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1.
RSC Adv ; 13(27): 18496-18510, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37346948

RESUMEN

New 2-oxo-chromene-7-oxymethylene acetohydrazide derivatives 4a-d were designed and synthesized with a variety of bioactive chemical fragments. The newly synthesized compounds were evaluated as acetylcholinesterase (AChE) inhibitors and antioxidant agents in comparison to donepezil and ascorbic acid, respectively. Compound 4c exhibited a promising inhibitory impact with an IC50 value of 0.802 µM and DPPH scavenging activity of 57.14 ± 2.77%. Furthermore, biochemical and haematological studies revealed that compound 4c had no effect on the blood profile, hepatic enzyme levels (AST, ALT, and ALP), or total urea in 4c-treated rats compared to the controls. Moreover, the histopathological studies of 4c-treated rats revealed the normal architecture of the hepatic lobules and renal parenchyma, as well as no histopathological damage in the examined hepatic, kidney, heart, and brain tissues. In addition, an in vivo study investigated the amelioration in the cognitive function of AD-rats treated with 4c through the T-maze and beam balance behavioural tests. Also, 4c detectably ameliorated MDA and GSH, reaching 90.64 and 27.17%, respectively, in comparison to the standard drug (90.64% and 35.03% for MDA and GSH, respectively). The molecular docking study exhibited a good fitting of compound 4c in the active site of the AChE enzyme and a promising safety profile. Compound 4c exhibited a promising anti-Alzheimer's disease efficiency compared to the standard drug donepezil.

2.
Toxicol Mech Methods ; 33(6): 463-479, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36775846

RESUMEN

Cuprizone (CUP) induces neurotoxicity and demyelination in animal models by provoking the activation of glial cells and the generation of reactive oxygen species (ROS). Sulforaphane (SF) is a phytochemical that exhibits a neuroprotective potential. In this study, we investigated the neurotherapeutic and pro-remyelinating activities of SF and SF-loaded within iron oxide nanoparticles (IONP-SF) in CUP-exposed rats. Magnetite iron oxide nanoparticles (IONPs) were prepared using the hydrothermal method that was further loaded with SF (IONP-SF). The loading of SF within the magnetite nanoparticles was assessed using FTIR, TEM, DLS, Zetasizer, and XPS. For the in vivo investigations, adult male Wistar rats (n = 40) were administrated either on a regular diet or a diet with CUP (0.2%) for 5 weeks. The rats were divided into four groups: negative control, CUP-induced, CUP + SF, and CUP + IONP-SF. CUP-exposed brains exhibited a marked elevation in lipid peroxidation, along with a significant decrease in the activities of glutathione peroxidase (GPx), and catalase (CAT). In addition, CUP intoxication downregulated the expression of myelin basic protein (MBP) and myelin proteolipid protein (PLP), upregulated the expression of Matrix metallopeptidase-9 (MMP-9) and S100ß, and increased caspase-3 immunoexpression, these results were supported histopathologically in the cerebral cortexes. Treatment of CUP-rats with either SF or IONP-SF demonstrated remyelinating and neurotherapeutic activities. We could conclude that IONP-SF was more effective than free SF in mitigating the CUP-induced downregulation of MBP, upregulation of S100ß, and caspase-3 immunoexpression.


Asunto(s)
Cuprizona , Nanopartículas , Ratas , Masculino , Animales , Caspasa 3 , Metaloproteinasa 9 de la Matriz , Subunidad beta de la Proteína de Unión al Calcio S100 , Ratas Wistar , Nanopartículas Magnéticas de Óxido de Hierro , Nanopartículas/toxicidad
3.
Biomarkers ; 27(4): 349-360, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35254184

