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1.
Pharm Biol ; 59(1): 799-810, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34190667

RESUMO

CONTEXT: Among the plants in the genus Barringtonia (Lecythidaceae) used as traditional medicines to treat arthralgia, chest pain, and haemorrhoids in Indonesia, Barringtonia racemosa L. and Barringtonia acutangula (L.) Gaertn. have demonstrated anti-inflammatory activity in systemic inflammatory models. OBJECTIVE: The anti-inflammatory activity of Barringtonia angusta Kurz has not been investigated. We prepared a methanol extract of the leaves and stems of B. angusta (Ba-ME) and systemically evaluated its anti-inflammatory effects in vitro and in vivo. MATERIALS AND METHODS: RAW264.7 cells stimulated with LPS or Pam3CSK4 for 24 h were treated with Ba-ME (12.5, 25, 50, 100, and 150 µg/mL), and NO production and mRNA levels of inflammatory genes were evaluated. Luciferase reporter gene assay, western blot analysis, overexpression experiments, and cellular thermal shift assay were conducted to explore the mechanism of Ba-ME. In addition, the anti-gastritis activity of Ba-ME (50 and 100 mg/kg, administered twice per day for two days) was evaluated using an HCl/EtOH-induced gastritis mouse model. RESULTS: Ba-ME dose-dependently suppressed NO production [IC50 = 123.33 µg/mL (LPS) and 46.89 µg/mL (Pam3CSK4)] without affecting cell viability. Transcriptional expression of iNOS, IL-1ß, COX-2, IL-6, and TNF-α and phosphorylation of Src, IκBα, p50/105, and p65 were inhibited by Ba-ME. The extract specifically targeted the Src protein by binding to its SH2 domain. Moreover, Ba-ME significantly ameliorated inflammatory lesions in the HCl/EtOH-induced gastritis model. DISCUSSION AND CONCLUSIONS: The anti-inflammatory activity of Ba-ME is mediated by targeting of the Src/NF-κB signalling pathway, and B. angusta has potential as an anti-inflammatory drug.


Assuntos
Anti-Inflamatórios/administração & dosagem , Barringtonia , Sistemas de Liberação de Medicamentos/métodos , Gastrite/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Quinases da Família src/antagonistas & inibidores , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/metabolismo , Relação Dose-Resposta a Droga , Gastrite/induzido quimicamente , Gastrite/metabolismo , Células HEK293 , Humanos , Masculino , Metanol/administração & dosagem , Metanol/metabolismo , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo , Folhas de Planta , Caules de Planta , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Quinases da Família src/metabolismo
3.
Expert Rev Clin Pharmacol ; 14(1): 131-139, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33306408

RESUMO

Objectives: The purpose of this study was to measure the level of lipid peroxidation and investigate the response of the glutathione system to toxic doses of ethylene glycol tetraacetate acid (EGTA), Ferrum Lek, methanol, and Depakine (valproate sodium). Methods: This study focused on analyzing the toxic effects of EGTA, Ferrum Lek and methanol on lipid peroxidation processes and glutathione levels in animals. The study involved 375 outbred adult mice, of both sexes, weighing 28-31 g, and 100 outbred rats, weighing 180-200 g. Results: After 14 days of valproate sodium/ademethionine treatment, the GR (glutathione reductase) activity in experimental animals continued to be higher than in controls. Using EGTA enhanced glutathione reductase and glutathione S transferase activities in the liver and kidney. The activity of glutathione peroxidase, however, increased only in the kidney (2.1-fold, p ≤ 0.001), while in the liver, a 31% drop was observed (p ≤ 0.05). The 15-mg and 30-mg doses of Ferrum Lek caused the liver level of thiobarbituric acid reactive substances to grow 3- and 3.5-fold, respectively (p ≤ 0.001). Conclusion: The results of the study indicate that poisoning affected practically all components of the glutathione system. The oxidative stress was likely to result from an increased generation of reactive oxygen species against the background of inhibited antioxidant protection.


Assuntos
Ácido Egtázico/envenenamento , Glutationa/metabolismo , Metanol/envenenamento , Compostos Organometálicos/envenenamento , Polissacarídeos/envenenamento , Animais , Animais não Endogâmicos , Antioxidantes/metabolismo , Relação Dose-Resposta a Droga , Ácido Egtázico/administração & dosagem , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Metanol/administração & dosagem , Camundongos , Compostos Organometálicos/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/administração & dosagem , Ratos , Espécies Reativas de Oxigênio/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Ácido Valproico/administração & dosagem , Ácido Valproico/toxicidade
4.
Eur. j. anat ; 24(3): 193-203, mayo 2020. tab, ilus, graf
Artigo em Inglês | IBECS | ID: ibc-191468

