AlCl3 Toxicity Research Articles

Protective effect of magnetic water against AlCl3-induced hepatotoxicity in rats

This study aimed to examine whether or not aluminum chloride (AlCl3)-induced hepatotoxicity might be mitigated using magnetic water (MW) in rats. This study involved 28 adult male rats randomly assigned into the following 4 groups (7 rats/group): normal control (Cnt), MW, AlCl3, and Al Cl3 + MW. The Cnt group orally received normal saline, the MW group drank MW ad libitum for 2 months, and the AlCl3 and AlCl3 + MW groups were orally administered AlCl3 (40 mg/kg b.w.) alone or in combination with MW for 2 months, respectively. MW reduced AlCl3 toxicity as proved at functional, molecular, and structural levels. Functionally, MW reduced serum levels of liver enzymes (ALT, AST, ALP, GGT), while increased total proteins, and albumin. MW also restored redox balance in the liver (lower MDA levels, higher activities of CAT and SOD enzymes, and upregulated expression of NrF2, HO-1, and GST genes. Molecularly, MW downregulated hepatic expression of the epigenetic (HDAC3), inflammatory (IL1β, TNFα, NFκβ), and endoplasmic reticulum stress (XBP1, BIP, CHOP) genes. Structurally, MW enhanced liver histology. With these results, we could conclude that MW has the potential to ameliorate the hepatotoxic effects of AlCl3 through targeting oxidative stress, inflammation, epigenesis, and endoplasmic reticulum stress.

Cardio and Neuroprotective Effects of Naringenin Against Aluminum Chloride-induced Oxidative Stress in Wistar Rats

Background: Plant secondary metabolites have been reported to offer a wide variety of medicinal purposes, including protection against heavy metal toxicity. Objectives: This study aimed to investigate the potentiality of naringenin a flavonoid in ameliorating the antioxidant defense system of neural and cardiac cells against aluminum chloride (AlCl3 ) toxicity in rats. Methods: The rats were divided into control (group 1), AlCl3 -treated (2), AlCl3+Naringenin-treated (3), and Naringenin-treated (4) groups. During experimentation, group 2 received an oral dose of 100 mg/kg/BW of AlCl3 , and group 3 received 100 mg/kg/BW of AlCl3 and 50 mg/ kg/BW of naringenin. In addition, group 4 received 50 mg/kg/BW of naringenin each day, while group 1 and all groups received a normal diet and water ad libitum for 30 days. The animals were sacrificed, and then blood, brain, and heart tissues were collected for biochemical and histological studies. Results: The results revealed that naringenin administration ameliorates the antioxidant defense system (catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase [GPx], and glutathione transferase) in AlCl3 toxicity in neural and cardiac tissues. AlCl3 caused oxidative tissue damage, showing a significant increase in malondialdehyde (MDA) (P<0.05) in both tissues. The levels of neurotransmitter acetylcholine esterase, nitric oxide, and lactate dehydrogenase (LDH) in the rats of group 3 were significantly (P<0.05) higher compared with AlCl3 -intoxicated rats. Furthermore, the AlCl3 -administered group had significantly (P<0.05) elevated levels of total cholesterol (TC), triglycerides, and low-density lipoprotein-cholesterol, with reduced high-density lipoprotein-cholesterol levels in comparison to the naringenin-treated and control groups. Naringenin treatment normalized the lipid profile. Histological analysis using the hematoxylin and eosin staining method revealed that AlCl3 caused degenerative changes in the cerebellum and cardiac tissues, which were ameliorated by co-treatment with naringenin. Conclusion: Naringenin has the potential to mitigate AlCl3 -induced oxidative stress (OS) in the neural and cardiac tissues of rats by enhancing the antioxidant defense system and reversing tissue injuries in the brain and heart.

