RESUMEN
Nonhealing diabetic wounds are predominantly attributed to the inhibition of angiogenesis, re-epithelialization, and extracellular matrix (ECM) synthesis caused by hypoxia. Although oxygen therapy has demonstrated efficacy in promoting healing, its therapeutic impact remains suboptimal due to unsustainable oxygenation. Here, this work proposes an oxygen-releasing hydrogel patch embedded with polyethylene glycol-modified calcium peroxide microparticles, which sustainably releases oxygen for 7 days without requiring any supplementary conditions. The released oxygen effectively promotes cell migration and angiogenesis under hypoxic conditions as validated in vitro. The in vivo tests in diabetic mice models show that the sustainably released oxygen significantly facilitates the synthesis of ECM, induces angiogenesis, and decreases the expression of inflammatory cytokines, achieving a diabetic wound healing rate of 84.2% on day 7, outperforming the existing oxygen-releasing approaches. Moreover, the proposed hydrogel patch is designed with porous, soft, antibacterial, biodegradable, and storage stability for 15 days. The proposed hydrogel patch is expected to be promising in clinics treating diabetic wounds.
Asunto(s)
Diabetes Mellitus Experimental , Hidrogeles , Oxígeno , Peróxidos , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Hidrogeles/química , Hidrogeles/farmacología , Ratones , Oxígeno/química , Peróxidos/química , Peróxidos/farmacología , Humanos , Polietilenglicoles/química , Neovascularización Fisiológica/efectos de los fármacos , Masculino , Células Endoteliales de la Vena Umbilical Humana , Movimiento Celular/efectos de los fármacosRESUMEN
PURPOSE: To evaluate the effectiveness of five alkaline peroxide-based effervescent tablets in reducing both biofilms and the food layer adhered on the cobalt-chromium surface. METHODS: Cobalt-chromium metal alloy specimens were contaminated with Candida albicans, Candida glabrata, Streptococcus mutans and Staphylococcus aureus. After biofilm maturation, the specimens were immersed in Polident 3 Minute, Polident for Partials, Efferdent, Steradent, Corega Tabs or distilled water (control). Residual biofilm rates were determined by colony forming units counts and biofilm biomass. In parallel, to investigate the denture cleaning capability of effervescent tablets, artificially contaminated removable partial dentures were treated with each cleanser. Data were analyzed by Kruskal-Wallis followed by Dunn post hoc test or ANOVA followed by Tukey post hoc test (α= 0.05). RESULTS: None of the hygiene solutions reduced C. albicans biofilm. Efferdent and Corega Tabs promoted reduction of C. glabrata biofilm, while Steradent was favorable against S. aureus biofilm. For S. mutans, lower biofilm rates were observed after immersion in Polident for Partials and Steradent. The effervescent tablets showed good cleaning performance, removing an artificial layer with carbohydrates, proteins, and fats, however, they were not effective in removing aggregated mature biofilm. CLINICAL SIGNIFICANCE: The different effervescent tablets presented favorable antimicrobial activity against C. glabrata, S. mutans and S. aureus on cobalt-chromium surfaces and showed cleaning capability. However, for an appropriate biofilm control, a complementary method should be evaluated since none of the peroxide-based solutions reduced C. albicans biofilms or substantially removed aggregated biofilm.
Asunto(s)
Dentadura Parcial Removible , Staphylococcus aureus , Candida albicans , Candida glabrata , Higiene , Limpiadores de Dentadura/farmacología , Comprimidos/farmacología , Peróxidos/farmacología , BiopelículasRESUMEN
Ochratoxin A (OTA) is second only to aflatoxin in toxicity among mycotoxins. Recent studies have shown that selenomethionine (SeMet) has a protective effect on mycotoxin-induced toxicity. The purpose of this study was to investigate the protective effect and mechanism of SeMet on OTA-induced liver injury in rabbits. Sixty 35-day-old rabbits with similar body weight were randomly divided into five groups: control group, OTA group (0.2 mg/kg OTA), OTA + 0.2 mg/kg SeMet group, OTA + 0.4 mg/kg SeMet group and OTA + 0.6 mg/kg SeMet group. Rabbits were fed different doses of the SeMet diet for 21 d, and OTA was administered for one week from day 15 (the control group was provided the same dose of NaHCO3 solution). The results showed that 0.4 mg/kg SeMet could significantly improve the liver injury induced by OTA poisoning. SeMet supplementation can improve the changes in physiological blood indexes caused by OTA poisoning in rabbits and alleviate pathological damage to the rabbit liver. SeMet also increased the activities of SOD, GSH-Px and T-AOC and significantly decreased the contents of ROS, MDA, IL-1ß, IL-6 and TNF-α, effectively alleviating the oxidative stress and inflammatory response caused by OTA poisoning. In addition, OTA poisoning inhibits Nrf2 and HO-1 levels, ultimately leading to peroxide reaction, while SeMet activates the Nrf2 signaling pathway and enhances the expression of the HO-1 downstream Nrf2 gene. These results suggest that Se protects the liver from OTA-induced hepatotoxicity by regulating Nrf2/HO-1 expression.
