Oleanolic acid: a novel cardioprotective agent that blunts hyperglycemia-induced contractile dysfunction

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dc.contributor.authorMapanga, Rudo Fen_ZA
dc.contributor.authorRajamani, Uthraen_ZA
dc.contributor.authorDlamini, Nonkululekoen_ZA
dc.contributor.authorZungu-Edmondson, Makhosazaneen_ZA
dc.contributor.authorKelly-Laubscher, Roisinen_ZA
dc.contributor.authorShafiullah, Mohammeden_ZA
dc.contributor.authorWahab, Athiqen_ZA
dc.contributor.authorHasan, Mohamed Yen_ZA
dc.contributor.authorFahim, Mohamed Aen_ZA
dc.contributor.authorRondeau, Philippeen_ZA
dc.date.accessioned2015-11-18T07:10:36Z
dc.date.available2015-11-18T07:10:36Z
dc.date.issued2012en_ZA
dc.description.abstractDiabetes constitutes a major health challenge. Since cardiovascular complications are common in diabetic patients this will further increase the overall burden of disease. Furthermore, stress-induced hyperglycemia in non-diabetic patients with acute myocardial infarction is associated with higher in-hospital mortality. Previous studies implicate oxidative stress, excessive flux through the hexosamine biosynthetic pathway (HBP) and a dysfunctional ubiquitin-proteasome system (UPS) as potential mediators of this process. Since oleanolic acid (OA; a clove extract) possesses antioxidant properties, we hypothesized that it attenuates acute and chronic hyperglycemia-mediated pathophysiologic molecular events (oxidative stress, apoptosis, HBP, UPS) and thereby improves contractile function in response to ischemia-reperfusion. We employed several experimental systems: 1) H9c2 cardiac myoblasts were exposed to 33 mM glucose for 48 hr vs. controls (5 mM glucose); and subsequently treated with two OA doses (20 and 50 µM) for 6 and 24 hr, respectively; 2) Isolated rat hearts were perfused ex vivo with Krebs-Henseleit buffer containing 33 mM glucose vs. controls (11 mM glucose) for 60 min, followed by 20 min global ischemia and 60 min reperfusion ± OA treatment; 3) In vivo coronary ligations were performed on streptozotocin treated rats ± OA administration during reperfusion; and 4) Effects of long-term OA treatment (2 weeks) on heart function was assessed in streptozotocin-treated rats. Our data demonstrate that OA treatment blunted high glucose-induced oxidative stress and apoptosis in heart cells. OA therapy also resulted in cardioprotection, i.e. for ex vivo and in vivo rat hearts exposed to ischemia-reperfusion under hyperglycemic conditions. In parallel, we found decreased oxidative stress, apoptosis, HBP flux and proteasomal activity following ischemia-reperfusion. Long-term OA treatment also improved heart function in streptozotocin-diabetic rats. These findings are promising since it may eventually result in novel therapeutic interventions to treat acute hyperglycemia (in non-diabetic patients) and diabetic patients with associated cardiovascular complications.en_ZA
dc.identifier.apacitationMapanga, R. F., Rajamani, U., Dlamini, N., Zungu-Edmondson, M., Kelly-Laubscher, R., Shafiullah, M., ... Rondeau, P. (2012). Oleanolic acid: a novel cardioprotective agent that blunts hyperglycemia-induced contractile dysfunction. <i>PLoS One</i>, http://hdl.handle.net/11427/15137en_ZA
dc.identifier.chicagocitationMapanga, Rudo F, Uthra Rajamani, Nonkululeko Dlamini, Makhosazane Zungu-Edmondson, Roisin Kelly-Laubscher, Mohammed Shafiullah, Athiq Wahab, Mohamed Y Hasan, Mohamed A Fahim, and Philippe Rondeau "Oleanolic acid: a novel cardioprotective agent that blunts hyperglycemia-induced contractile dysfunction." <i>PLoS One</i> (2012) http://hdl.handle.net/11427/15137en_ZA
dc.identifier.citationMapanga, R. F., Rajamani, U., Dlamini, N., Zungu-Edmondson, M., Kelly-Laubscher, R., Shafiullah, M., ... & Essop, M. F. (2011). Oleanolic acid: a novel cardioprotective agent that blunts hyperglycemia-induced contractile dysfunction. PloS one, 7(10), e47322. doi:10.1371/journal.pone.0047322en_ZA
