Mesh : Animals Ricin / toxicity Mice Lung / drug effects pathology Cytokines / metabolism Lung Injury / chemically induced pathology Female Disease Models, Animal

来  源:   DOI:10.1038/s41598-024-62222-9   PDF(Pubmed)

Abstract:
Ricin, an extremely potent toxin produced from the seeds of castor plant, Ricinus communis, is ribosome-inactivating protein that blocks cell-protein synthesis. It is considered a biological threat due to worldwide availability of castor beans, massive quantities as a by-product of castor oil production, high stability and ease of production. The consequence of exposure to lethal dose of ricin was extensively described in various animal models. However, it is assumed that in case of aerosolized ricin bioterror attack, the majority of individuals would be exposed to sublethal doses rather than to lethal ones. Therefore, the purpose of current study was to assess short- and long-term effects on physiological parameters and function following sublethal pulmonary exposure. We show that in the short-term, sublethal exposure of mice to ricin resulted in acute lung injury, including interstitial pneumonia, cytokine storm, neutrophil influx, edema and cellular death. This damage was manifested in reduced lung performance and physiological function. Interestingly, although in the long-term, mice recovered from acute lung damage and restored pulmonary and physiological functionality, the reparative process was associated with lasting fibrotic lesions. Therefore, restriction of short-term acute phase of the disease and management of long-term pulmonary fibrosis by medical countermeasures is expected to facilitate the quality of life of exposed survivors.
摘要:
蓖麻毒素,一种从蓖麻植物的种子中产生的非常有效的毒素,蓖麻,是核糖体失活蛋白,阻断细胞蛋白质的合成。由于蓖麻豆的全球供应,它被认为是一种生物威胁,大量作为蓖麻油生产的副产品,高稳定性和易于生产。在各种动物模型中广泛描述了暴露于致死剂量的蓖麻毒素的后果。然而,假设在气溶胶化蓖麻毒素生物恐怖袭击的情况下,大多数人将暴露于亚致死剂量,而不是致死剂量。因此,本研究的目的是评估亚致死性肺暴露后对生理参数和功能的短期和长期影响.我们表明,在短期内,小鼠亚致死性暴露于蓖麻毒素导致急性肺损伤,包括间质性肺炎,细胞因子风暴,中性粒细胞流入,水肿和细胞死亡。这种损害表现为肺性能和生理功能降低。有趣的是,虽然从长远来看,小鼠从急性肺损伤中恢复并恢复肺和生理功能,修复过程与持续性纤维化病变相关.因此,通过医学对策限制疾病的短期急性期和长期肺纤维化的管理有望提高暴露幸存者的生活质量。
公众号