Asunto(s)
Aflatoxinas , Ocratoxinas , Aflatoxinas/metabolismo , Animales , Antioxidantes/farmacología , Interleucina-6/metabolismo , Hígado/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Ocratoxinas/metabolismo , Estrés Oxidativo , Peróxidos/metabolismo , Peróxidos/farmacología , Conejos , Especies Reactivas de Oxígeno/metabolismo , Selenometionina/farmacología , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Chemodynamic therapy (CDT) is a promising hydroxyl radical (â¢OH)-mediated tumor therapeutic method with desirable tumor specificity and minimal side effects. However, the efficiency of CDT is restricted by the pH condition, insufficient H2O2 level, and overexpressed reductive glutathione (GSH), making it challenging to solve these problems simultaneously to improve the efficacy of CDT. Herein, a kind of polyvinylpyrrolidone-stabilized, sorafenib-loaded copper peroxide (CuO2-PVP-SRF) nanoparticle (NPs) was designed and developed for enhanced CDT against tumor cells through the synergetic pH-independent Fenton-like, H2O2 self-supplying, and GSH depletion strategy. The prepared CuO2-PVP-SRF NPs can be uptaken by 4T1 cells to specifically release Cu2+, H2O2, and SRF under acidic conditions. The intracellular GSH can be depleted by SRF-induced system xc- dysfunction and Cu2+-participated redox reaction, causing the inactivation of GPX4 and generating Cu+. A great amount of â¢OH was produced in this reducing capacity-disrupted condition by the Cu+-mediated Fenton-like reaction, causing cell apoptosis and lipid hydroperoxide accumulation-induced ferroptosis. They display an excellent 4T1 cell killing outcome through the improved â¢OH production capacity. The CuO2-PVP-SRF NPs display elevated therapeutic efficiency of CDT and show good promise in further tumor treatment applications.
Asunto(s)
Nanopartículas , Neoplasias , Línea Celular Tumoral , Cobre/farmacología , Glutatión , Humanos , Peróxido de Hidrógeno , Radical Hidroxilo , Peróxidos Lipídicos/farmacología , Neoplasias/tratamiento farmacológico , Oxidación-Reducción , Peróxidos/farmacología , Peróxidos/uso terapéutico , Povidona , Sorafenib/farmacología , Microambiente TumoralRESUMEN
Marsh rosemary (Ledum palustre, Ericaceae) has been widely used in the traditional medicine of various regions worldwide, and as insect repellent. Little is known on its essential oil insecticidal potential. This study explored the insecticidal effects of the essential oil obtained from L. palustre growing in Poland on selected insect pests and vectors. GC-MS analysis evidenced an uncommon chemotype characterized by ascaridole (35.3% as sum of cis-ascaridole and isoascaridole) and p-cymene (25.5%). The essential oil was effective against Culex quinquefasciatus, Spodoptera littoralis and Musca domestica, showing LC50/LD50 of 66.6 mg L-1, 117.2 µg larva-1 and 61.4 µg adult-1, respectively. It was not toxic to non-target Eisenia fetida earthworms and moderately toxic to Daphnia magna microcrustaceans, over the positive control α-cypermethrin. The essential oil cytotoxicity on human keratinocytes and fibroblasts showed high IC50 values (71.3 and 84.4 µg mL-1, respectively). Comet assay data highlighted no DNA damages. Based on our findings, this essential oil, characterized by the ascaridole/p-cymene chemotype, could be a candidate for the formulation of botanical insecticides; large-scale production of green insecticides by this rare species may be assured by ex situ cultivation and biotechnological techniques.