RESUMEN

CONTEXT: Nanotechnology is widely used nowadays in several fields of industry, engineering, and medicine, the biological action mechanisms of AgNPs, which mainly involve the release of silver ions (Ag+), generation of reactive oxygen species (ROS). OBJECTIVE: The potential toxicity AgNPs of damages to hepatic cells, hesperidin, and naringin role for their protective effect against the increase of ROS due to AgNPs toxicity. They can be restored, most cellular biochemical parameters, genotoxicity, mutagenicity, and histopathological analysis. MATERIALS AND METHODS: Toxicity was induced by an oral dose of Ag NPs of (20-100 nm) for one month, after that treated with hesperidin, naringin (100 mg/kg) for three weeks, malondialdehyde (MDA) levels, nitric oxide (NO), glutathione (GSH) and catalase were estimated. Also, aminotransferases (AST and ALT), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), albumin, and total bilirubin were determined, following Chromosomal aberrations, DNA breaks, and histological analyses. RESULTS: hesperidin, and naringin treatment, recorded amelioration in most biochemical, genetic, and spermatogenesis disturbances Also, histological Investigations were improved. CONCLUSION: Their biological safety problems, such as potential toxicity on cells, tissue, and organs should be paid enough attention, hesperidin and naringin amelioration fundamental alterations, as hepatic architectural and DNA damage, related to its role as an antioxidant and anti-inflammatory agent.


Asunto(s)
Hesperidina , Nanopartículas del Metal , Animales , Aberraciones Cromosómicas , Daño del ADN , Glutatión/metabolismo , Hesperidina/metabolismo , Hesperidina/farmacología , Humanos , Hígado/metabolismo , Masculino , Nanopartículas del Metal/toxicidad , Ratones , Estrés Oxidativo , Tamaño de la Partícula , Especies Reactivas de Oxígeno/metabolismo , Plata/metabolismo , Plata/toxicidad
4.
Biol Trace Elem Res ; 200(8): 3638-3665, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34704196

RESUMEN

Iron oxide nanoparticles (IONPs) are increasingly being employed for in vivo biomedical nanotheranostic applications. The development of novel IONPs should be accompanied by careful scrutiny of their biocompatibility. Herein, we studied the effect of administration of three formulations of IONPs, based on their starting materials along with synthesizing methods, IONPs-chloride, IONPs-lactate, and IONPs-nitrate, on biochemical and ultrastructural aspects. Different techniques were utilized to assess the effect of different starting materials on the physical, morphological, chemical, surface area, magnetic, and particle size distribution accompanied with their surface charge properties. Their nanoscale sizes were below 40 nm and demonstrated surface up to 69m2/g, and increased magnetization of 71.273 emu/g. Moreover, we investigated the effects of an oral IONP administration (100 mg/kg/day) in rat for 14 days. The liver enzymatic functions were investigated. Liver and brain tissues were analyzed for oxidative stress. Finally, a transmission electron microscope (TEM) and inductively coupled plasma optical emission spectrometer (ICP-OES) were employed to investigate the ultrastructural alterations and to estimate content of iron in the selected tissues of IONP-exposed rats. This study showed that magnetite IONPs-chloride exhibited the safest toxicological profile and thus could be regarded as a promising nanotherapeutic candidate for brain or liver disorders.


Asunto(s)
Nanopartículas de Magnetita , Nanopartículas , Animales , Encéfalo , Cloruros , Compuestos Férricos/química , Compuestos Férricos/toxicidad , Hierro , Nanopartículas Magnéticas de Óxido de Hierro/toxicidad , Nanopartículas de Magnetita/química , Nanopartículas/química , Nanopartículas/toxicidad , Ratas , Ratas Wistar
5.
Biol Trace Elem Res ; 198(1): 157-167, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32016825

