A Randomized Clinical Trial on Therapeutic Effects of Myrtus communis L. Cream on Chronic Skin Lesions and Quality of Life of Sulfur Mustard-exposed Veterans

Abstract: Sulfur mustard is one of the chemical warfare agent. It rapidly reacts with the cutaneous tissues and other tissues, leading to various devastating long-term effects on human health. Mustard-exposed veterans suffer from its chronic skin problems, including itching, burning sensation, and eczema. We aimed to evaluate the protective effects of Myrtus communis L. (myrtle) on chronic skin lesions and quality of life of sulfur mustard-exposed veterans. In this randomized, double-blind clinical trial, 60 sulfur mustard-exposed patients were evaluated. Thirty patients received myrtle essence 5% cream (case group) and 30 patients received Eucerin cream (placebo group) twice in a day for one month. Then, We assessed the chronic skin problems and itching-related parameters (such as the itching time, severity, distribution, frequency, and calculated itching score), duration of sleep, number of waking up at night, and quality of life in the both groups. Our analysis of data revealed that application of myrtle cream effectively decreased skin problems including; itching and burning sensation. Additionally, myrtle markedly decreased skin lesion symptoms such as excoriation in the case group as compared with before treatment. Noticeably, myrtle cream significantly improved quality of life of the patients in the case group. The present study provides more in-depth information regarding the protective role of myrtle on the sulfur mustard-induces skin complication. Also, myrtle effectively improved quality of life of the sulfur mustard-exposed veterans.

[Study of the prophylactic effects of amifostine on decrease of lung tissue injuries in the acute phase in rats exposed to sulfur mustard]

Inhalation of Sulfur mustard [HD] will cause lung epithelial inflammation and injury. There are different results from the prophylactic effects of amifostine [AM] on protection of lung epithelial tissue against HD. The aim of this study was to evaluate the prophylactic effects of AM on protection of rat lung tissue exposed to HD. In this study twenty Albino Wistar adult male rats weighting 200 +/- 20 grams were used. Rats were divided randomly into 4 groups [5 rats in each group] as below: Normal saline group [NS], AM group, HD group [0.25% HD] and HD+AM group. Normal saline and HD solution were injected by intra tracheal catheter. Animals in AM and HD+AM groups received AM by intra peritoneal injection for 14 days daily. All rats were killed after 14 days; parts of the base of right lungs were removed, fixed and processed for histological evaluation by Toluidine blue, H and E staining and apoptotic cell death study by the TUNEL Apoptosis Detection Kit. In addition, glutathione level was measured in all specimens. No significant differences were revealed between Saline and AM groups in any of the aforementioned tests. Significant reduction of mast cells in lung tissue of the HD+AM group was shown when compared to the HD group. Lung tissue inflammation in the HD group was significantly more severe as compared to HD+AM group. In addition, amifostine in HD+AM group could prevent excess reduction of GSH level. The number of apoptotic cells in the HD group was significantly higher than the HD+AM group. Administration of amifostine before exposure to HD in rats prevents collection of mast cells, and excess reduction of GSH level in lung tissue; in addition it can partially reduce pulmonary edema and alveolar cell death apoptosis

[Study of the effects of hexamethylentetramine on decrease of defects of the lung tissue in the rat exposed to sulfur mustard]

The aim of this study was to evaluate the effects of HMT on protection of lung tissue exposed to HD in the rat. In this study twenty Albino Wistar adult male rats weighting 200 +/- 20 gram were used. Rats divided randomly into 4 groups [each group has 5 rats] as below: Normal saline group [NS], HMT group, HD group [0.25% HD] and HD+HMT group. Normal saline and HD solution were injected by intra tracheal catather. Animals in HMT and HD+HMT groups received HMT by intra peritoneal injection for 14 days daily. All rats were killed after 14 days, a part of lung tissue were removed, fixed and processed for histological evaluation by H and E staining and apoptotic cell death study by TUNEL kit. In addition, biochemical study [catalase enzyme] was measured in all groups. Histological examination and cell counting data revealed that there were no significant differences between Saline and HMT groups. Alveolar hemorrhage and inflammation, as well as, the number of apoptotic cells in the HD group was significantly increased when compared to HD+HMT group. HMT have prophylactic and therapeutics effects in the lung tissue against HD

Bcl-2 protein expression in pulmonary specimens of sulfur mustard victims

Considering the role of sulfur mustard gas in development of acute and chronic pulmonary complications and the role of some genes including Bcl-2 in pulmonary fibrosis, we decided to study Bcl-2 gene expression in lung biopsy specimens of victims in comparison with normal lung. Lung biopsy specimens were taken from 13 sulfur mustard [SM] victims with pulmonary complication and were stained by Hematoxylin and Eosin [H and E] and avidin-biotin methods. We used normal lung blocks from forensic medicine as the normal group. These blocks were treated and stained with the same procedure as the case group. Both groups' blocks were studied by a pathologist simultaneously. The percentage of macrophages in sulfur mustard victims' specimens was significantly lower than that of the control group. There was also a significant increase in lymphocytes of victims in comparison with the normal group. Neutrophil percentage and Bcl-2 protein in these cells showed no significant difference between the two groups. Bcl-2 protein in fibroblasts and epithelial cells of sulfur mustard victims was significantly higher than the control group. According to the results of this study in comparison with the results of patients with idiopathic pulmonary fibrosis [IPF], pulmonary fibrosis can be confirmed as one of the late complications of SM victims. According to these results, upregulation of Bcl-2 protein and subsequent alveolar epithelial cell hyperplasia and proliferation of fibroblasts may be a mechanism for pulmonary fibrosis induced by mustard gas. It could be important for developing new strategies for the treatment of fatal complications of this chemical warfare

