Browsing by Subject "TRPA1"

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  • Bousquet, Jean; Le Moing, Vincent; Blain, Hubert; Czarlewski, Wienczyslawa; Zuberbier, Torsten; Torre, Raphael de la; Lozano, Nieves Pizarro; Reynes, Jacques; Bedbrook, Anna; Cristol, Jean-Paul; Cruz, Alvaro A.; Fiocchi, Alessandro; Haahtela, Tari; Iaccarino, Guido; Klimek, Ludger; Kuna, Piotr; Melén, Erik; Mullol, Joaquim; Samolinski, Boleslaw; Valiulis, Arunas; Anto, Josep M. (2021)
    COVID-19 is described in a clinical case involving a patient who proposed the hypothesis that Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-interacting nutrients may help to prevent severe COVID-19 symptoms. Capsules of broccoli seeds containing glucoraphanin were being taken before the onset of SARS-CoV-2 infection and were continued daily for over a month after the first COVID-19 symptoms. They were found to reduce many of the symptoms rapidly and for a duration of 6-12 h by repeated dosing. When the patient was stable but still suffering from cough and nasal obstruction when not taking the broccoli capsules, a double-blind induced cough challenge confirmed the speed of onset of the capsules (less than 10 min). A second clinical case with lower broccoli doses carried out during the cytokine storm confirmed the clinical benefits already observed. A third clinical case showed similar effects at the onset of symptoms. In the first clinical trial, we used a dose of under 600 mmol per day of glucoraphanin. However, such a high dose may induce pharmacologic effects that require careful examination before the performance of any study. It is likely that the fast onset of action is mediated through the TRPA1 channel. These experimental clinical cases represent a proof-of-concept confirming the hypothesis that Nrf2interacting nutrients are effective in COVID-19. However, this cannot be used in practice before the availability of further safety data, and confirmation is necessary through proper trials on efficacy and safety.
  • Albayrak, Ilyas (Helsingfors universitet, 2016)
    Tutkielmassa selvitettiin mantelitumakkeen osallisuutta neuropaattisen kivun säätelyssä sekä mantelitumakkeen patologisten muutosten aiheuttamaa laskevien kipua muuntelevien ratojen herkistymistä. Tutkielman kokeellisessa osassa selvitettiin aiheuttaako neuropaattiseen kiputilaan johtava hermovaurio mantelitumakkeessa oksidatiivista stressiä sekä TRPA1-reseptorin ilmentymistä, mikä johtaisi sentraaliseen sensitisaatioon. Neuropaattisen kivun mallina käytettiin SNI-tekniikalla (spared nerve injury) operoituja rottia, joiden mantelitumakkeeseen annosteltiin TRPA1-antagonistia. Lääkeaineen vaikutusta ja kipukäyttäytymisen muutosta tutkittiin ärsyttämällä koe-eläinten operoitua raajaa monofilamenteilla ja mittaamalla PWT-käyttäytymismallin (paw withdrawal threshold) mukaisia vasteita. Oikeaan mantelitumakkeeseen annosteltu TRPA1-antagonisti vähensi mekaanista hypersensitiviteettiä SNI-rotilla, mutta ei tuottanut muutosta terveillä yksilöillä. Tulos viittaa siihen että neuropaattinen kiputila aiheuttaa mantelitumakkeessa TRPA1:n ilmentymistä, mikä osallistuu mekaanisen hypersensitiviteetin muodostumiseen.
  • Wei, Hong; Wu, Hai-Yun; Chen, Zuyue; Ma, Ai-Niu; Mao, Xiao-Fang; Li, Teng-Fei; Li, Xin-Yan; Wang, Yong-Xiang; Pertovaara, Antti (2016)
    Spinal transient receptor potential ankyrin 1 (TRPA1) channel is associated with various pain hypersensitivity conditions. Spinally, TRPA1 is expressed by central terminals of nociceptive nerve fibers and astrocytes. Among potential endogenous agonists of TRPA1 is H2O2 generated by D-amino acid oxidase (DAAO) in astrocytes. Here we studied whether prolonged block of the spinal TRPA1 or astrocytes starting at time of injury attenuates development and/or maintenance of neuropathic hypersensitivity. Additionally, TRPA1 and DAAO mRNA were determined in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH). Experiments were performed in rats with spared nerve injury (SNI) and chronic intrathecal catheter. Drugs were administered twice daily for the first seven injury days or only once seven days after injury. Mechanical hypersensitivity was assessed with monofilaments. Acute and prolonged treatment with Chembridge-5861528 (a TRPA1 antagonist), carbenoxolone (an inhibitor of activated astrocytes), or gabapentin (a comparison drug) attenuated tactile allodynia-like responses evoked by low (2 g) stimulus. However, antihypersensitivity effect of these compounds was short of significance at a high (15 g) stimulus intensity. No preemptive effects were observed. In healthy controls, carbenoxolone failed to prevent hypersensitivity induced by spinal cinnamaldehyde, a TRPA1 agonist TRPA1 and DAAO mRNA in the DRG but not SDH were slightly increased in SNI, independent of drug treatment The results indicate that prolonged peri-injury block of spinal TRPA1 or inhibition of spinal astrocyte activation attenuates maintenance but not development of mechanical (tactile allodynia-like) hypersensitivity after nerve injury. (C) 2016 Elsevier Inc. All rights reserved.
  • ARIA Grp; the ARIA group; Bousquet, Jean; Cristol, Jean-Paul; Czarlewski, Wienczyslawa; Haahtela, Tari; Erhola, Marina; Koskinen, Seppo; Kuitunen, Mikael; Strandberg, Timo; Toppila-Salmi, Sanna; Von Hertzen, Leena (2020)
    There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.