gamma-Glutamyltranspeptidase in rat bronchoalveolar lavage fluid as a probe of 4-ipomeanol and alpha-naphthylthiourea-induced pneumotoxicity.
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.
Day
B J
BJ
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
Carlson
G P
GP
DeNicola
D B
DB
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000201:enzymology*; D004727:Endothelium / Q000187:drug effects / Q000201:enzymology; D007274:Injections, Intraperitoneal; D007770:L-Lactate Dehydrogenase / Q000032:analysis*; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013729:Terpenes / Q000008:administration & dosage / Q000633:toxicity*; D013890:Thiourea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000032:analysis*
D013729:Terpenes; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D013890:Thiourea; C005277:alpha-naphthyl thiourea; C001470:4-ipomeanol