Alterations in the serum levels of soluble L, P and E-selectin 20years after sulfur mustard exposure: Sardasht-Iran Cohort Study

Yaraee, Roya; Ghazanfari, Tooba; Faghihzadeh, Soghrat; Mostafaie, Ali; Soroush, Mohammad Reza; Inai, Kouki; Foroutan, Abbas; Shams, Jalaleddin; Naghizadeh, Mohammad Mehdi; Hassan, Zuhair Mohammad

doi:10.1016/j.intimp.2009.08.024

Cited by 13 publications

(8 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Associated long-term markers and sequelae of SM poisoning have recently been described in the Sardasht-Iran Study, and in other large cohorts of individuals exposed during the Iran-Iraq conflict of the late 1980's [11, 12]. Even 20 years after SM exposure, there is evidence of systemic and pulmonary inflammatory effects in survivors including alterations in serum levels of cell adhesion molecules (e.g., selectins), as well as interleukin (IL)-8 and IL-6 [11, 12].…”

Section: Acute and Chronic Pulmonary Effects Of Sm In Humansmentioning

confidence: 99%

“…Even 20 years after SM exposure, there is evidence of systemic and pulmonary inflammatory effects in survivors including alterations in serum levels of cell adhesion molecules (e.g., selectins), as well as interleukin (IL)-8 and IL-6 [11, 12]. Moreover, serum levels of inflammatory markers are directly related to pulmonary symptoms.…”

Section: Acute and Chronic Pulmonary Effects Of Sm In Humansmentioning

confidence: 99%

See 1 more Smart Citation

Sulfur mustard-induced pulmonary injury: Therapeutic approaches to mitigating toxicity

Weinberger¹,

Laskin²,

Sunil³

et al. 2011

Pulmonary Pharmacology & Therapeutics

101

View full text Add to dashboard Cite

Sulfur mustard (SM) is highly toxic to the lung inducing both acute and chronic effects including upper and lower obstructive disease, airway inflammation, and acute respiratory distress syndrome, and with time, tracheobronchial stenosis, bronchitis, and bronchiolitis obliterans. Thus it is essential to identify effective strategies to mitigate the toxicity of SM and related vesicants. Studies in animals and in cell culture models have identified key mechanistic pathways mediating their toxicity, which may be relevant targets for the development of countermeasures. For example, following SM poisoning, DNA damage, apoptosis, and autophagy are observed in the lung, along with increased expression of activated caspases and DNA repair enzymes, biochemical markers of these activities. This is associated with inflammatory cell accumulation in the respiratory tract and increased expression of tumor necrosis factor-α and other pro-inflammatory cytokines, as well as reactive oxygen and nitrogen species. Matrix metalloproteinases are also upregulated in the lung after SM exposure, which are thought to contribute to the detachment of epithelial cells from basement membranes and disruption of the pulmonary epithelial barrier. Findings that production of inflammatory mediators correlates directly with altered lung function suggests that they play a key role in toxicity. In this regard, specific therapeutic interventions currently under investigation include anti-inflammatory agents (e.g., steroids), antioxidants (e.g., tocopherols, melatonin, N-acetylcysteine, nitric oxide synthase inhibitors), protease inhibitors (e.g., doxycycline, aprotinin, ilomastat), surfactant replacement, and bronchodilators. Effective treatments may depend on the extent of lung injury and require a multi-faceted pharmacological approach.

show abstract

Section: Acute and Chronic Pulmonary Effects Of Sm In Humansmentioning

confidence: 99%

Section: Acute and Chronic Pulmonary Effects Of Sm In Humansmentioning

confidence: 99%

Sulfur mustard-induced pulmonary injury: Therapeutic approaches to mitigating toxicity

Weinberger¹,

Laskin²,

Sunil³

et al. 2011

Pulmonary Pharmacology & Therapeutics

101

View full text Add to dashboard Cite

show abstract

“…Late-onset complications from the gas exposure were found to appear almost 10 years after these exposures (Emad & Rezaian, 1997). Although many years have passed since the SM exposure, overactive inflammatory processes are still evident in many SM-exposed veterans (Weinberger et al, 2011;Yaraee et al, 2009). A systemic inflammation associated with pulmonary complications that is common among SM-exposed patients has been investigated (Attaran et al, 2009;Emad & Emad, 2007).…”

Section: Introductionmentioning

confidence: 99%

Comparative proteome analysis of peripheral neutrophils from sulfur mustard-exposed and COPD patients

