Abstract
ObjectiveHepatopulmonary syndrome (HPS) is characterized by hypoxia in patients with chronic liver disease. The mechanism of HPS includes pulmonary vasodilatation, inflammation, and angiogenesis. Prostaglandins synthesized by cyclooxygenases (COX) participate in vascular responsiveness, inflammation and angiogenesis, which can be modulated by COX inhibitors. We therefore evaluated the impact of COX inhibition in rats with common bile duct ligation (CBDL)-induced liver cirrhosis and HPS.MethodsCirrhotic rats were randomly allocated to receive non-selective COX inhibitor (indomethacin), selective COX-1 inhibitor (SC-560), or COX-2 inhibitor (celecoxib) for 14 days. After that, hemodynamic parameters, severity of hypoxia and intrapulmonary shunts, liver and renal biochemistry parameters, histological finding and protein expressions were evaluated.ResultsNon-selective COX inhibition by indomethacin improved hepatic fibrosis and pulmonary inflammation in cirrhotic rats with HPS. It also decreased mean arterial blood pressure, portal pressure, and alleviated hypoxia and intrapulmonary shunts. However, indomethacin increased mortality rate. In contrast, selective COX inhibitors neither affected hemodynamics nor increased mortality rate. Hypoxia was improved by SC-560 and celecoxib. In addition, SC-560 decreased intrapulmonary shunts, attenuated pulmonary inflammation and angiogenesis through down-regulating COX-, NFκB- and VEGF-mediated pathways.ConclusionSelective COX-1 inhibitor ameliorated HPS by mitigating hypoxia and intrapulmonary shunts, which are related to anti-inflammation and anti-angiogenesis.
Highlights
The hepatopulmonary syndrome (HPS) is a dreadful complication in patients with chronic liver disease [1]
Hypoxia was improved by SC-560 and celecoxib
Selective COX-1 inhibitor ameliorated HPS by mitigating hypoxia and intrapulmonary shunts, which are related to anti-inflammation and anti-angiogenesis
Summary
The hepatopulmonary syndrome (HPS) is a dreadful complication in patients with chronic liver disease [1]. Three important components of HPS have been identified, including hypoxia with elevation of alveolar arterial oxygen pressure gradient (AaPO2), intrapulmonary vasodilatation with increased intrapulmonary shunts, and chronic liver disease [1,2]. The intrapulmonary vasodilatation and increased shunts lead to abnormal gas exchange and hypoxia in HPS patients [2]. Prostacyclin is a vasodilatory prostanoid which is capable of increasing portal tributary blood flow and portal pressure [6]. It is synthesized through cyclooxygenases (COX) including COX-1 and COX-2. The previous studies have reported that COX inhibition attenuated collateral vasodilatation in portal hypertensive and cirrhotic rats [7,8]. The non-selective COX inhibitor (indomethacin), selective COX-1 inhibitor (5-(4-chlorophenyl)-1- (4-methoxyphenyl)-3-trifluoromethyl pyrazole, SC-560), and COX-2 inhibitor (celecoxib) were administered to evaluate their influences on HPS
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