Asunto(s)
Monoterpenos Ciclohexánicos/farmacología , Insecticidas/farmacología , Aceites Volátiles/farmacología , Peróxidos/farmacología , Rosmarinus/química , Animales , Línea Celular , Ensayo Cometa , Culex/efectos de los fármacos , Culicidae/efectos de los fármacos , Monoterpenos Ciclohexánicos/análisis , Cimenos/análisis , Cimenos/farmacología , Daphnia/efectos de los fármacos , Moscas Domésticas/efectos de los fármacos , Humanos , Repelentes de Insectos/análisis , Repelentes de Insectos/farmacología , Insecticidas/análisis , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Larva/efectos de los fármacos , Mosquitos Vectores/efectos de los fármacos , Mariposas Nocturnas/efectos de los fármacos , Aceites Volátiles/análisis , Oligoquetos/efectos de los fármacos , Peróxidos/análisis , Polonia , Piretrinas/análisis , Piretrinas/farmacología , Spodoptera/efectos de los fármacosRESUMEN
The antileishmanial activity of the essential oil (EO) from Chenopodium ambrosioides L. has been demonstrated in vitro and in animal models, attributed to the major components of the EO. This study focused on the effects of the three major EO compounds carvacrol, caryophyllene oxide (Caryo), and the antileishmanial endoperoxide ascaridole (Asc) on mitochondrial functions in Leishmania tarentolae promastigotes (LtP). EO and Caryo were able to partially inhibit the leishmanial electron transport chain, whereas other components failed to demonstrate a direct immediate effect. Caryo demonstrated inhibition of complex III activity in LtP and in isolated complex III from other species. The formation of superoxide radicals was studied in Leishmania by electron spin resonance spectroscopy in the presence of iron chelators wherein selected compounds failed to trigger a significant immediate additional superoxide production in LtP. However, upon prolonged incubation of Leishmania with Asc and especially in the absence of iron chelators (allowing the activation of Asc), an increased superoxide radical production and significant impairment of mitochondrial coupling in Leishmania was observed. Prolonged incubation with all EO components resulted in thiol depletion. Taken together, the major components of EO mediate their leishmanicidal activity via different mitochondrial targets and time profiles. Further studies are required to elucidate possible synergistic effects of carvacrol and Asc and the influence of minor compounds.
Asunto(s)
Chenopodium ambrosioides/química , Leishmania/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Aceites Volátiles/farmacología , Animales , Antiprotozoarios/farmacología , Bovinos , Monoterpenos Ciclohexánicos , Cimenos , Monoterpenos/farmacología , Peróxidos/farmacología , Sesquiterpenos Policíclicos , Saccharomyces cerevisiae , Sesquiterpenos/farmacología , SuperóxidosRESUMEN
Culex quinquefasciatus (Say, 1823), known as the domestic mosquito, is a common and abundant species throughout the world, and a cosmopolitan species. The adults of this mosquito are important in terms of public and animal health since they display adaptability to different hosts. In humans, they are responsible for the transmission of various diseases. One manner of control of this vector is the use of insecticidal or larvicidal products, which may have the drawback of toxicity to mammals and can be harmful to the environment. The present work evaluated the larvicidal potential of the essential oil (EO) and ascaridole-enriched fraction (EF4-5) obtained from the leaves of Peumus boldus Molina (boldo). The EO, obtained by steam distillation, was analyzed by GC/MS and fractionated on silica gel. EO and EF4-5, containing 31.4% and 89.5% ascaridole, respectively, were evaluated against C. quinquefasciatus at concentrations of 100, 50 and 25 µg/ml on the third and fourth instars. They showed lethal concentrations (LC50) of 82.14 and 41.85 µg/ml, respectively. Larvae treated with the EF4-5 showed morphological changes in the midgut, with cells possessing a cytoplasm that contained small vacuole-like structures, as well as a nucleus with decondensed chromatin and a cell apex with a short brush border. The cells of the fat body showed larger protein granules, which were acidophilic relative to the larvae of the control group. Moreover, the enriched fraction at a dose of 50 µg/ml showed a residual larvicidal effect according to exposure time on C. quinquefasciatus. This residual effect deserves consideration, since a long-term larvicidal product may be a useful tool for vector control.
