Therapeutics effect of N-acetyl cysteine on mustard gas exposed patients: Evaluating clinical aspect in patients with impaired pulmonary function test

Shohrati, Majid; Aslani, Jafar; Eshraghi, Mehdi; Alaeddini, Farshid; Ghanei, Mostafa

doi:10.1016/j.rmed.2007.10.004

Cited by 51 publications

(29 citation statements)

References 27 publications

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“…Ghanei and colleagues found that N-acetyl cysteine (NAC), a mucolytic medicine with antioxidant effect, improved the clinical symptoms of SM injured people,10,38,40 which is emphasised by our result.…”

Section: Discussionsupporting

confidence: 64%

HO1 mRNA and Protein do not Change in Parallel in Bronchial Biopsies of Patients after Long Term Exposure to Sulfur Mustard

Nourani

Yazdani

Roudkenar

et al. 2010

Gene�Regul Syst Bio

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Sulfur mustard (SM), is an alkylating agent and has been emerged as a chemical weapon in various battlefields. More recently, SM was employed in the Iraq conflict against Iranian military forces and civilians. Nowadays there are more than 40,000 people suffering from pulmonary lesions special chronic obstructive pulmonary disease (COPD) due to mustard gas in Iran. SM causes the endogenous production of reactive oxygen species (ROS).Heme oxygenases (HOs) are the rate-limiting enzyme for heme metabolism. Numerous studies have confirmed that HOs are concerned in diverse biological processes such as anti-oxidation.The present study was undertaken to consider the regulation of HO-1 and HO-2 n the human airway wall, and to suggest a probable role that HOs may play in cellular defense against oxidative stress due to SM.In this research ten unexposed SM individuals and twenty SM exposed patients were included. Evaluation of HO-1& HO -2 expressions in unexposed and SM exposed patients samples was performed by semiquantitative RT-PCR, real-time RT-PCR and Immunohistochemistry analysis.While unexposed SM samples expressed same levels of HOs, expression level of HO-1 was upregulated about 3.58 ± 1.93 folds in SM exposed patients in comparison with unexposed ones, we could not find any difference in expression of HO-2 n two groups. In contrast, Immunohistochemistry results showed negative HO-1 protein expression in SM injured patients.Our results revealed that HO1 may plays an important role in cellular protection against oxidative stress due to mustard gas toxicity in airway wall of SM exposed patients at mRNA level, but translational modifications might cause decrease in the amount of HO1 protein.

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Section: Discussionsupporting

confidence: 64%

HO1 mRNA and Protein do not Change in Parallel in Bronchial Biopsies of Patients after Long Term Exposure to Sulfur Mustard

Nourani

Yazdani

Roudkenar

et al. 2010

Gene�Regul Syst Bio

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“…We have previously observed that a 4-month administration of N-acetylcysteine in patients exposed to SM could significantly improve FEV1/FVC over placebo [14, 44]. …”

Section: Discussionmentioning

confidence: 99%

Discrepancy between mRNA and Protein Expression of Neutrophil Gelatinase-Associated Lipocalin in Bronchial Epithelium Induced by Sulfur Mustard

Ebrahimi

Roudkenar

Fooladi

et al. 2010

Journal of Biomedicine and Biotechnology

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Sulfur mustard (SM) is a potent vesicant that has been employed as a chemical weapon in various conflicts during the 20th century. More recently, mustard was used in the Iraq conflict against Iranian troops and civilians. At the present time there are more than 40.000 people suffering from pulmonary lesions special bronchiolitis obliterans (BOs) due to mustard gas. SM increases the endogenous production of reactive oxygen species (ROS). Neutrophil Gelatinase-associated Lipocalin 2 (Lcn2, NGAL) is a member of the lipocalin superfamily for which a variety of functions such as cellular protection against oxidative stress have been reported. Ten normal and Twenty SM-induced COPD patient individuals were studied. Assessment of NGAL expressions in healthy and the patients endobrinchial biopsies were performed by semiquantitative RT-PCR, real-time RT-PCR, and Immunohistochemistry analysis. While Normal control samples expressed same level of mRNA NGAL, expression level of mRNA-NGAL was upregulated about 1.4- to 9.8-folds compared to normal samples. No significant immunoreactivity was revealed in both samples. As we are aware this is the first report of induction of NGAL in patients exposed to SM. NGAL may play an important role in cellular protection against oxidative stress toxicity induced by mustard gas in airway wall of patients.

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“…In humans, NAC administered in conjunction with supportive measures, including humidified oxygen, bronchodilators, antibiotics, and chest physiotherapy, during the acute phase, reduces symptoms associated with vesicant exposure (Razavi et al, 2013). In the chronic phase, NAC improves pulmonary function and reduces cough and dyspnea caused by mustards; this is associated with decreased production of reactive oxygen species (Ghanei et al, 2008a; Razavi et al, 2013; Shohrati et al, 2008a). Oral NAC, alone or in combination with clarithromycin, has also been reported to contribute to improved lung function in patients with bronchiolitis obliterans due to SM inhalation (Shohrati et al, 2014).…”

Section: Targeting Reactive Oxygen and Nitrogen Speciesmentioning

confidence: 99%

Mustard vesicant-induced lung injury: Advances in therapy

Weinberger

Malaviya

Sunil

et al. 2016

Toxicology and Applied Pharmacology

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Most mortality and morbidity following exposure to vesicants such as sulfur mustard is due to pulmonary toxicity. Acute injury is characterized by epithelial detachment and necrosis in the pharynx, trachea and bronchioles, while long-term consequences include fibrosis and in some instances, cancer. Current therapies to treat mustard poisoning are primarily palliative and do not target underlying pathophysiologic mechanisms. New knowledge about vesicant-induced pulmonary disease pathogenesis has led to the identification of potentially efficacious strategies to reduce injury by targeting inflammatory cells and mediators including reactive oxygen and nitrogen species, proteases and proinflammatory/cytotoxic cytokines. Therapeutics under investigation include corticosteroids, N-acetyl cysteine, which has both mucolytic and antioxidant properties, inducible nitric oxide synthase inhibitors, liposomes containing superoxide dismutase, catalase, and/or tocopherols, protease inhibitors, and cytokine antagonists such as anti-tumor necrosis factor (TNF)-α antibody and pentoxifylline. Antifibrotic and fibrinolytic treatments may also prove beneficial in ameliorating airway obstruction and lung remodeling. More speculative approaches include inhibitors of transient receptor potential channels, which regulate pulmonary epithelial cell membrane permeability, non-coding RNAs and mesenchymal stem cells. As mustards represent high priority chemical threat agents, identification of effective therapeutics for mitigating toxicity is highly significant.

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Therapeutics effect of N-acetyl cysteine on mustard gas exposed patients: Evaluating clinical aspect in patients with impaired pulmonary function test

Abstract: Fourth months administration of NAC (1800 mg daily) can improve clinical conditions and spirometric findings in mustard exposed in BOS class 1 or 2.

Cited by 51 publications

References 27 publications

HO1 mRNA and Protein do not Change in Parallel in Bronchial Biopsies of Patients after Long Term Exposure to Sulfur Mustard

HO1 mRNA and Protein do not Change in Parallel in Bronchial Biopsies of Patients after Long Term Exposure to Sulfur Mustard

Discrepancy between mRNA and Protein Expression of Neutrophil Gelatinase-Associated Lipocalin in Bronchial Epithelium Induced by Sulfur Mustard

Mustard vesicant-induced lung injury: Advances in therapy

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