Effects of Buccholzia coriacea (wonderful kola) on hepatoprotective, nephrotective and oxidative stress of aluminium chloride induced wistar rats

Buchholzia coriacea seeds has been reported to have various medicinal properties. This study evaluates the effect of the aqueous extract of Buchholzia coriacea seed (wonderful kola), on Aluminium chloride induced liver toxicity in adult male Wistar rats. 24 rats weighing between 150 g - 210 g were divided into five groups. Group A- (the control group) received water and animal chow. Group B received 200mg/kg of AlCl3 only, Group C received aluminum chloride and vitamin C for 14 days. Group D received 250 mg/kg body weight body weight (Low Dose) of aqueous extract Buchholzia coriacea and (200 mg/kg) AlCl3. Group E received 1000mg/kg body weight (High Dose) of aqueous extract of Buchholziacoriacea and (250mg/kg) AlCl3. The animals were sacrificed, the liver and kidney was excised and processed for routine paraffin sections at 5micromes thick. Sections were stained with Haematoxylin and Eosin to demonstrate histoarchitecture. Biochemical analysis was also carried out to determine the effects on liver and kidney antioxidant enzymes. Histological assessment showed narrowed central vein, degeneration of hepatocytes and distortion of sinusoids in the AlCl3 alone treated groups. The histoarchitecture of the liver in the other groups showed improvement especially in Group E (High Dose of B. coriacea) and Group C (vitamin C and aluminum chloride only). The biochemical analysis on the other hand showed significantly reduced activities in GSH, SOD, CAT and significantly increased level of MDA in the AlCl3 only group. In the other groups, MDA levels reduced, GSH, SOD and CAT also increased enzymatic activities following the administration of B. coriacea. The study concludes that Buchholziacoriacea seed extract plays a role in protecting liver and kidney from AlCl3 toxicity.

Nephroprotective effects of silymarin and its fabricated nanoparticles against aluminum-induced oxidative stress, hyperlipidemia, and genotoxicity.

Aluminum (Al) is a ubiquitous element with proven nephrotoxicity. Silymarin (SM) is a mixture of polyphenolic components extracted from Silybum marianum and exhibited protective influences. However, SM bioactivity can be enhanced by its incorporation in chitosan (CS) through the use of nanotechnology. This work proposed to assess the protective influence of SM and its loaded chitosan nanoparticles (SM-CS-NPs) on aluminum chloride (AlCl3)-induced nephrotoxicity. Six groups were created randomly from 42 male Wistar rats and each one contains 7 rats (n = 7). Group I, acted as a control and received water. Group II received SM (15 mg/kg/day) and group III administered with SM-CS-NPs (15 mg/kg/day). Group IV received AlCl3 (34 mg/kg) and groups V and VI were treated with SM and SM-CS-NPs with AlCl3 respectively for 30 days. AlCl3 administration significantly elevated TBARS, H2O2, and kidney function levels besides LDH activity. Whereas GSH, CAT, SOD, GPx, GST, and GR values were all substantially reduced along with protein content, and ALP activity. Additionally, significant alterations in lipid profile, hematological parameters, and renal architecture were observed. Moreover, TNF-α, TGF-β, and MMP9 gene expression were upregulated in kidney tissues. The administration of SM or its nanoparticles followed by AlCl3 intoxication attenuated renal dysfunction replenished the antioxidant system, and downregulated TNF-α, TGF-β, and MMP9 gene expression in renal tissues compared to the AlCl3 group. SM-CS-NPs have more pronounced appreciated protective effects than SM and have the proficiency to balance oxidant/antioxidant systems in addition to their anti-inflammatory effect against AlCl3 toxicity.

Assessment of Histopathological Alterations and Oxidative Stress in the Liver and Kidney of Male Rats following Exposure to Aluminum Chloride.

The study aims to investigate the residual and histopathological effects of chronic aluminum chloride (AlCl3) toxicity in the kidney and liver of male rats. After 30-, 60-, and 90-day exposure period, analyses were conducted to assess the toxicity in the kidney and liver. The results showed that the concentration of AlCl3 in the kidney and liver increased significantly in 30-, 60-, and 90-day periods. The effects of oxidative stress on the kidneys and liver were dose- and time-dependent. Levels of malondialdehyde (MDA) significantly increased when exposed to AlCl3 groups. Conversely, the activity of antioxidant parameters, including reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), significantly decreased in the AlCl3 exposed groups, indicating compromised oxidant mechanisms. Both the kidney and liver exhibited severe tissue damage, including necrosis, fibrosis, and inflammatory cell infiltration, in rats exposed to AlCl3. Kidney sections showed hyperplasia of the epithelial cells lining the renal tubules, resembling finger-like structures. Liver sections displayed severe lobular hyperplasia and an increase in mitotic figures. Our study suggests that AlCl3 has a detrimental impact on these vital organs and emphasizes the importance of monitoring and mitigating aluminum exposure, particularly where it is present in high concentration.

