RESUMO
Background: Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual cognitive impairment, including loss of synapses and nerve cells involved in learning, memory, and habit formation processes. Bone Marrow Mesenchymal Stem Cells (BM-MSCs) are multipotent cells. Because of their self-renewable, differentiation, and immunomodulatory capabilities, they are commonly used to treat many disorders. Hence, the current study intends to examine the effect of BM-MSCs transplantation on Aluminum chloride (AlCl3)-induced cognitive problems, an experimental model resembling AD's hallmarks in rats. Methods: The study was conducted in 2022 at The Biomedical Laboratory Faculty of Medicine, Andalas University, Indonesia. Adult male Wistar rats (three groups: negative control; no intervention+treatment with PBS; positive control: AlCl3+treatment with aqua dest; AlCl3+BM-MSCs: AlCl3+treatment with BM-MSCs, n=5 each) were treated daily with AlCl3 orally for five days. Stem cells were intraperitoneally injected into rats at a dose of 1x106 cells/rat. The same quantity of phosphate-buffered saline was given to the control group. One month after stem cell injection, the rat brain tissue was removed and placed in the film bottles that had been created. The expression of neural progenitor cell markers, including nestin and sex-determining Y-box 2 (SOX-2), was analyzed using real-time polymerase chain reaction (RT-PCR). Rats' cognitive and functional memory were examined using Y-maze. Data were analyzed using SPSS software (version 26.0) with a one-way analysis of variance (ANOVA) test. Results: The gene expression of nestin (29.74±0.42), SOX-2 (31.44±0.67), and percent alternation of Y-maze (67.04±2.28) increased in the AlCl3+BM-MSCs group compared to that in the positive control group. RT-PCR analysis indicated that nestin (P<0.001) and SOX-2 (P<0.001) were significantly enhanced in the AlCl3+BM-MSCs group compared to the positive control group. This group also indicated an increased percent alternation of Y-maze (P<0.001) in the AlCl3+BM-MSCs group compared to the positive control group. Conclusion: Due to its potential effects on cell therapy, BM-MSCs were found effective in a rat model of AD on the impairment of the rats' behavior and increased expression of neural progenitor cell markers.
Assuntos
Cloreto de Alumínio , Doença de Alzheimer , Modelos Animais de Doenças , Células-Tronco Mesenquimais , Nestina , Ratos Wistar , Fatores de Transcrição SOXB1 , Animais , Cloreto de Alumínio/farmacologia , Ratos , Masculino , Doença de Alzheimer/terapia , Nestina/genética , Transplante de Células-Tronco Mesenquimais/métodos , Compostos de Alumínio/farmacologia , Aprendizagem Espacial/efeitos dos fármacos , Aprendizagem Espacial/fisiologia , Cloretos , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologiaRESUMO
This work outlines the first microwave (MW)-assisted protocol for the production of biofuel precursor furfural (FF) from the raw agricultural waste almond hull (AH), olive stone (OS), and the winemaking-derived grape stalk (GS), grape marc (GM) and exhausted grape marc (EGM) through a one-pot synthesis process. To enhance the overall yield, a catalytic process was firstly developed from xylose, major constituent of hemicellulose present in lignocellulosic biomass. This method afforded FF with 100 % selectivity, yielding over 85 % in isolated product when using H2SO4, as opposed to a 37 % yield with AlCl3·6H2O, at 150 °C in only 10 min. For both catalysts, the developed methodology was further validated, proving adaptable and efficient in producing the targeted FF from the aforementioned lignocellulosic raw materials. More specifically, the employment of AlCl3·6H2O resulted in the highest selectivity (up to 89 % from GM) and FF yield (42 % and 39 % molar from OS and AH, respectively), maintaining notable selectivity for the latter (61 and 48 % from AH and OS). At this regard, and considering the environmental factor of sustainability, it is important to point out the role of AlCl3·6H2O in contrast to H2SO4, thus mitigating detrimental substances. This study provides an important management of agricultural waste through sustainable practises for the development of potential bio-based chemicals, aligning with Green Chemistry and process intensification principles.
Assuntos
Furaldeído , Micro-Ondas , Prunus dulcis , Vinho , Furaldeído/análogos & derivados , Vinho/análise , Prunus dulcis/química , Biocombustíveis/análise , Vitis , Lignina/química , Óleos de Plantas/química , Catálise , Cloreto de Alumínio , Olea/químicaRESUMO
The present study aimed to investigate the effect of catechin-loaded Chitosan-Alginate nanoparticles (NPs) on cognitive function in an aluminum chloride (AlCl3)-induced rat model of Alzheimer's disease (AD). The Catechin-loaded Chitosan-Alginate nanocarriers were synthesized through ionotropic gelation (IG) method. Physio-chemical characterization was conducted with the Zetasizer Nano system, the scanning electron microscope, and the Fourier transform infrared spectroscopy. The experiments were performed over 21 days on six groups of male Wistar rats. The control group, AlCl3 treated group, Catechin group, nanocarrier group, treatment group 1 (AlCl3 + Catechin), and treatment group 2 (AlCl3 + nanocarrier). A behavioral study was done by the Morris water maze (MWM) test. In addition, the level of oxidative indices and acetylcholine esterase (AChE) activity was determined by standard procedures at the end of the study. AlCl3 induced a significant increase in AChE activity, along with a significant decrease in the level of Catalase (CAT) and total antioxidant capacity (TAC) in the hippocampus. Moreover, the significant effect of AlCl3 was observed on the behavioral parameters of the MWM test. Both forms of Catechin markedly improved AChE activity, oxidative biomarkers, spatial memory, and learning. The present study indicated that the administration of Catechin-loaded Chitosan-Alginate NPs is a beneficial therapeutic option against behavioral and chemical alteration of AD in male Wistar rats.