RESUMO

The degenerative and inflammatory changes were reported in cardiac tissues of rats exposed to zidovudine (ZDV). This study was designed to ex-amine the histochemical changes in the myocardi-um of adult Wistar rats exposed to ZDV and ad-ministered with methanolic extract of Buchholzia coriacea (MEBC) seed. Forty-eight healthy Wistar rats weighing 150-155 g. were randomly assigned into eight groups of six rats each. Group A served as control and received distilled water; group B received 100 mg/kg of ZDV; group C received 600 mg/kg of MEBC; group D received 100 mg/kg of vitamin C; group E received 100 mg/kg of vitamin C and ZDV; group F received 150 mg/kg of MEBC and 100 mg/kg of ZDV; group G received 300 mg/kg of MEBC and 100 mg/kg of ZDV, and group H received 600 mg/kg of MEBC and 100 mg/kg of ZDV. Treatment lasted for a period of 56 days. Blood was collected separately into clean capped plain tubes for biochemical parameters. Heartswere excised, fixed in 10% formal saline and pro-cessed for histology. ZDV induced a significant increase in the serum concentration of Nitric Oxide (NO) and Cardiac Troponin I (cTnI) in the ZDV-alone group when compared to control (p < 0.05). Also, there was reduction in activity of the Glutathi-one reductase (GR) enzyme in the ZDV-alone group relative to control (P = 0.0006, F = 7.0). Distor-tion of the cross banding pattern of cardiac muscle fibres in ZDV-alone group was manifested. These effects were reversed by administration of MEBC compared to vitamin C group


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Assuntos
Animais , Ratos , Ventrículos do Coração/anatomia & histologia , Metanol/administração & dosagem , Zidovudina/efeitos adversos , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/veterinária , Coração/anatomia & histologia , Capparaceae , Extratos Vegetais/administração & dosagem , Ventrículos do Coração/efeitos dos fármacos , Zidovudina/administração & dosagem , Ratos Wistar/anatomia & histologia , Coração/efeitos dos fármacos , Técnicas Histológicas , Fotomicrografia , Antioxidantes/administração & dosagem , Sementes
5.
Theriogenology ; 149: 16-24, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32229351

RESUMO

Spotted wolffish Anarhichas minor reproduction in captivity is dependent on in vitro fertilization. However, low sperm volume with relatively low cell concentration and the lack of gametes synchronization (simultaneous availability of mature eggs and sperm) represent a challenge for the industry. Thus, the development of protocols for sperm storage are crucial. Four sequential experiments were conducted to optimize a sperm cryopreservation protocol for this species. First, three different cryoprotectants (DMSO; 1, 2-propanediol; and methanol) at different concentrations (5, 10, and 20%) were tested for their toxicity. No significant differences (p > 0.05) were detected between the control samples and cryoprotectants at concentration up to 10% DMSO, 10% propanediol, and 20% methanol in terms of motility parameters. Second, using the highest non-toxic concentrations of cryoprotectants, sperm was cryopreserved in 0.5 mL straws, at different distances from the liquid nitrogen (1.5, 2.5, 4.5, and 7.5 cm) that correspond to different freezing rates. Motility parameters after freezing/thawing decreased for all the cryoprotectants (p < 0.001), however, methanol had the lowest protective capacity while DMSO the highest. Afterwards, two different thawing rates (1 min at 5 °C; and 25 s at 10 °C) were tested using only 10% DMSO and 10% propanediol. Both for the DMSO and propanediol, there were no significant differences (p > 0.05) between the two thawing rates. The best results were obtained using 10% DMSO. Finally, the fertilization capacity of cryopreserved sperm (10% DMSO and thawed at 5 °C for 1 min) was tested against fresh sperm using two spermatozoa:egg ratios and 4 h gametes contact time. The ratio of eggs with normal cell cleavage, abnormal cleavage or undeveloped were counted at the 2-4 cell stage. Cryopreserved sperm showed lower fertilization capacity at a concentration of 5 × 104 spermatozoa:egg compared with fresh sperm (p < 0.001). At a concentration of 5 × 105 spermatozoa:egg, similar fertilizations rates to the fresh sperm were obtained. The presence of the cryoprotectant DMSO during the 4 h contact time did not affect the fertilization rate or the percentage of embryos with abnormal cleavage (p > 0.05). To cryopreserve spotted wolffish sperm it is recommended to use 10% DMSO, loaded in 0.5 mL straws, freeze at a height between 4.5 (-14.05 °C/min) and 7.5 cm (-5.9 °C/min) from liquid nitrogen for 10 min and thaw for 1 min at 5 °C (177.9 °C/min). In vitro fertilization with cryopreserved sperm should be performed with a concentration of at least 5 × 105 spermatozoa per egg.


