Day B J, Carlson G P, DeNicola D B
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
J Pharmacol Methods. 1990 Aug;24(1):1-8. doi: 10.1016/0160-5402(90)90044-l.
Bronchoalveolar lavage fluid analysis has gained popularity as a rapid in vivo screen to evaluate the toxicity of both systemic and inhaled pneumotoxicants and is used in addition to the more commonly evaluated pathologic changes. This study evaluated gamma-glutamyltranspeptidase (GGT) in the bronchoalveolar lavage fluid (BALF) along with the more commonly measured enzyme, lactate dehydrogenase (LDH), as a useful indicator of acute lung injury from systematically administered pneumotoxicants. Adult male rats were injected ip with 2, 3, or 3.5 mg/kg body weight of alpha-naphthylthiourea (ANTU) or 5, 10, or 20 mg/kg of 4-ipomeanol, and measurements were made 8 or 24 hr postdose, respectively. ANTU, which selectively damages pulmonary endothelial cells, caused extensive pleural effusions with striking increases in BALF protein and white blood cell (WBC) content. 4-Ipomeanol, which selectively damages nonciliated bronchiolar Clara cells, caused dose dependent increases in both GGT and LDH activities in the BALF with GGT being increased at all doses tested. BALF protein content was also increased in the 4-ipomeanol-treated groups, but this change was not dose dependent. Analysis of GGT in BALF was a sensitive method to assess cytotoxicity associated with 4-ipomeanol-induced injury but was less useful in monitoring pulmonary endothelial cell damage induced by ANTU. Measurements of BALF protein and WBC content proved to be better in assessing injury by agents such as ANTU that primarily affect vascular permeability.
支气管肺泡灌洗术作为一种快速的体内筛查方法，用于评估全身性和吸入性肺毒物的毒性，已越来越受到关注，并且除了更常用的病理变化评估之外也会使用该方法。本研究评估了支气管肺泡灌洗术（BALF）中的γ-谷氨酰转肽酶（GGT）以及更常用的酶——乳酸脱氢酶（LDH），作为系统给予肺毒物所致急性肺损伤的有用指标。成年雄性大鼠腹腔注射2、3或3.5mg/kg体重的α-萘基硫脲（ANTU）或5、10或20mg/kg的4-异亚丙基丙酮醇，分别在给药后8或24小时进行测量。选择性损伤肺内皮细胞的ANTU导致广泛的胸腔积液，BALF蛋白和白细胞（WBC）含量显著增加。选择性损伤无纤毛细支气管克拉拉细胞的4-异亚丙基丙酮醇导致BALF中GGT和LDH活性呈剂量依赖性增加，在所测试的所有剂量下GGT均增加。4-异亚丙基丙酮醇治疗组的BALF蛋白含量也增加，但这种变化不呈剂量依赖性。分析BALF中的GGT是评估与4-异亚丙基丙酮醇诱导损伤相关的细胞毒性的敏感方法，但在监测ANTU诱导的肺内皮细胞损伤方面不太有用。测量BALF蛋白和WBC含量被证明在评估主要影响血管通透性的药物（如ANTU）所致损伤方面更有效。