Asunto(s)
Culex/efectos de los fármacos , Monoterpenos/química , Aceites Volátiles/farmacología , Peróxidos/química , Peumus/química , Animales , Monoterpenos Ciclohexánicos , Cromatografía de Gases y Espectrometría de Masas , Larva/efectos de los fármacos , Dosificación Letal Mediana , Espectroscopía de Resonancia Magnética , Monoterpenos/farmacología , Aceites Volátiles/química , Peróxidos/farmacología , Extractos Vegetales/farmacología , Hojas de la Planta/químicaRESUMEN
OBJECTIVES: The aims of the study are to prepare novel stain removal gel-based formulations containing papain or bromelain and to investigate their stain removal effect when applied to enamel. MATERIALS AND METHODS: Experimental bromelain- and papain-based stain removal gels were prepared. Next, enamel/dentin tooth samples (6 × 6 mm2, 4 mm in thickness) were obtained from bovine teeth, stained in coffee solution for 1 week, and measured with a digital spectrophotometer (Easyshade, Vita Zahnfabrik) for color assessment (baseline). The samples were then randomly allocated into four groups (n = 7), according to the stain removal agent applied: ContrastPM+ (Discus Dental, LLC), which is based on 20 wt.% carbamide peroxide (positive control); bromelain-based; papain-based; and no agent (negative control). The materials were applied once a week, three times per day, during 4 weeks, and following the directions of use from positive control. The samples were measured again with the Easyshade and using the CIEL * a * b * color system. The color change (ΔE *) results were obtained by subtracting the baseline values from the final color values obtained at each time point. The data were statistically analyzed using two-way repeated-measures analysis of variance and Student Newman Keuls's test as a post hoc test (α = 5 %). RESULTS: All stain removal agents produced greater color change than the negative control (p < .001), with the positive control demonstrating greater ΔE * values when compared to the experimental gels (p ≤ .004). The second application of all gels resulted in greater ΔE * values compared to the first application (p ≤ .025), although no color change was observed after the third application (p ≥ .051), regardless of the material evaluated. CLINICAL SIGNIFICANCE: The proposed gels containing proteolytic enzymes (bromelain or papain) of vegetal origin may hold significant clinical potential as active agents for the preparation of stain removal agents free of hydrogen/carbamide peroxide.
Asunto(s)
Bromelaínas/farmacología , Esmalte Dental/efectos de los fármacos , Papaína/farmacología , Peróxidos/farmacología , Extractos Vegetales/farmacología , Blanqueadores Dentales/farmacología , Decoloración de Dientes/tratamiento farmacológico , Urea/análogos & derivados , Animales , Peróxido de Carbamida , Bovinos , Geles , Distribución Aleatoria , Resultado del Tratamiento , Urea/farmacologíaRESUMEN
Vibrio parahaemolyticus is a common marine food-borne enteropathogen. In this study, we examined the antioxidative activity, growth, biofilm formation, and cell mobility of an oxyR deletion mutant and its genetically complementary strain of V. parahaemolyticus. oxyR is the regulator of catalase and ahpC genes. Protection against extrinsic H2O2 and against the organic peroxides cumene hydroperoxide and tert-butyl hydroperoxide was weaker in the deletion mutant than in its parent strain. Expression of the major functional antioxidative genes, ahpC1 and VPA1418, was markedly decreased in the oxyR mutant. Growth of this mutant on agar medium was significantly inhibited by autoclaved 0.25% glucose and by 0.25% dipotassium hydrogen phosphate, 0.5% monosaccharides (glucose, galactose, xylose, and arabinose), or 114.8 mM phosphates. The inhibition of the growth of this oxyR mutant by extrinsic peroxides, autoclaved sugars, and phosphates was eliminated by the complementary oxyR gene or by the addition of catalase to the autoclaved medium, while no inhibition of growth was observed when filter-sterilized sugars were used. The formation of biofilm and swimming mobility were significantly inhibited in the oxyR mutant relative to that in the wild-type strain. This investigation demonstrates the antioxidative function of oxyR in V. parahaemolyticus and its possible roles in biofilm formation, cell mobility, and the protection of growth in heated rich medium.