Assuntos
Criopreservação/veterinária , Crioprotetores/administração & dosagem , Perciformes/fisiologia , Preservação do Sêmen/veterinária , Espermatozoides/fisiologia , Animais , Criopreservação/instrumentação , Criopreservação/métodos , Crioprotetores/toxicidade , Dimetil Sulfóxido/administração & dosagem , Fertilização In Vitro/métodos , Fertilização In Vitro/veterinária , Masculino , Metanol/administração & dosagem , Propilenoglicol/administração & dosagem , Preservação do Sêmen/métodos , Motilidade dos Espermatozoides/fisiologia , Espermatozoides/efeitos dos fármacos
6.
Hypertension ; 75(2): 383-392, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31838904

RESUMO

High blood pressure is a risk factor for cardiovascular diseases. Ang II (angiotensin II), a key pro-hypertensive hormone, mediates target organ consequences such as endothelial dysfunction and cardiac hypertrophy. S1P (sphingosine-1-phosphate), produced by Sphk1 (sphingosine kinase 1), plays a pivotal role in the pathogenesis of hypertension and downstream organ damage, as it controls vascular tone and regulates cardiac remodeling. Accordingly, we aimed to examine if pharmacological inhibition of Sphk1 using selective inhibitor PF543 can represent a useful vasoprotective and cardioprotective anti-hypertensive strategy in vivo. PF543 was administered intraperitoneally throughout a 14-day Ang II-infusion in C57BL6/J male mice. Pharmacological inhibition of Sphk1 improved endothelial function of arteries of hypertensive mice that could be mediated via decrease in eNOS (endothelial nitric oxide synthase) phosphorylation at T495. This effect was independent of blood pressure. Importantly, PF543 also reduced cardiac hypertrophy (heart to body weight ratio, 5.6±0.2 versus 6.4±0.1 versus 5.9±0.2 mg/g; P<0.05 for Sham, Ang II+placebo, and Ang II+PF543-treated mice, respectively). Mass spectrometry revealed that PF543 elevated cardiac sphingosine, that is, Sphk1 substrate, content in vivo. Mechanistically, RNA-Seq indicated a decreased expression of cardiac genes involved in actin/integrin organization, S1pr1 signaling, and tissue remodeling. Indeed, downregulation of Rock1 (Rho-associated coiled-coil containing protein kinase 1), Stat3 (signal transducer and activator of transcription 3), PKC (protein kinase C), and ERK1/2 (extracellular signal-regulated kinases 1/2) level/phosphorylation by PF543 was observed. In summary, pharmacological inhibition of Sphk1 partially protects against Ang II-induced cardiac hypertrophy and endothelial dysfunction. Therefore, it may represent a promising target for harnessing residual cardiovascular risk in hypertension.


Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/tratamento farmacológico , Lisofosfolipídeos/genética , Metanol/análogos & derivados , Pirrolidinas/administração & dosagem , RNA/genética , Esfingosina/análogos & derivados , Remodelação Ventricular/fisiologia , Animais , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Hipertensão/genética , Hipertensão/metabolismo , Injeções Intraperitoneais , Lisofosfolipídeos/antagonistas & inibidores , Lisofosfolipídeos/metabolismo , Masculino , Metanol/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Transdução de Sinais , Esfingosina/antagonistas & inibidores , Esfingosina/genética , Esfingosina/metabolismo , Sulfonas , Remodelação Ventricular/efeitos dos fármacos
8.
BMC Ophthalmol ; 19(1): 124, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31174513

RESUMO

BACKGROUND: To analyze the clinical features and prognosis of the visual loss resulted from inhalational methanol poisoning in 8 Chinese patients. METHODS: Eight consecutive patients seen at the Beijing Tongren Hospital of Capital Medical University, Beijing, China between January 2003 to August 2017, with complains of vision loss in both eyes, identified as inhalational methanol poisoning. Detailed medical history was extracted. All patients underwent optic nerve and brain magnetic resonance imaging (MRI) scan, laboratory tests, and visual function analysis. Treatment protocols were large dosage of methylprednisolone and B vitamins over 3 months. Patients were seen at 3-month intervals until a year. RESULTS: Eight patients with optic neuropathy caused by inhalation toxicity of methanol were under observation, whose methanol-contact time spans were form 4 days to 5 years for occupational exposure. All the patients had acute onset, transient systemic symptoms on early stage, both eyes involved with severe visual impairment (visual acuity 0.1 or even worse). Retrobulbar optic nerves (ONs) were the major sites involved. Optic nerve MRI scan showed increased signal of bilateral ONs in the orbit and the canal parts, with enhancement. After treatment, the visual function of these patients got improved in different degree in a year follow-up, but not satisfactorily. CONCLUSIONS: Inhalational methanol toxicity may lead to serious damage to ON in a process of chronic intoxication with acute attack, and with poor prognosis.