Smart Hesperidin/Chitosan Nanogel Mitigates Apoptosis and Endoplasmic Reticulum Stress in Fluoride and Aluminum-Induced Testicular Injury

Fluoride and aluminum are ubiquitous toxic metals with adverse reproductive effects. The citrus flavonoid hesperidin has protective activities but poor solubility and bioavailability. Nanoparticulate delivery systems can improve flavonoid effectiveness. We conducted this study to prepare a pH-responsive chitosan-based nanogel for hesperidin delivery and evaluate its effectiveness against sodium fluoride (NaF) and aluminum chloride (AlCl3) induced testicular toxicity in mice. The nanogel was synthesized using 2 kGy gamma irradiation, enabling a size under 200 nm and enhanced hesperidin release at pH 6 matching testicular acidity. Male mice received 200 mg/kg AlCl3 and 10 mg/kg NaF daily for 30 days. Hesperidin nanogel at 20 mg/kg was administered orally either prophylactically (pretreatment) or after intoxication (posttreatment). The results showed that AlCl3 + NaF induced severe oxidative stress, hormonal disturbance, apoptosis, and endoplasmic reticulum stress, evidenced by significant changes in the studied parameters and testicular histological damage. Hesperidin nanogel administration significantly inhibited oxidative stress markers, restored luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels, and alleviated tissue damage compared to the intoxicated group. It also downregulated the expression level of pro-apoptotic genes Bax, caspase-3, caspase-9, and P38MAPK, while upregulating the expression level of the anti-apoptotic BCL2 gene. Endoplasmic reticulum stress sensors PERK, ATF6, and IRE-α were also downregulated by the nanogel. The chitosan-based nanogel enhanced the delivery and efficacy of poorly bioavailable hesperidin, exhibiting remarkable protective effects against AlCl3 and NaF reproductive toxicity. This innovative nanosystem represents a promising approach to harnessing bioactive phytochemicals with delivery challenges, enabling protective effects against chemical-induced testicular damage.Graphical

Repro-protective activity of amygdalin and spirulina platensis in niosomes and conventional forms against aluminum chloride–induced testicular challenge in adult rats: role of CYP11A1, StAR, and HSD-3B expressions

The male reproductive system is negatively influenced by Al exposure. Al represented a considerable hazard to men’s reproduction capabilities. Amygdalin (AMG) and spirulina platensis (SP) have been considered to have a strong antioxidant and repro-protective activity; also, targeted drug delivery systems called niosomes improve the distribution of water-soluble medications like amygdalin and spirulina. Current study targeted to determine the effectiveness of AMG and SP against negative reproductive impact resulted by aluminum chloride (AlCl3) toxicity. Sixty adult male albino rats were separated into 6 groups, including the control group, which received distilled water; AlCl3 group, which received AlCl3; AMG+AlCl3 group, which received AlCl3+AMG; AMGLN+AlCl3 group, which received AlCl3+amygdalin-loaded niosomes; SP+AlCl3 group, which received AlCl3+SP; and SPLN+AlCl3 group, which received AlCl3+spirulina-loaded niosomes. All treatments were orally gavaged daily for 5 weeks, and rats were weighed weekly. At the termination of the experiment, some males (three from each group) were used for fertility traits via mating thirty virgin rat females (in a ratio of 1:2 and 2:3 male:female, respectively) followed by recording of birth weights and litter size (number of pups per each female) at birth to assess males’ reproductive capability. Other males were euthanized for collection of serum, epididymal semen samples, and tissue samples for biochemical, sperm evaluation, gene expression, and histopathological measurements. There are a considerable number of negative impacts of AlCl3 on male fertility clarified by declined serum testosterone levels; an increased oxidative stress (MDA, TAC); deteriorated semen quality; down-regulation of CYP11A1, StAR, and HSD-3b gene expressions; and testicular tissue degenerative changes. In addition, litter size (number of pups per each female) and birth weights of pups obtained from mated females were affected. AMG and SP treatments, either in niosomal or conventional form, alleviated the AlCl3 negative effects by reducing oxidative stress; increasing testosterone levels; improving semen quality; upregulating of CYP11A1, StAR, and HSD-3b gene expressions; and reducing degenerative changes of testicular tissue. Besides, negative reproductive effect was diminished as observed by changes in the litter size (number of pups per each female) and birth weights of pups obtained from mated females. AMG and SP treatments (either in niosomal or conventional form), ameliorated the AlCl3 negative effects as they possess powerful antioxidant activity, as well as they have the ability to improve the reproductive activity of affected males.Graphical abstract

