title: Lactate dehydrogenase activity and isozyme patterns in tissues and bronchoalveolar lavage fluid from rats treated with monocrotaline pyrrole.
abstract: Monocrotaline pyrrole (MCTP), a putative, toxic metabolite of monocrotaline, induces delayed and progressive lung injury, vascular remodeling, and pulmonary hypertension in rats. The lung injury is characterized by increased wet lung-to-body weight ratio followed by increases in lactate dehydrogenase (LDH) activity and protein concentration in the cell-free bronchoalveolar lavage fluid (BALF) and increased cellularity of BALF. We evaluated total LDH activity and isozyme patterns in the tissues, cell lysates, sera and cell-free BALF of rats after treatment with MCTP to determine the source of increased LDH activity. Male Sprague-Dawley rats were given a single injection of MCTP (3.5 mg/kg) or an equal volume of the N,N-dimethylformamide (DMF) vehicle in the tail vein on Day 0. Rats were killed at 4, 8, or 14 days after toxicant administration, and several markers of lung injury, LDH activity, and isozyme patterns of various tissues, cells, and body fluids were determined. At 8 and 14 days, the lungs from MCTP-treated rats had multifocal, irregularly shaped lesions of hemorrhage and consolidation. At Day 14 only, the hearts of MCTP-treated rats appeared enlarged and there was right cardioventricular hypertrophy. Rats treated with MCTP had no macroscopic lesions in kidneys, liver, or skeletal muscle. Compared to controls, MCTP-treated animals had no change in total LDH activity or isozyme patterns of samples of lungs, heart, skeletal muscle, liver, kidneys, or erythrocyte lysates. Changes in LDH activity in the cell-free BALF and BALF cell pellet from rats treated with MCTP were characterized by increases in isozymes LDH4 and LDH5 and an elevated LDH4/LDH5 ratio in the BALF only. Our results suggest the most probable source of the increased LDH activity in cell-free BALF of MCTP-treated rats originates from the lung tissue and is consistent with a contribution from the pulmonary vascular endothelium, a source rich in LDH4. A combination of plasma, macrophages, and neutrophils in the pulmonary tissue may also have made minor contributions to the increase in cell-free BALF LDH activity, particularly to the activity of LDH5.
authors.affiliation: Department of Pathology, Michigan State University, East Lansing 48824.
authors.forename: A E
authors.initials: AE
authors.lastname: Schultze
authors.forename: K P
authors.initials: KP
authors.lastname: Gunaga
authors.forename: J G
authors.initials: JG
authors.lastname: Wagner
authors.forename: C M
authors.initials: CM
authors.lastname: Hoorn
authors.forename: W R
authors.initials: WR
authors.lastname: Moorehead
authors.forename: R A
authors.initials: RA
authors.lastname: Roth
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004586:Electrophoresis; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology; D004912:Erythrocytes / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology; D006984:Hypertrophy / Q000139:chemically induced; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000187:drug effects*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology; D008297:Male; D016686:Monocrotaline / Q000031:analogs & derivatives* / Q000633:toxicity; D009504:Neutrophils / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D007527:Isoenzymes; C014114:monocrotaline pyrrole; D016686:Monocrotaline; D007770:L-Lactate Dehydrogenase