Asunto(s)
Proteínas Bacterianas/metabolismo , Biopelículas/crecimiento & desarrollo , Factores de Transcripción/metabolismo , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/fisiología , Proteínas Bacterianas/genética , Derivados del Benceno/farmacología , Biopelículas/efectos de los fármacos , Catalasa/metabolismo , Medios de Cultivo/química , Regulación Bacteriana de la Expresión Génica , Prueba de Complementación Genética , Glucosa/farmacología , Peróxido de Hidrógeno , Monosacáridos/farmacología , Peróxidos/farmacología , Fosfatos/farmacología , Eliminación de Secuencia , Factores de Transcripción/genética , Vibriosis/microbiología , Vibrio parahaemolyticus/efectos de los fármacos , Vibrio parahaemolyticus/crecimiento & desarrollo , terc-Butilhidroperóxido/farmacologíaRESUMEN
The chronicity of osteoarthritis (OA), characterized by pain and inflammation in the joints, is linked to a glutamate receptor, N-methyl-D-aspartate (NMDA). The use of plant species such as Chenopodium ambrosioides L. (Amaranthaceae) as NMDA antagonists offers a promising perspective. This work aims to analyze the antinociceptive and anti-inflammatory responses of the crude hydroalcoholic extract (HCE) of C. ambrosioides leaves in an experimental OA model. Wistar rats were separated into six groups (n = 24): clean (C), negative control (CTL-), positive control (CTL+), HCE0.5, HCE5 and HCE50. The first group received no intervention. The other groups received an intra-articular injection of sodium monoiodoacetate (MIA) (8 mg/kg) on day 0. After six hours, they were orally treated with saline, Maxicam plus (meloxicam + chondroitin sulfate) and HCE at doses of 0.5 mg/kg, 5 mg/kg and 50 mg/kg, respectively. After three, seven and ten days, clinical evaluations were performed (knee diameter, mechanical allodynia, mechanical hyperalgesia and motor activity). On the tenth day, after euthanasia, synovial fluid and draining lymph node were collected for cellular quantification, and cartilage was collected for histopathological analysis. Finally, molecular docking was performed to evaluate the compatibility of ascaridole, a monoterpene found in HCE, with the NMDA receptor. After the third day, HCE reduced knee edema. HCE5 showed less cellular infiltrate in the cartilage and synovium and lower intensities of allodynia from the third day and of hyperalgesia from the seventh day up to the last treatment day. The HCE5 and HCE50 groups improved in forced walking. In relation to molecular docking, ascaridole showed NMDA receptor binding affinity. C. ambrosioides HCE was effective in the treatment of OA because it reduced synovial inflammation and behavioral changes due to pain. This effect may be related to the antagonistic effect of ascaridole on the NMDA receptor.
Asunto(s)
Chenopodium ambrosioides/química , Osteoartritis/tratamiento farmacológico , Dolor/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Analgésicos/administración & dosificación , Analgésicos/farmacología , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Monoterpenos Ciclohexánicos , Modelos Animales de Enfermedad , Simulación del Acoplamiento Molecular , Monoterpenos/administración & dosificación , Monoterpenos/química , Monoterpenos/farmacología , Dolor/etiología , Peróxidos/administración & dosificación , Peróxidos/química , Peróxidos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Ratas , Ratas Wistar , Líquido Sinovial/efectos de los fármacos , Resultado del TratamientoRESUMEN
Avian influenza outbreaks have occurred during winter months, and effective disinfection of poultry premises at freezing temperatures is needed. The commercial disinfectants Virkon and Accel, supplemented with an antifreeze agent [propylene glycol (PG), methanol (MeOH), or calcium chloride (CaCl2)], were evaluated for their effectiveness in killing avian influenza virus (AIV) at -20°C or 21°C. An AIV suspension was applied to stainless steel disks, air-dried, and covered with a disinfectant or antifreeze agent for 5 to 30 min. Virkon (2%) and Accel (6.25%) with 30% PG, 20% MeOH, or 20% CaCl2 inactivated 6 log10 AIV within 5 min at -20°C and 21°C. At these temperatures PG and MeOH alone did not kill AIV, but the 20% CaCl2 solution alone inactivated 5 log10 AIV within 10 min. The results suggested that CaCl2 is potentially useful to enhance the effectiveness of disinfection of poultry facilities after outbreaks of AIV infection in warm and cold seasons.
Les poussées de cas d'influenza aviaire se sont produites durant les mois d'hiver, et une désinfection efficace des sites d'élevage à des températures de congélation est nécessaire. Les désinfectants commerciaux Virkon et Accel, auxquels on ajouta un antigel [propylène glycol (PG), méthanol (MeOH), ou chlorure de calcium (CaCl2)], furent évalués pour leur efficacité à tuer le virus de l'influenza aviaire (VIA) à −20 °C ou 21 °C. Une suspension de VIA fut appliquée à des disques d'acier inoxydable, séchés à l'air, et recouverts avec un désinfectant ou d'antigel pour une durée de 5 à 30 minutes. Le Virkon (2 %) et l'Accel (6,25 %) avec 30 % PG, 20 MeOH, ou 20 % CaCl2 ont inactivé 6 log10 de VIA en-dedans de 5 min à −20 °C et 21 °C. À ces températures le PG et le MeOH seuls n'ont pas réussi à tuer le VIA, mais la solution de CaCl2 à 20 % seule a inactivé 5 log10 de VIA en-dedans de 10 min. Les résultats suggèrent que le CaCl2 est potentiellement utile pour augmenter l'efficacité de la désinfection des exploitations avicoles suite à des poussées de cas d'infection par le VIA en saison chaude ou froide.(Traduit par Docteur Serge Messier).