Anticholinesterase and Antioxidant Potential of Aqueous Phyllanthus amarus Leaf Extract in Aluminium Chloride-Exposed Drosophila melanogaster

Aluminium chloride (AlCl3) toxicity is associated with several neurodegenerative disorders, including Alzheimer’s dis-ease, via mechanisms of oxidative stress, impairment of cholinergic neurotransmission, and enhancement of acetyl-cholinesterase activity. Phyllanthus amarus (P. amarus) is a widely used medicinal plant with reported antioxidant properties, and accordingly, this study investigated the anticholinesterase and antioxidant potential of P. amarus against AlCl3-induced toxicity in Drosophila melanogaster. 200 drosophilas were divided into four groups, with 50 per group. The control group was reared on a cornmeal diet, while the AlCl3 group was treated with 40 mM of AlCl3 via their diet. The P. amarus group was treated with 2.5 mg of P. amarus, while the co-treatment group was co-treated with 40 mM AlCl3 and 2.5 mg of P. amarus via their diet for seven days. At the end of the experimental period, negative geotaxis was carried out to evaluate locomotor performance. The drosophilas were thereafter homogenised, and the supernatants were used to assay for acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) activities. Results showed a significant decrease in the survival rate, climbing activity, SOD, and CAT, as well as a significant increase in MDA and AChE activity in AlCl3-exposed drosophilas. However, co-treatment with P. amarus was able to significantly attenuate the toxicity of AlCl3. Taken together, the protective effect of P. amarus against AlCl3 is mediated possibly through its anti-cholinesterase and antioxidant properties and could therefore be relevant in the development of novel therapeutic agents useful for the treatment of AlCl3 toxicity and its related disorders

Anticholinesterase activity and antioxidant effect of vitamin E in aluminium chloride induced toxicity in <i>Drosophila melanogaster</i>

Background: Aluminium chloride (AlCl3) toxicity has been reported to be linked with impaired locomotion, memory, learning, oxidative stress and impairment of cholinergic function which are synonymous with features seen in Alzehmiers disease (AD). Vitamin E has been put forward as a possible therapeutic intervention for AD. However, there are controversies as to whether Vitamin E is beneficial in the management of AD. Anticholinesterase activity and antioxidant potential of vitamin E was evaluated in aluminium chloride induced toxicity in Drosophila Melanogaster.Methods: A 2.5mg dose of Vitamin E was considered the appropriate standard for this study after exposure of flies to varying doses of vitamin E in a 15-day survival study. Group I served as control while group II were treated with 40mM aluminium chloride (AlCl3) via their diet. Group III were treated with 2.5mg of Vitamin E via their diet and Group IV were co-administered with 40 mM AlCl3 and 2.5mg of Vitamin E via their diet. The flies were maintained on these treatments at room temperature for seven (7) days. Negative geotaxis was carried out to assess for locomotor performance (climbing activity). The impact of 40 mM AlCl3 and/0r 2.5mg of Vitamin E on the survival rate of flies was also evaluated by carrying out a 15-day survival study At the end of the experimental period, the flies were homogenized and the supernatants were used to assay for, malonaldehyde (MDA) concentration, acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) activities.Results: AlCl3 significantly reduced (P<0.05) the survival rate, decreased the climbing activity of flies, elevated MDA concentration and AChE activities of flies. SOD, CAT and GST activities were also significantly reduced (P<0.05) in AlCl3 treated flies. In the co treatment protocol, vitamin E was able to significantly improve (P<0.05) the survival rate, improved their climbing activity and ameliorated AlCl3 increase in AChE activity and MDA concentration in these flies. In addition, vitamin E significantly attenuated (P<0.05) AlCl3 induced decrease in SOD, CAT and GST activities.Conclusion: This study has shown that vitamin E has both antioxidant and anti-cholinesterase activities and could be of therapeutic benefits against AlCl3 induced toxicity and associated diseases like Alzheimer’s disease.

