Impact of carbon monoxide releasing oCOm-21 on the NLRP3 inflammasome
|dc.contributor.author||Payne, Fergus Micheal|
|dc.description.abstract||During cardiac bypass procedure, the heart is subjected to repeat cycles of ischaemia reperfusion injury (IRI). This is highly detrimental to clinical outcomes in patients, presenting as myocardial dysfunction and contributing to extensive organ injury, morbidity and mortality. Pro-inflammatory signalling has been identified as a key contributor in the pathogenesis of cardiac remodelling. This IRI-linked signalling mechanism has been identified to involve the NLRP3 inflammasome to produce myocardial inflammation and dysfunction. Carbon monoxide (CO), a secondary messenger, has repeatedly been established to act through vasodilatory, anti-inflammatory, anti-thrombotic and anti-apoptotic pathways to provide protection. Recent research highlighted the capability of CO releasing compounds to reduce injury associated with the inflammasome. Therefore, this study aimed to test whether a novel organic CO releasing molecule, oCOm-21, could produce an anti-inflammatory effect by reducing NLRP3 levels within both non-hypertrophic and moderately hypertrophic CYP1a1-Ren2 rat hearts undergoing IRI. Histology was performed to evaluate the damage in both non-hypertrophic and moderately hypertrophic hearts. The vehicle controls in both groups sustained more extensive damage than oCOm-21 treated hearts. Results obtained from immunofluorescence staining indicated that non-hypertrophic hearts treated with 3 µM and 10 µM of oCOm-21 had a 2.0- and 3.0-fold decrease in NLRP3 respectively, when compared to the vehicle hearts (P < 0.01). Concurrently, there was a 2.0-fold decrease in NLRP3 staining within moderately hypertrophic hearts treated with 3 µM oCOm-21 when compared to the vehicle control (P < 0.05). No significance was observed for both moderately and non-hypertrophic rat hearts treated with 1 µM oCOm-21 vs. the vehicle control (P > 0.05). Western blotting with densitometry analysis however, failed to show a significant decrease in NLRP3 levels between vehicle control and oCOm-21 treated hearts (P > 0.05). These preliminary results strengthen the hypothesis that IRI evokes an inflammatory response, resulting in cardiac damage, which may be attenuated with oCOm-21 via the inhibition of inflammasomes. Although the immunohistochemical results demonstrates a promising link between CO and NLRP3 inhibition, the lack of reproducibility with western blotting requires additional research.|
|dc.publisher||University of Otago|
|dc.rights||All items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.|
|dc.subject||Ischaemia reperfusion injury|
|dc.title||Impact of carbon monoxide releasing oCOm-21 on the NLRP3 inflammasome|
|thesis.degree.discipline||Pharmacology and Toxicology|
|thesis.degree.name||Bachelor of Biomedical Sciences with Honours|
|thesis.degree.grantor||University of Otago|
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