Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin

Toxicology and Applied Pharmacology
Anil K JainRajesh Agarwal

Abstract

Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as ev...Continue Reading

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Citations

May 18, 2016·Experimental and Molecular Pathology·Gabriella M CompostoDiane E Heck
Jun 22, 2016·Annals of the New York Academy of Sciences·Neera Tewari-Singh, Rajesh Agarwal
Jun 22, 2016·Annals of the New York Academy of Sciences·Dinesh G GoswamiRajesh Agarwal
Jul 8, 2016·Annals of the New York Academy of Sciences·Carl W WhiteLivia A Veress
Jul 25, 2017·Cutaneous and Ocular Toxicology·Lopa M DasKurt Q Lu
Oct 3, 2019·Critical Reviews in Toxicology·Leila EtemadMahdi Balali-Mood
Sep 7, 2018·Frontiers in Pharmacology·Alexsander R CarvalhoLuís C N da Silva
Mar 3, 2020·Experimental and Molecular Pathology·Gabriella WahlerLaurie B Joseph
Jan 26, 2021·Signal Transduction and Targeted Therapy·Mingliang ChenZhongmin Zou
Feb 6, 2020·Toxicology Letters·Joanna A RuszkiewiczAswin Mangerich

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