Febuxostat attenuates aluminum chloride-induced hepatorenal injury in rats with the impact of Nrf2, Crat, Car3, and MNK-mediated apoptosis

Aluminum (Al) is a ubiquitous xenobiotic with known toxicity for both humans and animals. Our study was conducted to investigate the protective role of febuxostat (Feb) against aluminum chloride (AlCl3)-induced hepatorenal injury in rats. Hepatorenal injury was induced by oral administration of AlCl3 (40 mg/kg b.w.), for 2 months. Twenty-four male Sprague–Dawley rats were randomly allocated into four groups (six rats/group). The first group received the vehicle thought the experiment. The second group was considered as a control positive group. The third and fourth groups received oral treatment of Feb (10 mg/kg.b.w.) and (15 mg/kg.b.w.), respectively with AlCl3, concurrently for 2 months. Twenty-four hours, after the last treatment, serum biochemical, molecular, histopathology, and immunohistochemical studies were evaluated. Our findings showed that rats intoxicated with Alcl3 had disturbed biochemical picture. In addition, intoxication with AlCl3 increased oxidative stress and apoptosis, as demonstrated by an increase in malodialdeyde (MDA), carnitine o-acetyltransferase (Crat), and carbonic anhydrase (Car3) with a decrease in glutathione (GSH), MAP kinase-interacting serine/threonine kinase (MNK) and nuclear factor-erythroid 2-related factor 2 (Nrf2) mRNA expression. Furthermore, the levels of tumor necrosis factor-alpha (TNF-α) and the levels of caspase-3 were elevated with sever hepatic and renal pathological changes. Conversely, Feb (15 mg/kg.b.w.) could improve the serum biochemical indices and repressed MDA, Crat, and Car3 levels, whereas it increased GSH, MNK, and Nrf2 levels. Feb inhibited the apoptotic effect of AlCl3 in the liver and kidney by decreasing caspase-3 and TNF-α expression. The protective effect of Feb against AlCl3 toxicity was confirmed by histopathological findings. Moreover, molecular docking studies supported the anti-inflammatory effect of Feb due to its significant binding interactions with cyclooxygenase-1 (COX-1), NF-kappa-B-inducing kinase (NIK), and mitogen-activated protein kinases-p38 (MAPK-p38). The findings suggest that Feb system Feb can avert Alcl3-induced hepatotoxicity and nephrotoxicity by enhancing the antioxidant defense system, and inhibiting the inflammatory cascade and apoptosis.

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.

Preliminary Evidence That Fiji Water Has Protective Effects against Aluminum Toxicity in Honey Bees (Apis mellifera).

Researchers have determined that bioavailable aluminum chloride (AlCl3) may affect honey bee behavior (e.g., foraging patterns and locomotion) and physiology (e.g., abdominal spasms). The purpose of these experiments was to determine if Fiji water reduces the impacts of AlCl3 toxicity in bees by measuring circadian rhythmicity (number of times bees crossed the centerline during the day and night), average daily activity (average number of times bees crossed the centerline per day), and mortality rates (average number of days survived) using an automated monitor apparatus. Overall, the AlCl3 before and after Fiji groups had significantly higher average daily activity and rhythmicity rates compared to their respective AlCl3 before and after deionized water (DI) groups. One of the AlCl3 before DI groups exhibited no difference in rhythmicity rates compared to its respective AlCl3 after Fiji group. Overall, these results suggest that Fiji water might exert protective effects against AlCl3. The AlCl3 groups paired with Fiji water had higher activity and rhythmicity levels compared to the AlCl3 groups paired with DI. It is important for researchers to continue to study aluminum and possible preventatives for aluminum uptake.

Cationic biopolymer decorated Asiatic Acid and Centella asiatica extract incorporated liposomes for treating early-stage Alzheimer's disease: An In-vitro and In-vivo investigation.