Assuntos
Alginatos , Cloreto de Alumínio , Doença de Alzheimer , Catequina , Quitosana , Nanopartículas , Ratos Wistar , Animais , Catequina/administração & dosagem , Catequina/farmacologia , Cloreto de Alumínio/toxicidade , Quitosana/química , Quitosana/administração & dosagem , Alginatos/química , Alginatos/administração & dosagem , Masculino , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/metabolismo , Ratos , Administração Oral , Cognição/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Modelos Animais de Doenças , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Portadores de Fármacos/químicaRESUMO
ETHNOPHARMACOLOGY RELEVANCE: Ganoderma leucocontextum T.H. Li, W. Q. Deng M. Wang & H.P.Hu. is a highland herbal medicine that has been shown to nourish the nervesand prolong life. Nevertheless, there is no evidence to indicate that Ganoderma leucocontextum triterpenoids (GLTs) reduce the damage triggered by Alzheimer's disease (AD). AIM OF THE STUDY: The aim of this investigation was to ascertain the protective effects of GLTs on AD mice models and cells, as well as to look into potential pathways. MATERIALS AND METHODS: In this study, the phytochemical characterization of GLTs was performed by High Performance Liquid Chromatography (HPLC) and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). The AD mouse model was induced by injecting intraperitoneally with D-galactose (120 mg/kg) and administering orally with aluminum chloride (20 mg/kg) daily for 28 days. After that, donepezil (5 mg/kg) and GLTs (0.4, 0.8, and 1.6 g/kg) were administered orally for 35 days. During the treatment period, aluminum chloride (20 mg/kg) and D-galactose (120 mg/kg) were continuously administered. And the behavior of the animals and the molecular changes of the hippocampus were determined after the whole experimental procedure. Furthermore, BV-2 cells were employed to validate GLTs' anti-neuroinflammatory properties. RESULTS: The total triterpenoids content was 443.12 ± 0.21 g/kg and was inferred to contain 19 classes of substances such as organic acids, amino acids, vitamins, flavonoids, and other chemicals in GLTs. Treatment of D-galactose/aluminum chloride-induced mouse with GLTs can ameliorate AD symptoms, counteract cognitive decline, improve Aß1-42 deposition, reduce the expression level of pro-apoptotic proteins, and attenuate the activation of hippocampal microglia and astrocytes. GLTs significantly increased the expression of antioxidant enzymes and significantly reduced the expression of inflammatory factors. GLTs inhibits nuclear factor kappa B (NF-κB) nuclear translocation and preserves myd88/traf6-mediated mitogen-activated protein kinase (MAPK) phosphorylation. Furthermore, GLTs (2 and 5 mg/mL) inhibited the generation of nitric oxide and protected lipopolysaccharide (1 mg/L)-induced neuroinflammation in BV-2 cells. CONCLUSIONS: Taken together, Ganoderma leucocontextum triterpenoids can improve cognitive functions, including learning and memory, by reducing neuroinflammation and oxidative stress, preventing apoptosis, and controlling amyloid genesis.
Assuntos
Cloreto de Alumínio , Doença de Alzheimer , Encéfalo , Galactose , Ganoderma , Triterpenos , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/induzido quimicamente , Ganoderma/química , Triterpenos/farmacologia , Triterpenos/isolamento & purificação , Camundongos , Cloreto de Alumínio/toxicidade , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Masculino , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/isolamento & purificação , Peptídeos beta-Amiloides/metabolismo , Linhagem CelularRESUMO
Chronic exposure to heavy metals as aluminum chloride (AlCl3) could result in severe health hazards such as chronic renal injury. The present study aimed to evaluate the therapeutic potential of adipose tissue-derived stem cells (ASCs) in comparison to their microvesicles (MV) in AlCl3-induced chronic renal injury. Forty-eight adult male Wistar rats were divided into four groups: Control group, AlCl3-treated group, AlCl3/ASC-treated group, and AlCl3/MV-treated group. Biochemical studies included estimation of serum urea and creatinine levels, oxidative biomarkers assay, antioxidant biomarkers, serum cytokines (IL-1ß, IL-8, IL-10, and IL-33), real time-PCR analysis of renal tissue MALT1, TNF-α, IL-6, and serum miR-150-5p expression levels. Histopathological studies included light and electron microscopes examination of renal tissue, Mallory trichrome stain for fibrosis, Periodic acid Schiff (PAS) stain for histochemical detection of carbohydrates, and immunohistochemical detection of Caspase-3 as apoptosis marker, IL-1B as a proinflammatory cytokine and CD40 as a marker of MVs. AlCl3 significantly deteriorated kidney function, enhanced renal MDA and TOS, and serum cytokines concentrations while decreased the antioxidant parameters (SOD, GSH, and TAC). Moreover, serum IL-10, TNF-α, miR-150-5p, and renal MALT1 expression values were significantly higher than other groups. Kidney sections showed marked histopathological damage in both renal cortex and medulla in addition to enhanced apoptosis and increased inflammatory cytokines immunoexpression than other groups. Both ASCs and MVs administration ameliorated the previous parameters levels with more improvement was detected in MVs-treated group. In conclusion: ASCs-derived MVs have a promising ameliorating effect on chronic kidney disease.
