Molecular and cellular mechanism of lung injuries due to exposure to sulfur mustard: a review

Abstract

The marked difference in biopersistence and pathological response between chrysotile and amphibole asbestos has been well documented. This study is unique in that it has examined a commercial chrysotile product that was used as a joint compound. The pathological response was quantified in the lung and translocation of fibers to and pathological response in the pleural cavity determined. This paper presents the final results from the study. Rats were exposed by inhalation 6 h/day for 5 days to a well-defined fiber aerosol. Subgroups were examined through 1 year. The translocation to and pathological response in the pleura was examined by scanning electron microscopy and confocal microscopy (CM) using noninvasive methods.The number and size of fibers was quantified using transmission electron microscopy and CM. This is the first study to use such techniques to characterize fiber translocation to and the response of the pleural cavity. Amosite fibers were found to remain partly or fully imbedded in the interstitial space through 1 year and quickly produced granulomas (0 days) and interstitial fibrosis (28 days). Amosite fibers were observed penetrating the visceral pleural wall and were found on the parietal pleural within 7 days postexposure with a concomitant inflammatory response seen by 14 days. Pleural fibrin deposition, fibrosis, and adhesions were observed, similar to that reported in humans in response to amphibole asbestos. No cellular or inflammatory response was observed in the lung or the pleural cavity in response to the chrysotile and sanded particles (CSP) exposure. These results provide confirmation of the important differences between CSP and amphibole asbestos.

From the Cover: Catalytic Antioxidant Rescue of Inhaled Sulfur Mustard Toxicity

“…The catalytic antioxidant treatment significantly attenuated SM-mediated increases in TNF-a, IL-6, KC/GRO, and IL-1b at 24 h. Transforming growth factor b1 (TGFb1) is commonly associated with lung injury and repair responses (Liu, 2008;Tatler and Jenkins, 2012). TGFb1 has been implicated in the development of pulmonary fibrosis in chronic models of SM exposure (Aghanouri et al, 2004;Emad and Emad, 2007;Ghanei and Harandi, 2011;Poursaleh et al, 2012). SM exposure significantly increased BALF TGFb1 levels nearly 10-fold over Sham PBS at 24 h post-exposure (Fig.…”

“…Inhaled SM may cause death or the development of severe chronic airway disorders in survivors (Poursaleh et al, 2012). Inhaled SM causes acute sloughing of the epithelial surfaces, formation of occlusive casts, and can lead to chronic respiratory problems such as bronchiolitis obliterans and COPD (Ghanei and Harandi, 2011;Veress et al, 2013). A hindrance in developing treatments for SM inhalation is due to our poor understanding of its pathogenesis.…”

Sulfur Mustard Exposure and Cardiovascular Effects: A Review

“…It seems that late toxic effects of SM are more important and more serious than the acute effects (37). There are cellular and molecular evidences that support the late systemic impacts of SM.…”

“…It has also been documented that COPD, as a form of local airway inflammation, releases inflammatory mediators into the systemic circulation and may contribute to an increase in cardiovascular disorders in these patients (42). Furthermore, it was recommended that TGF-β plays a significant role in the progression and development of both coronary atherosclerosis (43) and SM lung injury (37).…”

“…When antioxidant supply is not sufficient (such as in SM injured patients, in whom the oxidative stressantioxidants balance is disturbed), the oxidative stress can damage the cardiovascular tissue more freely and effectively than in normal people (37). Therefore, although a definite heart toxicity of SM has not yet been explained, these patients have more predisposing factors (in terms of genomics, proteomics and metabolomics) to cardiovascular diseases, especially CAD.…”