The Role of Cyclooxygenase and Lipoxygenase Mediators in Oxidant-induced Lung Injury

Farrukh, I. S.; Michael, J. R.; Peters, S. P.; Sciuto, Alfred M.; Adkinson, N. Franklin; Freeland, Howard S.; Paky, A.; Spannhake, E. W.; Summer, Warren R.; Gurtner, G. H.

doi:10.1164/ajrccm/137.6.1343

Cited by 48 publications

(16 citation statements)

References 15 publications

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“…Ischemia was continued for 60 min, during which lungs were ventilated with 5% CO2 in air, followed by reperfusion at 12 ml/min for 3 min. This regimen for indomethacin treatment essentially abolished production ofthromboxane B2 assayed in the lung homogenate and perfusion medium with a radioimmunoassay kit (Amersham Corp., Arlington Heights, IL) (data not shown) consistent with previous results of others with perfused rabbit lungs (19). Ischemia produced a significant increase in TBARS in ischemic lungs even in the presence of indomethacin.…”

Section: Resultssupporting

confidence: 89%

“…The increase in lipid peroxidation products could represent either the generation of eicosanoids from arachidonic acid or the less specific peroxidation of membrane or other tissue lipids. Based on studies with inhibitors of the cyclooxygenase and lipoxygenase pathways, -40-50% of the increase in lipid peroxidation products in this study was related to activation of eicosanoid metabolism by ischemia, compatible with previous reports of increased eicosanoid production during oxidative injury (19). Conversely, more than half ofthe lipid peroxidation products presumably arose from attack on tissue lipids.…”

Section: Discussionsupporting

confidence: 89%

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Oxygen-dependent lipid peroxidation during lung ischemia.

Fisher

Dodia²,

Tan³

et al. 1991

J. Clin. Invest.

143

101

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The effect of alveolar oxygen tension on lung lipid peroxidation during lung ischemia was evaluated by using isolated rat lungs perfused with synthetic medium. After a 5-min equilibration period, global ischemia was produced by discontinuing perfusion while ventilation continued with gas mixtures containing 5% CO2 and a fixed oxygen concentration between 0 and 95%. Lipid peroxidation was assessed by measurement of tissue thiobarbituric acid-reactive products and conjugated dienes. Control studies (no ischemia) showed no change in parameters of lipid peroxidation during 1 h of perfusion and ventilation with 20% or 95% 02. With 60 min of ischemia, there was increased lipid peroxidation which varied with oxygen content of the ventilating gas and was markedly inhibited by ventilation with N2. Perfusion with 5-, 8-, 11-, 14-eicosatetraynoic acid indicated that generation of eicosanoids during ischemia accounted for -40-50% of lung lipid peroxide production. Changes of CO2 content of the ventilating gas (to alter tissue pH) or of perfusate glucose concentration had no effect on lipid peroxidation during ischemia, but perfusion at 8% of the normal flow rate prevented lipid peroxidation. Lung dry/wet weight measured after 3 min of reperfusion showed good correlation between lung fluid accumulation and lipid peroxidation. These results indicate that reperfusion is not necessary for lipid peroxidation with ischemic insult of the lung and provide evidence that elevated Po2 during ischemia accelerates the rate of tissue injury. (J. Clin. Invest. 1991. 88:674479.)

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Section: Resultssupporting

confidence: 89%

Section: Discussionsupporting

confidence: 89%

Oxygen-dependent lipid peroxidation during lung ischemia.

Fisher

Dodia²,

Tan³

et al. 1991

J. Clin. Invest.

143

101

View full text Add to dashboard Cite

show abstract

“…Results from this study and previous ones do not indicate that elevated PUFA work through accentuating the development of the pulmonary antioxidant enzymes or surfactant production, nor through enhancing the ability of the newborn animal to mount a protective increase in pulmonary antioxidant enzymes in response to hyperoxic exposure. Other investigators have suggested a role for lung eicosanoids in the development of (or protection from) oxygen toxicity (22)(23)(24)(25). In our present study, we were unable to demonstrate differences in PGE2, 6-keto-PGF,-a (the metabolite of prostacyclin), or in the LTC4-F4 in lung tissue of either diet group either in air or hyperoxia ( Table 5).…”

Section: Discussionmentioning

confidence: 99%

Intralipid Increases Lung Polyunsaturated Fatty Acids and Protects Newborn Rats from Oxygen Toxicity

