PDF(Pubmed)
Abstract：
Gulf War Illness (GWI) describes a series of symptoms suffered by veterans of the Gulf war, consisting of cognitive, neurological and gastrointestinal dysfunctions. Two chemicals associated with GWI are the insecticide permethrin (PER) and the nerve gas prophylactic pyridostigmine-bromide (PB). In this study we assessed the effects of PER and PB exposure on the pathology and subsequent alcohol (EtOH)-induced liver injury, and the influence of a macrophage depletor, PLX3397, on EtOH-induced liver damage in PER/PB-treated mice. Male C57BL/6 mice were injected daily with vehicle or PER/PB for 10 days, followed by 4 months recovery, then treatment with PLX3397 and a chronic-plus-single-binge EtOH challenge for 10 days. PER/PB exposure resulted in the protracted increase in liver transaminases in the serum and induced chronic low-level microvesicular steatosis and inflammation in GWI vs Naïve mice up to 4 months after cessation of exposure. Furthermore, prior exposure to PER/PB also resulted in exacerbated response to EtOH-induced liver injury, with enhanced steatosis, ductular reaction and fibrosis. The enhanced EtOH-induced liver damage in GWI-mice was attenuated by strategies designed to deplete macrophages in the liver. Taken together, these data suggest that exposure to GWI-related chemicals may alter the liver\'s response to subsequent ethanol exposure.
摘要：
海湾战争疾病（GWI）描述了海湾战争退伍军人遭受的一系列症状，由认知组成，神经和胃肠道功能障碍。与GWI相关的两种化学物质是杀虫剂氯菊酯（PER）和神经气体预防性溴吡啶斯的明（PB）。在这项研究中，我们评估了PER和PB暴露对病理和随后的酒精（EtOH）诱导的肝损伤的影响，以及巨噬细胞耗竭的影响，PLX3397,对PER/PB处理的小鼠中EtOH诱导的肝损伤。雄性C57BL/6小鼠每天注射媒介物或PER/PB，持续10天，随后恢复了4个月，然后用PLX3397和慢性加单次暴饮暴食EtOH挑战治疗10天。PER/PB暴露导致血清中肝脏转氨酶的长期增加，并在GWI和未接触小鼠中诱导慢性低水平微泡脂肪变性和炎症。此外，先前暴露于PER/PB也导致对EtOH诱导的肝损伤的反应加剧，脂肪变性增强，导管反应和纤维化。GWI小鼠中增强的EtOH诱导的肝损伤通过设计用于消耗肝脏中的巨噬细胞的策略而减弱。一起来看,这些数据表明,接触GWI相关化学物质可能会改变肝脏对随后乙醇暴露的反应.