Assuntos
Metanol/envenenamento , Nervo Óptico/efeitos dos fármacos , Transtornos da Visão/induzido quimicamente , Acuidade Visual/fisiologia , Doença Aguda , Administração por Inalação , Adulto , Encéfalo/diagnóstico por imagem , Doença Crônica , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Metanol/administração & dosagem , Pessoa de Meia-Idade , Nervo Óptico/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Solventes/envenenamento , Transtornos da Visão/diagnóstico , Transtornos da Visão/fisiopatologia , Acuidade Visual/efeitos dos fármacos , Adulto Jovem
9.
Alcohol ; 75: 99-103, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30640075

RESUMO

This study assessed the ethanol and methanol contents of homemade spirit (Kachasu) sold in Blantyre, Malawi. The likelihood of ethanol and methanol toxicity, respectively, was determined through Monte Carlo simulations using reported Kachasu intake volumes of 21 consumers and the determined methanol and ethanol contents. Ethanol concentration, in samples from 20 different distillers, ranged from 11 to 55% v/v. Methanol was detected in 10 of the 20 samples (0.01-0.28% v/v). The likely mean ethanol intake of drinkers in Blantyre was found to be 214 ± 93 mL per day (90% CI, 68.9-373.4 mL), and mean methanol intake was 0.44 ± 0.37 mL (90% CI, 0.03-1.17 mL). The intake values translated to mean blood ethanol and methanol concentrations of 38 ± 16 mg/mL and 0.05 ± 0.04 mg/mL, respectively. Therefore, the risk of methanol toxicity was considered as negligible. However, there was a high risk of ethanol toxicity. Since production and selling of Kachasu are already illegal in Malawi, enforcement of regulations should be strengthened to reverse the current situation where Kachasu is being distilled and sold openly even within cities. Consumers should also be sensitized about the likely risks associated with consumption of Kachasu in Malawi so that they can make informed choices.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Bebidas Alcoólicas/efeitos adversos , Etanol/efeitos adversos , Metanol/efeitos adversos , Saúde Pública/tendências , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/tendências , Etanol/administração & dosagem , Etanol/sangue , Humanos , Drogas Ilícitas/efeitos adversos , Drogas Ilícitas/sangue , Malaui/epidemiologia , Masculino , Metanol/administração & dosagem , Metanol/sangue , Distribuição Aleatória , Açúcares/efeitos adversos , Zea mays/efeitos adversos
10.
Int. j. morphol ; 37(1): 237-240, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-990033

RESUMO

SUMMARY: Brassica juncea (Indian mustard) seeds are consumed in treatment of high blood pressure, headache and prevention of heart disease. The aim of the present study was to investigate the effects of methanol extract of Brassica juncea seeds [BJME] on the heart and liver of adult Albino Wistar rats. A total of 24 albino rats of both sexes were divided into 6 groups [I - VI] of 4 rats per group. Groups I to IV received graded doses of the methanol extract by oral gavage while groups V and VI (controls) received 2 ml/kg body weight of 3 % Tween 80 and water respectively via oral gavage once daily. Treatment lasted for four weeks and the serum levels of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were estimated. The animals were sacrificed and the heart and liver tissues were excised for further histological processing for light microscopy. There was significant increase in AST and ALT levels following BJME treatment when compared to the controls. ALP activity did not differ significantly among the treatment and control groups. Histopathological changes consistent with toxic injury were observed in the heart and liver tissues of BJME- treated rats. In conclusion, the results of this study show that sub-acute administration of methanol seed extract of Brassica juncea can exert cardiotoxic and hepatotoxic effects in rats.


RESUMEN: Las semillas de Brassica juncea (mostaza india) se consumen en el tratamiento de la hipertensión arterial, el dolor de cabeza y la prevención de enfermedades del corazón. El objetivo del presente estudio fue investigar los efectos del extracto de metanol de semillas de Brassica juncea [BJME] en el corazón y el hígado de ratas Albino Wistar adultas. Un total de 24 ratas albinas de ambos sexos se dividieron en 6 grupos [I - VI] de 4 ratas por grupo. Los grupos I a IV recibieron dosis del extracto de metanol por sonda oral progresivamente, mientras que los grupos V y VI (control) recibieron 2 ml / kg de peso corporal de 3 % de 80 y agua, respectivamente, por sonda oral una vez al día. El tratamiento duró cuatro semanas y se estimaronlos niveles séricos de aspartato transaminasa (AST), alanina transaminasa (ALT) y fosfatasa alcalina (ALP). Los animales se sacrificaron y fueron analizados los tejidos del corazón y el hígado, para un procesamiento histológico adicional con microscopía óptica. Hubo un aumento significativo en los niveles de AST y ALT después del tratamiento con BJME en comparación con los controles. La actividad de ALP no difirió significativamente entre los grupos de tratamiento y control. Se observaron cambios histopatológicos compatibles con lesiones tóxicas en los tejidos del corazón y el hígado de ratas tratadas con BJME. En conclusión, los resultados de este estudio muestran que la administración subaguda de extracto de semilla de metanol de Brassica juncea puede ejercer efectos cardiotóxicos y hepatotóxicos en ratas.


