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dc.contributor.authorOi, Massa
dc.contributor.authorDonner, Daniel
dc.contributor.authorPeart, Jason
dc.contributor.authorBeck, Belinda
dc.contributor.authorWendt, Lauren
dc.contributor.authorHeadrick, John P
dc.contributor.authordu Toit, Eugene F
dc.date.accessioned2019-05-29T13:05:52Z
dc.date.available2019-05-29T13:05:52Z
dc.date.issued2018
dc.identifier.issn0014-2999
dc.identifier.doi10.1016/j.ejphar.2018.02.050
dc.identifier.urihttp://hdl.handle.net/10072/380939
dc.description.abstractStatins are effective in management of dyslipidaemia, and a cornerstone of CVD prevention strategies. However, the impacts of their pleiotropic effects on other cardiovascular risk factors and myocardial responses to infarction are not well characterised. We hypothesised that pravastatin treatment in obesity improves lipid profiles, insulin-resistance and myocardial resistance to ischaemia/reperfusion (I/R) injury. Wistar rats were fed a control (C) chow or high carbohydrate and fat diet (HCFD) for 16 weeks with vehicle or pravastatin (prava 7.5 mg/kg/day) treatment for 8 weeks. At 16 weeks HOMAs were performed, blood samples collected and hearts excised for Langendorff perfusions/biochemical analyses. Anti-oxidant activity and proteins regulating mitochondrial fission/fusion and apoptosis were assessed. The HCFD increased body weight (736±15 vs. 655±12 g for C; P<0.001), serum triglycerides (2.91±0.52 vs. 1.64±0.26 mmol/L for C; P<0.001) and insulin-resistance (HOMA- 6.9±0.8 vs. 4.2±0.5 for C; P<0.05) while prava prevented diet induced changes and paradoxically increased lipid peroxidation. The HCFD increased infarct size (34.1±3.1% vs. 18.8±3.0% of AAR for C; P<0.05), which was unchanged by prava in C and HCFD animals. The HCFD decreased cardiac TxR activity and mitochondrial MFN-1 and increased mitochondrial DRP-1 (reducing MFN-1:DRP-1 ratio) and Bax expression, with the latter changes prevented by prava. While unaltered by diet, cytosolic levels of Bax and caspase-3 were reduced by prava in C and HCFD hearts (without changes in cleaved caspase-3). We conclude that obesity, hyper-triglyceridemia and impaired glycemic control in HCFD rats are countered by prava. Despite improved risk factors, prava did not reduce myocardial infarct size, potentially reflecting its complex pleiotropic impacts on cardiac GPX activity and MFN-1, DRP-1, caspase-3 and Bcl-2 proteins.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier Science
dc.publisher.placeNetherlands
dc.relation.ispartofpagefrom148
dc.relation.ispartofpageto157
dc.relation.ispartofjournalEuropean Journal of Pharmacology
dc.relation.ispartofvolume826
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences not elsewhere classified
dc.subject.fieldofresearchZoology
dc.subject.fieldofresearchCognitive and computational psychology
dc.subject.fieldofresearchSocial and personality psychology
dc.subject.fieldofresearchcode3214
dc.subject.fieldofresearchcode321499
dc.subject.fieldofresearchcode3109
dc.subject.fieldofresearchcode5204
dc.subject.fieldofresearchcode5205
dc.titlePravastatin improves risk factors but not ischaemic tolerance in obese rats
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.description.versionAccepted Manuscript (AM)
gro.facultyGriffith Health, School of Medical Science
gro.rights.copyright© 2018 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorHeadrick, John P.
gro.griffith.authorBeck, Belinda R.
gro.griffith.authorPeart, Jason N.
gro.griffith.authorWendt, Lauren
gro.griffith.authorDu Toit, Eugene


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