Association of Nitric Oxide With Delayed Skin Problems After Sulfur Mustard Exposure: Part of Sardasht-Iran Cohort Study

Abstract

Background: Exposure to Sulfur Mustard (SM) leads to short- and long-term adverse effects on various organs, including the skin. Despite several studies on long-term clinical manifestations of skin toxicity in SM-exposed individuals, the pathogenesis of SM-induced skin disorders is not fully understood. Materials and Methods: As part of Sardasht-Iran Cohort Study (SICS), this study aimed to find out the possibility of any correlation between the serums level of Nitric Oxide (NO) and skin problems due to the long-term effect of SM as well as the kind of skin illness. In this historical cohort study, 372 male SM-exposed subjects and 128 age-matched unexposed controls were studied. Clinical evaluation was carried out for all participants, and their serum concentration of NO was measured. Results: According to our results, the Mean±SD serum level of NO in the exposed group with skin disorders were significantly higher than that in the exposed group without skin disorders (1483.00±488.754µg/mL vs. 1364.50±487.887µg/mL; P=0.024). Also, among the exposed group, there was a significant elevation of serum NO associated with the type of lesion. For ezxample, specific lesions like mustard scar were associated with higher levels of NO compared to non-specific lesions like xerosis, itching, seborrheic dermatitis, etc. Also, a significant elevation in serum NO levels was found in the exposed subjects with pigmentation disorders (both hypo- and hyper-pigmentation) compared to the exposed participants without these skin problems (PConclusion: Our results show the highest serum level of NO in the exposed group with specific lesions and the lowest or normal level of NO in the unexposed group with no skin illness. The elevated serum levels of NO may be associated with the progression of some skin complications in the SM-exposed subjects. This finding serves as a basis for further research on the molecular mechanisms and pathways involved in the pathogenesis of skin disorders in SM-exposed patients.