No abstract

Changes in several biomarkers in bronchoalveolar lavage fluid (BALF) during an early stage of lung injury induced with oleic acid were examined in guinea pigs. In addition, a possible contribution of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and xanthine oxidase to the oxidative changes in the lung injury was investigated. An intravenous injection of oleic acid increased the levels of lipid peroxidation products, lactate dehydrogenase, and total proteins, decreased the ratio of glutathione to glutathione disulfide in the BALF, and also affected the levels of other oxidative biomarkers such as superoxide dismutase and catalase in the BALF in a dose-dependent manner. Diphenyleneiodonium chloride, a NADPH oxidase inhibitor, inhibited the oxidative changes in the BALF and the decrease in partial pressure of oxygen in artery induced with oleic acid, while allopurinol, a xanthine oxidase inhibitor, had no inhibitory effects. The results demonstrate that oxidative stress would be an important mechanism of oleic acid-induced lung injury, and indicate that the NADPH oxidase-dependent pathway contributes significantly to the generation of reactive oxygen species in oleic acid-induced lung injury.Key words oleic acid; acute lung injury; oxidative stress; nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; diphenyleneiodonium chloride; bronchoalveolar lavage fluid 424

The fluorescence characteristics of various methoxycoumarin fluorophores for the development of fluorescence reagents were examined in relation to their structures. The fluorescence emission mechanisms were also considered from the viewpoint of the intramolecular charge-transfer (CT) between methoxyl substituents and the coumarin ring. The arrangement of 6-methoxyl and 3-acetyl group pairs on the coumarin ring significantly contributed to the fluorescence enhancement through the intramolecular CT. We found that the structural features of methoxycoumarins required for intense fluorescence are to hold both diether bonds at the 6-and 7-positions and an electron-withdrawing group at the 3-position, as shown in 3-acetyl-6,7-dimethoxycoumarin with 0.52 in quantum yield.

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.

No abstract