RESUMEN

The wide application of nanotechnology merits the need to clarify their nanotoxicity. In vivo studies have raised concerns about the toxicity of titanium dioxide nanoparticles (TiO2 NPs), but there are limited data on chromosomal abnormalities induced in hepatic tissue. In this article, the toxicity of three IP doses of TiO2 NPs (80 nm) (50, 250, and 500 mg/kg) through three time intervals (up to 7, 15, and 45 days) on liver tissue was assessed. Hepatic catalase (CAT), glutathione (GSH), nitric oxide (NOx), and malondialdehyde (MDA) levels varied with the administered dose and exposure time of TiO2 NPs. As a result, TiO2 NPs caused a statistically significant decrease in hepatic CAT and GSH activities and a significant alleviation in MDA and NOx levels (p < 0.05), suggesting that the liver exposed to these various doses of TiO2 NPs suffered from severe oxidative stress. The extent of depletion of antioxidant enzymes and the elevation of MDA and NOx in the liver exposed to the highest dose and duration of TiO2 NPs 500 mg for 45 days was the greatest, suggesting that the toxicity might be dose and time dependent. Further, C-reactive protein (CRP) as an inflammatory marker was also alleviated, in addition to the apparent chromosomal aberration and liver pathologies including necrotic and fibrotic hepatocytes after exposure to 250 and 500 mg/kg of TiO2 NPs for 14 and 45 days that were deduced. Hence, nanotechnology-based industries are growing rapidly leading to large-scale production of engineered nanoparticles. They contribute to increased chances of human NPs exposure and health risk.


Asunto(s)
Nanopartículas del Metal , Nanopartículas , Proteína C-Reactiva/metabolismo , Aberraciones Cromosómicas/inducido químicamente , Humanos , Hígado/metabolismo , Nanopartículas del Metal/toxicidad , Estrés Oxidativo , Titanio/toxicidad
6.
Biomarkers ; 24(5): 492-498, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31099265

RESUMEN

Objective: The aim of the present work is to evaluate the toxicity of titanium dioxide nanoparticles (TiO2NPs) according to their doses and particle sizes. Materials and methods: The effect of five days oral administration of TiO2NPs (21 and 80 nm) with different doses (50, 250 and 500 mg/kg body weight) was assessed in mice via measurement of oxidative stress markers; glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nitric oxide (NO), liver function indices; aspartate and alanine aminotransferases (AST and ALT), chromosomal aberrations and liver histopathological pattern. Results: The results revealed drastic alterations in all the measured parameters and showed positive correlation with the gradual dose increment. In addition, the smaller particle size of TiO2NPS (21 nm) had more adverse effect in all the selected biochemical parameters, genetic aberrations and histological investigations. Conclusions: Toxicity of TiO2NPs increases in a dose-dependent manner and vice versa with particles size. The evaluated biomarkers are good indicators for TiO2NPs toxicity. More detailed studies are required before the recommendation of TiO2NPS as food additives.


Asunto(s)
Biomarcadores/sangre , Nanopartículas/toxicidad , Titanio/toxicidad , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Catalasa/sangre , Aberraciones Cromosómicas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Glutatión/sangre , Hígado/metabolismo , Hígado/patología , Malondialdehído/sangre , Ratones , Nanopartículas/metabolismo , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula , Superóxido Dismutasa/sangre , Titanio/metabolismo
7.
Saudi Pharm J ; 26(2): 224-231, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30166920

RESUMEN

The present study involves the preparation of cubic liquid crystalline nanoparticles (cubsomes) for liver targeting to assess the potential of a formulated bioactive polysaccharide isolated from the hot aqueous extract of Ulva fasciata as an alternative natural agent with anti-hyperlipidaemic activity. Cubosomal nanoparticles were prepared by disrupting the cubic gel phase of the polysaccharide and water in the presence of a surfactant. Different lipid matrices and stabilizers were tested. All the formulations were in the nanosize range and showed sufficient negative charge to inhibit the aggregation of the cubosomes. Drug entrapment efficiencies (EEs%) were determined and in vitro release studies were performed. Transmission electron microscopy (TEM) and differential scanning calorimetry were used to analyze the loaded cubosomal nanoparticles containing glyceryl monostearate (GMO 2.25 g), poloxamer 407 (0.25 g) and 50 mg of the polysaccharide. A preclinical study comparing the cubic liquid crystalline nanoparticles containing polysaccharide to fluvastatin as a reference drug in hyperlipidaemic rats was conducted. The rats treated with the polysaccharide- loaded cubosomes showed significant decreases in total cholesterol (TC), triglycerides (TG) and total lipid (TL) compared to the untreated HL rats. In addition, oxidative stress and antioxidant biomarkers were measured in the HL rats. Compared to the untreated HL rats, the cubosome treated rats showed a significant reduction in malondialdehyde (MDA), whereas insignificant changes were detected in nitric oxide (NO), glutathione (GSH) levels and total antioxidant capacity (TAC). Further, vascular and intercellular adhesion molecules (VCAM, ICAM), and myeloperoxidase were demonstrated. A histopathological examination was conducted to study the alterations in histopathological lesions and to document the biochemical results. In conclusion, this study demonstrates the superiority of using a natural lipid regulator such as polysaccharide loaded cubosomes instead of fluvastatin.

