Effects of rosuvastatin on ADMA, rhokinase, NADPH oxidase, caveolin-1, hsp 90 and NFkB levels in a rat model of myocardial ischaemia-reperfusion : cardiovascular topic

Abstract

SummaryAimEndothelial dysfunction, oxidative stress and inflammation are among the most important mechanisms of ischaemia–reperfusion (I/R) injury. Besides their cholesterol-lowering effects, statins are known to provide protection against myocardial dysfunction and vascular endothelial injury via nitric oxide-dependent mechanisms. The aim of this study was to investigate the effects of rosuvastatin on certain intermediates involved in the generation of nitric oxide (asymmetrical dimethyl arginin, ADMA, caveolin-1 and hsp 90), oxidative stress (rhokinase, NADPH oxidase) and inflammation (NFkB), using an in vivo model of myocardial infarction in the rat.MethodsAdult male Sprague Dawley rats were divided into three groups (control, I/R and I/R after 15 days of rosuvastatin administration). Reperfusion was applied for 120 min following left anterior descending coronary artery ischaemia for 30 min. Caveolin-1, hsp 90 and NFkB levels were evaluated with the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and ADMA, rhokinase and NADPH oxidase levels were evaluated with ELISA.ResultsWhile NFkB and hsp 90 levels were higher in the I/R group, their levels were significantly lower in the rosuvastatin group. While ADMA and NADPH oxidase levels significantly increased with I/R, they were lower in the rosuvastatin-treated group, but not statistically significant. Rhokinase levels were significantly lower in the rosuvastatin group. Caveolin-1 levels were not different between the groups.ConclusionOur results suggest that ADMA, rhokinase, NADPH oxidase, hsp 90 and NFkB could facilitate I/R injury, and rosuvastatin significantly reduced levels of these parameters. These results indicate that rosuvastatin may have a protective role in I/R injury via mechanisms targeting inflammation, endothelial dysfunction and oxidative stress.

Activated ROCK/Akt/eNOS and ET-1/ERK pathways in 5-fluorouracil-induced cardiotoxicity: modulation by simvastatin

“…Moreover, ROS activate other molecules, such as COX isoforms that also contribute to endothelial dysfunction 73 ; all of which are facts that support the current findings. On the other hand, the aptitude of Sim for reducing Nox activity, lipid peroxidation, ET-1/ERK 1/2 signal and COX-2 enzyme, as well as the enhancement of the defense molecule coincides with previous reports 59 , 74 , 75 and highlights its anti-oxidant and anti-inflammatory effects that are partially responsible for its cardioprotective effect against 5-FU.…”

Over-expression of growth differentiation factor 15 (GDF15) preventing cold ischemia reperfusion (I/R) injury in heart transplantation through Foxo3a signaling

“…It has been reported that the NFκB signaling pathway is activated during I/R which leads to inflammatory response [ 27 ]. The Rel A p65 subunit involved in this pathway is up-regulated in injured hearts [ 28 ] and the depletion of p65 protects the injured heart [ 29 ].…”

“…Recent studies have shown that there is a link between Foxo3 and NFκB signaling, both of which play important role in anti-apoptosis and oxidative stess [ 27 , 43 ]. In an aging related study, Salminen et al reported that Foxo signaling acted as an antagonist of NFκB [ 44 ].…”

The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats

“…The S group and I/R group were given normal diet. The I/R + RSV group was administered RSV dissolved in distilled water via oral gavage at a dose of 10 mg/kg/day for 7 days continuously [ 12 , 13 ], the I/R + DGZ group received 1 mg/kg/day DGZ dissolved in distilled water by oral gavage for 7 days continuously [ 11 ], and the I/R + RSV + DGZ group received RSV 10 mg/kg/day and DGZ 1 mg/kg/day simultaneously via oral gavage for 7 days consecutively. The animals were forbidden to feed overnight before experiment, but were given free access to water.…”