kg) and combination of donepezil (10 mg/kg) and gallic acid (50 mg/kg), respectively, in addition to AlCl3. Treatments were administered orally by gavage. At the end of the study, animals were sacrificed and activities of acetylcholinesterase, butyrylcholinesterase, superoxide dismutase (SOD) and catalase as well as levels of malondialdehyde (MDA), total thiol and nitric oxide (NO) were evaluated in the brain. Histopathological study was conducted on the hippocampus of experimental animals. Results showed that AlCl3 significantly (p < 0.05) increased brain activities of cholinesterases and levels of MDA and NO with a concomitant decrease in total thiol level as well as activities of SOD and catalase. Donepezil only and combination of donepezil and gallic acid reversed these alterations. Also, combination of donepezil and gallic acid significantly (p < 0.05) improved antioxidant status better than donepezil only. It could be concluded that a synergy might exist between gallic acid and donepezil especially in ameliorating oxidative stress associated with AlCl3-induced neurotoxicity.

The protective effect of esculetin against aluminium chloride-induced reproductive toxicity in rats.

One of the prominent health problems caused by Aluminium was the decrease in male fertility rates. In the study, the protective effect of Esculetin (ESC) against the reproductive toxicity induced by Aluminium chloride (AlCl3 ) was investigated. For this purpose, AlCl3 was administrated to Wistar Albino rats at a dose of 34 mg/kg and ESC was administrated at a dose of 50 mg/kg for 70 days. It was determined that AlCl3 treatment reduced sperm motility and concentration, increased dead/live rate and abnormal sperm rate. It decreased serum testosterone level, and co-treatment of ESC significantly regulated these values. In the AlCl3 -treated group, MDA level increased and GSH level, GPx and CAT activities decreased compared with those of the control group. However, co-treatment of ESC showed an amelioratory effect on the values except for CAT activity. It was observed that the expression level of NRF-2 increased in the ESC and AlCl3  + ESC groups, and NF-κB increased in the AlCl3 group with the control group. It was determined that Caspase-3 expression decreased, and Bcl-2 expression increased in AlCl3  + ESC group compared to AlCl3 group. It was also determined that AlCl3 -induced tissue injury was significantly prevented by ESC co-treatment.

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.

The concurrent exposure to aluminium and fructose induces liver injury in rats: Protection by monoammonium glycyrrhizinate.

Aluminium is a ubiquitous element that occurs naturally in the soil making human exposure to it unavoidable. It is implicated in the aetiology of different neurodegenerative diseases and can induce liver injury. In addition, insulin resistance (IR) plays an essential role in the pathogenesis and the progression of liver disorders. The increased consumption of fructose contained in soft drinks and western pattern diet results in IR that along with the wide distribution of aluminium make the concurrent exposure conceivable and increase the risk of liver injury. Therefore, the present study explores the hepatotoxic effects of aluminium and fructose administered concurrently and evaluates the possible protection by monoammonium glycyrrhizinate (MAG). Liver injury was induced by the administration of aluminium chloride (34 mg/kg/d) plus 10% (w/v) fructose in drinking water. Male rats were treated with either MAG (40 mg/kg/d) or silymarin (SIL, 100 mg/kg/d). The concurrent administration of aluminium and fructose (FRUAL) induced liver injury manifested as a significant elevation of serum liver enzymes activities, bilirubin level, and prothrombin time, as well as reduction of albumin level. On the other hand, the administration of MAG improved the FRUAL-induced aberrations of liver function tests and hepatic cytoarchitecture. We assume that the MAG-induced suppression of oxidative stress, toll-like receptor 4 pathway activation, inflammation, and apoptosis might play a crucial role in the hepatoprotective effect of MAG in this model. Intriguingly, the hepatoprotective effect MAG against FRUAL-induced liver injury surpasses that of the gold standard SIL, suggesting MAG as a better alternative to SIL.

Tyrosol prevents AlCl3 induced male reproductive damage by suppressing apoptosis and activating the Nrf-2/HO-1 pathway.

Aluminium is a ubiquitous element that occurs naturally in the soil making human exposure to it is unavoidable. Tyrosol is present in olive oil and is known to have antioxidant effects. Therefore, the present study explores the toxic effects of aluminium chloride (AlCl3 ) and evaluates the possible protection by tyrosol in male rats. Testicular injury was induced by the administration of AlCl3 (34 mg kg-1  day-1 ). Rats were treated with either tyrosol (20 mg kg-1 day-1 ) or AlCl3 (34 mg kg-1 day-1 ). The experiment lasted for 10 weeks. Biochemical, histopathological and protein expression profiles were determined to decipher the role of tyrosol in protecting the cellular damage. Further, histomorphometric analyses of testes showed deranged architecture along with other noted abnormalities. AlCl3 group rats' testes showed decreased GSH levels, CAT activities, Nrf-2, HO-1, bcl-2 expressions and sperm motility whereas increased caspase-3 expressions, MDA levels, abnormal and dead/live sperm ratio. However, tyrosol treatment attenuated these changes. The present results demonstrate the beneficial role of tyrosol treatment in AlCl3 induced testicular toxicity alterations of rat.

