TRPA1: Acrolein meets its target

Achanta, Satyanarayana; Jordt, Sven‐Eric

doi:10.1016/j.taap.2017.03.007

Cited by 30 publications

(39 citation statements)

References 63 publications

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“…Furthermore, it has been demonstrated that reactive aldehydes suppress mitochondrial respiration [101], modify ion-channel conductance pathways [102], and diminish myofilament sensitivity and cardiac contraction [103]. Intriguingly, Wang et al [19] found that acrolein effectively propagates myocardial ischaemic injury and suppresses nitric oxide (NO • )-induced cardioprotection in mice by a mechanism involving attenuation of protein kinase C (PKC ) signal transduction.…”

Section: Atherosclerosis and Its Cardiovascular Disease Sequelaementioning

confidence: 99%

Potential Adverse Public Health Effects Afforded by the Ingestion of Dietary Lipid Oxidation Product Toxins: Significance of Fried Food Sources

et al. 2020

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Exposure of polyunsaturated fatty acid (PUFA)-rich culinary oils (COs) to high temperature frying practices generates high concentrations of cytotoxic and genotoxic lipid oxidation products (LOPs) via oxygen-fueled, recycling peroxidative bursts. These toxins, including aldehydes and epoxy-fatty acids, readily penetrate into fried foods and hence are available for human consumption; therefore, they may pose substantial health hazards. Although previous reports have claimed health benefits offered by the use of PUFA-laden COs for frying purposes, these may be erroneous in view of their failure to consider the negating adverse public health threats presented by food-transferable LOPs therein. When absorbed from the gastrointestinal (GI) system into the systemic circulation, such LOPs may significantly contribute to enhanced risks of chronic non-communicable diseases (NCDs), e.g. , cancer, along with cardiovascular and neurological diseases. Herein, we provide a comprehensive rationale relating to the public health threats posed by the dietary ingestion of LOPs in fried foods. We begin with an introduction to sequential lipid peroxidation processes, describing the noxious effects of LOP toxins generated therefrom. We continue to discuss GI system interactions, the metabolism and biotransformation of primary lipid hydroperoxide LOPs and their secondary products, and the toxicological properties of these agents, prior to providing a narrative on chemically-reactive, secondary aldehydic LOPs available for human ingestion. In view of a range of previous studies focused on their deleterious health effects in animal and cellular model systems, some emphasis is placed on the physiological fate of the more prevalent and toxic α,β-unsaturated aldehydes. We conclude with a description of targeted nutritional and interventional strategies, whilst highlighting the urgent and unmet clinical need for nutritional and epidemiological trials probing relationships between the incidence of NCDs, and the frequency and estimated quantities of dietary LOP intake.

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Section: Atherosclerosis and Its Cardiovascular Disease Sequelaementioning

confidence: 99%

Potential Adverse Public Health Effects Afforded by the Ingestion of Dietary Lipid Oxidation Product Toxins: Significance of Fried Food Sources

et al. 2020

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“…Recent studies show that pro-resolving agents work through G protein-coupled receptors (GPCRs), such as ALX/FPR2, GPR18 and GPR32, whereas a few other studies show that these agents work through inhibition of transient receptor potential channels (35, 42, 59-61). Achanta et al, Bessac et al, and Stenger et al, have shown the involvement of transient receptor potential ankyrin repeat 1 (TRPA1) ion channel in mediating the effects of CEES and CS tear gas agents using in vitro and in vivo studies (6, 52, 62-64). Park et al and others showed that RvD1 and RvD2 regulate TRPA1 currents in mouse DRG neurons (35, 59, 65).…”