8.
Biomed Pharmacother ; 93: 837-851, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28715867

RESUMEN

Alzheimer's disease (AD) is a grave and prevailing neurodegenerative disease, characterized by slow and progressive neurodegeneration in different brain regions. Aluminum (Al) is a potent and widely distributed neurotoxic metal, implicated in the neuropathogenesis of AD. This study aimed to evaluate the possible neurorestorative potential of Vitis vinifera Leaves Polyphenolic (VLP) extract in alleviating aluminum chloride (AlCl3)-induced neurotoxicity in male rats. AlCl3 neurotoxicity induced a significant decrease in brain/serum acetylcholine (ACh) contents and serum dopamine (DA) levels, along with a significant increment of brain/serum acetylcholinesterase (AChE) activities. In addition, Al treatment resulted in significantly decreased serum levels of both total antioxidant capacity (TAC) and brain-derived neurotrophic factor (BDNF), and significantly increased serum levels of both interleukin-6 (IL-6) and total homocysteine (tHcy), as compared to control. Behavioral alterations, assessed by the T-maze test, showed impaired cognitive function. Furthermore, AD-brains revealed an increase in DNA fragmentation as evidenced by comet assay. AlCl3 induction also caused histopathological alterations in AD-brain. Treatment of AD-rats with VLP extract (100mg/kg body weight/day) improved neurobehavioral changes, as evidenced by the improvement in brain function, as well as, modulation of most biochemical markers, and confirmed by T-maze test, the histopathological study of the brain and comet assay. The current work indicates that the VLP extract has neuroprotective, antioxidative, anti-inflammatory, and anti-amnesic activities against AlCl3-induced cerebral damages and neurocognitive dysfunction.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Biomarcadores/metabolismo , Extractos Vegetales/farmacología , Polifenoles/farmacología , Vitis/química , Acetilcolinesterasa/metabolismo , Cloruro de Aluminio , Compuestos de Aluminio/farmacología , Enfermedad de Alzheimer/metabolismo , Animales , Antioxidantes/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Cloruros/farmacología , Cognición/efectos de los fármacos , Homocisteína/metabolismo , Interleucina-6/metabolismo , Masculino , Fármacos Neuroprotectores/farmacología , Hojas de la Planta/química , Ratas , Ratas Wistar
9.
Biomed Pharmacother ; 90: 466-472, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28391168

RESUMEN

The toxic impact of titanium dioxide nanoparticles (TiO2NPs) on human health is of prime importance owing to their wide uses in many commercial industries. In the present study, the effect of different doses and exposure time durations of TiO2NPs (21nm) inducing oxidative stress, biochemical disturbance, histological alteration and cytogenetic aberration in mice liver and bone marrow was investigated. Different doses of (TiO2NPs) (50, 250 and 500mg/kg body weight) were each daily intrapertioneally injected to mice for 7, 14 and 45days. Aspartate and alanine aminotransferases (AST &ALT), gamma glutamyl transpeptidase (GGT), total protein, total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and nitric oxide (NO) levels were measured. The work was extended to evaluate the liver histopathological pattern and the chromosomal aberration in mice spinal cord bone marrow. The results revealed severe TiO2NPs toxicity in a dose and time dependent manner with positive correlation (r=0.98) for most investigated biochemical parameters. The same observation was noticed for the histological analysis. In case of cytogenetic study, chromosomal aberrations were demonstrated after injection of TiO2NPs with 500mg/kg b. wt. for 45days. In conclusion, the selected biochemical parameters and the liver architectures were influenced with dose and time of TiO2NPs toxicity, while the genetic disturbance started at the high dose of exposure and for long duration. Further studies are needed to fulfil the effect of TiO2NPs on pharmaceutical and nutritional applications.