Background:Asiatic acid (AA) is a naturally occurring triterpenoid derivative of Centella asiatica (CA) with neuroprotective effect.The study aimed to design an ideal oral drug delivery system to treat Alzheimer's disease (AD) and develop chitosan-embedded liposomes comprising an extract of CA (CLCAE) and compare them with the chitosan-coated liposomes of asiatic acid (CLAA) for oral delivery to treat the initial phases of AD. Methods:The solvent evaporation technique was used to develop CLCAE and CLAA, optimised with the experiment's design, and was further evaluated. Results:Nuclear magnetic resonance (NMR) studies confirmed coating with chitosan. Transmission electron microscopy(TEM) and atomic force microscopy (AFM) indicated the successful formation of CLCAE and CLAA. Differential scanning colorimetry (DSC) confirmed the drug-phospholipid complex. Furthermore, the rate of in vitrorelease of CLCAE and CLAA was found to be 69.43±0.3 % and 85.3±0.3 %, respectively, in 24 h. Ex vivopermeation of CLCAE and CLAA was found to be 48±0.3 % and 78±0.3 %, respectively. In the Alcl3-induced AD model in rats, disease progression was confirmed by Y-maze, the preliminary histopathology evaluation showed significantly higher efficacy of the prepared liposomes (CLCAE and CLAA) compared to the Centella asiatica extract (CAE) and they were found to have equivalent efficacy to the standard drug (rivastigmine tartrate). The considerable increase in pharmacodynamic parameters in terms of neuronal count in the CLAA group indicated the protective role against Alcl3 toxicity and was also confirmed by assessing acetylcholine (Ach) levels. The pharmacokinetic study, such as C max, T max, and area under curve (AUC) parameters, proved an increase in AA bioavailability in the form of CLAA compared to the pure AA and CLCAE forms. Conclusion:The preclinical study suggested that CLAA was found to have better stability and an ideal oral drug delivery system to treat AD.

Bromelain Modulates Liver Injury, Hematological, Molecular, and Biochemical Perturbations Induced by Aluminum via Oxidative Stress Inhibition.

Aluminum (Al) is an important factor in the environment as it is used in agriculture and several industries leading to hazardous effects via oxidative stress. Bromelain is a cheap extract from the byproduct waste of Ananas comosus stem. It has been used in several biological and therapeutic applications. So, this study was undertaken to assess the hepatoprotective potential of bromelain versus oxidative stress induced by aluminum chloride in rats. Results revealed that administration of AlCl3 reduced the body and liver weights and increased Al concentration in the blood and liver tissue. Also, AlCl3 caused valuable changes in hematological parameters and increased TBARS and H2O2 concentrations in rat liver. Enzymatic (SOD, CAT, GPx, GR, and GST) and nonenzymatic (GSH) antioxidants and protein content were significantly decreased. Furthermore, alterations in liver biomarkers such as bilirubin level and enzyme activities in both serum and liver homogenate (LDH, ALP, AST, and ALT) were detected. AlCl3 also caused inflammation as indicated by upregulation of the inflammation-related genes [interleukin 1 beta (IL-1β)], tumor necrosis factor-alpha (TNF-α), as well as matrix metalloproteinase (MMP9), and downregulation of nuclear factor erythroid 2 (Nrf2) expression. In addition, histopathological examination showed significant variations in the liver that confirms the biochemical results. Otherwise, bromelain intake alone slumped lipid peroxidation and gotten better antioxidant status significantly. Moreover, supplementation with bromelain before AlCl3 intoxication restores enzymatic and nonenzymatic antioxidants as well as biochemical indices and tissue architecture with respect to the AlCl3 group. In conclusion, bromelain proved its remarkable protective power to abolish AlCl3 toxicity. So, it might represent a new strategy in the therapy of metal toxicity by its antioxidant capacity.

Centella asiatica L. Urban protects against cognitive dysfunction in alluminum chloride-induced neurotoxicity in rats via inhibition of acetylcholinesterase level

ABSTRACT Aluminum (Al) is a ubiquitous element on planet earth and its exposure to human systems is increasing steadily due to industrialization. Its accumulation in the biological systems have deleterious effects such as neurodegeneration and cognitive impairment. Centella asiatica L. (CA) is a herb used in the Ayurveda system of medicine as a neurotonic and for enhancement of memory. This study aimed at assessing the protective role of CA in aluminum chloride (AlCl3) induced cognitive dysfunction in rats. Results have shown that AlCl3 toxicity caused significant (p < 0.05) cognitive dysfunction of both spatial and non-spatial memory in rats, histopathological aberration of cerebral cortex and significant (p < 0.05) increase in the level of acetylcholinesterase in their brain. However, administration of CA irrespective of the dose given prevented all the observed changes which are comparable to a standard drug donepezil. CA prevented cognitive impairment and neurodegeneration in rats by decreasing the level of acetylcholinesterase. Hence, CA could be developed as a memory enhancing drug.

