Involvement of thromboxane A2 (TXA2) in the early stages of oleic acid-induced lung injury and the preventive effect of ozagrel, a TXA2 synthase inhibitor, in guinea-pigs.
An intravenous injection of oleic acid into animals can produce a lung injury with hypoxaemia and pulmonary vascular hyper-permeability. Although oleic acid lung injury is used as a model of acute respiratory distress syndrome (ARDS), the precise mechanisms of the lung injury are still unclear. We have investigated whether thromboxane A(2) (TXA(2)) participated in the lung injury and have evaluated the efficacy of ozagrel, a TXA(2) synthase inhibitor, on the lung injury in guinea-pigs. Oleic acid injection increased the plasma level of TXB(2), a stable metabolite of TXA(2), and the time-course of plasma TXB(2) was similar to that of the decreased partial oxygen pressure of arterial blood (Pao(2)) induced with oleic acid. Ozagrel administered intravenously 30 min before oleic acid injection prevented the decrease in Pao(2) and pulmonary vascular hyper-permeability. It also prevented increases in lactate dehydrogenase activity, a measure of lung cell injury, TXB(2 )and its weight ratio to 6-keto prostaglandin F(1alpha) in bronchoalveolar lavage fluid. Although ozagrel administered simultaneously with oleic acid ameliorated the decrease in Pao(2), post treatment showed little effect. We suggest that TXA(2) participated in the oleic acid lung injury, as an "early phase" mediator, and rapidly-acting TXA(2) synthase inhibitors were effective in the prevention of acute lung injury.
Ishitsuka
Yoichi
Y
Department of Clinical Chemistry and Informatics, Graduate school of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Moriuchi
Hiroshi
H
Hatamoto
Keita
K
Yang
Changqing
C
Takase
Junko
J
Golbidi
Saeid
S
Irikura
Mitsuru
M
Irie
Tetsumi
T
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D008171:Lung Diseases / Q000378:metabolism* / Q000503:physiopathology; D008689:Methacrylates / Q000494:pharmacology*; D019301:Oleic Acid; D013928:Thromboxane A2 / Q000096:biosynthesis* / Q000097:blood; D013929:Thromboxane B2 / Q000096:biosynthesis; D014655:Vascular Resistance
D004791:Enzyme Inhibitors; D008689:Methacrylates; D019301:Oleic Acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D007770:L-Lactate Dehydrogenase; C034364:ozagrel