Assuntos
Ratos Wistar , Animais , Masculino , Ratos , Micropartículas Derivadas de Células/metabolismo , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Citocinas/metabolismo , Citocinas/sangue , Rim/patologia , Rim/metabolismo , Cloreto de Alumínio/efeitos adversos , Estresse Oxidativo , Células-Tronco/metabolismo , Tecido Adiposo/metabolismo , Transplante de Células-Tronco , Biomarcadores/sangueRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive impairment and memory loss. In this study, AD was experimentally induced in rats using aluminum chloride (AlCl3) and D-galactose (D-gal). Fisetin (Fis), a natural compound with antioxidant and anti-inflammatory properties, has potential for neurodegeneration management, but its low bioavailability limits clinical applications. To address this, we synthesized and characterized Pluronic-2-Acrylamido-2-methylpropane sulfonic acid (PLUR-PAMPS) nanogels using gamma radiation and successfully loaded Fis onto them (Fis-PLUR-PAMPS). The optimal formulation exhibited minimal particle size, a highly acceptable polydispersity index, and the highest zeta-potential, enhancing stability and solubilization efficiency. Our goal was to improve Fis's bioavailability and assess its efficacy against AlCl3/D-gal-induced AD. Male albino Wistar rats were pre-treated orally with Fis (40 mg/kg) or Fis-PLUR-PAMPS for seven days, followed by a seven-day intraperitoneal injection of AlCl3 and D-gal. Behavioral assessments, histopathological analysis, and biochemical evaluation of markers related to AD pathology were conducted. Results demonstrated that Fis-PLUR-PAMPS effectively mitigated cognitive impairments and neurodegenerative signs induced by AlCl3/D-gal. These findings suggest that Fis-PLUR-PAMPS nanogels enhance Fis's bioavailability and therapeutic efficacy, offering a promising approach for AD management.
Assuntos
Doença de Alzheimer , Apoptose , Modelos Animais de Doenças , Flavonóis , Nanogéis , Animais , Doença de Alzheimer/tratamento farmacológico , Ratos , Masculino , Flavonóis/farmacologia , Flavonóis/química , Apoptose/efeitos dos fármacos , Nanogéis/química , Poloxâmero/química , Ratos Wistar , Disfunção Cognitiva/tratamento farmacológico , Cloreto de Alumínio , Flavonoides/farmacologia , Flavonoides/química , Flavonoides/síntese química , Portadores de Fármacos/química , Galactose/químicaRESUMO
Aluminum chloride (AlCl3) is a potent neurotoxic substance known to cause memory impairment and oxidative stress-dependent neurodegeneration. Naringenin (NAR) is a dietary flavonoid with potent antioxidant and anti-inflammatory properties which was implemented against AlCl3-induced neurotoxicity to ascertain its neuroprotective efficacy. Experimental neurotoxicity in mice was induced by exposure of AlCl3 (10 mg/kg, p.o.) followed by treatment with NAR (10 mg/kg, p.o.) for a total of 63 days. Assessed the morphometric, learning memory dysfunction (novel object recognition, T- and Y-maze tests), neuronal oxidative stress, and histopathological alteration in different regions of the brain, mainly cortex, hippocampus, thalamus, and cerebellum. AlCl3 significantly suppressed the spatial learning and memory power which were notably improved by administration of NAR. The levels of oxidative stress parameters nitric oxide, advanced oxidation of protein products, protein carbonylation, lipid peroxidation, superoxide dismutase, catalase, glutathione reductase, reduced glutathione, and the activity of acetylcholine esterase were altered 1.5-3 folds by AlCl3 significantly. Treatment of NAR remarkably restored the level of oxidative stress parameters and maintained the antioxidant defense system. AlCl3 suppressed the expression of neuronal proliferation marker NeuN that was restored by NAR treatment which may be a plausible mechanism. NAR showed therapeutic efficacy as a natural supplement against aluminum-intoxicated memory impairments and histopathological alteration through a mechanism involving an antioxidant defense system and neuronal proliferation.
