Nourazarian Alireza, Aghaei-Zarch Seyed Mohsen, Panahi Yasin
Department of Basic Medical Sciences, Khoy University of Medical Sciences, Khoy, Iran.
Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Arch Toxicol. 2025 May 7. doi: 10.1007/s00204-025-04033-z.
Sulfur mustard (SM), a potent alkylating agent, has been widely used in chemical warfare, causing severe acute and long-term health complications. While its immediate toxic effects are well documented, the late-onset complications remain poorly understood. Chronic exposure to SM has been linked to persistent oxidative stress, inflammation, and genomic instability, contributing to the progression of various diseases, including pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), and cancer. This review explores the emerging role of telomere biology in the delayed pathophysiology of SM exposure. Evidence suggests that telomere shortening and dysregulation of telomeric repeat-containing RNA (TERRA) may serve as key molecular indicators of SM-induced aging and cellular dysfunction. Furthermore, inflammatory pathways, particularly NF-κB and TGF-β signaling, appear to be closely associated with telomere attrition, perpetuating chronic inflammation and fibrosis. By integrating oxidative stress, inflammation, and telomere dynamics, we propose a novel model linking telomere biology to SM-induced late complications. Understanding these mechanisms could pave the way for targeted therapeutic strategies, including antioxidant and epigenetic interventions, to mitigate long-term effects. Future research should focus on validating telomere-based biomarkers for early detection and exploring novel interventions to alleviate SM-induced chronic health conditions.
硫芥(SM)是一种强效烷基化剂,已被广泛用于化学战,会导致严重的急性和长期健康并发症。虽然其即时毒性作用已有充分记录,但迟发性并发症仍知之甚少。长期接触SM与持续的氧化应激、炎症和基因组不稳定有关,会促使包括肺纤维化、慢性阻塞性肺疾病(COPD)和癌症在内的各种疾病发展。本综述探讨了端粒生物学在SM暴露延迟病理生理学中的新作用。有证据表明,端粒缩短和含端粒重复序列RNA(TERRA)的失调可能是SM诱导衰老和细胞功能障碍的关键分子指标。此外,炎症途径,特别是NF-κB和TGF-β信号通路,似乎与端粒损耗密切相关,会使慢性炎症和纤维化持续存在。通过整合氧化应激、炎症和端粒动态变化,我们提出了一个将端粒生物学与SM诱导的晚期并发症联系起来的新模型。了解这些机制可为包括抗氧化和表观遗传干预在内的靶向治疗策略铺平道路,以减轻长期影响。未来的研究应侧重于验证基于端粒的生物标志物以进行早期检测,并探索新的干预措施以缓解SM诱导的慢性健康状况。