Asunto(s)
Aberraciones Cromosómicas/efectos de los fármacos , Nanopartículas del Metal/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Titanio/efectos adversos , Alanina Transaminasa/metabolismo , Animales , Antioxidantes/metabolismo , Catalasa/metabolismo , Daño del ADN/efectos de los fármacos , Glutatión/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones
10.
Toxicol Ind Health ; 32(4): 753-68, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24280655

RESUMEN

The present work aims to evaluate the protective and ameliorative effects of two plant-derived proteins obtained from the seeds of Cajanus cajan and Caesalpinia gilliesii(Leguminosae) against the toxic effects of acetaminophen in kidney after chronic dose through determination of certain biochemical markers including total urea, creatinine, and kidney marker enzyme, that is, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In addition histopathological examination of intoxicated and treated kidney with both proteins was performed. The present results show a significant increase in serum total urea and creatinine, while significant decrease in GAPDH. Improvement in all biochemical parameters studied was demonstrated, which was documented by the amelioration signs in rats kidney architecture. Thus, both plant protein extracts can counteract the nephrotoxic process, minimize damage to the kidney, delay disease progression, and reduce its complications.


Asunto(s)
Acetaminofén/toxicidad , Lesión Renal Aguda/inducido químicamente , Fabaceae/química , Riñón/efectos de los fármacos , Extractos Vegetales/farmacología , Proteínas de Plantas/farmacología , Sustancias Protectoras/farmacología , Lesión Renal Aguda/metabolismo , Animales , Cajanus , Creatinina/sangre , Riñón/enzimología , Riñón/patología , Masculino , Extractos Vegetales/química , Proteínas de Plantas/química , Sustancias Protectoras/química , Ratas , Ratas Wistar , Semillas/química , Urea/sangre
11.
Toxicol Ind Health ; 32(5): 877-907, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-24414985

RESUMEN

This study aims to evaluate two proteins derived from the seeds of the plants Cajanus cajan (Leguminosae) and Caesalpinia gilliesii (Leguminosae) for their abilities to ameliorate the toxic effects of chronic doses of acetoaminphen (APAP) through the determination of certain biochemical parameters including liver marker enzymes: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin. Also, total protein content and hepatic marker enzyme, lactate dehydrogenase were studied. Moreover, liver antioxidants, glutathione (GSH), nitric oxide, and lipid peroxides were determined in this study. Hepatic adenosine triphosphatase (ATPase), adenylate energy charge (ATP, adenosine diphosphate, adenosine monophosphate, and inorganic phosphate), and phosphate potential, serum interleukin-6, tumor necrosis factor-α, and myeloperoxidase were also examined in the present study. On the other hand, histopathological examination of intoxicated and liver treated with both proteins was taken into consideration. The present results show disturbances in all biochemical parameters and hepatic toxicity signs including mild vascular congestion, moderate inflammatory changes with moderate congested sinusoids, moderate nuclear changes (pyknosis), moderate centrilobular necrosis, fatty changes, nuclear pyknosis vascular congestion, and change in fatty centrilobular necrosis liver. Improvement in all biochemical parameters studied was noticed as a result of treatment intoxicated liver with C. gilliesii and C. cajan proteins either paracetamol with or post paracetamol treatment. These results were documented by the amelioration signs in rat's hepatic architecture. Thus, both plant protein extracts can upregulate and counteract the inflammatory process, minimize damage of the liver, delay disease progression, and reduce its complications.