Asunto(s)
Desinfectantes/farmacología , Congelación , Peróxido de Hidrógeno/farmacología , Virus de la Influenza A/efectos de los fármacos , Peróxidos/farmacología , Ácidos Sulfúricos/farmacología , Animales , Cloruro de Calcio , Embrión de Pollo , Vivienda para Animales , Metanol , Propilenglicol , Inactivación de Virus/efectos de los fármacosRESUMEN
The antimalarial activity of peroxides most likely originates from their interaction with iron(II) species located inside the malaria parasite, which forms destructive radical species through a Fenton-like mechanism. This article reports the first evaluation of the in vitro antimalarial activity of three peroxides of the class 1,2-dioxetanes against Plasmodium falciparum; the results reveal that the studied 3-methoxy-1,2-dioxetanes display significant antimalarial activity, at a similar level as artemisinin and also that their reactivity toward iron(II) correlate linearly with their antimalarial activity.
Asunto(s)
Antimaláricos/química , Antimaláricos/farmacología , Peróxidos/química , Peróxidos/farmacología , Plasmodium falciparum/efectos de los fármacos , Animales , Artemisininas/farmacología , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Eritrocitos/efectos de los fármacos , Eritrocitos/parasitología , Hemólisis/efectos de los fármacos , Humanos , Técnicas In Vitro , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/parasitología , Plasmodium falciparum/crecimiento & desarrollo , Plasmodium falciparum/patogenicidadRESUMEN
UNLABELLED: Chenopodium ambrosioides have been used during centuries by native people to treat parasitic diseases. AIMS OF THE STUDY: To compare the in vivo anti-leishmanial activity of the essential oil (EO) from C. ambrosioides and its major components (ascaridole, carvacrol and caryophyllene oxide). MATERIALS AND METHODS: Anti-leishmanial effect was evaluated in BALB/c mice infected with Leishmania amazonensis and treated with the EO, main compounds and artificial mix of pure components by intralesional route at 30 mg/kg every 4 days during 14 days. Diseases progression and parasite burden in infected tissues were determined. RESULTS: EO prevented lesion development compared (p<0.05) with untreated animals and treated with vehicle. In addition, the efficacy of EO was also statistically superior (p<0.05) compared with the glucantime-treated animals. No potential effects were observed with pure components treatment. Mix of pure compounds cause death of animals after 3 days of treatment. CONCLUSIONS: Our results demonstrate the superiority of EO against experimental cutaneous leishmaniasis caused by L. amazonensis.
Asunto(s)
Antiprotozoarios/farmacología , Chenopodium ambrosioides/química , Leishmania/efectos de los fármacos , Leishmaniasis Cutánea/tratamiento farmacológico , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Animales , Antiprotozoarios/química , Antiprotozoarios/aislamiento & purificación , Monoterpenos Ciclohexánicos , Cimenos , Femenino , Inyecciones Intralesiones , Meglumina/farmacología , Antimoniato de Meglumina , Ratones , Ratones Endogámicos BALB C , Monoterpenos/química , Monoterpenos/aislamiento & purificación , Monoterpenos/farmacología , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificación , Compuestos Organometálicos/farmacología , Peróxidos/química , Peróxidos/aislamiento & purificación , Peróxidos/farmacología , Aceites de Plantas/química , Aceites de Plantas/aislamiento & purificación , Sesquiterpenos Policíclicos , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacologíaRESUMEN
Selenium (Se) supplementation was tested in a group of healthy men from Auckland, New Zealnd with selenized yeast (Selplex, 200 µg/day) as the supplementation mode. A set of biomarkers, including DNA damage levels and seleno-antioxidant enzyme levels, were evaluated at pre- and postsupplementation time points. Supplementation produced significant increases in serum Se levels, red blood cell (RBC) thioredoxin reductase (TR) activity and peroxide-induced DNA damage, when the mean baseline serum Se level was 110 ng/ml. Those with higher baseline serum Se levels gained less serum Se and showed a significant reduction of RBC glutathione peroxidase (GPx) activity by supplementation. The optimum benefits of supplementation on DNA stability are observed when the serum Se level reaches between >120 and <160 ng/ml. However, the most significant observation was that those with highest baseline DNA damage benefit the most from Se supplementation, whereas those having lower baseline DNA damage are disadvantaged. A dose of 200 µg/day selenized yeast was also shown to be a safer supplementation option compared to a similar dose of selenomethionine (SeMet). This study highlights the requirement for prestratification of a population by standing serum Se level and baseline DNA damage level, before any Se supplementation is carried out.