Assuntos
Cloreto de Alumínio , Flavanonas , Transtornos da Memória , Estresse Oxidativo , Animais , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Cloreto de Alumínio/toxicidade , Masculino , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
OBJECTIVE: Aluminum is a widely used metal in homes and industries. Xylopia aethiopica is an important medicinal plant with antioxidant properties. The objective of this study is to investigate the ameliorative potential of Xylopia aethiopica on aluminum-induced ovarian toxicity in Wistar rat. METHODS: Twenty-five rats were randomized into five groups with five rats per group. Group 1 received only distilled water; Group 2: received 150mg/kg of aluminum chloride; Group 3: received 150mg/kg aluminum chloride with 100/kg Xylopia aethiopica seed extracts; Group 4: received 150mg/kg aluminum chloride with 50 mg/kg Xylopia aethiopica seed extracts, and Group 5: received 150mg/kg aluminum chloride with 50mg/Kg zinc sulphate. For twenty-one days, all administrations were done orally. The rats were then sacrificed following chloroform anesthesia. The ovaries were harvested for histological examination. RESULTS: The data were analyzed on IBM SPSS software version 21 and the differences in mean values were considered significant at p<0.05. Xylopia aethiopica extracts significantly (p<0.05) reversed the detrimental effects of aluminum chloride on luteinizing hormone, follicle stimulating hormone, progesterone and estradiol. The histological analysis of the ovaries showed a significant improvement in rats treated with Xylopia aethiopica extract and zinc sulphate. However, Xylopia aethiopica was more effective in a dose-dependent manner. CONCLUSIONS: This study suggests that Xylopia aethiopica has ameliorative potential on aluminum-induced toxicity in the ovaries of adult female Wistar Rats.
Assuntos
Ovário , Extratos Vegetais , Ratos Wistar , Xylopia , Animais , Feminino , Extratos Vegetais/farmacologia , Ratos , Ovário/efeitos dos fármacos , Ovário/patologia , Xylopia/química , Cloreto de Alumínio/toxicidade , Estradiol , Alumínio/toxicidade , Hormônio Foliculoestimulante/sangueRESUMO
Aluminum (Al) overexposure damages various organ systems, especially the nervous system. Regularly administered aluminum chloride (AlCl3) to rats causes dementia and pathophysiological alterations linked to Alzheimer's disease (AD). Taxifolin's neuroprotective effects against AlCl3-induced neurotoxicity in vitro and in vivo studies were studied. Taxifolin (0.1, 0.3, 1, 3, and 10 µM) was tested against AlCl3 (5 mM)-induced neurotoxicity in C6 and SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Additionally, neural morphology was examined by confocal microscopy. Additionally, taxifolin's mode of binding with the co-receptor of toll-like receptor 4 (TLR4), human myeloid differentiation-2 (hMD-2) was investigated. AlCl3 (25 mg/kg/d, i.p.) was administered to rats for 14 d, and from the eighth day, taxifolin (1, 2, and 5 mg/kg/d, i.p.) was given along with AlCl3. This study assessed memory impairment using the Morris water maze, plus maze, and pole tests. This study also performed measurement of oxidant (malondialdehyde [MDA] and nitrite), antioxidant (reduced glutathione), and inflammatory (myeloperoxidase [MPO] activity, TLR4 expression) parameters in rats' brain in addition to histopathology. The docking score for taxifolin with hMD-2 was found to be -4.38 kcal/mol. Taxifolin treatment reduced the neurotoxicity brought on by AlCl3 in both C6 and SH-SY5Y cells. Treatment with 10 µM taxifolin restored AlCl3-induced altered cell morphology. AlCl3 administration caused memory loss, oxidative stress, inflammation (increased MPO activity and TLR4 expression), and brain atrophy. Taxifolin treatment significantly improved the AlCl3-induced memory impairment. Taxifolin treatment also mitigated the histopathological and neurochemical consequences of repeated AlCl3 administration in rats. Thus, taxifolin may protect the brain against AD.
Assuntos
Cloreto de Alumínio , Encéfalo , Fármacos Neuroprotetores , Quercetina , Receptor 4 Toll-Like , Animais , Humanos , Masculino , Ratos , Cloreto de Alumínio/toxicidade , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/metabolismo , Linhagem Celular Tumoral , Demência/induzido quimicamente , Demência/tratamento farmacológico , Demência/prevenção & controle , Demência/patologia , Relação Dose-Resposta a Droga , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Quercetina/análogos & derivados , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos Wistar , Receptor 4 Toll-Like/metabolismoRESUMO
BACKGROUND: 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. METHODS: 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. RESULTS: 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-ß, 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-ß, and MMP9 gene expression in renal tissues compared to the AlCl3 group. CONCLUSION: 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.