Shahriary

Mehrani

Ghanei

et al. 2014

Journal of Immunotoxicology

View full text Add to dashboard Cite

Respiratory disorders in sulfur mustard (SM)-exposed and chronic obstructive pulmonary disease (COPD) patients are mostly associated with neutrophilic inflammation, severe airflow limitation, and oxidative stress. The objective of this study was to establish whether neutrophil (PMN) proteomes in these diseases were similar or differed. Blood neutrophil proteomes from healthy, SM-exposed, and COPD subjects were analyzed using two-dimensional gel electrophoresis followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF MS). Elastase activity was determined kinetically. The results showed that levels of S100 calcium-binding protein (CBP) A12, S100 CBP A8, glyceraldehyde-3-phosphate dehy-drogenase, superoxide dismutase, and protein disulfide isomerase proteinsas well as elastase activity -were significantly increased in PMN from 'diseased' hosts compared to in cells from healthy controls. In contrast, coactosin-like protein, RhoGDP dissociation inhibitor, and actin isoforms were significantly decreased in diseased subjects' PMN compared to PMN of healthy controls. Moreover, serpin B1 and coronin-1A were expressed only in PMN of the healthy subjects. Lastly, S100 CBP A9, endoplasmic reticulum (ER)-60 protease, and glutathione-S-transferase isoforms were differentially expressed in the cells from the SMexposed and COPD subjects. These results show that serpin B1, an efficient inhibitor of neutrophil serine proteases, was not detectable, and elastase activity significantly increased in PMN from both SM-exposed and COPD patients. It seems that, apart from inflammation and oxidative stress, a protease:anti-protease imbalance exists within PMN of both COPD and SM-exposed patients.

show abstract

“…These cytokines, on their own, can evoke the release of IL-6 and IL-8 via autocrine or paracrine routes and thereby trigger an inflammatory response (Losa Garcia et al, 1999). There are proof-of-concept studies that clearly indicate a heightened state of inflammation in SM-intoxicated veterans, accompanied by increased pulmonary and systemic levels of IL-6 and IL-8, even 20 years post-exposure (Pourfarzam et al, 2009;Yaraee et al, 2009). Overall, it appears that counterbalancing the T H 1/T H 2 system in favor of T H 2 cytokines is an important underlying mechanism in the development of SMinduced inflammation.…”

Section: Discussionmentioning

confidence: 99%

Effect of recombinant human IFNγ in the treatment of chronic pulmonary complications due to sulfur mustard intoxication

Panahi¹,

Ghanei²,

Vahedi³

et al. 2013

Journal of Immunotoxicology

View full text Add to dashboard Cite

Pulmonary problems are among the most common chronic complications of sulfur mustard (SM) intoxication and adversely affect patients' quality-of-life. The present trial investigated the impact of immunotherapy with interferon (IFN)-g on quality-of-life, respiratory symptoms, and circulating immunologic and oxidative parameters in patients suffering from chronic SMinduced complications. Patients (n ¼ 15) were administered IFNg (100 mg) every other day for a period of 6 months. Assessment of quality-of-life [using St. George respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) indices], the severity and frequency of respiratory symptoms, and serum levels of immunologic [including interleukin (IL)-2, IL-4, IL-6, IL-10, IFNg, calcitonin gene related peptide (CGRP), matrix metallopeptidase (MMP)-9, and tumor necrosis factor (TNF)-a], oxidative stress [malondialdehyde (MDA) as well as total and reduced glutathione, and catalase and superoxide dismutase (SOD) activity], and fibrogenic [transforming growth factor (TGF)-b] parameters were performed at baseline and at trial end. The results indicated that IFNg therapy is associated with improvements in SGRQ (p50.001) and CAT (p50.001) scores, decreased severity of cough (p ¼ 0.001), dyspnea (p50.001), and morning dyspnea (p50.001), reduced frequency of sputum production (p50.001) and hemoptysis (p50.001), and elevated FEV 1 (p ¼ 0.065). Serum levels of IL-4 (p50.001), IL-6 (p50.001), IL-10 (p50.001), CGRP (p50.001), MMP-9 (p ¼ 0.001), TNFa (p50.001), TGFb (p50.001) and MDA (p ¼ 0.001) were decreased while those of IL-2 (p50.001), IFNg (p50.001), and both total (p ¼ 0.005) and reduced glutathione (p ¼ 0.061) increased by the end of the trial. It was concluded that IFNg has favorable effects on the quality-of-life and alleviates respiratory symptoms in patients suffering from chronic SM-induced pulmonary complications. A modulation of cytokines and oxidative stress appears responsible for the clinical efficacy of IFNg.

show abstract

Alterations in the serum levels of soluble L, P and E-selectin 20years after sulfur mustard exposure: Sardasht-Iran Cohort Study

Cited by 13 publications

References 36 publications

Sulfur mustard-induced pulmonary injury: Therapeutic approaches to mitigating toxicity

Sulfur mustard-induced pulmonary injury: Therapeutic approaches to mitigating toxicity

Comparative proteome analysis of peripheral neutrophils from sulfur mustard-exposed and COPD patients

Effect of recombinant human IFNγ in the treatment of chronic pulmonary complications due to sulfur mustard intoxication

Contact Info

Product

Resources

About