Protective effect of ethanolic and water extracts of sea buckthorn (Hippophae rhamnoides L.) against the toxic effects of mustard gas.

Ethanolic extract of H. rhamnoides L. leaf (HL-EOH), water and ethanolic extract of H. rhamnoides fruit (HF-W and HF-EOH), and H. rhamnoides flavone from fruit (HR-flavone) were evaluated against percutaneously administered sulphur mustard (SM), a chemical warfare agent. The animals administered with SM (9.7, 19.3 and 38.7 mg/kg) died at various days depending upon the dose and there was a significant reduction in the body weight. The H. rhamnoides extracts (1 g/kg; 3 doses; po) significantly protected the lethality, with a protective index of 2.4, 1.7, 1.7 and 2.2 for HL-EOH, HF-W, HF-EOH and HR-flavone respectively. Reduced glutathione (GSH) and oxidized glutalthione (GSSG) levels were reduced, and malondialdehyde (MDA) was elevated after percutaneous administration of SM. Oral administration of HL-EOH and HR-flavone significantly protected the body weight loss. Recovery in the levels of GSH, GSSG and MDA were also observed following oral administration of HL-EOH and HR-flavone. All the extracts were non-toxic and the LD50 was more than 5 g/kg. The present study shows that percutaneous administration of SM induces oxidative stress and ethanolic extract of leaf of H. rhamnoides and H. rhamnoides flavone from fruit can significantly protect it.

Skin lesions in 800 Iranian victims of mustard gas, 14-20 years after exposure

Mustard gas is a disabling chemical weapon and was widely used in First World War and Iraq-Iran war. Its toxic effects could be acute or chronic and they could particularly affect lungs, eyes and skin.To study the frequency of chronic complications of sulfur mustard gas in Iranian victims 14 to 20 years after exposure. This descriptive cross-sectional study was performed on 800 patients that were randomly selected from different provinces of Iran, who had been exposed to sulfur mustard gas during 1983 to 1988. These patients were clinically re-evaluated in 2002-2003 and laboratory tests were performed if necessary. The mean age of the patients at the time of study was 39.3 [ +/- 9.8] years. Three types of skin lesions were observed. Non-specific lesions including 39.6% xerosis, 19% pigmentary disorders, 17.4% cherry angioma, 12.7% seborrheic dermatitis, 12.2% eczema [dermatitis], 11.6% acneiform lesions, 7% tinea versicolor, 5.1% urticaria,, 3.6% vitiligo, 2.5% alopecia areata, 2% psoriasis, and 1.3% aphthous stomatitis. Specific skin lesion called mustard scar was defined according to morphology, location, history and observed in 44 [5.5%] patients. Malignant neoplasms including basal cell carcinoma, Bowen's disease, squamous cell carcinoma, mycosis fungoides and dermatofibrosarcoma protuberans occurred in 9 victims [1.1%]. Mustard gas can cause acute and late-onset skin lesions. Specific lesion of mustard gas called mustard scar is the most important finding of this study

Dose response of sulphur mustard: behavioral and toxic signs in rats.

The present study elucidates the behavioral and toxic signs in rats following dermal application of sulphur mustard (SM). Graded doses of SM (0.10, 0.25, 0.50, 0.75 and 1.0 LD50) were topically applied to male Wister rats. The body weight as well as behavioral/toxic signs and symptoms were recorded at 1, 2, 3, and 4th day after application of SM. Sulphur mustard consistently decreased body weights of rats in a dose and time dependent manner with maximum decrease on 3rd day post treatment. Sedation and diarrhea were significant in response to doses of SM intoxication in rats. It is concluded that the body weight, sedation and diarrhea may be used as a reliable parameter in evaluating SM intoxication. It is also suggested that hydration and hypertonic saline must be used as a rescue agent within 1-3 days after exposure to SM.

Characterization of immune response to mustard gas using a new fluoroimmunoassay

One way to confront chemical warfare in order to reduce their harmful effects, is to use the body's defense mechanisms. In order to do so firstly mustard gas [HD] was injected in an animal model in the form of an immunogen and the induced humoral immune response was investigated by two different immunological methods such as the Ouchterlony test and a new liquid phase fluoroimmunoassay. It was proved that the animal model had produced specific antibodies against mustard gas which could specifically interact with the chemical gas