Asunto(s)
Acetaminofén/toxicidad , Caesalpinia/química , Cajanus/química , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Extractos Vegetales/farmacología , Proteínas de Plantas/farmacología , Adenosina Trifosfatasas/metabolismo , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Bilirrubina/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Glutatión/metabolismo , Interleucina-6/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Óxido Nítrico/metabolismo , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismo
12.
Cell Physiol Biochem ; 35(6): 2402-11, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25896716

RESUMEN

BACKGROUND/AIM: The present study investigated the in vitro and in vivo effects of individual and combined doses of idebenone, carnosine and vitamin E on ameliorating some of the biochemical indices of nano-sized titanium dioxide (n-TiO2) in mice liver. METHODS: The in vitro cytotoxic effect of nano-sized anatase TiO2 (21 nm) on hepatic cell lines (HepG 2) was investigated. Additionally, n-TiO2 was orally administered (150 mg/kg/day) for 2 weeks, followed by a daily intragastric gavage of the aforementioned antioxidants for 1 month. RESULTS: n-TiO2 induced significant cytotoxicity in hepatic cell lines and elevated the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic total antioxidant capacity (TAC) and nitrite/nitrate (NOx) levels. Meanwhile, glutathione-S-transferase (GST) activity was significantly reduced. Moreover, RT-PCR and western blot analysis showed that n-TiO2 significantly altered the mRNA and protein expressions of transforming growth factor-beta (TGF-ß1) and Smad-2, as well as vascular endothelium growth factor (VEGF). Histopathological examination of hepatic tissue reinforced these results. CONCLUSION: Idebenone, carnosine and vitamin E ameliorated the deviated parameters with the combination regimen demonstrating the most pronounced effect. Oxidative stress, liver fibrosis and angiogenesis may be implicated in n-TiO2-induced liver toxicity.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Carnosina/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Titanio/efectos adversos , Ubiquinona/análogos & derivados , Vitamina E/farmacología , Alanina Transaminasa/sangre , Animales , Antioxidantes/metabolismo , Aspartato Aminotransferasas/sangre , Línea Celular Tumoral , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Glutatión Transferasa/metabolismo , Células Hep G2 , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/metabolismo , Masculino , Ratones , Nitratos/metabolismo , Nitritos/metabolismo , Proteína Smad2/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Ubiquinona/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo
13.
Exp Toxicol Pathol ; 67(4): 305-14, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25739888

RESUMEN

This study investigates the efficacy of idebenone, carnosine and vitamin E in ameliorating some of the biochemical indices induced in the liver of titanium dioxide nanoparticles (TiO2 NPs) intoxicated mice. Nano-anatase TiO2 (21 nm) was administered (150 mg/kg/day) for 2 weeks followed by the aforementioned antioxidants either alone or in combination for 1 month. TiO2 NPs significantly increased serum liver function enzyme activities, liver coefficient and malondialdehyde levels in hepatic tissue. They also suppressed hepatic glutathione level and triggered an inflammatory response via the activation of macrophages and the enhancement of tumor necrosis factor-α and interleukin-6 levels. Moreover, the mRNA expression of nuclear factor-erythroid-2-related factor 2, nuclear factor kappa B and Bax was up-regulated whereas that of Bcl-2 was down-regulated following TiO2 NPs. Additionally, these NPs effectively activated caspase-3 and caused liver DNA damage. Oral administration of idebenone (200mg/kg), carnosine (200mg/kg) and vitamin E (100mg/kg) alleviated the hazards of TiO2 NPs with the combination regimen showing a relatively higher effect. The histopathological examination reinforced these findings. In conclusion, oxidative stress could be regarded as a key player in TiO2 NPs-induced liver injury. The study also highlights the anti-inflammatory and the anti-apoptotic potentials of these antioxidants against the detrimental effects of TiO2 NPs.


