Antonini J M, Reasor M J
Robert C. Byrd Health Sciences Center, Department of Pharmacology and Toxicology, West Virginia University, Morgantown 26506-9223.
J Toxicol Environ Health. 1994 Sep;43(1):85-101. doi: 10.1080/15287399409531906.
The objective of our study was to investigate whether coating the surface of silica with Survanta, a commercially available, bovine pulmonary surfactant, would reduce the in vitro cytotoxicity to alveolar macrophages (AMs), as well as attenuate lung damage in vivo following intratracheal instillation of silica. In the in vitro studies, alveolar macrophages from male Fischer 344 rats were incubated for 1 and 24 h with native or Survanta-treated silica (0.5 mg/ml). At both time points, the native, uncoated silica caused a dramatic loss of AM viability. The AMs were protected, however, when the silica was treated with the Survanta surfactant. This protective effect was significantly greater after 1 h when compared with 24 h. In the in vivo studies, a high dose of silica (10 mg/100 g body weight) was suspended in Survanta and intratracheally instilled into the lungs of male Fischer 344 rats. A number of biochemical and cellular parameters were measured within the bronchoalveolar lavage fluid (BALF) 1 and 14 d after the instillation exposures to assess lung damage. One day after the instillations, the suspension of silica in Survanta resulted in significant reductions in the silica-induced increases in total protein, beta-glucuronidase activity, and influx of neutrophils (PMNs) into the airspaces of the lungs. Fourteen days after the instillation exposures, this protective effect was lost. When Survanta was instilled into the lungs 15 min after the intratracheal instillation of silica, a significant reduction also was demonstrated in the silica-induced elevations in BALF total protein, beta-glucuronidase activity, and influx of PMNs 1 d after the instillation exposures. In an attempt to protect silica-exposed lungs over a longer period of time, Survanta was instilled into the lung 15 min after the silica instillation, and then every other day over a 7-d treatment period. Twenty-four hours after the last Survanta instillation, slight but significant decreases in the silica-induced elevations in BALF total protein and beta-glucuronidase activity were observed. The Survanta treatment, however, had no effect in preventing the infiltration of PMNs into the airspaces of the lungs. The results of this study indicate that artificially coating the silica with surfactant phospholipid offers short-term protection against its toxicity under both in vitro and in vivo conditions.
我们研究的目的是调查用一种市售的牛肺表面活性剂Survanta包被二氧化硅表面，是否会降低其对肺泡巨噬细胞（AMs）的体外细胞毒性，以及减轻气管内注入二氧化硅后在体内造成的肺损伤。在体外研究中，将来自雄性Fischer 344大鼠的肺泡巨噬细胞与天然的或经Survanta处理的二氧化硅（0.5 mg/ml）孵育1小时和24小时。在这两个时间点，天然的、未包被的二氧化硅均导致AMs活力显著丧失。然而，当二氧化硅用Survanta表面活性剂处理时，AMs受到了保护。与24小时相比，1小时后的这种保护作用明显更强。在体内研究中，将高剂量的二氧化硅（10 mg/100 g体重）悬浮于Survanta中，经气管内注入雄性Fischer 344大鼠的肺中。在注入暴露后1天和14天，对支气管肺泡灌洗液（BALF）中的一些生化和细胞参数进行测量，以评估肺损伤情况。注入后1天，二氧化硅在Survanta中的悬浮液使二氧化硅诱导的总蛋白增加、β-葡萄糖醛酸酶活性增加以及中性粒细胞（PMNs）流入肺腔的情况显著减少。注入暴露后14天，这种保护作用消失。当在气管内注入二氧化硅15分钟后将Survanta注入肺中时，在注入暴露后1天，二氧化硅诱导的BALF总蛋白升高、β-葡萄糖醛酸酶活性升高以及PMNs流入情况也显著降低。为了在更长时间内保护暴露于二氧化硅的肺，在二氧化硅注入后15分钟将Survanta注入肺中，然后在7天的治疗期内每隔一天注入一次。在最后一次注入Survanta 24小时后，观察到二氧化硅诱导的BALF总蛋白和β-葡萄糖醛酸酶活性升高略有但显著降低。然而，Survanta处理对防止PMNs渗入肺腔没有作用。本研究结果表明，用表面活性剂磷脂人工包被二氧化硅在体外和体内条件下均能对其毒性提供短期保护。
