Effect of slow release pentoxifylline and captopril on delayed pulmonary complications of mustard gas in animal models

Considering the effect of pentoxifylline on the immune system and reducing oxidative stress and also the anti-oxidative properties of captopril, these drugs are indicated for prevention and treatment of delayed pulmonary complications due to exposure to sulfur mustard [SM]. Therefore, we decided to study the effect of slow release pentoxifylline and captopril on SM-induced delayed pulmonary complications in animal models. Pentoxifylline and captopril were administered for two weeks to mice exposed to sulfur mustard. Biochemical and pathological analyses included: hydroxyproline assay, alveolar space percentage and severity of inflammatory cell infiltration. The results were compared between groups using ANOVA statistical test. Hydroxyproline content of the lungs was significantly lower in the negative control group in comparison to positive control, captopril intervention and pentoxifylline intervention groups. There was no significant difference between groups in image analysis figures. However, there was a significant difference in extent of fibrosis, inflammation, and lymphocyte and PMN percentage between different groups. Pentoxifylline only resulted in decreased pulmonary inflammation without any effects on other indices. On the other hand, increase in hydroxyproline content of the lung in the captopril group compared to controls showed that captopril had accelerated the process of fibrosis. Hence, more research is recommended to study the effect of captopril on pulmonary fibrosis

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