Asunto(s)
Suplementos Dietéticos , Selenio/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , ADN/sangre , ADN/efectos de los fármacos , Daño del ADN , Glutatión Peroxidasa/sangre , Humanos , Masculino , Persona de Mediana Edad , Nueva Zelanda , Peróxidos/farmacología , Selenio/sangre , Telomerasa/sangre , LevadurasRESUMEN
Although antischistosomal properties of peroxides were studied in recent years, systematic structure-activity relationships have not been conducted. We evaluated the antischistosomal potential of 64 peroxides belonging to bridged 1,2,4,5-tetraoxanes, alphaperoxides, and tricyclic monoperoxides. Thirty-nine compounds presented IC50 values <15 µM on newly transformed schistosomula. Active drugs featured phenyl-, adamantane-, or alkyl residues at the methylene bridge. Lower susceptibility was documented on adult schistosomes, with most hit compounds being tricyclic monoperoxides (IC50: 7.7-13.4 µM). A bridged 1,2,4,5-tetraoxane characterized by an adamantane residue showed the highest activity (IC50: 0.3 µM) on adult Schistosoma mansoni . Studies with hemin and heme supplemented medium indicated that antischistosomal activation of peroxides is not necessarily triggered by iron porphyrins. Two compounds (tricyclic monoperoxide; bridged 1,2,4,5-tetraoxane) revealed high worm burden reductions in the chronic (WBR: 75.4-82.8%) but only moderate activity in the juvenile (WBR: 18.9-43.1%) S. mansoni mouse model. Our results might serve as starting point for the preparation and evaluation of related derivatives.
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Compuestos Bicíclicos Heterocíclicos con Puentes/química , Compuestos Heterocíclicos con 3 Anillos/química , Peróxidos/química , Esquistosomicidas/química , Tetraoxanos/química , Animales , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Enfermedad Crónica , Femenino , Hemo/metabolismo , Hemina/metabolismo , Compuestos Heterocíclicos con 3 Anillos/farmacología , Ensayos Analíticos de Alto Rendimiento , Ratones , Peróxidos/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/parasitología , Esquistosomicidas/farmacología , Relación Estructura-Actividad , Tetraoxanos/farmacologíaRESUMEN
BACKGROUND: Because the effects of dental bleaching on enamel needs to be clarified in vivo, the authors conducted a study to determine calcium and phosphorus concentrations in enamel after the application of different bleaching treatments. METHODS: The authors applied four agents (10 percent and 20 percent carbamide peroxide [both recommended for home use], 38 percent and 35 percent hydrogen peroxide [both applied in the dental office]) to the enamel of 80 participants, who were divided into four groups of 20. The authors collected enamel microbiopsy specimens from incisors before (baseline), during (seven, 14 and 21 days) and after (seven and 14 days) the bleaching treatments. They analyzed calcium and phosphorus concentrations by using a spectrophotometer. RESULTS: The authors analyzed data by using the Friedman test and the Kruskal-Wallis test, followed by the Dunn test (α= .05). There were no statistical differences between the evaluation results, regardless of which bleaching gel was used, for determining the concentration of either calcium or phosphorus. CONCLUSIONS: Home-use and in-office bleaching gels did not alter the concentrations of calcium and phosphorus concentrations on the enamel surface in vivo. CLINICAL IMPLICATIONS: In vivo, different dental bleaching techniques did not alter the inorganic composition of enamel.
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Calcio/análisis , Esmalte Dental/química , Fósforo/análisis , Blanqueadores Dentales/farmacología , Blanqueamiento de Dientes , Adolescente , Adulto , Peróxido de Carbamida , Esmalte Dental/efectos de los fármacos , Femenino , Dureza/efectos de los fármacos , Humanos , Peróxido de Hidrógeno/farmacología , Masculino , Peróxidos/farmacología , Espectrofotometría , Estadísticas no Paramétricas , Propiedades de Superficie/efectos de los fármacos , Blanqueamiento de Dientes/métodos , Urea/análogos & derivados , Urea/farmacología , Adulto JovenRESUMEN
Re-investigation of the methanolic extract of the sponge Diacarnus megaspinorhabdosa afforded one new norsesterpene cyclic peroxide diacarperoxide S (2), in addition to two known compounds sigmosceptrellin B (1) and nebularine (3). The structures of the isolated compounds were established on the basis of one and two dimensional NMR spectroscopic studies (1H, 13C, DEPT, COSY, HMQC, HMBC, and ROESY) as well as on mass spectral analysis. The isolated compounds were evaluated for their cytotoxic as well as antimicrobial activities.
