10 research outputs found

    Hydrogen sulfide donors alleviate itch secondary to the activation of type-2 protease activated receptors (PAR-2) in mice.

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    Published onlineJOURNAL ARTICLEHydrogen sulfide (H2S) has been highlighted as an endogenous signaling molecule and we have previously found that it can inhibit histamine-mediated itching. Pruritus is the most common symptom of cutaneous diseases and anti-histamines are the usual treatment; however, anti-histamine-resistant pruritus is common in some clinical settings. In this way, the involvement of mediators other than histamine in the context of pruritus requires new therapeutic targets. Considering that the activation of proteinase-activated receptor 2 (PAR-2) is involved in pruritus both in rodents and humans, in this study we investigated the effect of H2S donors on the acute scratching behavior mediated by PAR-2 activation in mice, as well as some of the possible pharmacological mechanisms involved. The intradermal injection of the PAR-2 peptide agonist SLIGRL-NH2 (8-80nmol) caused a dose-dependent scratching that was unaffected by intraperitoneal pre-treatment with the histamine H1 antagonist pyrilamine (30mg/kg). Co-injection of SLIGRL-NH2 (40nmol) with either the slow-release H2S donor GYY4137 (1 and 3nmol) or the spontaneous donor NaHS (1 and 0.3nmol) significantly reduced pruritus. Co-treatment with the KATP channel blocker glibenclamide (200nmol) or the nitric oxide (NO) donor sodium nitroprusside (10nmol) abolished the antipruritic effects of NaHS; however, the specific soluble guanylyl cyclase inhibitor ODQ (30μg) had no significant effects. The transient receptor potential ankyrin type 1 (TRPA1) antagonist HC-030031 (20μg) significantly reduced SLIGRL-NH2-induced pruritus; however pruritus induced by the TRPA1 agonist AITC (1000nmol) was unaffected by NaHS. Based on these data, we conclude that pruritus secondary to PAR-2 activation can be reduced by H2S, which acts through KATP channel opening and involves NO in a cyclic guanosine monophosphate (cGMP)-independent manner. Furthermore, TRPA1 receptors mediate the pruritus induced by activation of PAR-2, but H2S does not interfere with this pathway. These results provide additional support for the development of new therapeutical alternatives, mainly intended for treatment of pruritus in patients unresponsive to anti-histamines.MNM and SKPC are recipients of fellowships from the National Council for Scientific and Technological Development (CNPq) and grants from the Sao Paulo Research Foundation (FAPESP). RT, MW and MEW would like to thank the Brian Ridge Scholarship for its support (RT)

    Aedes aegypti salivary gland extract alleviates acute itching by blocking TRPA1 channels

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    Aedes aegypti (Ae. aegypti) saliva induces a variety of anti-inflammatory and immunomodulatory activities. Interestingly, although it is known that mosquito bites cause allergic reactions in sensitised hosts, the primary exposure of humans to Ae. aegypti does not evoke significant itching. Whether active components in the saliva of Ae. aegypti can counteract the normal itch reaction to injury produced by a histaminergic or non-histaminergic pathway in vertebrate hosts is unknown. This study investigated the effects of Ae. aegypti mosquito salivary gland extract (SGE) on sensitive reactions such as itching and associated skin inflammation. Acute pruritus and plasma extravasation were induced in mice by the intradermal injection of either compound 48/80 (C48/80), the Mas-related G protein-coupled receptor (Mrgpr) agonist chloroquine (CQ), or the transient receptor potential ankyrin 1 (TRPA1) agonist allyl isothiocyanate (AITC). The i.d. co-injection of Ae. aegypti SGE inhibited itching, plasma extravasation, and neutrophil influx evoked by C48/80, but it did not significantly affect mast cell degranulation in situ or in vitro. Additionally, SGE partially reduced CQ- and AITC-induced pruritus in vivo, suggesting that SGE affects pruriceptive nerve firing independently of the histaminergic pathway. Activation of TRPA1 significantly increased intracellular Ca2+ in TRPA-1-transfected HEK293t lineage, which was attenuated by SGE addition. We showed for the first time that Ae. aegypti SGE exerts anti-pruriceptive effects, which are partially regulated by the histamine-independent itch TRPA1 pathway. Thus, SGE may possess bioactive molecules with therapeutic potential for treating nonhistaminergic itch

    Evaluación de la capacidad antioxidante de los compuestos fenólicos de la tuna morada (Opuntia ficus-indica) del Distrito de San Bartolomé, Huarochirí, Lima

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    TesisLIMAEscuela Profesional de Ingeniería y ArquitecturaProcesamiento, seguridad y gestión en la Industria alimentariaEl objetivo de esta investigación fue evaluar la capacidad antioxidante de los compuestos fenólicos de la tuna morada (Opuntia ficus-indica) del distrito de San Bartolomé, Huarochirí, Lima, para lo cual fueron consideradas las siguientes variables: concentración de etanol (40% y 80%) y temperatura (30%C y 60°C) en relación al contenido de fenoles totales (mg ácido gálico/L de muestra) y porcentaje de la capacidad antioxidante. El desarrollo de los experimentos se realizó según el diseño factorial 2² con 3 puntos centrales. Se caracterizó fisicoquímicamente a la tuna morada obteniendo un pH de 6.61, una acidez de 0.06 g. de ácido cítrico/100 mL muestra, 11.67°Brix y un índice de madurez de 182.86 =8.96. La cuantificación de fenoles totales fue realizada de acuerdo al método espectrofotométrico Folin-Ciocalteau y la capacidad antioxidante según Mensor et al. (2001). El mayor contenido de compuestos fenólicos fue de 1002.47 mg ácido gálico/L de muestra y con una capacidad antioxidante del 40.18% a una concentración de etanol de 80%, y a una temperatura de 60°C

    Vida en anaquel de galletas saladas utilizando pruebas aceleradas

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    El presente trabajo de investigación tuvo como objetivo estimar el tiempo de vida en anaquel de galletas de soda a través del empleo de pruebas aceleradas. Las galletas se sometieron a ambientes de almacenamiento de 35, 45 y 55 °C a 80 por ciento de humedad relativa en las tres cámaras. Se evaluaron los parámetros: humedad, actividad de agua y dureza instrumental, los cuales fueron modelados a una reacción de orden uno reportando que el tiempo de vida útil de las galletas saladas, para cada parámetro, fue de 123, 179 y 271 días, respectivamente. El tiempo de vida útil estaba predispuesto por la humedad crítica (6,38% b.h.), debido a que fue el parámetro que se vio más afectado por las condiciones de almacenamiento. Finalmente, se realizó un recuento de mohos, para evaluar la inocuidad del alimento, encontrándose que el alimento se mantuvo dentro de los límites establecidos por la NTP con valores < 10 al inicio y al final del almacenamiento

    Hydrogen sulfide: An endogenous regulator of the immune system

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