ArticleThe American journal of pathology2016
Molecular Mechanism Underlying Pathogenesis of Lewisite-Induced Cutaneous Blistering and Inflammation: Chemical Chaperones as Potential Novel Antidotes.
Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Emulsome-Based Nanocarrier System for Controlled 4-Phenylbutyric Acid Delivery and Mechanistic Mitigation of Arsenical-Induced Skin Injury via Foam Application.Pharmaceutics · 2025Article
- Current progress in research on ocular injury caused by exposure to vesicants.Progress in retinal and eye research · 2025Review
- Sustained delivery of 4-phenylbutyric acid via chitosan nanoparticles in foam for decontamination and treatment of lewisite-mediated skin injury.International journal of pharmaceutics · 2025Article
- Guardians Turned Culprits: NETosis and Its Influence on Pulmonary Fibrosis Development.Molecular biotechnology · 2025Review
- Chronic kidney disease amplifies severe kidney injury and mortality in a mouse model of skin arsenical exposure.American journal of physiology. Renal physiology · 2025Article
- Common molecular profile of multiple structurally distinct warfare arsenicals in causing cutaneous chemical vesicant injury.Scientific reports · 2025Article
- Relevance of the Platelet-activating factor system in chemical warfare agents-induced effects.Free radical biology & medicine · 2025Review
- Development of 4-phenylbutyric acid microsponge gel formulations for the treatment of lewisite-mediated skin injury.Drug delivery and translational research · 2025Article
- Inhibition of BRD4 prevents peribronchial fibrosis in mice with cutaneous lewisite exposure.Frontiers in molecular biosciences · 2025Article
- Enhancing topical delivery of ISRIB: Optimizing cream formulations with chemical enhancers and pH adjustment.International journal of pharmaceutics · 2024Article
- A Murine Model of Vesicant-Induced Acute Lung Injury.The Journal of pharmacology and experimental therapeutics · 2024Article
- HSP90, a Common Therapeutic Target for Suppressing Skin Injury Caused by Exposure to Chemically Diverse Classes of Blistering Agents.The Journal of pharmacology and experimental therapeutics · 2024Article
- Cutaneous Arsenical Exposure Induces Distinct Metabolic Transcriptional Alterations of Kidney Cells.The Journal of pharmacology and experimental therapeutics · 2024Article
- Microneedle-mediated transdermal delivery of N-acetyl cysteine as a potential antidote for lewisite injury.International journal of pharmaceutics · 2023Article
- Phenylarsine oxide induced corneal injury involves oxidative stress mediated unfolded protein response and ferroptotic cell death: Amelioration by NAC.Free radical biology & medicine · 2023Article
- Enhanced Transdermal Delivery of N-Acetylcysteine and 4-Phenylbutyric Acid for Potential Use as Antidotes to Lewisite.AAPS PharmSciTech · 2023Article
- Mechanistic understanding of the toxic effects of arsenic and warfare arsenicals on human health and environment.Cell biology and toxicology · 2023Review
- Retinal injury mouse model and pathophysiological assessment of the effect of arsenical vesicants.Experimental eye research · 2023Article
- Role of hair follicles in the pathogenesis of arsenical-induced cutaneous damage.Annals of the New York Academy of Sciences · 2022Article
- Development of BRD4 inhibitors as anti-inflammatory agents and antidotes for arsenicals.Bioorganic & medicinal chemistry letters · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Lewisite is a potent arsenic-based chemical warfare agent known to induce painful cutaneous inflammation and blistering. Only a few modestly effective antidotes have so far been described in the literature. However, the discovery of effective antidotes for lewisite was hampered by the paucity of the exact molecular mechanism underlying its cutaneous pathogenesis. We investigated the molecular mechanism underlying lewisite-induced cutaneous blistering and inflammation and describe its novel antidotes. On the basis of our initial screening, we used a highly sensitive murine model that recapitulates the known human pathogenesis of arsenicals-induced cutaneous inflammation and blistering. Topically administered lewisite induced potent acute inflammation and microvesication in the skin of Ptch1(+/-)/SKH-1 mice. Even at a very low dose, lewisite up-regulates unfolded protein response signaling, inflammatory response, and apoptosis. These cutaneous lesions were associated with production of reactive oxygen species and extensive apoptosis of the epidermal keratinocytes. We confirmed that activation of reactive oxygen species-dependent unfolded protein response signaling is the underlying molecular mechanism of skin damage. Similar alterations were noticed in lewisite-treated cultured human skin keratinocytes. We discovered that chemical chaperone 4-phenyl butyric acid and antioxidant N-acetylcysteine, which significantly attenuate lewisite-mediated skin injury, can serve as potent antidotes. These data reveal a novel molecular mechanism underlying the cutaneous pathogenesis of lewisite-induced lesions. We also identified novel potential therapeutic targets for lewisite-mediated cutaneous injury.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.