Dietary red palm oil-supplementation offers cardioprotection against Ischaemia/Reperfusion injury : possible cellular mechanisms involved

[摘要] ENGLISH ABSTRACT: Activation of the NO-cGMP pathway is associated with myocardial protectionagainst ischaemia/reperfusion injury. However, high-cholesterol diets alterfunction of this pathway and these alterations have been implicated in bothischaemic/reperfusion injury and the development of ischaemic heart disease.Little is known about the effects of supplements such as Red Palm Oil (RPO)on the myocardial NO-cGMP-signalling pathway. RPO consists of saturated,mono-unsaturated and poly-unsaturated fatty acids and is rich in antioxidantssuch as β-carotene and Vitamin E (tocopherols and tocotrienols). The aims ofthis study were: 1) to determine whether dietary RPO-supplemention protectsagainst ischaemia/reperfusion injury in rats fed a standard rat chow (control)and cholesterol-enriched diets and 2) if so, to investigate possible mechanismsfor this protection.Male Long-Evans rats were fed a standard rat chow or a standard rat chowplus cholesterol and/or RPO-supplementation for 6 weeks. Myocardialfunctional recovery was measured and hearts were freeze-clamped fordetermination of myocardial phospholipid, cAMP/cGMP concentrations, totalmyocardial nitric oxide concentrations, lipid hydroperoxide production andsuperoxide dismutase- and nitric oxide synthase activity in isolated rat heartssubjected to 25 minutes of normothermic total global ischaemia. In addition,the degree of phosphorylation of extracellular signal-regulated kinase (ERK),p38, c-Jun N-terminal protein kinase (JNK) and protein kinase B (PKB/Akt)was investigated. Furthermore, the effect of RPO-supplementation oncaspase-3 activation and poly (ADP-ribose) polymerase (PARP)-cleavage inhearts subjected to ischaemia and reperfusion was also investigated. Our data show that dietary RPO-supplementation protects the hearts of rats ona standard rat chow (control) and hypercholesterolaemic diet againstischaemia/reperfusion injury as reflected by improved aortic output recovery.Increased intracellular cardiomyocyte NO concentrations as observed incontrol hearts supplemented with RPO after 120 minutes hypoxia maycontribute to the elevated cGMP concentration and may confer some of thecardioprotection to the ischaemic/reperfused heart. Although improvedfunctional recovery with RPO-supplementation of a high-cholesterol diet wasalso associated with an increase in intracellular cardiomyocyte NO productionafter hypoxia compared to the non-hypoxic conditions, it could not be linked toincreased NO-cGMP signalling. These data are in agreement with otherstudies, which showed that high-cholesterol diet impairs NO-cGMP signallingand confirms our hypothesis that elevated cGMP concentrations may not bethe only mechanism of protection. We have also shown that RPOsupplementationcaused increased phosphorylation of p38 and PKB, reducedphosphorylation of JNK and attenuation of PARP cleavage, which maycontribute to the protection of the cell against apoptosis.Based on our results we propose that the myocardial protection offered byRPO-supplementation of rats on a normal and hypercholesterolaemic diet maybe associated with either its antioxidant characteristics and/or changes in thefatty acid composition of the myocardium during ischaemia/reperfusion.Furthermore, we demonstrated for the first time that RPO-supplementationprotects the isolated perfused working rat heart during reperfusion fromischaemia/reperfusion-induced injury through a MAPK-dependent pathway.

[发布机构] Stellenbosch University