Assuntos
Rim , Nanopartículas , Estresse Oxidativo , Substâncias Protetoras , Ratos Wistar , Silimarina , Animais , Estresse Oxidativo/efeitos dos fármacos , Masculino , Silimarina/farmacologia , Nanopartículas/química , Nanopartículas/toxicidade , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Cloreto de Alumínio/toxicidade , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/induzido quimicamente , Ratos , Antioxidantes/farmacologia , Quitosana/química , Quitosana/farmacologia , Alumínio/toxicidadeRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder that impairs mental ability and interrupts cognitive function. Heavy metal exposure like aluminum chloride is associated with neurotoxicity linked to neuro-inflammation, oxidative stress, accumulation of amyloid plaques, phosphorylation of tau proteins associated with AD like symptoms. The objective of the present investigation was to assess the effect 3-acetyl coumarin (3AC) in a rat model of AD. Preliminary screening was performed with SWISS ADME to check for the bioavailability of 3-AC and likeness score which proved favorable. 3-AC docked against Caspase 3, NF-κß and tau protein kinase I exhibited good binding energies. Male rats were divided into six groups (n = 5). AlCl3 (100 mg/kg BW) was administered for 28 days before starting treatment to induce AD. Normal control rats received vehicle. Treatment groups received 10, 20 and 30 mg/kg 3-AC for 28 days. Rivastigmine (2 mg/kg) was the standard. Behavioral tests (EPM, MWM) were performed at 7-day intervals throughout study period. Rats showed improved spatial memory and learning in treatment groups during behavioral tests. Rats were euthanized on day 28. Inflammatory markers (IL-1ß, IL-16 and TNFα) exhibited significant improvement (p < 0.001) in treated rats. Oxidative stress enzymes (SOD, CAT, GSH, MDA) were restored. Caspase3 and NF-κß quantified through qRT-PCR also decreased significantly (p < 0.001) when compared to disease control group. Levels of acetyl cholinesterase, dopamine and noradrenaline were also restored in treated rats significantly (p < 0.001). 3-AC treatment restored neuroprotection probably because of anti-inflammatory, anti-oxidant and anti-cholinesterase potential; hence, this can be considered a promising therapeutic potential alternative.
Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Ratos , Masculino , Animais , Cloreto de Alumínio/efeitos adversos , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Compostos de Alumínio/uso terapêutico , Compostos de Alumínio/toxicidade , Cloretos/toxicidade , Cloretos/uso terapêutico , Ratos Wistar , Estresse Oxidativo , Antioxidantes/farmacologia , Inflamação/tratamento farmacológico , Inflamação/complicações , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Modelos Animais de DoençasRESUMO
Rutin, a phenolic compound, exhibits a diverse range of biological properties, including antioxidant, anti-inflammatory, and antimicrobial effects. In this study, we aimed to investigate the potential of rutin, a naturally occurring plant bioactive molecule, to mitigate the neurotoxic effects induced by aluminum chloride (AlCl3). Over a period of 6 weeks, rats were intraperitoneally injected with AlCl3 at a weekly dose of 60 mg/kg, while rutin treatment was administered orally via gavage at a daily dose of 30 mg/kg. AlCl3 exposure resulted in a significant increase lipid peroxidation (LPO) by 316.24%, nitrate levels by 504.14%, and tumor necrosis factor-alpha (TNF-α) levels by 93.82% in brain mitochondria. Additionally, AlCl3 exposure led to a reduction in glutathione levels and the activity of antioxidant enzymes, including superoxide dismutase (SOD) by 19.74%, glutathione peroxidase (GPx) by 44.76%, and catalase by 50.50%. There was also a significant decline in the activity of mitochondrial complex enzymes. In contrast, rutin treatment significantly enhanced the activity of antioxidant enzymes while concurrently reducing lipid peroxidation levels in rats. Specifically, rutin administration exerted a modulatory effect on the inflammatory response triggered by aluminum exposure, effectively suppressing the excessive production of nitrate and TNF-α. These findings highlight the potential of rutin as an effective therapeutic strategy in mitigating and combating neuro-inflammation and oxidative stress associated with aluminum-induced toxicity, thereby effectively restoring mitochondrial function.
Assuntos
Cloreto de Alumínio , Peroxidação de Lipídeos , Mitocôndrias , Rutina , Animais , Rutina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ratos , Masculino , Cloreto de Alumínio/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Síndromes Neurotóxicas/prevenção & controle , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Ratos Wistar , Alumínio/toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Modelos Animais de Doenças , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/prevenção & controle , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/tratamento farmacológicoRESUMO
Alzheimer's disease (AD) is a degenerative neurological disorder with unclear pathogenesis. Single-target drugs have very limited efficacy in treating AD, but synthetic multi-target drugs have poor efficacy and safety. Therefore, finding suitable natural multi-target drugs against AD is of great interest for research studies. We chose two flavonols, myricetin and morin, for the relevant study. In this study, we used microinjection of Aß1-42 oligomers into the CA1 region of rat hippocampus, combined with gavage of Aluminum chloride hexahydrate (AlCl3·6H2O) solution to establish AD rat models, and myricetin and morin were selected as intervening drugs to explore the protective effects against neurological impairment. Experimental results showed that myricetin or morin could reduce the production of Aß, Tubulin-associated unit (Tau), and Phosphorylated tubulin-associated unit (p-Tau), down-regulate the expression of relevant inflammatory factors, reduce hippocampal cell apoptosis in rats. There was a significant increase in the activity of adenosine triphosphatase, catalase, total superoxide dismutase, and the content of glutathione in the brain tissue. However, the content of malondialdehyde, inducible nitric oxide synthase, and the activity of acetylcholinesterase were decreased in the brain tissue. These two flavonols can regulate the imbalance of monoamine and amino acid neurotransmitter levels. In conclusion, Myricetin or morin can effectively improve learning and memory dysfunction in AD rats induced by Aß1-42/Al3+ through anti-oxidative stress and anti-apoptotic features.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Modelos Animais de Doenças , Flavonas , Flavonoides , Fármacos Neuroprotetores , Fragmentos de Peptídeos , Animais , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/patologia , Ratos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Fragmentos de Peptídeos/toxicidade , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Masculino , Ratos Sprague-Dawley , Cloreto de Alumínio/toxicidade , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Estresse Oxidativo/efeitos dos fármacosRESUMO