Section: Discussionmentioning

confidence: 99%

Accelerating Inflammation Resolution to Counteract Chemical Cutaneous Injury

Achanta¹,

Chintagari

Balakrishna

et al. 2019

Preprint

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Running title: Lipid mediators mitigate chemical skin injury Abbreviations:RvD1 (Resolvin D1); RvD2 (Resolvin D2); CS (2-Chlorobenzalmalononitrile); CEES (2-chloroethylethyl-sulfide); SM (sulfur mustard); HD (sulfur mustard); MMP-9 (matrix metallo protein-9), IL-1β (Interleukin-1 beta), KC/CXCL1 (keratinocyte chemoattractant)/(chemokine (C-X-C motif) ligand 1); CXCL2 (chemokine (C-X-C motif) ligand 2); IL-6 (interleukin-6); ELISA (enzyme linked immune sorbent assay); PBS (phosphate buffer saline); MEVM (mouse ear vesicant model); i.p (intraperitoneal); i.v (intravenous); NSAIDs (nonsteroidal anti-inflammatory drugs) AbstractChemical exposure to vesicants such as sulfur mustard (SM), and electrophilic riot control agents such as 2-chlorobenzalmalononitrile (CS) tear gas agent, cause strong cutaneous inflammation. Classical antiinflammatory treatments have focused on interference with target initiation and maintenance of inflammation, with mixed outcomes. Inflammation is broadly classified into three temporal phases, initiation, amplification and maintenance, and resolution. Resolution of inflammation was thought to be a passive process but the recent body of literature shows that resolution is an active process and is mediated by fatty acid-derived mediators (specialized pro-resolving mediators, SPMs). We hypothesized that accelerating resolution phase of inflammation may attenuate the exaggerated inflammatory response following chemical threat exposure, leading to decreased morbidity and improved recovery. In this study, SPMs, such as Resolvin D1 (RvD1) and Resolvin D2 (RvD2), were administered to mice at nanogram doses post-exposure to an SM analog, 2-chloroethyl-ethyl-sulfide (CEES) or CS tear gas agent.SPMs decreased edema (ear thickness and punch biopsy weights), pro-inflammatory cytokines (IL-1β, CXCL1/KC, MIP2) and protease marker (MMP-9), and vascular leakage (determined by IRDye 800 CW PEG) while improving histopathology in cutaneous chemical injury mouse models. These results support our hypothesis and pave the way for SPMs for further development as potential medical countermeasures for chemical threat agents-induced skin injuries.A new area of inflammation research has focused on the process of inflammation resolution (29-32). Resolution of inflammation was thought to occur due to the lack of inflammatory drive when concentrations of inflammation-initiating and -maintaining mediators are removed or in decline.However, new studies show that the resolution of inflammation is an active mechanism involving the activation of signaling pathways during inflammation initiation, and the later generation of fatty-acidderived specialized pro-resolving mediators (SPMs) that activate resolution mechanisms. These mediators include resolvins, lipoxins, protectins, and maresins. Resolvins and protectins are omega-3 fatty acids derived from docosahexaenoic acid (DHA; C22:6) or eicosapentaenoic acid (EPA; C20:5),We appreciate thoughtful discussions of Drs. Conflict of interestAuthors do not have any conflicts of interes...

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“…Acrolein probably activates TRPA1 receptor via covalent binding to the TRPA1 protein that opens the cation conducting channel. This leads to neuronal depolarization and calcium ion influx into the sensory nerve endings, resulting in sensory irritation [ 27 ]. Considering the mechanism of covalent binding to TRPA1, modification of the TRPA1 protein and the resulting irritation will build up gradually over time.…”

Section: Discussionmentioning

confidence: 99%

Measures of odor and lateralization thresholds of acrolein, crotonaldehyde, and hexanal using a novel vapor delivery technique

et al. 2017

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IntroductionHumans are exposed to aldehydes in a variety of environmental situations. Aldehydes generally have a strong odor and are highly irritating to the mucous membranes. Knowledge about odor perception and especially irritation potency in humans is thus essential in risk assessment and regulation, e.g. setting occupational exposure limits. However, data on odor and irritation are lacking or limited for several aldehydes. The aim of the study was to determine the odor and lateralization thresholds of some commonly occurring aldehydes. Acrolein and crotonaldehyde where chosen as they are formed when organic material is heated or burned, e.g. during cigarette smoking. n-Hexanal was also included as it is emitted from wood pellets and fibreboard.Material and methodsTo study odor and lateralization thresholds of these aldehydes, a novel, inexpensive olfactometer was designed to enable delivery of reliable and stable test concentrations and thus valid measures of thresholds. The delivery system consists of seven syringe pumps, each connected to a Tedlar bag containing a predefined concentration of the tested aldehyde vapor. To validate the threshold measures, a test-retest was performed with a separate method, namely odor delivery via amber bottles. Twenty healthy naïve individuals were tested.ResultsThe median odor thresholds of acrolein, crotonaldehyde and hexanal were 17, 0.8, and 97 ppb, respectively. No lateralization threshold could be identified for acrolein (highest tested concentration was 2 940 ppb in 5 subjects), whereas the medians were 3 and 390 ppb for the latter two. In addition, odor thresholds for n-hexanal were also determined using two methods where similar results were obtained, suggesting that the olfactometer presentation method is valid.ConclusionWe found olfactory detection and lateralization thresholds (except for acrolein) in alliance with, or lower than, previously reported in naïve subjects. The new olfactometer allows better control of presentations timing and vapor concentration.

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TRPA1: Acrolein meets its target

Cited by 30 publications

References 63 publications

Potential Adverse Public Health Effects Afforded by the Ingestion of Dietary Lipid Oxidation Product Toxins: Significance of Fried Food Sources

Potential Adverse Public Health Effects Afforded by the Ingestion of Dietary Lipid Oxidation Product Toxins: Significance of Fried Food Sources

Accelerating Inflammation Resolution to Counteract Chemical Cutaneous Injury

Measures of odor and lateralization thresholds of acrolein, crotonaldehyde, and hexanal using a novel vapor delivery technique

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