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

Ishitsuka, Yoichi; Moriuchi, Hiroshi; Hatamoto, Keita; Yang, Chen; Takase, Junko; Golbidi, Saeid; Irikura, Mitsuru; Irie, Tetsumi

doi:10.1211/0022357023150

Cited by 29 publications

(30 citation statements)

References 36 publications

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“…The maximum increase, approximately 2.5-fold of that at 0 h, was observed 3 h after OA injection. This result is in good agreement with previous results evaluated by Evans blue extravasation (4). OA increased the number of leucocytes in BALF.…”

supporting

confidence: 93%

“…Lung injury in male Hartley guinea pigs (420 -500 g) was induced as described previously (4,9). Briefly, guinea pigs were anesthetized with pentobarbital sodium (Nembutal Initially, we examined the change in time course parameters in the lung injury system.…”

mentioning

confidence: 99%

“…To evaluate efficacy, 80 mg/ kg ozagrel, identified in our previous study (4) as the dosage capable of fully inhibiting TXA 2 production, was administered intravenously 30 min prior to OA injection; lung injury parameters were measured 3 h after OA injection. To ascertain the effect on TXA 2 production, we measured the levels of TXB 2 in BALF 1.5 h after OA injection.…”

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confidence: 99%

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A Selective Thromboxane A2 (TXA2) Synthase Inhibitor, Ozagrel, Attenuates Lung Injury and Decreases Monocyte Chemoattractant Protein-1 and Interleukin-8 mRNA Expression in Oleic Acid–Induced Lung Injury in Guinea Pigs

et al. 2009

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Abstract. This study examined the effect of ozagrel, a thromboxane A 2 synthase inhibitor, on the accumulation of leucocytes and chemokine mRNA expression in lungs experimentally injured using oleic acid (OA). OA injection into guinea pigs rapidly increased thromboxane A 2 generation and subsequently increased total protein concentration and the numbers of macrophages and neutrophils in bronchoalveolar lavage fluid and increased monocyte chemoattractant protein-1 and interleukin-8 mRNA expression in the whole lung. Administration of ozagrel prevented these changes associated with OA injection. Ozagrel is a promising drug candidate for preventing acute lung injury.

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A Selective Thromboxane A2 (TXA2) Synthase Inhibitor, Ozagrel, Attenuates Lung Injury and Decreases Monocyte Chemoattractant Protein-1 and Interleukin-8 mRNA Expression in Oleic Acid–Induced Lung Injury in Guinea Pigs

et al. 2009

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“…In oleic acid lung injury, there is an increase in plasma level of TXB 2 , a stable metabolite of TXA 2 , which is correlated with decreased partial oxygen pressure of arterial blood Pa O 2 . Treatment with a TXA 2 synthase inhibitor before oleic acid injection prevents the decrease in Pa O 2 and pulmonary vascular hyperpermeability (41). These data suggest that TXA 2 participates in the oleic acid lung injury as an early phase mediator.…”

Section: Role Of Pg In the Pathogenesis Of Inflammation And Acute Lunmentioning

confidence: 68%

Involvement of cyclooxygenase-2 and prostaglandins in the molecular pathogenesis of inflammatory lung diseases

Park¹,

Christman²

2006

American Journal of Physiology-Lung Cellular and Molecular Phys

165

139

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Park, Gye Young, and John W. Christman. Involvement of cyclooxygenase-2 and prostaglandins in the molecular pathogenesis of inflammatory lung diseases. Am J Physiol Lung Cell Mol Physiol 290: L797-L805, 2006; doi:10.1152/ajplung.00513.2005.-Inducible cyclooxygenase (COX-2) and its metabolites have diverse and potent biological actions that are important for both physiological and disease states of lung. The wide variety of prostaglandin (PG) products are influenced by the level of cellular activation, the exact nature of the stimulus, and the specific cell type involved in their production. In turn, the antiand proinflammatory response of PG is mediated by a blend of specific surface and intracellular receptors that mediate diverse cellular events. The complexity of this system is being at least partially resolved by the generation of specific molecular biological research tools that include cloning and characterization of the enzymes distal to COX-2 and the corresponding receptors to the final cellular products of arachidonic metabolism. The most informative of these approaches have employed genetically modified animals and specific receptor antagonists to determine the exact role of specific COX-2-derived metabolites on specific cell types of the lung in the context of inflammatory models. These data have suggested a number of cell-specific, pathway-specific, and receptor-specific approaches that could lead to effective therapeutic interventions for most inflammatory lung diseases. asthma; acute lung injury; pulmonary fibrosis ASPIRIN IS AN ANCIENT REMEDY that was first marketed in 1898 and launched more than a century of research that has focused on the involvement of cyclooxygenase (COX) and its enzymatic products in diverse physiological and pathophysiological events. Thirty years after prostaglandins (PG) were identified, Orloff et al. (79a) elucidated their molecular structure and demonstrated that they were derived from arachidonic acid via the COX reaction. This seminal work was greatly advanced when John Vane (102) first demonstrated that aspirin and indomethacin inhibited COX in cell-free homogenated lung tissue from guinea pigs. For their contributions of identifying COX, prostanoids products, and effective pharmacological inhibitors, Bergstrom, Samuelsson, and Vane shared The Noble Prize for Physiology or Medicine in 1982. Armed with these molecular tools and the analytic chemistry necessary to measure prostanoids, many investigators have examined the role of COX-2 and its metabolites in diverse and potent biological action on individual organs and mediators of organ interactions, including work that identified a prominent role in normal physiology and disease state of lung. Although there are several recent general reviews about COX and PG (18,33,73,74,90), none are specifically focused on information about the role of COX-2 and its metabolites in inflammatory lung diseases. Here, we will mainly focus on recent developments and updated information regarding the role of COX-2 in lung disease with a...