Aluminum is a potent neurotoxin, responsible for memory impairment and cognitive dysfunction. The neurotoxic effect of aluminum on cognitive impairment is well documented, however, exposure to aluminum in a time-dependent manner and post-exposure self-recovery still needs to be elaborated. This research aimed to (1) study the time-dependent effect of aluminum exposure by administering a total dose of 5850 mg/kg of Al over two different time periods: 30 and 45 days (130 and 195 mg/kg of AlCl3 respectively), and (2) study 20 days post-exposure self-recovery effect in both aluminum-exposed groups by giving distilled water. Cognitive abilities were investigated through Morris water maze test and hole board test and compared in both exposure and recovery groups. Oxidative stress markers and neurotransmitter levels were measured for both exposure and recovery groups. To understand the mechanism of aluminum exposure and recovery, immunohistochemical analysis of synaptophysin (Syp) and glial fibrillary acidic protein (GFAP) was performed. Results showed cognitive dysfunction, oxidative stress-induced damage, reduced neurotransmitter levels, decreased immunoreactivity of Syp, and increased GFAP. However, these parameters showed a larger improvement in the recovery group where rats were given aluminum for 30 days period in comparison to recovery group followed by 45 days of aluminum exposure. These results suggest that restoration of cognitive ability is affected by the duration of aluminum exposure. The study findings provide us with insight into the adverse effects of aluminum exposure and can be utilized to guide future preventive and therapeutic strategies against aluminum neurotoxicity.
Assuntos
Alumínio , Neurotransmissores , Estresse Oxidativo , Ratos Wistar , Animais , Estresse Oxidativo/efeitos dos fármacos , Ratos , Masculino , Alumínio/toxicidade , Neurotransmissores/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Memória Espacial/efeitos dos fármacos , Sinaptofisina/metabolismo , Fatores de Tempo , Proteína Glial Fibrilar Ácida/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Cloreto de AlumínioRESUMO
Studies have revealed neurotoxicity, hepatotoxicity, and developmental and reproductive toxicity in mice exposed to aluminum. However, relatively few studies have been conducted to clarify the mechanism underlying the impact of embryonic exposure to aluminum on the development of the male reproductive system in offspring. Pregnant mice were administered aluminum chloride (AlCl3) by gavage from day 12.5 of gestation until birth. Our findings demonstrated that embryonic exposure to AlCl3 disrupted testicular development and spermatogenesis by impairing testicular architecture, reducing sperm count, and upregulating the expression of tight junction (TJ) protein between Sertoli cells (SCs). Further in vitro studies revealed that treatment with AlCl3 stabilized TJ proteins Occludin and ZO-1 expression by inhibiting ERK signaling pathway activation, thereby upregulating Slc25a5 expression which induced ATP production leading to disruption of cytoskeletal protein homeostasis. Therefore, the study provided a new mechanistic insight into how AlCl3 exposure interfered with testicular development and spermatogenesis while suggesting that Slc25a5 might be a target affected by AlCl3 influencing cell metabolism.
Assuntos
Alumínio , Junções Íntimas , Gravidez , Feminino , Masculino , Camundongos , Animais , Cloreto de Alumínio , Alumínio/metabolismo , Junções Íntimas/metabolismo , Sêmen , Testículo/metabolismo , Espermatogênese , Proteínas de Junções Íntimas/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Fraxinus excelsior L. (FE), commonly known as the ash, belongs to the Oleaceae family and has shown several pharmacological and biological properties, such as antioxidant, immunomodulatory, neuroprotective, and anti-inflammatory effects. It has also attracted the most attention toward neuroinflammation. Moreover, FE bark and leaves have been used to treat neurological disorders, aging, neuropathic pain, urinary complaints, and articular pain in traditional and ethnomedicine. Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder resulting from the involvement of amyloid-beta, metal-induced oxidative stress, and neuroinflammation. AIM OF THE STUDY: The objective of the current study was to assess the neuroprotective effects of hydromethanolic extract from FE bark in an AlCl3-induced rat model of AD. MATERIALS AND METHODS: The maceration process was utilized to prepare the hydromethanolic extract of FE bark, and characterized by LC-MS/MS. To assess the anti-AD effects of the FE extract, rats were categorized into five different groups, AlCl3; normal control; FE-treated groups at 50, 100, and 200 mg/kg. Passive avoidance learning test, Y-maze, open field, and elevated plus maze behavioral tests were evaluated on days 7 and 14 to analyze the cognitive impairments. Zymography analysis, biochemical tests, and histopathological changes were also followed in different groups. RESULTS: LC-MS/MS analysis indicated the presence of coumarins, including isofraxidin7-O-diglucoside in the methanolic extract of FE as a new isofraxidin derivative in this genus. FE significantly improved memory and cognitive function, maintained weight, prevented neuronal damages, and preserved the hippocampus's histological features, as demonstrated by behavioral tests and histopathological analysis. FE increased anti-inflammatory MMP-2 activity, whereas it decreased that of inflammatory MMP-9. Moreover, FE increased plasma antioxidant capacity by enhancing CAT and GSH while decreasing nitrite levels in the serum of treated groups. In comparison between the treated groups, the rats that received high doses of the FE extract (200 mg/kg) showed the highest therapeutic effect. CONCLUSION: FE rich in coumarins could be an effective anti-AD adjunct agent, passing through antioxidant and anti-inflammatory pathways. These results encourage further studies for the development of this extract as a promising agent in preventing, managing, or treating AD and related diseases.
