ABSTRACT
BACKGROUND: Sulfur mustard (SM) is a toxic gas that causes chronic inflammation and oxidative stress leading to cell senescence. This study aimed to evaluate two indicators of biological aging (i.e., serum lipofuscin level and leukocyte telomere length) and assess their relationship based on the severity of SM exposure in the long term. METHODS: The study was performed on two groups of male participants. 1) SM-exposed group (exposed to SM once in 1987), 73 volunteers. 2) Non-exposed group, 16 healthy volunteers. The SM-exposed group was categorized into three subgroups based on the severity of SM exposure and body damage (asymptom, mild, and severe). The blood sample was prepared from members of each group. The serum lipofuscin, TGF-ß, malondialdehyde (MDA), c-reactive protein (CRP), and leukocyte telomere length (TL) were measured in all participants. RESULTS: The MDA level was increased in the SM-exposed group (mean = 39.6 µM, SD = 16.5) compared to the non-exposed group (mean = 21.1 µM, SD = 10.3) (P < 0.05). The CRP level was also increased in the SM-exposed group (mean = 5.12 mg/l, SD = 3.36) compared to the non-exposed group (mean = 3.51 mg/l, SD = 1.21), while the TGF-ß level was decreased (P < 0.05) in the SM-exposed group (mean = 52.6 pg/ml, SD = 18.7) compared to the non-exposed group (mean = 68.9 pg/ml, SD = 13.8). The relative TL was shorter in the SM-exposed group (mean = 0.40, SD = 0.28) than in the non-exposed group (mean = 2.25, SD = 1.41) (P < 0.05). The lipofuscin level was higher in the total SM-exposed group (mean = 1.44 ng/ml, SD = 0.685) than in the non-exposed group (mean = 0.88 ng/ml, SD = 0.449) (P < 0.05). The MDA and CRP levels were increased in the SM-exposed subgroups of asymptom, mild, and severe than the non-exposed group, while TGF-ß level and TL were decreased in those subgroups. The lipofuscin level was higher in the SM-exposed subgroups of mild and severe than in the non-exposed group. The regression analysis determined a negative correlation between lipofuscin level and TL. The lipofuscin/TL ratio was higher in the total SM-exposed group (mean = 6.36, SD = 5.342) than in the non-exposed group (mean = 0.51, SD=0.389). This ratio was also higher in the SM-exposed subgroups of asymptom, mild, and severe than in the non-exposed group. The lipofuscin/TL ratio did not differ between mild and severe subgroups. CONCLUSION: The delayed toxicity of SM is associated with chronic oxidative stress, continuous inflammatory stimulation, increased lipofuscin, and telomere shortening. Future studies are needed to verify the suitability of serum lipofuscin to telomere length ratio in determining the severity of SM toxicity.
