geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard


, : Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard. Toxicology and Applied Pharmacology 280(2): 236-244

Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal-epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure.

US$19.90

PMID: 25127551

DOI: 10.1016/j.taap.2014.07.016


Other references

Mundy-Castle, A.C., 1970: Epilepsy and the electroencephalogram in Ghana. African Journal of Medical Sciences 1(2): 221-236

Hirano, N.; Koppers, A.A.P.; Takahashi, A.; Fujiwara, T.; Nakanishi, M., 2008: Bathymetry of seamounts, knolls and petit spot monogenetic volcanoes. Japan Geoscience Union Meeting

Fisher, A., 1985: International development: coordination is the key. Agrologist 14(4): 16-17

Ozdemir, M.; Demirkesen, C.; Arzuhal, N.; Tüzün, Yçýn., 2002: Mucin-poor follicular mycosis fungoides. International Journal of Dermatology 41(2): 112-114

Sonathi, V.; Hatzikou, M.; Baldwin, M.; Panitti, E.; Tzortzaki, E., 2014: Economic Evaluation of Omalizumab Compared With Standard Therapy in the Treatment of Severe Allergic Asthma in Adult Patients in Greece: a Cost Effectiveness Analysis Based on Clinical Trial and Real-World Data. Value in Health 17(7): A597-A598

Davidai, S.; Gilovich, T., 2017: The Ideal Road Not Taken: The Self-Discrepancies Involved in People's Most Enduring Regrets. Research on the structural features of people's most enduring regrets has focused on whether they result from having acted or having failed to act. Here we focus on a different structural feature, their connection to a person's self-conc...

Evangelista, E.A.; Kaspera, Rüdiger.; Mokadam, N.A.; Jones, J.P.; Totah, R.A., 2014: Activity, inhibition, and induction of cytochrome P450 2J2 in adult human primary cardiomyocytes. Cytochrome P450 2J2 plays a significant role in the epoxidation of arachidonic acid to signaling molecules important in cardiovascular events. CYP2J2 also contributes to drug metabolism and is responsible for the intestinal clearance of ebastine....

Hart, J.; Brunt, E.M.; Fain, J.S.; Goldstein, N.S.; Kuan, S.F.; Lones, M.L., 1998: Reproducibility of the Banff schema for grading acute liver allograft rejection. Laboratory Investigation 78(1): 152A, Jan

Cetin Y.; Grube D., 1991: Topology of chromogranins in secretory granules of endocrine cells. Chromogranins A and B are glycoproteins originally detected in the adrenal medulla. These proteins are also presented in a variety of neuroendocrine cells. The subcellular distribution of the chromogranins, and particularly their intra-granular to...

Gebo, K.A.; Fleishman, J.A.; Reilly, E.D.; Moore, R.D., 2005: High rates of primary Mycobacterium avium complex and Pneumocystis jiroveci prophylaxis in the United States. National data from the mid-1990s demonstrated that many eligible patients with HIV infection do not receive prophylaxis for opportunistic infections (OIs) and that racial and gender disparities existed in OI prophylaxis receipt. We examined whethe...