Assuntos
Doença de Alzheimer , Fraxinus , Fármacos Neuroprotetores , Ratos , Animais , Cloreto de Alumínio/farmacologia , Cloreto de Alumínio/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Fraxinus/metabolismo , Doenças Neuroinflamatórias , Casca de Planta/metabolismo , Cromatografia Líquida , Ratos Wistar , Modelos Animais de Doenças , Espectrometria de Massas em Tandem , Estresse Oxidativo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Cumarínicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
The present investigation examined the impact of pomegranate (Punica granatum L.) juice on trace elements, minerals, and oxidative stress in relation to the potential harm inflicted by aluminum chloride (AlCl3) in rats. Rats were split into four groups at random for this purpose: control (C), pomegranate juice (PJ), aluminum chloride (A), and PJ + A. For 30 days, PJ was orally administered by gavage at a rate of 4 mL/kg every other day, whereas AlCl3 was administered intraperitoneally at 8.3 mg/kg. Spectrophotometric analysis was used to measure the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) enzyme activity in various tissues. In addition, high-resolution continuum source flame atomic absorption spectrometry (HR-CS FAAS) was used to determine the amounts of the elements Al, Cu, Fe, Mn, Zn, Ca, and Mg in the tissues. It was discovered that when PJ therapy was applied to all tissues, the antioxidant enzymes SOD and CAT activity increased, the GSH level rose, and the MDA level, a sign of lipid peroxidation, decreased. Al and Ca levels increased in the A group relative to the C group in all tissues, whereas they decreased in the A + PJ group relative to the A group. Group A exhibited a proportionate increase in Fe levels in the liver and renal tissues compared with group C. Furthermore, the A group's brain tissue had a higher Fe level than the C group's. The A + PJ group's brain tissue had a lower Fe level than the A group's. Our findings demonstrate that PJ therapy greatly decreased Al buildup and oxidative stress in tissues while controlling variations in trace element levels. In addition, it is concluded that PJ might have value as a strong chelating agent to prevent Al poisoning.
Assuntos
Sucos de Frutas e Vegetais , Estresse Oxidativo , Punica granatum , Oligoelementos , Animais , Estresse Oxidativo/efeitos dos fármacos , Punica granatum/química , Oligoelementos/análise , Oligoelementos/metabolismo , Ratos , Sucos de Frutas e Vegetais/análise , Masculino , Minerais/análise , Minerais/metabolismo , Cloreto de Alumínio , Alumínio/toxicidade , Ratos Wistar , Superóxido Dismutase/metabolismo , Catalase/metabolismo , Cloretos , Antioxidantes/metabolismoRESUMO
OBJECTIVE: The aim: To conduct a morphometric analysis of the features of the remodeling of vessels of the hemomicrocirculatory channel of the testicles under the action of aluminum chloride on the body. PATIENTS AND METHODS: Materials and methods: The testicles of 52 white male Wistar rats were morphologically studied, which were divided into two groups: intact and animals injected with aluminum chloride at a dose of 100 mg/kg. RESULTS: Results: The long-term effect of aluminum chloride on the body led to pronounced changes in the quantitative morphological indicators of the vessels of the hemomicrocirculatory channel of the testes compared to the control ones. The diameter of arterioles of the left testicle decreased by 18.4%, precapillary arterioles by 19.1%, hemocapillaries by 10.1%. The diameter of the postcapillary venules of the left testicle increased by 26.3%, the venules by 26.4%, and the density of microvessels decreased by 30.0%, which indicated the deterioration of its blood supply. The degree of remodeling of microvessels in the right testis was less pronounced. The diameter of arterioles of the right testicle decreased by 17.1%, precapillary arterioles by 18.4 %, and hemocapillaris by 9.1%. The diameter of the postcapillary venules of the right testicle increased by 25.5%, the venules by 27.0%, and the density of microvessels decreased by 25.8%. CONCLUSION: Conclusions: Long-term action (during the month) of aluminum chloride on the body leads to pronounced remodeling of the vessels of the hemomicrocirculatory channel of the testicles, which is characterized by a pronounced narrowing of its supply (arterioles, precapillary arterioles), exchange (hemocapillaries) links.