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Peróxidos/aislamiento & purificación , Poríferos/metabolismo , Terpenos/aislamiento & purificación , Animales , Bacterias/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Peróxidos/química , Peróxidos/farmacología , Terpenos/química , Terpenos/farmacologíaRESUMEN
In the present work we describe the structure and anti-inflammatory activity of a new compound, kramecyne, isolated from a methanol extract of Krameria cytisoides (Krameriaceae). The structure of kramecyne was determined by IR, NMR, MS, and elemental analysis, which indicated that the structure corresponded to a hexamer of cyclic peroxide monomers. This compound exhibited good anti-inflammatory activity in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema (51.8 ± 6.9% inhibition) and carrageenan-induced rat paw edema models at doses of 50 mg/kg. The compound significantly reduced edema to 63.1% after 1.0 h, and the effect was unchanged for 5 h. Kramecyne did not present acute toxicity, even at doses of 5,000 mg/kg.
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Antiinflamatorios/química , Antiinflamatorios/farmacología , Éteres Cíclicos/química , Éteres Cíclicos/farmacología , Krameriaceae/química , Peróxidos/química , Peróxidos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Animales , Edema/inducido químicamente , Edema/tratamiento farmacológico , Masculino , Ratones , Ratas , Ratas Wistar , Relación Estructura-ActividadRESUMEN
Pathologic processes in glaucoma include increased apoptosis, accumulation of extracellular material in the trabecular meshwork and optic nerve, condensations of the cytoskeleton and precocious cellular senescence. Oxidative stress was shown to generate these alterations in primary ocular cells. Fatty acids omega-3 and -6 are alleged to constitute a prophylaxis against these deleterious effects. Here, we tested actual preventive effects omega-3 and -6 against peroxide induced stress responses in primary human trabecular meshwork cells. Changes of mitochondrial activity, proliferation, heat shock proteins, extracellular matrix components, and inflammatory markers were evaluated. Alterations of the cytoskeleton were evaluated by phalloidin labeling. Here we report a repressive effect of omega-6 on metabolic activity and proliferation, which was not detected for omega-3. Both agents were able to prevent the anti-proliferative effect of H2O2, but only omega-3 prevented metabolic repression. Expression of heat shock protein 27 was unaltered by both fatty acids, whereas heat shock protein 90 was significantly induced by both. Omega-6 increased fibronectin and connective tissue growth factor synthesis, as well as the amount of secreted fibronectin. Omega-3, instead, induced plasminogen activator inhibitor 1 synthesis. H2O2 further increased fibronectin production in omega-6 supplemented cells, which was not the case in omega-3 treated cells. H2O2 stimulation of plasminogen activator inhibitor 1 and connective tissue growth factor was repressed by both fatty acids. Both fatty acids appeared to abolish H2O2 mediated stimulation of nuclear factor κB and IL-6, but not IL-1α and IL-8. H2O2 induced formation of cross-linked actin networks and stress fibers, which was reduced by preemptive application of omega-3. Omega-6, in contrast, had no protective effect on that, and even seemed to promote condensation. Based on the observed side effects of omega-6, omega-3 appears to be the more beneficial fatty acid in respect of prophylactic intake for prevention of a glaucomatous disease.
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Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/farmacología , Glaucoma/prevención & control , Estrés Oxidativo/efectos de los fármacos , Malla Trabecular/efectos de los fármacos , Actinas/metabolismo , Células Cultivadas , Humanos , Peróxidos/farmacología , Malla Trabecular/citología , Malla Trabecular/metabolismoRESUMEN
BACKGROUND: This study evaluated the impact of bleaching teeth using blends of a CPP-ACP paste (MI Paste; MI) and carbamide/hydrogen peroxides in different proportions on surface properties of bleached enamel. METHODS: Ninety bovine incisors were bleached with 7.5% hydrogen peroxide (HP), 16% carbamide peroxide (CP), MI and blends of HP or CP:MI at three proportions (1:1, 2:1, 1:2). Hardness and roughness were measured at baseline and after bleaching. Enamel morphology was evaluated by Scanning Electron Microscopy (SEM). The data were analyzed by two-way ANOVA for repeated measurements and Tukey's test. RESULTS: Most of the samples bleached with MI in combination with peroxides presented increased hardness and roughness which were associated to mineral deposition, as observed by SEM images. Blends with higher fractions of MI did not offer superior benefits. CONCLUSIONS: The use of a CPP-ACP paste mixed to carbamide/hydrogen peroxides can decrease adverse side-effects from tooth bleaching on an enamel surface.