Prophylactic Effect of A Probiotic Strain Lactobacillus Rhamnosus Against Aluminum Chloride-Induced Intoxication in Wistar Rats: Neurobehavioral and Hematobiochemical Studies

Purpose: Aluminum (Al) and its various forms are environmental xenobiotics that pose great threats to public health. The probiotic strain has been reported to have important protective effects against aluminum cytotoxicity. Therefore, the current study was designed to assess the disruption of neurobehavioral and hematobiochemical parameters caused by chronic exposure to AlCl3, and then explore the protective effects of the probiotic strain Lactobacillus rhamnosus against these adverse in male rats. Method: Thirty-two animals were gathered into four groups: The first group served as control. The second group received 100mg AlCl3/kg bw for 12 weeks. However, the third group was administered 10mL probiotic strain /Kg (108 CFU/ml) bw/d daily for 4 weeks. Finally, group 4 received AlCl3 for 12 weeks, then the treatment was continued with probiotic for 4 weeks. Results: AlCl3 produced a decrease in body and brain weights with respect to their control. The results obtained also showed significant depression and anxiety-like behavior in the intoxicated animals, with a disturbance of the tested hematobiochemical parameters, particularly in renal and hepatic biomarkers. Overall, probiotics prevented enduring AlCl3-induced depression-like behavior in intoxicated rats. The results of the hematobiochemical, renal and hepatic analyses show a correction of the values after the administration of probiotics compared to those of intoxicated and untreated animals. Conclusion: The probiotic lactobacilli would be an alternative to reduce AlCl3 toxicity.

Anticholinesterase activity and Antioxidant Effect of Vitamin E in Aluminum Chloride Induced Toxicity in Drosophila Melanogaster

BackgroundAluminum chloride (AlCl3) has been used to model neurotoxicity and Alzheimer’s disease (AD) like neurodegeneration in various animal models (Bondy, 2010). AlCl3 toxicity has been reported to be associated with impaired locomotor performance, learning, memory, oxidative stress and cholinergic impairment which are features seen in AD patients (Ribes et al., 2008). AlCl3acts as a cholinotoxin (Gulya et al., 1990) and cause alterations on the cholinergic activity, a key event in the neurochemistry of AD (Rakonczay et al., 2005). Reduced cholinergic function in the brain has been shown to result in memory impairment in AD (Mukherjee et al., 2007). The use of compounds to inhibit acetylcholinesterase (AChE) activity (to reduce the hydrolysis of acetylcholine) has been a therapeutic approach in managing AD (Taylor and Radić 1994). Vitamin E has been proposed as a potential clinical intervention for AD given its antioxidant and anti‐inflammatory characteristics. However, there are very few studies on its anticholinesterase activity and there also controversies as to whether vitamin E is beneficial in AD. We therefore evaluated the anticholinesterase and antioxidant activity of vitamin E in aluminium chloride induced toxicity in Drosophila melanogaster.MethodsD. melanogaster (Harwich strain, 3‐5 days) were utilized for this study. In order to determine the appropriate dose of vitamin E to be utilized for this study, a 15 days survival study (where mortality rate was recorded daily) was carried out with varying dose of Vitamin E (2.5mg and 5mg). Subsequently, 2.5mg of vitamin E produced the least mortality of flies and was utilized for this study. The choice of concentration for AlCl3was based on previous studies on aluminum toxicity in D. melanogaster [Wu et al., 2012; Ogunsuyi, 2020]. Flies (both genders) were divided into 4 groups with 50 flies per vial. Group I served as control and were reared on their cornmeal diet while group II were treated with 40mM aluminum chloride (AlCl3) via their diet. Group III flies were fed with normal diet containing 2.5mg of vitamin E while Group IV were co‐administered with 40 mM AlCl3and 2.5mg of vitamin E via their diet. The flies were maintained on these treatments at room temperature for seven (7) days. All experiments were carried out in five replicates (n=5). Negative geotaxis was carried out to assess for locomotion deficit. At the end of the experimental period, the flies were homogenized and the supernatant were used to assay for AchE activity, malonaldehyde (MDA) concentration, superoxide dismutase (SOD), catalase (CAT) and glutathione S‐transferase (GST) activities.ResultsAlCl3induced toxicity reduced the survival rate, decreased the climbing activity, elevated MDA concentration and AChE activities of flies. SOD, CAT and GST activities were also reduced in AlCl3treated flies. Vitamin E was able to improve the survival rate, restored AlCl3induced reduction in climbing activity, ameliorated AlCl3 increase in AChE activity and MDA concentration in flies. In addition, Vitamin E attenuated AlCl3induced inhibition of SOD, CAT and GST activities.ConclusionThis study has shown that Vitamin E has both antioxidant and anticholinesterase activities and can be regarded as a therapeutic agent against AlCl3 induced toxicity and associated diseases.