Protective effect of raisin (currant) against spatial memory impairment and oxidative stress in Alzheimer disease model.

Objectives: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive pathological changes of the brain. A number of studies demonstrated compelling evidence of the importance of oxidative processes in AD pathogenesis. Raisin contains polyphenol, phenolic acid, and tannin compounds, which have antioxidant and anti-inflammatory properties. The present study was aimed to evaluate the protective effect of raisin on neurobehavioral and histological changes in rats with Alzheimer. Methods: Animal model of AD was induced by intraperitoneal injection of aluminium chloride for 60 days (100 mg/kg body weight). During these 60 days both Alzheimer's and control rats were given 6 g of raisin per rat. At the end of the treatment, blood was collected for biochemical assessment. We used a Morris water task and passive avoidance test to assess spatial memory. Results: Our results showed that aluminium exposure significantly decreased the memory in the MWT and passive avoidance test, but in the raisin + AlCl3 group, it significantly increased spatial memory in both tests. Also, Aluminium exposure significantly increased malondialdehyde (MDA) and decreased ferric reducing ability of plasma (ferric reducing/antioxidant power (FRAP)), while treatment with raisin significantly decreased MDA and increased FRAP in plasma of blood. Discussion: Our findings showed that raisin has a neuroprotective effect and improves the spatial memory in AD animal models.

[Influence of aluminum chloride exposure on embryonic development of zebrafish and neurobehavior of juvenile fish].

Objective: To investigate the influence of aluminum chloride (AlCl(3)) solution on the embryon-ic development of zebrafish and neurobehavior of juvenile fish. Methods: The embryos of zebrafishat 6 hours after fertilization were exposed to AlCl(3) solution at a concentration of 0, 55.0, 60.5, 66.6, 73.5, 80.5, or 100.0 mg/L, and embryonic hatching rates at 48 and 72 hours after fertilization were calculated. The embryos of zebrafishat 6 hours after fertilization were exposed to AlCl(3) solution at a concentration of 0, 60.0, 72.0, 86.4, 103.7, or 124.4 mg/L, and the embryonic mortality rates at 12, 24, 48, 72, and 96 hours after fertilization were calculat-ed. The embryos of zebrafish at 6 hours after fertilization were exposed to AlCl(3) solution at a concentration of 0, 50, 100, 200, 400, or 800 µg/L, and the changes in the neurobehavior of juvenile fish were observed after hatching, including touch-escape reaction at 72 hours after fertilization and autonomic movement and panic es-cape reflex at 7 days after fertilization. Results: Compared with the 0 mg/L group, the≥66.6 mg/L group had a sig-nificant reduction in embryonic hatching rate at 48 and 72 hours after fertilization, and the ≥72.0 mg/L group had a significant increase in embryonic mortality rate at 96 hours after fertilization (P<0.05) . Compared with the 0 µg/L group, the≥100 µg/L group had a significant reduction in the number of times of touch-escape reaction (P<0.05) .Compared with the 0 and 50 µg/L groups, the 100-800 µg/L groups had significant reductions in total movement distance and average speed (P<0.05) . Compared with the dark period before illumination, all groups had a significant increase in movement speed during the light period of the panic escape reflex test (i.e., the third minute) (P<0.05) ; within 2 minutes after the light was turned off, there was no significant change in movement speed in the 0-200 µg/L groups (P>0.05) ; the 400 and 800 µg/L groups had a significant increase in movement speed (P<0.05) . Conclusion: AlCl(3) exposure may cause embryonic developmental disorder in zebrafish and ab-normal neurobehavior in juvenile fish.

The protective properties of melatonin against aluminium-induced neuronal injury.

Aluminium (Al) toxicity is closely linked to the pathogenesis of Alzheimer's disease (AD). This experimental study investigated the neuroprotective effect of melatonin (Mel; 10 mg/kg bwt) on aluminium chloride (AlCl3 ; 34 mg/kg bwt) induced neurotoxicity and oxidative stress in rats. Adult male albino Wistar rats were injected with AlCl3 for 7 days. The effect on brain structure, lipid peroxidation (LPO), nitric oxide (NO) levels, glutathione (GSH) content, antioxidant enzymes (SOD, CAT, GPx and GR), apoptotic proteins (Bax and Bcl-2) and an apoptotic enzyme (caspase-3) was investigated. No apparent changes occurred following the injection of melatonin. Melatonin pretreatment of the AlCl3 -administered rats reduced brain damage, and the tissues appeared like those of the control rats. Compared to treatment with AlCl3 , pretreatment with melatonin decreased LPO and NO levels and increased the GSH content and antioxidant enzyme activity. Moreover, melatonin increased the levels of the anti-apoptotic protein, Bcl-2, decreased the levels of the pro-apoptotic protein, Bax, and inhibited caspase-3 activity. Therefore, our results indicate that melatonin may provide therapeutic value against aluminium-induced oxidative stress and histopathological alternations in the rat brain and that these effects may be related to anti-apoptotic and antioxidant activities.