Assuntos
Testículo , Masculino , Ratos , Animais , Cloreto de Alumínio , Ratos Wistar , Arteríolas , VênulasRESUMO
Introduction: Aluminium, a ubiquitous metal implicated in some neurodegenerative diseases is linked to activation of free oxygen species. The antioxidant-rich plants, Moringa oleifera (MO) is reported to protect against Aluminium activities. This study investigated the actions of MO leaf extract (MOLE) against Aluminium chloride (AlCl3)- induced hippocampal cellular changes and serum levels of alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) in adult Wistar rats.Materials and Methods: Thirty Wistar rats weighing between 150 g and 220 g were grouped (n=5) into; 1-control (5 mL/kg distilled water), 2-AlCl3 (100 mg/kg), 3-low dose MOLE (250 mg/kg), 4-high dose MOLE (1,000 mg/kg), 5-concurrent AlCl3 and low dose MOLE, and 6-concurrent AlCl3 and high dose MOLE. All administrations were by oral gavages for 21 days. On day 22, following deep anaesthesia and cardiac puncture, blood was obtained for serum enzyme analysis, and the brain perfusion fixed, harvested and processed for histological study.Results: Results showed significantly (p < 0.05) higher ALP level in the AlCl3 group compared with the control, as well as the other test groups. However, there was no significant (p > 0.05) AST and ALT levels. The hippocampal CA3 of the AlCl3 group showed hypertrophic cells, with some of the cells having karyorrhectic features. The concurrent AlCl3 and low and high doses, MOLE groups showed less of these adverse features.Conclusion: These results suggest that MOLE may protect enzymatic activities against Aluminium chloride. However, its action on hippocampus is still subject to further investigation.
Introducción: El aluminio, un metal presente en diversos lugares implicado en algunas enfermedades neurodegenerativas, está relacionado con la activación de especies reactivas de oxígeno. Se informa que las plantas ricas en antioxidantes, Moringa oleifera (MO) protegen contra la acción del aluminio. Este estudio investigó las acciones del extracto de hoja de MO (MOLE) en los cambios celulares del hipocampo inducidos por el cloruro de aluminio (AlCl3) y los niveles séricos de fosfatasa alcalina (ALP), aspartato transaminasa (AST) y alanina transaminasa (ALT) en ratas Wistar adultas.Materiales y métodos: SE utilizaron treinta ratas Wistar divididas en 5 grupos, los animales pesaban entre 150 gy 220 g; 1 control (5 ml / kg de agua destilada), 2-AlCl3 (100 mg / kg), 3 MOLE de dosis baja (250 mg / kg), 4 MOLE de dosis alta (1000 mg / kg), 5 AlCl3 concurrente y MOLE de dosis baja, y MOLE 6-concurrente y MOLE de dosis alta. Todas las administraciones fueron por sonda oral durante 21 días. El día 22, después de la anestesia profunda y la punción cardíaca, se obtuvo sangre para el análisis de las enzimas séricas y la perfusión cerebral se fijó, recogió y procesó para el estudio histológico.Resultados: Los resultados mostraron un nivel de ALP significativamente (p <0.05) más alto en el grupo AlCl3 en comparación con el control, así como en los otros grupos de prueba. Sin embargo, no hubo niveles significativos (p> 0.05) de AST y ALT. El hipocampo CA3 del grupo AlCl3 mostró células hipertróficas, y algunas de las células tenían características cariorrecticas. Los grupos de AlCl3 concurrentes y dosis bajas y altas, MOLE mostraron menos de estas características adversas.Conclusión: Estos resultados sugieren que MOLE puede proteger las actividades enzimáticas contra el cloruro de aluminio. Sin embargo, su acción sobre el hipocampo aún está sujeta a más investigaciones.
Assuntos
Animais , Ratos , Moringa oleifera/anatomia & histologia , Cloreto de Alumínio/administração & dosagem , Hipocampo/anatomia & histologia , Ratos WistarRESUMO
Abstract Glucosamine is known as anti-inflammatory, antioxidant and as neuroprotective as well as using to treat many of diseases. This work aimed to investigate the remedial effect of glucosamine (20mg/kg b.wt) against the damage induced by a single dose of γ-radiation (8Gy) or aluminium chloride (AlCl3) (100mg/kg b.wt) in the heart and brain tissues of female rats. Serum aspartate aminotransferase (AST), cholesterol, triglycerides (TGs), LDH and creatine kinase (CPK) were measured. Moreover, gene expression of amyloid protein precursor (APP) and seladin-1 were estimated in the brain tissue. Also, acetylcholinesterase activity (AChE) and p-tau protein expression were estimated in brain homogenate. Metallothioneine (MT) was estimated in the heart and brain tissues. Heart and brain histopathological examination was performed. Irradiation significantly decreased serum AST, CPK and LDH, as well as MT levels in heart and brain tissues. Also, gene expression of seladin-1 decreased. On the other hand, irradiation significantly increased serum TGs level and brain AchE activity, tau protein, and β-amyloid percursor (APP). AlCl3 administration (21 days) induced disturbance in most of the estimated parameters, especially AST, TGs, and MT. Glucosamine treatment with irradiation or AlCl3 improved most of the measured parameters. In addition, histopathological examination confirmed the biochemical results. In conclusion: Glucosamine could be used to improve the heart and brain damages induced by γ-radiation exposure or AlCl3.