Leukotoxin (9,10-epoxy-12-octadecenoate) impairs energy and redox state of isolated perfused rat lung

被引:9
作者
Akai, M [1 ]
Ishizaki, T
Matsukawa, S
Shigemori, K
Miyamori, I
机构
[1] Fukui Med Univ, Fac Med, Dept Internal Med 3, Matsuoka, Fukui 91011, Japan
[2] Fukui Med Univ, Fac Med, Cent Res Labs, Matsuoka, Fukui 91011, Japan
关键词
leukotoxin; endothelin-1; energy balance; redox state; antioxidant state; nitric oxide; superoxide anion; free radical;
D O I
10.1016/S0891-5849(98)00102-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We investigated the perturbation of energy balance and redox state in leukotoxin (9, 10-epoxy-12-octadecenoate) (Lx)- and endothelin-1 (ET-1)-induced lung injury, using isolated perfused rat lungs. To examine any relationship between these parameters, intracellular levels of adenine nucleotides, pyridine coenzymes and glutathione were determined by reversed-phase high-performance liquid chromatography (HPLC) in the freeze-dried tissues of isolated rat lungs. The tissue samples were perfused with a physiological salt solution containing either Lx only, Lx plus N-G-monomethyl-L-arginine (L-NMMA), Lx plus N-G-monomethyl-D-arginine (D-NMMA), Lx plus superoxide dismutase (SOD) or ET-1 only. In isolated perfused lung tissue, 10 mu mol of Lx caused permeability-increased lung injury, and 10 nM of ET-1, which caused a comparable increase in wet lung weight, evoked pulmonary capillary hypertensive lung injury. Lx-injured lungs showed decreases in the contents of ATP, NADPH, NADH, reduced glutathione (GSH), (2ATP + ADP)/2(ATP + ADP + AMP) ratio (energy charge) and NADH/NAD(+) ratio, and increased the contents of ADP and AMP compared with the vehicle control and ET-1-injured lungs. Such effects of Lx were significantly attenuated by pretreatment with 0.4 mM L-NMMA or 500 units/ml of SOD, but not with 0.4 mM D-NMMA. On the other hand, the ET-1-injured lung evidenced decreased tissue GSH. These findings indicate that Lx shifted the lung redox state toward oxidation and that Lx-induced lung injury was involved in the imbalance of the energy and redox state via production of nitric oxide and/or superoxide anion. (C) 1998 Elsevier Science Inc.
引用
收藏
页码:596 / 604
页数:9
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