Assuntos
Animais , Ratos , Extratos Vegetais/farmacologia , Metanol/farmacologia , Coração/efeitos dos fármacos , Fígado/efeitos dos fármacos , Mostardeira/química , Aspartato Aminotransferases/análise , Sementes , Fatores de Tempo , Extratos Vegetais/administração & dosagem , Ratos Wistar , Alanina Transaminase/análise , Metanol/administração & dosagem , Fosfatase Alcalina/análise
11.
Ann Bot ; 122(5): 849-860, 2018 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-29579139

RESUMO

Background and Aims: Methanol is a volatile organic compound released from plants through the action of pectin methylesterases (PMEs), which demethylesterify cell wall pectins. Plant PMEs play a role in developmental processes but also in responses to herbivory and infection by fungal or bacterial pathogens. However, molecular mechanisms that explain how methanol could affect plant defences remain poorly understood. Methods: Using cultured cells and seedlings from Arabidopsis thaliana and tobacco BY2 expressing the apoaequorin gene, allowing quantification of cytosolic Ca2+, a reactive oxygen species (ROS) probe (CLA, Cypridina luciferin analogue) and electrophysiological techniques, we followed early plant cell responses to exogenously supplied methanol applied as a liquid or as volatile. Key Results: Methanol induces cytosolic Ca2+ variations that involve Ca2+ influx through the plasma membrane and Ca2+ release from internal stores. Our data further suggest that these Ca2+ variations could interact with different ROS and support a signalling pathway leading to well known plant responses to pathogens such as plasma membrane depolarization through anion channel regulation and ethylene synthesis. Conclusions: Methanol is not only a by-product of PME activities, and our data suggest that [Ca2+]cyt variations could participate in signalling processes induced by methanol upstream of plant defence responses.


Assuntos
Arabidopsis/fisiologia , Cálcio/metabolismo , Etilenos/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Equorina/metabolismo , Apoproteínas/metabolismo , Arabidopsis/efeitos dos fármacos , Membrana Celular/fisiologia , Células Cultivadas , Citosol/metabolismo , Metanol/administração & dosagem , Proteínas de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes/metabolismo , Plântula/efeitos dos fármacos , Plântula/fisiologia , /efeitos dos fármacos
12.
Microb Pathog ; 117: 315-319, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29366865

RESUMO

Respiratory bacterial infections are responsible for significant mortality across the world and with emergence of drug resistant bacterial strains there is urgent need to look for new treatment options. In this study we evaluated the antimicrobial activity of methanolic extract of Bergenia purpurasceus in vitro and in neonatal rats. The results of the present study revealed that the methanolic extract exhibits antimicrobial activity against all the bacterial species with MIC ranging from 75 to 150 µg/ml. The antibacterial activity of the Bergenia purpurasceus extract was also determined in the neonatal rat models wherein it was observed that administration of 50 and 100 mg/kg doses of Bergenia purpurasceus extract improved the survival of the neonatal rats infected with S. aureus. Furthermore, the extract showed considerable antioxidant activity which was positively associated with the phenolics and flavonoids content. Finally the constituents responsible for the bioactivity of the extract were identified and found to be bergenin, catechin, naringenin, myricetin and gallic acid. Takentogether, these results indicate that Bergenia purpurasceus extract could prove useful for the treatment of bacterial respiratory infections.


Assuntos
Antibacterianos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Metanol/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Infecções Respiratórias/microbiologia , Saxifragaceae/química , Animais , Antibacterianos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Benzopiranos/química , Benzopiranos/farmacologia , Catequina/química , Catequina/farmacologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Flavanonas/química , Flavanonas/farmacologia , Ácido Gálico/química , Ácido Gálico/farmacologia , Metanol/administração & dosagem , Metanol/química , Testes de Sensibilidade Microbiana , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Folhas de Planta/química , Ratos , Infecções Respiratórias/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade
13.
Curr Drug Deliv ; 15(7): 987-997, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29268685

RESUMO

BACKGROUND: Biodegradable nanoparticles with diameters between 100 nm and 500 nm are of great interest in the contexts of targeted delivery. OBJECTIVE: The present work provides a review concerning the effect of binary organic solvents together with emulsifier on particle size as well as the influence of particle size on the in vitro drug release and uptake behavior. METHODS: The polymeric lipid nanoparticles (PLNs) with different particle sizes were prepared by using binary solvent dispersion method. Various formulation parameters such as binary organic solvent composition and emulsifier types were evaluated on the basis of their effects on particle size and size distribution. PLNs had a strong dependency on the surface tension, intrinsic viscosity and volatilization rate of binary organic solvents and the hydrophilicity/hydrophobicity of emulsifiers. Acetone-methanol system together with pluronic F68 as emulsifier was proved to obtain the smallest particle size. Then the PLNs with different particle sizes were used to investigate how particle size at nanoscale affects interacted with tumor cells. RESULTS: As particle size got smaller, cellular uptake increased in tumor cells and PLNs with particle size of ~120 nm had the highest cellular uptake and fastest release rate. The paclitaxel (PTX)-loaded PLNs showed a size-dependent inhibition of tumor cell growth, which was commonly influenced by cellular uptake and PTX release. CONCLUSION: The PLNs would provide a useful means to further elucidate roles of particle size on delivery system of hydrophobic drugs.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Ácido Láctico/administração & dosagem , Nanopartículas/administração & dosagem , Paclitaxel/administração & dosagem , Ácido Poliglicólico/administração & dosagem , Acetona/administração & dosagem , Acetona/química , Antineoplásicos Fitogênicos/química , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Emulsificantes/administração & dosagem , Emulsificantes/química , Humanos , Ácido Láctico/química , Lipídeos/administração & dosagem , Lipídeos/química , Células MCF-7 , Metanol/administração & dosagem , Metanol/química , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Nanopartículas/ultraestrutura , Paclitaxel/química , Tamanho da Partícula , Poloxâmero/administração & dosagem , Poloxâmero/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Solventes/administração & dosagem , Solventes/química
14.
Artigo em Inglês | MEDLINE | ID: mdl-28971609