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“…However, in FES-induced ALI, cytosolic PLA 2 (cPLA 2 ) might play a crucial role for the initiation of acute inflammation in the lung, as cPLA 2 s are abundant in the lung and mononuclear phagocytes are enriched with cPLA 2 9 . Besides, cPLA 2 mediates arachidonic acid-induced tissue injury which comprises the activation of NADPH oxidase and inflammatory reaction irrespective of free radicals 10 . In OA-induced ALI, neutrophils play a crucial role along with its accumulation and migration to the lung provoking epithelial and endothelial injury by oxidative stress and release of proteases 11 .…”

Section: Introductionmentioning

confidence: 99%

A Study on the Mechanism of Immunomodulating Effects of Moxifloxacin in Oleic Acid-Induced Acute Lung Injury

Lee

2011

Tuberc Respir Dis

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Background: It was hypothesized that the immunomodulating effects of moxifloxacin contribute to ameliorate oleic acid (OA)-induced acute lung injury (ALI) by suppression of cytosolic phospholipase A2 (cPLA2). This was based on observations from experiments on rats associated with neutrophilic respiratory burst, cPLA2 activity, and expressions of cPLA2, TNFα, and COX-II in the lung. Methods: ALI was induced by intravenous injection of OA in male Sprague-Dawley rats. Five hours after OA injection, protein content in bronchoalveolar lavage (BAL), lung myeloperoxidase (MPO) activity, and numbers of BAL neutrophils were measured. As an index of oxidative stress-induced lung injury, the content of malondialdehyde (MDA) in lung tissues was also determined. Lung histology, immunohistochemistry and determination of activity of cPLA2 in lung tissues were carried out. In addition, Western blotting of TNFα and COX-II in lung tissues was performed.Results: The accumulation of neutrophils in the lungs was observed after OA injection. BAL protein was increased along with neutrophilic infiltration and migration by OA. Moxifloxacin decreased all of these parameters of ALI and ameliorated ALI histologically. The increased malondialdehyde (MDA) in the lung by OA was also decreased by moxifloxacin. Moxifloxacin not only suppressed cPLA2 expression in the lungs and neutrophils but also decreased cPLA2 activity in lung tissues of rats given OA. The enhanced expressions of TNFα and COX-2 in the lung tissues of rats given OA were also suppressed by moxifloxacin. Conclusion: Moxifloxacin inhibited cPLA2 and down-regulated TNFα and COX-2 in the lungs of rats given OA, which resulted in the attenuation of inflammatory lung injury.

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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

Cited by 29 publications

References 36 publications

A Selective Thromboxane A2 (TXA2) Synthase Inhibitor, Ozagrel, Attenuates Lung Injury and Decreases Monocyte Chemoattractant Protein-1 and Interleukin-8 mRNA Expression in Oleic Acid–Induced Lung Injury in Guinea Pigs

A Selective Thromboxane A2 (TXA2) Synthase Inhibitor, Ozagrel, Attenuates Lung Injury and Decreases Monocyte Chemoattractant Protein-1 and Interleukin-8 mRNA Expression in Oleic Acid–Induced Lung Injury in Guinea Pigs

Involvement of cyclooxygenase-2 and prostaglandins in the molecular pathogenesis of inflammatory lung diseases

A Study on the Mechanism of Immunomodulating Effects of Moxifloxacin in Oleic Acid-Induced Acute Lung Injury

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