-
The Journal of Pharmacology and... Jan 2024Nitrogen mustard (NM) is a known surrogate of sulfur mustard, a chemical-warfare agent that causes a wide range of ocular symptoms, from a permanent reduction in visual...
Nitrogen mustard (NM) is a known surrogate of sulfur mustard, a chemical-warfare agent that causes a wide range of ocular symptoms, from a permanent reduction in visual acuity to blindness upon exposure. Although it has been proposed that the two blistering agents have a similar mechanism of toxicity, the mode of NM-induced cell death in ocular tissue has not been fully explored. Therefore, we hypothesized that direct ocular exposure to NM in mice leads to retinal tissue injury through chronic activation of the unfolded protein response (UPR) PERK arm in corneal cells and VEGF secretion, eventually causing cell death. We topically applied NM directly to mice to analyze ocular and retinal tissues at 2 weeks postexposure. A dramatic decline in retinal function, measured by scotopic and photopic electroretinogram responses, was detected in the mice. This decline was associated with enhanced TUNEL staining in both corneal and retinal tissues. In addition, exposure of corneal cells to NM revealed 228 differentially and exclusively expressed proteins primarily associated with the UPR, ferroptosis, and necroptosis. Moreover, these cells exhibited activation of the UPR PERK arm and an increase in VEGF secretion. Enhancement of VEGF staining was later observed in the corneas of the exposed mice. Therefore, our data indicated that the mechanism of NM-induced ocular toxicity should be carefully examined and that future research should identify a signaling molecule transmitted via a prodeath pathway from the cornea to the retina. SIGNIFICANCE STATEMENT: This study demonstrated that NM topical exposure in mice results in dramatic decline in retinal function associated with enhanced TUNEL staining in both corneal and retinal tissues. We also found that the NM treatment of corneal cells resulted in 228 differentially and exclusively expressed proteins primarily associated with ferroptosis. Moreover, these cells manifest the UPR PERK activation and an increase in VEGF secretion. The latter was also found in the corneas of the cexposed mice.
Topics: Animals; Mice; Mechlorethamine; Vascular Endothelial Growth Factor A; Toxic Optic Neuropathy; Cornea; Chemical Warfare Agents; Mustard Gas; Unfolded Protein Response
PubMed: 37914413
DOI: 10.1124/jpet.123.001814 -
Science and Technology of Advanced... 2024A series of porous organic polymers based on a singlet oxygen generating oxoporphyinogen ('') has been successfully prepared from a pseudotetrahedral -tetraamine...
A series of porous organic polymers based on a singlet oxygen generating oxoporphyinogen ('') has been successfully prepared from a pseudotetrahedral -tetraamine precursor () by its reaction with tetracarboxylic acid dianhydrides under suitable conditions. Of the compounds studied, those containing naphthalene () and perylene () spacers, respectively, have large surface areas (~530 m g). On the other hand, the derivative with a simple benzene spacer () exhibits the best O generating capability. Although the starting -tetraamine precursor is a poor O generator, its incorporation into POPs leads to a significant enhancement of O productivity, which is largely due to the transformation of NH groups to electron-withdrawing diimides. Overall O production efficacy of s under irradiation by visible light is significantly improved over the common reference material . All the materials , and promote oxidation of thioanisole involving conversion of ambient triplet state oxygen to singlet oxygen under visible light irradiation and its reaction with the sulfide. Although the reaction rate of the oxidation promoted by POPs is generally lower than for conventional materials (such as ) or previously studied derivatives, undesired overoxidation of the substrate to methyl phenyl sulfone is suppressed. For organic sulfides, selectivity of oxidation is especially important for detoxification of mustard gas (bis(2-chloroethyl)sulfide) or similarly toxic compounds since controlled oxidation leads to the low toxicity bis(2-chloroethyl)sulfoxide while overoxidation leads to intoxification (since bis(2-chloroethyl)sulfone presents greater toxicity to humans than the sulfide substrate). Therefore, POPs capable of promoting selective oxidation of sulfides to sulfoxides have excellent potential to be used as mild and selective detoxification agents.
PubMed: 38440402
DOI: 10.1080/14686996.2024.2322458 -
Heliyon Jan 2024The primary objective of this study was to analyze the long-term survival of 48,067 chemical warfare survivors who suffered from pulmonary, cutaneous, and ocular lesions...
BACKGROUND
The primary objective of this study was to analyze the long-term survival of 48,067 chemical warfare survivors who suffered from pulmonary, cutaneous, and ocular lesions in the decades following the Iran-Iraq war.
METHODS
The data for this study were obtained from the Veterans and Martyr Affair Foundation (VMAF) database. The survivors were divided into two groups based on whether they were evacuated/admitted (EA) to a hospital or not evacuated/admitted (NEA) to a hospital. The proportional hazard (PH) assumption for age categories, gender, exposure statuses, and eye severity was not satisfied. Therefore, we used a Generalized Gamma (GG) distribution with an Accelerated Failure Time (AFT) model for analysis.
RESULTS
The study included a total of 48,067 observations, and among them, 4342 (9.03 %) died during the study period. The mean (SD) age of the survivors was 55.99 (7.9) years. The mortality rate increased with age, and higher rates were observed in males. Survival probabilities differed significantly among age categories, provinces, lung severity, and eye severity based on log-rank tests (p-value<0.05 for all). The GG model results showed that higher age and being male were associated with a shorter time to death. The study also found that the mortality rate was significantly higher in the EA group compared to the NEA group.
CONCLUSION
The present study showed no significant difference in survival time between the EA and NEA groups. The findings suggest that pulmonary lesions caused by mustard gas are more likely to be fatal compared to skin and eye lesions. The results also indicate a potential association between survival time and the severity of lung damage.
PubMed: 38312548
DOI: 10.1016/j.heliyon.2024.e24535 -
Polymers Jun 2024Ultraviolet (UV) curing is an efficient and environmentally friendly curing method. In this paper, UV-cured polyurethane acrylates (PUAs) were investigated as potential...
Ultraviolet (UV) curing is an efficient and environmentally friendly curing method. In this paper, UV-cured polyurethane acrylates (PUAs) were investigated as potential military coatings to serve as barriers against chemical warfare agents (CWAs). Seven UV-cured PUA coatings were formulated utilizing hydroxyethyl methacrylate-capped hexamethylene diisocyanate trimer (HEMA-Htri) and trimethylolpropane triacrylate-capped polycarbonate prepolymer (PETA-PCDL) as the PUA monomers. Isobornyl acrylate (IBOA) and triethyleneglycol divinyl ether (DVE-3) were employed as reactive diluents. Gas chromatography was utilized to investigate the constitutive relationships between the structures of the PUA coatings and their protective properties against simulant agents for CWAs, including dimethyl methylphosphonate (DMMP), a nerve agent simulant, and 2-chloroethyl ethyl sulfide (CEES), a mustard simulant. The glass transition temperature () and crosslinking density () of PUAs were found to be crucial factors affecting their ability to serve as barriers against CWAs. The incorporation of IBOA units led to enhanced and barrier performance of the PUAs, resulting in a DMMP retention of less than 0.5% and nearly 0 retention of CEES. However, an excessive introduction of polycarbonate chains decreased the and barrier performance of the PUAs. These findings may offer valuable insights for enhancing the protection of UV-cured PU coatings against CWAs.
PubMed: 38891524
DOI: 10.3390/polym16111578