RESUMO

Grapefruit can augment oral medication bioavailability through irreversible (mechanism-based) inhibition of intestinal CYP3A4. Supplementary data from our recent coffee-drug interaction clinical study showed some subjects had higher area under the plasma drug concentration - time curve (AUC) and plasma peak drug concentration (Cmax) of the CYP3A4 probe felodipine compared to aqueous control. It was hypothesized that coffee might interact like grapefruit in responsive individuals. Beans from six geographical locations were consistently brewed into coffee that was separated chromatographically to a methanolic fraction for in vitro inhibition testing of CYP3A4 metabolism of felodipine at 1% coffee strength. The effect of simultaneous incubation and 10-min preincubation with coffee fractions determined whether coffee had direct and mechanism-based inhibitory activity. A subsequent five-way randomized balanced controlled crossover clinical study evaluated the clinical pharmacokinetic interaction with single-dose felodipine. Grapefruit juice, water, or three of the in vitro tested coffees were ingested at 300 mL alone 1 h before and then with felodipine. In vitro, all six coffees decreased felodipine metabolism for both simultaneous and preincubation exposure compared to corresponding control. Five coffees demonstrated mechanism-based inhibition. Grapefruit increased felodipine AUC0-8 (25 vs. 13 ng.h/mL, P < 0.001) and Cmax (5.8 vs. 2.7 ng/mL, P < 0.001) and decreased dehydrofelodipine/felodipine AUC0-8 ratio (0.84 vs. 1.29, P < 0.001), while the three coffees caused no change in these parameters compared to water. Despite high in vitro potency of CYP3A4 inhibition, the coffees did not cause a clinical pharmacokinetic interaction possibly from insufficient amount of inhibitor(s) in coffee reaching intestinal CYP3A4 during the absorption phase of felodipine. The results of this study highlight the need for follow-up clinical testing when in vitro results indicate the possibility of an interaction.


Assuntos
Citrus paradisi/química , Café/química , Citocromo P-450 CYP3A/metabolismo , Felodipino/administração & dosagem , Extratos Vegetais/farmacologia , Adulto , Área Sob a Curva , Café/classificação , Estudos Cross-Over , Regulação para Baixo , Felodipino/farmacocinética , Feminino , Interações Alimento-Droga , Humanos , Técnicas In Vitro , Masculino , Metanol/administração & dosagem , Metanol/farmacocinética , Pessoa de Meia-Idade
15.
Biomed Pharmacother ; 95: 167-174, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28843148

RESUMO

Plants are considered as one of the best sources of diabetic therapy. Being a reliable and sustainable medicinal hub, this study directs the use of Syzygium mundagam in exploring the antidiabetic property. Streptozotocin-Nicotinamide (STZ-NA) induced diabetic rats were treated with Syzygium mundagam bark methanol extract (SMBM). Based on acute toxicity study, the doses of the extract were fixed as 100 and 200mg/kg. Glibenclamide was used as reference drug. The blood glucose level and body weight of the rats were monitored for 28days. After the treatment, rats were sacrificed and the blood biochemical, serum and histopathological parameters were analysed. The in vivo antioxidant levels in liver and kidney were also estimated. SMBM extract (200mg/kg) could significantly reduce the blood glucose level from 580.60mg/dL to 237.60mg/dL on day 28. An accelerated reduction in body weight was observed in diabetic control rats and inhibited by the extract during the study. The haematological parameters were normal compared to normal rats. The values of serum parameters like triglycerides, high-density lipoprotein (HDL), cholesterol and very low-density lipoprotein (VLDL) were close to the values of normal rats. After the treatment, Superoxide dismutase (SOD), Glutathione (GSH) and Glutathione reductase (GR) levels in liver and kidney were found accountable for their antioxidant properties during diabetic condition. The degree of protection set by SMBM extract was clear enough in the histopathology of liver, kidney and pancreas. The phenolic compounds studied in SMBM can be related to these activities. This study proves the ability of Syzygium mundagam to combat the diabetic condition and provides an insight on hidden properties of plants which can be utilized as novel drugs for existing disease complications.


