Investigating the possible cytoprotective effects of melatonin isomer against simulated ischemic injury

Simple item page
dc.contributor.advisorLecour, Sandrineen_ZA
dc.contributor.advisorAdam, Tasneemen_ZA
dc.contributor.authorVictor, Laikynen_ZA
dc.date.accessioned2018-01-22T12:44:56Z
dc.date.available2018-01-22T12:44:56Z
dc.date.issued2017en_ZA
dc.description.abstractIntroduction: The presence of melatonin in wine contributes to the cardioprotective effect of regular and moderate consumption of wine against lethal ischemia/reperfusion injury. Recently, the presence of melatonin isomers has been identified in red wine, but whether or not these isomers confer any physiological properties is unknown. Aim: The aim of our study was to establish a cell culture model of simulated ischemia to study and compare the possible cytoprotective effects of dietary melatonin and a melatonin isomer against an ischemic insult and to explore the possible role of melatonin receptors in this effect. Methods: H9C2 cardiac fibroblast cells were subjected to simulated ischemia by exposure to 1mM H₂O₂ following a 30min pre-treatment with 75ng/L (dietary concentration), 1μM (pharmacological concentration, 0.232mg/L) melatonin or/and 75mg/L (dietary concentration) melatonin isomer. To determine the role of melatonin receptors, cells were pre-treated with the melatonin receptor inhibitor, luzindole (10 μM) for 1h prior to H₂O₂ treatment. At the end of the simulated ischemic insult, cell viability was assessed using trypan blue staining. Mitochondrial respiration in permeabilized H9C2 cells was measured using the Oroboros Instrument, at two different time points: at the end of a 30min pre-treatment with either 75ng/L melatonin or 75mg/L melatonin isomer, or the afore mentioned pre-treatments prior to a 15min treatment of 1mM H₂O₂. Results: A simulated ischemic insult with 1mM H₂O₂ reduced cell viability from 92.9±1.5% to 28.4±1.4% (p<0.001 vs control). Pre-treatment with the dietary concentrations of melatonin or the melatonin isomer improved the cell viability to a similar extent as a pre-treatment with the pharmacological concentration of melatonin (74.4±3.1%, 73.9±2.7% and 69.0±1.2%, p<0.001 vs H₂O₂ and p<0.01 vs H₂O₂ respectively). A combined pre-treatment of melatonin and the melatonin isomer did not add further cytoprotective benefit. Addition of luzindole fully abolished the cytoprotective effect of dietary melatonin (29.7±2.4%, p<0.001 vs H₂O₂ + Mel), but only partially abolished the cytoprotective effect of the melatonin isomer (41.4±3.6%). Both dietary concentrations of melatonin and the melatonin isomer did not affect mitochondrial respiration in permeabilized H9C2 cells. Conclusion: Our findings suggest that both dietary melatonin and the melatonin isomer confer cytoprotection against a simulated ischemic insult, an effect which is mediated, at least in part, via the activation of melatonin receptors. Both melatonin and melatonin isomers present the advantage to be potentially safe and inexpensive therapies against ischemic heart disease.en_ZA
dc.identifier.apacitationVictor, L. (2017). <i>Investigating the possible cytoprotective effects of melatonin isomer against simulated ischemic injury</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Department of Medicine. Retrieved from http://hdl.handle.net/11427/26869en_ZA
dc.identifier.chicagocitationVictor, Laikyn. <i>"Investigating the possible cytoprotective effects of melatonin isomer against simulated ischemic injury."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Department of Medicine, 2017. http://hdl.handle.net/11427/26869en_ZA
dc.identifier.citationVictor, L. 2017. Investigating the possible cytoprotective effects of melatonin isomer against simulated ischemic injury. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Victor, Laikyn AB - Introduction: The presence of melatonin in wine contributes to the cardioprotective effect of regular and moderate consumption of wine against lethal ischemia/reperfusion injury. Recently, the presence of melatonin isomers has been identified in red wine, but whether or not these isomers confer any physiological properties is unknown. Aim: The aim of our study was to establish a cell culture model of simulated ischemia to study and compare the possible cytoprotective effects of dietary melatonin and a melatonin isomer against an ischemic insult and to explore the possible role of melatonin receptors in this effect. Methods: H9C2 cardiac fibroblast cells were subjected to simulated ischemia by exposure to 1mM H₂O₂ following a 30min pre-treatment with 75ng/L (dietary concentration), 1μM (pharmacological concentration, 0.232mg/L) melatonin or/and 75mg/L (dietary concentration) melatonin isomer. To determine the role of melatonin receptors, cells were pre-treated with the melatonin receptor inhibitor, luzindole (10 μM) for 1h prior to H₂O₂ treatment. At the end of the simulated ischemic insult, cell viability was assessed using trypan blue staining. Mitochondrial respiration in permeabilized H9C2 cells was measured using the Oroboros Instrument, at two different time points: at the end of a 30min pre-treatment with either 75ng/L melatonin or 75mg/L melatonin isomer, or the afore mentioned pre-treatments prior to a 15min treatment of 1mM H₂O₂. Results: A simulated ischemic insult with 1mM H₂O₂ reduced cell viability from 92.9±1.5% to 28.4±1.4% (p<0.001 vs control). Pre-treatment with the dietary concentrations of melatonin or the melatonin isomer improved the cell viability to a similar extent as a pre-treatment with the pharmacological concentration of melatonin (74.4±3.1%, 73.9±2.7% and 69.0±1.2%, p<0.001 vs H₂O₂ and p<0.01 vs H₂O₂ respectively). A combined pre-treatment of melatonin and the melatonin isomer did not add further cytoprotective benefit. Addition of luzindole fully abolished the cytoprotective effect of dietary melatonin (29.7±2.4%, p<0.001 vs H₂O₂ + Mel), but only partially abolished the cytoprotective effect of the melatonin isomer (41.4±3.6%). Both dietary concentrations of melatonin and the melatonin isomer did not affect mitochondrial respiration in permeabilized H9C2 cells. Conclusion: Our findings suggest that both dietary melatonin and the melatonin isomer confer cytoprotection against a simulated ischemic insult, an effect which is mediated, at least in part, via the activation of melatonin receptors. Both melatonin and melatonin isomers present the advantage to be potentially safe and inexpensive therapies against ischemic heart disease. DA - 2017 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2017 T1 - Investigating the possible cytoprotective effects of melatonin isomer against simulated ischemic injury TI - Investigating the possible cytoprotective effects of melatonin isomer against simulated ischemic injury UR - http://hdl.handle.net/11427/26869 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/26869
dc.identifier.vancouvercitationVictor L. Investigating the possible cytoprotective effects of melatonin isomer against simulated ischemic injury. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Department of Medicine, 2017 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/26869en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherCardiovascular Researchen_ZA
dc.titleInvestigating the possible cytoprotective effects of melatonin isomer against simulated ischemic injuryen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMSc (Med)en_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
thesis_hsf_2017_victor_laikyn..pdf
Size:
2.3 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Masters