dc.identifier.ris TY - Journal Article AU - Mapanga, Rudo F AU - Rajamani, Uthra AU - Dlamini, Nonkululeko AU - Zungu-Edmondson, Makhosazane AU - Kelly-Laubscher, Roisin AU - Shafiullah, Mohammed AU - Wahab, Athiq AU - Hasan, Mohamed Y AU - Fahim, Mohamed A AU - Rondeau, Philippe AB - Diabetes constitutes a major health challenge. Since cardiovascular complications are common in diabetic patients this will further increase the overall burden of disease. Furthermore, stress-induced hyperglycemia in non-diabetic patients with acute myocardial infarction is associated with higher in-hospital mortality. Previous studies implicate oxidative stress, excessive flux through the hexosamine biosynthetic pathway (HBP) and a dysfunctional ubiquitin-proteasome system (UPS) as potential mediators of this process. Since oleanolic acid (OA; a clove extract) possesses antioxidant properties, we hypothesized that it attenuates acute and chronic hyperglycemia-mediated pathophysiologic molecular events (oxidative stress, apoptosis, HBP, UPS) and thereby improves contractile function in response to ischemia-reperfusion. We employed several experimental systems: 1) H9c2 cardiac myoblasts were exposed to 33 mM glucose for 48 hr vs. controls (5 mM glucose); and subsequently treated with two OA doses (20 and 50 µM) for 6 and 24 hr, respectively; 2) Isolated rat hearts were perfused ex vivo with Krebs-Henseleit buffer containing 33 mM glucose vs. controls (11 mM glucose) for 60 min, followed by 20 min global ischemia and 60 min reperfusion ± OA treatment; 3) In vivo coronary ligations were performed on streptozotocin treated rats ± OA administration during reperfusion; and 4) Effects of long-term OA treatment (2 weeks) on heart function was assessed in streptozotocin-treated rats. Our data demonstrate that OA treatment blunted high glucose-induced oxidative stress and apoptosis in heart cells. OA therapy also resulted in cardioprotection, i.e. for ex vivo and in vivo rat hearts exposed to ischemia-reperfusion under hyperglycemic conditions. In parallel, we found decreased oxidative stress, apoptosis, HBP flux and proteasomal activity following ischemia-reperfusion. Long-term OA treatment also improved heart function in streptozotocin-diabetic rats. These findings are promising since it may eventually result in novel therapeutic interventions to treat acute hyperglycemia (in non-diabetic patients) and diabetic patients with associated cardiovascular complications. DA - 2012 DB - OpenUCT DO - 10.1371/journal.pone.0047322 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Oleanolic acid: a novel cardioprotective agent that blunts hyperglycemia-induced contractile dysfunction TI - Oleanolic acid: a novel cardioprotective agent that blunts hyperglycemia-induced contractile dysfunction UR - http://hdl.handle.net/11427/15137 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15137
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0047322
dc.identifier.vancouvercitationMapanga RF, Rajamani U, Dlamini N, Zungu-Edmondson M, Kelly-Laubscher R, Shafiullah M, et al. Oleanolic acid: a novel cardioprotective agent that blunts hyperglycemia-induced contractile dysfunction. PLoS One. 2012; http://hdl.handle.net/11427/15137.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDepartment of Human Biologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© Mapanga et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherGlucoseen_ZA
dc.subject.otherHearten_ZA
dc.subject.otherReperfusionen_ZA
dc.subject.otherApoptosisen_ZA
dc.subject.otherIschemiaen_ZA
dc.subject.otherHyperglycemiaen_ZA
dc.subject.otherDiabetes mellitusen_ZA
dc.subject.otherOxidative stressen_ZA
dc.titleOleanolic acid: a novel cardioprotective agent that blunts hyperglycemia-induced contractile dysfunctionen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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