Table 3:
Studies on the toxic effect of vesicants (sulfur mustard, nitrogen mustard, and CEES).
| Pyridostigmine Bromide | |||
|---|---|---|---|
| Study (Ref #) | Model | Exposure | Results |
| Bryant et al., 2021 (23) | Male and female C57BL/6 mice (WT, NLRP3−/−, and STINGgt/gt) | 0.7 mg/kg PB and 200 mg/kg Per in 50 mL DMSO daily for 10 days | Greater neuroinflammation and cognitive impairment in female mice; greater peripheral inflammation in males |
| Hernandez et al., 2020 (25) | Male and female C57BL/6 mice | 90 mg/mL PB in drinking water for 7 days; 0.07 mg/mL PEA in drinking water for one month | PB alone increased fecal pellet production and colonic transit time only in females, PB+PEA increased myenteric neurons and muscarinic M3 receptors only in females |
| Sulfur Mustard | |||
| Study (Ref #) | Model | Exposure | Results |
| Inturi et al., 2014 (117) | JB6 cells | 0.75 mM nitrogen mustard | Decreased cell growth; cell cycle arrest |
| Byers et al, 2000 (120) | Hairless guinea pigs | 7 minutes exposure to 10 mL sulfur mustard in vapor cups | Sulfur mustard depletes NAD+, leading to ATP deficiency and cell death |
| Malaviya et al., 2010 (124) | Male Crl:CD (SD) rats | 0.7, 1.0, or 1.4 mg/kg sulfur mustard via inhalation | Damage, cell death, and inflammation in the lungs |
| Chevillard et al., 1992 (127) | Respiratory epithelial (tracheae of male New Zealand white rabbits) | 0.1 mM sulfur mustard | Cessation of ciliary beating |
| Malaviya et al., 2020 (129) | Male Wistar rats | 0.06-0.6 mg/kg sulfur mustard via inhalation | Increased TNF-α in lungs |
| Feng et al., 2019 (130) | Male ICR mice | 40 mg/kg SM for survival and respiratory function experiments; 30 mg/kg SM for other experiments | Increased pro-inflammatory cytokine expression in lungs |
| Sunil et al., 2011 (133) | Male Wistar rats | 0.25 mg/kg nitrogen mustard | Alveolar macrophages increased in size and number; increased neutrophil numbers |
| Gray et al., 2010 (145) | MLE-15 murine lung epithelial cells | 100 mg/mL CEES | NADPH cytochrome P450 reductase inhibited in CEES-treated cells |
| Xiaoji et al., 2016 (157) | Male Sprague-Dawley rats | 2 mg/kg SM | Tissue damage and inflammatory cell infiltration in the lungs |
| McGraw et al., 2018 (158) | Male Sprague-Dawley rats | 1.0 +/− 0.05 mg/kg SM | Decreased lung function; development of bronchiolitis obliterans and pulmonary fibrosis |
| Jugg et al., 2016 (159) | Female large white pigs | 60 or 100 mg/kg SM | Lung damage and alterations in pathways such as the Nrf2 pathway |
| Rana et al., 2020 (162) | Male Sprague-Dawley rats | 15 minutes exposure to CEES vapor | Epithelial damage, decreased microRNA-140-5p, increased pro-inflammatory cytokines, and increased superoxide dismutase |
| Sunil et al., 2020 (163) | Male and female C57BL6/J mice | 0.8 mg/kg NM | Tissue damage and inflammation in the lung |
| Cruz-Hernandez et al., 2021 (164) | Male C57BL/6J and KitW-sh mice; BMMCs from C57BL/6J mice | 0.125 mg/kg NM | Inflammation and lung injury occurred in C57BL/6 mice, but not in the mast cell-deficient mice |
| Malaviya et al., 2015 (165) | Male Wistar rats | 0.125 mg/kg NM; 15 mg/kg anti-TNFa antibody every nine days after NM exposure | Anti-TNFa antibody reduced M1 macrophage numbers and TGF-b levels |
| Solopov et al., 2020 (167) | Male C57BL/6J mice | 0.312 or 0.625 mg/kg NM | Increased pro-fibrotic biomarkers and collagen expression at 10 and 30-days post-exposure |
| Tekiner et al., 2009 (176) | Male brown rats | 800 mg/m3/min NM for 10 minutes; 100 mg/kg/day proanthocyanin | Vascular edema, abnormal neuronal and glial processes, and altered cellular components in the brain; proanthocyanin alleviated NM-induced oxidative stress |
| Gao et al., 2011 (177) | Male Crl:CD SD BR rats | 0.25 mg SM in 100 mL inhaled over 50 minutes; 10, 20, or 40 mg/kg roxithromycin | Roxithromycin improved lung function in SM-exposed rats |
| Calvet et al., 1994 (178) | Male Hartley guinea pigs | 0.3 mL/kg SM injected into trachea; trachea incubated with 10−5 M phosphoramidon | Phosphoramidon inhibited SM-induced sensitivity to substance P |
| Calvet et al., 1996 (179) | Male Hartley guinea pigs | 0.3 mL/kg SM (stored 100 mg/mL in EtOH and then diluted 1:100 in 0.9% NaCl) given intratracheally; 3 mg/kg betamethasone in drinking water for seven days | Betamethasone repaired airway damage caused by SM |
| Wigenstam et al., 2012 (180) | Female C57BL/6 mice | 1 mg/kg melphalan; 10 mg/kg dexamethasone given 1, 2, or 6 hours after melphalan exposure | Dexamethasone reduced inflammatory cell infiltration in lungs of SM-exposed mice |
| O’Neill et al., 2010 (181) | Male Sprague-Dawley rats | 5% CEES in ethanol at 12.7 cc/hour for 15 minutes; 5 mg/kg AEOL 10150 injected at 1 or 9-hours post-exposure | AEOL 10150 decreased markers of oxidative stress in SM-exposed rats |
| Sharma et al., 2010 (186) | Female Swiss mice | 11.9 mg/kg HN-1, 20.0 mg/kg HN-2, 7.1 mg/kg HN-3, or 8.1 mg/kg SM | Differences in toxic effects and efficacy of antidotes seen between mustard compounds |