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

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

Pomegranate juice moderates anxiety- and depression-like behaviors in AlCl3-treated male mice

PurposeAluminum trichloride (AlCl3) exposure was proven to encourage some behavioral deficits and eventually induces anxiety and depression in rodents animals. Therefore, this experiment aimed to scout about the effects of pomegranate juice on anxiety- and depression-like behaviors caused by AlCl3 in male mice. MethodsSix groups of male mice were administrated orally for 35 days by PJ and AlCl3. The control group (G-I) received tap water, while the PJ groups (G-II and G-III) were treated with 20 % and 40 % PJ, respectively. The AlCl3 group (G-IV) was treated with 400 mg/kg/day of AlCl3, and the last two groups (G-V and G-VI) were treated with AlCl3 and 20 % PJ or 40 % PJ, respectively. Then, the open-field (O-F), elevated plus maze (EPM), tail suspension (TS), forced swimming (FS), and light/dark box (L/DB) tests were applied for anxiety- and depression-like behavior studies. In addition, neurotransmitters and oxidative parameters in the brain were evaluated. The plasma cortisol was measured at the end of the experiment. ResultsBehavioral analyses showed that PJ inhibited AlCl3-induced depressive and anxiogenic effects in the O-F, EPM, TS, FS, L/DB tests. In addition, neurochemical results indicated that PJ at 20 % concentration minimized the AlCl3 toxicity on dopamine (DOP), serotonin (SER), and acetylcholinesterase (AChE) levels in the for-brain of male mice. Moreover, PJ moderated the AlCl3 effects by decreasing the level of thiobarbituric acid reactive substances (TBARS), and enhancing catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST) and glutathione (GSH) activities. The plasma cortisol increased in male mice treated with AlCl3 and in a group treated with a high dose of PJ. ConclusionOur results proposed that the anxiety- and depression-like behaviors induced by AlCl3 exposure in male mice can be ameliorated by PJ treatment, probably through the inhibition of oxidative damage and minimizing the changes in neurotransmitters and hormonal activity.

Kolaviron ameliorates toxic effects of aluminum chloride on the hippocampus of fetal Wistar rats in utero: Biochemical and ultrastructural observations

BACKGROUND: This study was designed to investigate the biochemical and ultrastructural effects of kolaviron (Kv) on the hippocampus of fetal Wistar rats exposed to aluminum chloride (AlCl3) toxicity in utero. MATERIALS AND METHODS: Fifty female Wistar rats were selected at random and mated. Following confirmation of mating, pregnant rats were assigned into five groups (n = 5). Controls: Group A received distilled water; Group B: 0.6 ml of corn oil; Group C: 200 mg/kg of Kv; Group D: 100 mg/kg of AlCl3 and Group E 100 mg/kg of AlCl3 and 200 mg/kg of Kv. Administration was done from days 8-10 and 15-17 of gestation during the 2nd and 3rd weeks respectively. Biochemical analyses were investigated to assess oxidative stress levels, while transmission electron microscopy (TEM) examined ultrastructural changes. Pregnant animals were sacrificed on day 20 of gestation; fetuses, their brains, and hippocampi were excised, respectively. Hippocampal tissues of fetuses were homogenized in 0.25 M of sucrose solution for biochemical assay while some were fixed in 2.5% phosphate-buffered saline-based glutaraldehyde for TEM. RESULTS: Elevated levels of Al, malondialdehyde, nitric oxide, and interleukin 6 were observed in the hippocampi of fetuses whose mothers received AlCl3. TEM revealed loss of nuclear membrane and increased condensation of chromatin materials in the same group. However, significant reduction of these enzymes including improved ultrastructural alterations were observed in the fetal hippocampus of the AlCl3 + Kv-treated group. CONCLUSION: This study showed that Kv significantly reduced neurodegenerative effects induced by AlCl3 in the hippocampii of fetal Wistar rats in utero probably owing to its antioxidant and anti-inflammatory properties.