Asunto(s)
Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Hígado/efectos de los fármacos , Titanio/toxicidad , Animales , Inmunohistoquímica , Masculino , Nanopartículas del Metal/toxicidad , Ratones , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
14.
Indian J Clin Biochem ; 29(4): 418-29, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25298623

RESUMEN

Anabasis articulata (Forssk) Moq. (Chenopodiaceae) is an herb, grows in Egypt, and used in folk medicine to treat diabetes, fever, and kidney infections. The protective and therapeutic effects of the ethanol extract of A. articulata aerial parts were evaluated against dimethylnitrosamine (DMN)-induced liver fibrosis, compared with the standard drug, silymarin. Hepatic hydroxyproline content, serum transforming growth factor-ß1 (TGF-ß1), interleukin 10 (IL-10) and fructosamine were measured as liver fibrosis markers. Hepatic malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), glutathione reductase (GR) and glutathione content (GSH) were measured as oxidant/antioxidant markers. Parallel histopathological investigations were also performed. Protective and therapeutic administration of A. articulata (100 mg/kg daily for 4 weeks), markedly prevented DMN-induced loss in body and liver weights. The extract significantly inhibited the elevation of hepatic hydroxyproline, NO and MDA (P < 0.05), as well as serum fructosamine, and TGF-ß1 (P < 0.05) induced by DMN while it restored IL-10 to normal level in both protective and therapeutic groups. Furthermore, A. articulata prevented the depletion in CAT, GR, and GSH levels (P ≤ 0.05). In addition, oral administration of A. articulata extract and silymarin to both protective and therapeutic groups reduced the increase in liver function enzyme activities; alanine and aspartate amintransferases, gamma-glutamyl transferase in addition to alkaline phosphatase, and caused significant increase in serum albumin concentration as compared to DMN group. These data corresponded closely with those obtained for the drug silymarin. Histopathological studies confirmed the biochemical data and revealed remarkable improvement in liver architecture. Thus, it could be concluded that, A. articulata extract exhibited in vivo hepatoprotective and therapeutic effects against DMN-induced liver injury and may act as a useful agent in controlling the progression of hepatic fibrosis through reduction of oxidative stress and improving liver function.

15.
Exp Parasitol ; 132(2): 171-9, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22771439

RESUMEN

Schistosomiasis is considered the second most pre-valiant worldwide parasitic disease ranked next to malaria. It has significant economic and public health consequences in many developing countries. Several ways have been practiced in order to bring the disease under an adequate control through the breakage of the life cycle of the parasite. Snail control could be regarded as a rapid and efficient of reducing or eliminating transmission and remains among the methods of choice for schistosomiasis control. The aim of this work is to evaluate the role of Haplophyllum tuberculatum (family Rutaceae) as a plant molluscicide. The mortality rate of Biomphalaria alexandrina snails were monitored after treatment with three extracts of the plant aerial parts; petroleum ether, chloroform and ethanol. Chloroform extract that recorded the most potent effect was further evaluated through measuring the toxicity pattern against B. alexandrina snails, egg laying capacity, cercarial shedding, phenol oxidase enzyme and the levels of steroid sex hormones. Histopathological examination of hepatopancreas and ovotestis of treated snails were also done for result confirmation. Treatment of snails by chloroform extract recorded reduction in egg laying capacity, decrease in cercarial shedding, diminution in phenol oxidase enzyme, disturbance in steroid sex hormones and sever alternation of the histopathological picture of snails tissue. In conclusion, H. tuberculatum recorded molluscicidal potency against B. alexandrina snails. Further studies are needed for its environmental applications.