Assuntos
Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Metanol/administração & dosagem , Casca de Planta , Extratos Vegetais/administração & dosagem , Syzygium , Administração Oral , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Complicações do Diabetes/sangue , Complicações do Diabetes/patologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Feminino , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/isolamento & purificação , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Wistar , Resultado do Tratamento
16.
Cryobiology ; 77: 19-24, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28602768

RESUMO

Cryopreservation of fish embryos requires the swift uptake of considerable amounts of cryoprotectant (CPA) but this process is hampered by the low permeability of the egg chorion. This study examined the relative efficiency of ultrasound to promote the incorporation of CPAs in two different embryonic developmental stages (somites and tail elongation) of Japanese whiting Sillago japonica and performed a preliminary cryopreservation trial using the best conditions determined during the study. Embryos tolerated ultrasound densities up to 37.5 W/cm2 well for up to 3 min but had significant mortality at 50 W/cm2. Hatching rates of somites embryos sonicated at 37.5 W/cm2 for 1-3 min in 10 and 20% Me2SO solutions were comparable (61-72%) to that of sonication in artificial seawater (65-86%) but decreased sharply at the concentration of 30% (0-55%); at similar conditions, tail elongation embryos had comparatively lower survival. Me2SO content of sonicated embryos at the somites and tail elongation stages increased significantly by 58-191% and 27-123%, respectively, compared to controls exposed to Me2SO without ultrasound. Pre-exposure to Me2SO before sonication increased the CPA uptake further by 36% without impairing survival. A preliminary cryopreservation trial after ultrasound-mediated impregnation of somites embryos with a CPA solution containing 20% PG and 10% MeOH did not yield live embryos after freeze-thawing but resulted in a significant decrease of nucleation temperature and increase of the proportion of morphologically intact embryos after freeze-thawing. These results suggest that sonication might be useful for fish embryo cryopreservation although it may require combination with other techniques to enhance CPA permeation.


Assuntos
Criopreservação/métodos , Crioprotetores/administração & dosagem , Dimetil Sulfóxido/administração & dosagem , Embrião não Mamífero , Ondas Ultrassônicas , Animais , Crioprotetores/farmacologia , Dimetil Sulfóxido/farmacologia , Peixes , Congelamento , Metanol/administração & dosagem , Metanol/farmacologia , Perciformes , Permeabilidade , Propilenoglicol/administração & dosagem , Propilenoglicol/farmacologia
17.
Molecules ; 22(4)2017 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-28333074

RESUMO

Diabetes mellitus is an endocrine disease of multiple aetiologies in insulin secretion. A deficiency in insulin results in hyperglycemia with metabolic disturbances of biomolecules. Moringa oleifera (MO) is endemic in the tropics with a variety of ethnomedicinal importance. The leaf of this plant has been reported to possess antioxidant and medicinal properties that may be helpful in the treatment and management of diabetes and its associated complications. Diabetes was induced intraperitoneally in rats by a single dose of streptozotocin (55 mg/kg) and treated with methanolic extract of Moringa oleifera (250 mg/kg b.wt) for six weeks. Forty-eight (48) adult male Wistar strain rats were randomly divided into four groups: normal control (NC), Moringa oleifera treated control rats (NC + MO), diabetic rats (DM) and Moringa oleifera treated diabetic rats (DM + MO). Estimation of antioxidant capacity, total polyphenols, flavonoids and flavonols content of Moringa oleifera extract was performed and serum biochemical markers were evaluated. Antioxidants such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) activities, glutathione (GSH) and inflammatory biomarkers were determined in the kidney. Results showed high antioxidant capacities of MO extract and improved serum biochemical markers, whilst lipid peroxidation (MDA) levels were reduced in non-diabetic and diabetic rats after MO treatment when compared to normal control. Subsequent administration of MO led to an increased concentration of serum albumin, globulin and total protein with a decrease in the level of MDA, and improvements in CAT, SOD, GSH, GPx, (tumour necrosis factor-alpha)TNF-α and (interleukin-6)IL-6. MO contains potent phytochemical constituents that offer protective action against diabetic-induced renal damage, reactive oxygen species (ROS) and inflammation and could therefore play a role in reducing diabetic complications, particularly in developing countries such as in Africa where the majority cannot afford orthodox medicine.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metanol/administração & dosagem , Moringa oleifera/química , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Interleucina-6/metabolismo , Rim/efeitos dos fármacos , Rim/enzimologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Metanol/química , Metanol/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Estreptozocina
18.
Am J Drug Alcohol Abuse ; 42(6): 633-639, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27463192

