ArticleToxicology letters2015
Nitrogen mustard exposure of murine skin induces DNA damage, oxidative stress and activation of MAPK/Akt-AP1 pathway leading to induction of inflammatory and proteolytic mediators.
Article in Toxicology letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 65 citations in OpenAlex.
- Nitrogen mustard induces dynamic nuclear protein spectrum change and DNA-protein crosslinking, with p97 mediating repair.Heliyon · 2024Article
- PTEN Mediates the Silencing of Unintegrated HIV-1 DNA.Viruses · 2024Article
- Dexamethasone targets actin cytoskeleton signaling and inflammatory mediators to reverse sulfur mustard-induced toxicity in rabbit corneas.Toxicology and applied pharmacology · 2024Article
- RETRACTED: Mitigation of Nitrogen Mustard-Induced Skin Injury by theThe Journal of pharmacology and experimental therapeutics · 2024Article
- Dermal Exposure to Vesicating Nettle Agent Phosgene Oxime: Clinically Relevant Biomarkers and Skin Injury Progression in Murine Models.The Journal of pharmacology and experimental therapeutics · 2024Article
- Phenylarsine oxide induced corneal injury involves oxidative stress mediated unfolded protein response and ferroptotic cell death: Amelioration by NAC.Free radical biology & medicine · 2023Article
- Topical application of synthetic melanin promotes tissue repair.NPJ Regenerative medicine · 2023Article
- Article
- Dysregulation of the mTOR pathway by mechlorethamine.Toxicology · 2023Article
- Melatonin as Modulator for Sulfur and Nitrogen Mustard-Induced Inflammation, Oxidative Stress and DNA Damage: Molecular Therapeutics.Antioxidants (Basel, Switzerland) · 2023Review
- Therapeutic Potential of Mesenchymal Stem Cell-Secreted Factors on Delay in Corneal Wound Healing by Nitrogen Mustard.International journal of molecular sciences · 2022Article
- Nitrogen Mustard Alkylates and Cross-Links p53 in Human Keratinocytes.Chemical research in toxicology · 2022Article
- The chemistry and efficacy benefits of polysaccharides fromFrontiers in pharmacology · 2022Review
- Small-interfering RNA for c-Jun attenuates cell death by preventing JNK-dependent PARP1 cleavage and DNA fragmentation in nitrogen mustard-injured immortalized human bronchial epithelial cells.Toxicology research · 2021Article
- Vitamin D3 ameliorates nitrogen mustard-induced cutaneous inflammation by inactivating the NLRP3 inflammasome through the SIRT3-SOD2-mtROS signaling pathway.Clinical and translational medicine · 2021Article
- Targeting TRPV1-mediated autophagy attenuates nitrogen mustard-induced dermal toxicity.Signal transduction and targeted therapy · 2021Article
- Combination of ebselen and hydrocortisone substantially reduces nitrogen mustard-induced cutaneous injury.Current research in toxicology · 2021Article
- DNA damage signaling in the cellular responses to mustard vesicants.Toxicology letters · 2020Article
- Livin Regulates H2A.XFrontiers in oncology · 2019Article
- Cellular and molecular mechanisms of sulfur mustard toxicity on spermatozoa and male fertility.Toxicology research · 2018Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Our recent studies in SKH-1 hairless mice have demonstrated that topical exposure to nitrogen mustard (NM), an analog of sulfur mustard (SM), triggers the inflammatory response, microvesication and apoptotic cell death. Here, we sought to identify the mechanism/s involved in these NM-induced injury responses. Results obtained show that NM exposure of SKH-1 hairless mouse skin caused H2A.X and p53 phosphorylation and increased p53 accumulation, indicating DNA damage. In addition, NM also induced the activation of MAPKs/ERK1/2, JNK1/2 and p38 as well as that of Akt together with the activation of transcription factor AP1. Also, NM exposure induced robust expression of pro-inflammatory mediators namely cyclooxygenase 2 and inducible nitric oxide synthase and cytokine tumor necrosis factor alpha, and increased the levels of proteolytic mediator matrix metalloproteinase 9. NM exposure of skin also increased lipid peroxidation, 5,5-dimethyl-2-(8-octanoic acid)-1-pyrroline N-oxide protein adduct formation, protein and DNA oxidation indicating an elevated oxidative stress. We also found NM-induced increase in the homologous recombinant repair pathway, suggesting its involvement in the repair of NM-induced DNA damage. Collectively, these results indicate that NM induces oxidative stress, mainly a bi-phasic response in DNA damage and activation of MAPK and Akt pathways, which activate transcription factor AP1 and induce the expression of inflammatory and proteolytic mediators, contributing to the skin injury response by NM. In conclusion, this study for the first time links NM-induced mechanistic changes with our earlier reported murine skin injury lesions with NM, which could be valuable to identify potential therapeutic targets and rescue agents.
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