1991

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ABSTRACT. Intralipid, derived from soybean oil and con-6-keto-PGF,-a, 6-keto-prostaglandin FI-a taining a high percentage of n-6 family polyunsaturated LTC4-F4, leukotrienes C4-F4 fatty acids (PUFA) and also linolenic acid, an n-3 family BPD, bronchopulmonary dysplasia PUFA, is commonly the first fat source provided to very P/S, polyunsaturated/saturated fatty acid ratio low birth weight premature infants. Following up on our previous reports that newborn rats born to dams fed high-PUFA diets demonstrate superior tolerance to hyperoxia, we examined whether the high-PUFA fat source Intralipid might also protect against oxygen toxicity. Adult female With the progression of modern neonatal intensive care, rats were fed either regular Rat Chow or fat-free diet greater numbers of VLBW oxygen-and ventilator-requiring precontaining 20%-Intralipid as the fat source for 3 wk before mature infants are surviving. However, despite favorable outand then throughout pregnancy and lactation. One-and 5-comes in terms of mortality, these infants are at extremely high d-old offspring of Intralipid diet-fed dams demonstrated risk of developing the chronic lung process known as BPD, significant increases in lung lipid n-6 family PUFA plus considered to be related, at least in part, to the damaging effect elevated linolenic acid compared with regular diet-fed off-of oxygen on the lung (1). Because of the overwhelming clinical spring. These characteristic fatty acid patterns, apparent problems that these VLBW premature infants experience in the in total lung lipids, were even more pronounced in the first several days of life, nutritional needs are frequently not the triglyceride fraction compared with the phospholipid frac-highest priority in their care. In fact, common nursery practices tion. Associated with these fatty acid changes were signif-consist of a several-day interval between the birth of a VLBW icantly improved hyperoxic survival rates (89 out of oxygen-requiring premature infant and the initial administration 95 = 94% survival after 7 d of >95% O2 exposure) in of lipid nutrition. Because of the vulnerability of the VLBW Intralipid offspring (versus 89 out of 106 = 84%, p < 0.05 premature infant to the effects of a delay in lipid nutrition (2) in regular diet offspring) and evidence of superior clinical/ and the possible role that lipids might play in protecting the lung pathologic status. No differences in pulmonary antioxidant from oxygen toxicity, the early withholding of lipid nutrition enzyme or surfactant system development, response of from these critically ill neonates might increase their risk of antioxidant enzymes to hyperoxic exposure, or lung pros-developing the chronic lung disease and damage of BPD. taglandin EZ, 6-keto PGFI-a or leukotrienes C4-F, were Evidence is available from the literature to suggest that lung present. These findings continue to support the hypothesis lipid composition is related to hyperoxic tolerance and protection that increasing lung PUFA content may provide increased against hypero...

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“…The treatment of rabbits with the hemolytic agent, phenylhydrazine [162], or hemorrhagic events [163] cause a > 1000-fold rise in 15-LO levels in heart, lung, and aorta. An infusion of the oxidant tert-butyl hydroperoxide in isolated rabbit lung elevates LTB 4 , C 4 , D 4 , and E 4 content by two-to three-fold [164]. A significant rise in 15-HETE occurs when human bronchial epithelial cells are exposed in vitro to toluene di-isocyanate [165].…”

Section: Modulation Of Lipoxygenase Activitymentioning

confidence: 92%

Lipoxygenase - a versatile biocatalyst for biotransformation of endobiotics and xenobiotics

Kulkarni¹

2001

CMLS, Cell. Mol. Life Sci.

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Lipoxygenase, a member of the arachidonate cascade enzymes, dioxygenates polyenoic fatty acids to finally yield products with profound and distinct biological activity. This review summarizes the available evidence for another role played by lipoxygenases in the metabolism of endobiotics and xenobiotics. Although other mechanisms exist, a direct hydrogen abstraction by the enzyme and the peroxyl radical-dependent chemical oxidation appear to be central to the co-oxidase activity of lipoxygenases. Besides polyunsaturated fatty acids, H2O2, fatty acid hydroperoxides, and synthetic organic hydroperoxides support the lipoxygenase-catalyzed xenobiotic oxidation. The major reactions documented thus far include oxidation, epoxidation, hydroxylation, sulfoxidation, desulfuration, dearylation, and N-dealkylation. It is noteworthy that lipoxygenases are also capable of glutathione conjugation of certain xenobiotics. The enzyme system appears to be inducible following exposure to chemicals. Lipoxygenases are inhibited by a large number of chemicals, some of which also serve as co-substrates. Available data suggest that lipoxygenases contribute to in vivo metabolism of xenobiotics in mammals.

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The Role of Cyclooxygenase and Lipoxygenase Mediators in Oxidant-induced Lung Injury

Cited by 48 publications

References 15 publications

Oxygen-dependent lipid peroxidation during lung ischemia.

Oxygen-dependent lipid peroxidation during lung ischemia.

Intralipid Increases Lung Polyunsaturated Fatty Acids and Protects Newborn Rats from Oxygen Toxicity

Lipoxygenase - a versatile biocatalyst for biotransformation of endobiotics and xenobiotics

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