Characterization of prefrontal cortex microstructure and antioxidant status in a rat model of neurodegeneration induced by aluminium chloride and multiple low-dose streptozotocin.

Diabetes mellitus (DM) is a risk factor for Alzheimer's disease (AD), and several individuals with AD are diabetic. Most non-transgenic animal models of AD make use of oral treatment with aluminium chloride (AlCl(3)) to induce brain lesions pathognomonic of the disease. Moreover, streptozotocin (STZ) can induce pathological features of either AD or DM depending on the mode of treatment. In the present study, we characterised prefrontal microanatomy and antioxidant defence system in a rat model of AD confounded by DM, with the objective of assessing the suitability of this model in the study of sporadic AD with DM co-morbidity. Adult Wistar rats were randomly assigned to receive either intraperitoneal STZ (30 mg/kg/day for 3 days; to induce DM), oral AlCl(3) (500 mg/kg/day for 4 weeks; to induce some brain lesions characteristic of AD); or both STZ and AlCl(3) (to induce AD with DM co-morbidity). Untreated rats served as controls. During treatment, blood glucose levels and body weights were evaluated repeatedly in all rats. At euthanasia, prefrontal cortex was homogenized in phosphate buffer solution and the supernatants assayed for some antioxidant enzymes (catalase, CAT; superoxide dismutase, SOD; and reduced glutathione, GSH). Moreover, following perfusion-fixation of the brain, frontal lobes were processed by the haematoxylin and eosin (H&E) or Congo red technique. Our findings showed that in rats co-administered AlCl(3) and STZ (AD + DM rats), prefrontal levels of GSH reduced significantly (p < 0.05), while reductions in SOD and CAT were not significant (p > 0.05) compared with the controls. Moreover, in this model of AD with DM co-morbidity, extensive neuronal cell loss was observed in the prefrontal cortex, but Congophilic deposits were not present. The neurodegenerative lesions and antioxidant deficits characteristic of this AlCl(3) + STZ (AD + DM) rat model were more pronounced than similar lesions associated with mono-treatment with either STZ (DM) or AlCl(3) (AD) alone; and this makes the AlCl(3) + STZ model a suitable option for the study of neurodegenerative diseases (such as AD) with DM co-morbidity.

Comparative evaluation of botulinum toxin versus iontophoresis with topical aluminium chloride hexahydrate in treatment of palmar hyperhidrosis.

BACKGROUND: Hyperhidrosis is generalised or focal excessive sweating and carries a substantial psychological and social burden. This study compares botulinum toxin versus iontophoresis with topical aluminium chloride hexahydrate in palmar hyperhidrosis. METHODS: The study included 60 cases of palmar hyperhidrosis randomly allocated to 2 groups. One group was given botulinum toxin type A 100 units per palm and the other group subjected to digital iontophoresis with topical application of aluminium chloride hexahydrate lotion for 4 weeks. They were assessed 4 weeks later and those without improvement were crossed over to the other arm for another 4 weeks. Those with improvement were followed up in the same arm for 6 months. RESULTS: Botulinum therapy showed significant improvement in the initial (80%) as well as cross over cases (75%) as compared to iontophoresis and aluminium chloride (47%) for initial cases and (17%) for cross over cases. CONCLUSION: Better improvements were seen with botulinum therapy than with iontophoresis and topical therapy. Residual effects of relief lasted on an average for 4 months for botulinum toxin whereas it was one month with iontophoresis and topical therapy. Advantage with iontophoresis and topical therapy was that it was non invasive and did not require regional anaesthesia as with botulinum therapy.

Coenzyme q10 abrogated the 28 days aluminium chloride induced oxidative changes in rat cerebral cortex.

OBJECTIVE: The present study was designed to elucidate the impact of oral administration of aluminium chloride for 28 days with respect to oxidative stress in the cerebral cortex of female rats. Further, to investigate the potentials of Coenzyme (Co) Q10 (4, 8, and 12 mg/kg, i.p.) in mitigating the detrimental changes. MATERIALS AND METHODS: Biochemical estimations of cerebral lipid peroxidation (LPO), reduced glutathione (GSH), vitamin E and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were carried out after 28 days of aluminium chloride (AlCl3) and Co Q10 exposures along with histopathological examination of cerebral cortex of the rats. RESULTS: Subacute exposure to AlCl3(5 mg/kg) led to significant decrease in levels of GSH, vitamin E and activities of SOD, CAT, GPx, and an increase in LPO of cerebral cortex. These aberrations were restored by Co Q10 (12 mg/kg, i.p.). This protection offered was comparable to that of L-deprenyl (1 mg/kg, i.p.) which served as a reference standard. Histopathological evaluations confirmed that the normal cerebral morphology was maintained by Co Q10. CONCLUSION: Thus, AlCl3 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in cerebral cortex of female Wistar rats. Supplementation with intraperitoneal Co Q10 abrogated these deleterious effects of AlCl3.

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.

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.

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.

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.