Asunto(s)
Biomphalaria , Moluscocidas , Extractos Vegetales , Rutaceae/química , Animales , Biomphalaria/enzimología , Biomphalaria/parasitología , Biomphalaria/fisiología , Biomphalaria/ultraestructura , Cercarias/fisiología , Hormonas Esteroides Gonadales/metabolismo , Hepatopáncreas/efectos de los fármacos , Hormonas de Invertebrados/metabolismo , Dosificación Letal Mediana , Monofenol Monooxigenasa/metabolismo , Oviposición/efectos de los fármacos , Schistosoma mansoni/fisiología
16.
Mem Inst Oswaldo Cruz ; 105(7): 879-88, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21120357

RESUMEN

Despite effective chemotherapy, schistosomiasis remains the second largest public health problem in the developing world. Currently, vaccination is the new strategy for schistosomiasis control. The presence of common antigenic fractions between Schistosoma mansoni and its intermediate host provides a source for the preparation of a proper vaccine. The objective of this paper is to evaluate the nucleoprotein extracted from either susceptible or resistant snails to protect against schistosomiasis. The vaccination schedule consisted of a subcutaneous injection of 50 µg protein of each antigen followed by another inoculation 15 days later. Analyses of marker enzymes for different cell organelles [succinate dehydrogenase, lactate dehydrogenase (LDH), glucose-6-phosphatase, acid phosphatase and 5'-nucleotidase] were carried out. Energetic parameters (ATP, ADP, AMP, phosphate potentials, inorganic phosphate, amino acids and LDH isoenzymes) were also investigated. The work was extended to record worm and ova counts, oogram determination in the liver and intestine and the histopathological pattern of the liver. The nucleoprotein of susceptible snails showed reduction in worm and ova counts by 70.96% and 51.31%, respectively, whereas the nucleoprotein of resistant snails showed reductions of 9.67% and 16.77%, respectively. In conclusion, we found that the nucleoprotein of susceptible snails was more effective in protecting against schistosomiasis.


Asunto(s)
Aminoácidos/análisis , Biomphalaria/parasitología , Hígado/parasitología , Nucleoproteínas/inmunología , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/inmunología , Animales , Biomphalaria/inmunología , Interacciones Huésped-Parásitos , Hígado/química , Hígado/enzimología , Hígado/patología , Masculino , Ratones , Nucleoproteínas/administración & dosificación , Recuento de Huevos de Parásitos , Esquistosomiasis mansoni/parasitología
17.
Mem. Inst. Oswaldo Cruz ; 105(7): 879-888, Nov. 2010. ilus, tab
Artículo en Inglés | LILACS | ID: lil-566177

RESUMEN

Despite effective chemotherapy, schistosomiasis remains the second largest public health problem in the developing world. Currently, vaccination is the new strategy for schistosomiasis control. The presence of common antigenic fractions between Schistosoma mansoni and its intermediate host provides a source for the preparation of a proper vaccine. The objective of this paper is to evaluate the nucleoprotein extracted from either susceptible or resistant snails to protect against schistosomiasis. The vaccination schedule consisted of a subcutaneous injection of 50 µg protein of each antigen followed by another inoculation 15 days later. Analyses of marker enzymes for different cell organelles [succinate dehydrogenase, lactate dehydrogenase (LDH), glucose-6-phosphatase, acid phosphatase and 5'-nucleotidase] were carried out. Energetic parameters (ATP, ADP, AMP, phosphate potentials, inorganic phosphate, amino acids and LDH isoenzymes) were also investigated. The work was extended to record worm and ova counts, oogram determination in the liver and intestine and the histopathological pattern of the liver. The nucleoprotein of susceptible snails showed reduction in worm and ova counts by 70.96 percent and 51.31 percent, respectively, whereas the nucleoprotein of resistant snails showed reductions of 9.67 percent and 16.77 percent, respectively. In conclusion, we found that the nucleoprotein of susceptible snails was more effective in protecting against schistosomiasis.


Asunto(s)
Animales , Masculino , Ratones , Aminoácidos , Biomphalaria , Hígado , Nucleoproteínas/inmunología , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/inmunología , Biomphalaria/inmunología , Interacciones Huésped-Parásitos , Hígado , Hígado/enzimología , Hígado/patología , Nucleoproteínas , Recuento de Huevos de Parásitos , Esquistosomiasis mansoni
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