RESUMO

BACKGROUND: Methanol-induced optic neuropathy (MTON) is frequently seen in countries where alcohol consumption is banned or poorly regulated. MTON frequently results in blindness and there is no empirically validated treatment. OBJECTIVE: To evaluate the effect of erythropoietin (EPO) as an adjunctive treatment for MTON. METHODS: In this nonrandomized interventional comparative study, all participants were diagnosed with MTON and received the steroid methylprednisolone. Eleven participants received intravenous EPO (10000 IU twice a day) for three days as an adjuvant to methylprednisolone (EPO group); 11 participants in a historical control group received methylprednisolone only (control group). Main outcomes were best-corrected visual acuity (BCVA), peripapillary retinal nerve fiber layer thickness (PRNFLT), and visual field mean deviation (MD). RESULTS: Mean BCVA improved significantly in both groups: from 2.93 ± 0.55 to 1.75 ± 1.16 LogMAR at month 3 (p < 0.001) in the EPO group, and from 2.65 ± 0.68 to 2.19 ± 0.75 at final visit in the control group (p = 0.001). The final BCVA was significantly better in the EPO group (p = 0.012). The mean PRNFLT decreased in both groups. However, at the final follow-up, PRNFLT was significantly thinner in the control group (53 ± 6 vs. 77 ± 26 microns, respectively; p < 0.001). CONCLUSION: Intravenous EPO plus high-dose intravenous steroid may be an effective combination therapy for the patients with MTON.


Assuntos
Eritropoetina/uso terapêutico , Metanol/efeitos adversos , Metilprednisolona/uso terapêutico , Doenças do Nervo Óptico/tratamento farmacológico , Administração Intravenosa , Adulto , Quimioterapia Combinada , Eritropoetina/administração & dosagem , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Masculino , Metanol/administração & dosagem , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Fibras Nervosas/metabolismo , Doenças do Nervo Óptico/induzido quimicamente , Retina/metabolismo , Resultado do Tratamento , Acuidade Visual , Campos Visuais
19.
Br Poult Sci ; 57(5): 601-611, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27376436

RESUMO

The aims of the present study were to examine whether collagen exists in egg, particularly in egg yolk; to establish a Fourier transform-near infrared (FT-NIR) measurement method for collagen in egg and to assess the possibility of increasing the collagen content by feeding hens a diet containing wood charcoal powder containing wood vinegar liquid (WCV). The collagen in eggs from 67-week-old hens fed on the dietary 0 and 9.9 g/kg WCV diets was investigated using a combination of histochemical, matrix-assisted laser desorption ionisation with time-of-flight mass spectrometry (MALDI-TOF MS), Fourier transform infrared (FT-IR) and FT-NIR approaches. All approaches used to identify collagen in egg yolk yielded positive results. The collagen in egg yolk measured using colorimetry, collagen in egg yolk, egg white and eggshell membrane using FT-NIR and collagen in egg yolk determined by treating the egg yolk with collagenase were abundant after feeding a dietary WCV (p<0.05). These results suggest that egg yolk contains collagen, that the collagen in egg can be measured using FT-NIR, and that the collagen content of egg yolk can be increased by feeding dietary WCV diets.


Assuntos
Ácido Acético/administração & dosagem , Carvão Vegetal/administração & dosagem , Galinhas/fisiologia , Colágeno/química , Dieta/veterinária , Suplementos Nutricionais , Metanol/administração & dosagem , Óvulo/química , Ração Animal/análise , Animais , Relação Dose-Resposta a Droga , Gema de Ovo/química , Feminino , Pós , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/veterinária , Espectroscopia de Infravermelho com Transformada de Fourier/veterinária , Madeira
20.
Anal Cell Pathol (Amst) ; 2016: 4598454, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27066393

RESUMO

Many studies have reported that methanol toxicity to primates is mainly associated with its metabolites, formaldehyde (FA) and formic acid. While methanol metabolism and toxicology have been best studied in peripheral organs, little study has focused on the brain and no study has reported experimental evidence that demonstrates transformation of methanol into FA in the primate brain. In this study, three rhesus macaques were given a single intracerebroventricular injection of methanol to investigate whether a metabolic process of methanol to FA occurs in nonhuman primate brain. Levels of FA in cerebrospinal fluid (CSF) were then assessed at different time points. A significant increase of FA levels was found at the 18th hour following a methanol injection. Moreover, the FA level returned to a normal physiological level at the 30th hour after the injection. These findings provide direct evidence that methanol is oxidized to FA in nonhuman primate brain and that a portion of the FA generated is released out of the brain cells. This study suggests that FA is produced from methanol metabolic processes in the nonhuman primate brain and that FA may play a significant role in methanol neurotoxicology.


Assuntos
Encéfalo/metabolismo , Formaldeído/metabolismo , Metanol/metabolismo , Animais , Formaldeído/líquido cefalorraquidiano , Injeções Intraventriculares , Macaca mulatta , Masculino , Metanol/administração & dosagem , Metanol/líquido cefalorraquidiano , Oxirredução , Fatores de Tempo
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