Penehyclidine Hydrochloride Preconditioning Provides Cardioprotection in a Rat Model of Myocardial Ischemia/Reperfusion Injury

Abstract

To investigate the impacts and related mechanisms of penehyclidine hydrochloride (PHC) on ischemia/reperfusion (I/R)-induced myocardial injury. A rat model of myocardial I/R injury was established by the ligation of left anterior descending coronary artery for 30 min followed by 3 h perfusion. Before I/R, the rats were pretreated with or without PHC. Cardiac function was measured by echocardiography. The activities/levels of myocardial enzymes, oxidants and antioxidant enzymes were detected. Evans blue/TTC double staining was performed to assess infarct size. Cardiomyocyte apoptosis was evaluated by TUNEL assay. The release of inflammatory cytokines and inflammatory mediators was detected by ELISA. Western blot was performed to analyze the expression of COX-2, IκB, p-IκB and NF-κB. Meanwhile, the rats were given a single injection of H-PHC before I/R. The effects of PHC on myocardial infarct and cardiac function were investigated after 7 days post-reperfusion. We found that PHC remarkably improved cardiac function, alleviated myocardial injury by decreasing myocardial enzyme levels and attenuated oxidative stress in a dose-dependent manner. Additionally, PHC preconditioning significantly reduced infarct size and the apoptotic rate of cardiomyocytes. Administration of PHC significantly decreased serum TNF-α, IL-1β, IL-6 and PGE2 levels and myocardium COX-2 level. Meanwhile, the expression levels of p-IκB and NF-κB were downregulated, while IκB expression was upregulated. H-PHC also exerted long-term cardioprotection in a rat model of I/R injury by decreasing infarct size and improving cardiac function. These results suggest that PHC can efficiently protect the rats against I/R-induced myocardial injury.

Anti-inflammatory effect of lycopene in SW480 human colorectal cancer cells

“…NF-κB is activated constitutively in many tumors/tumor cells, including human CRC cells [3819]. This is one of the major reasons why the chemotherapeutic agents are ineffective in inducing apoptosis in cancer cells including CRC [815]. Constitutively active NF-κB provides growth and survival signals in human malignancies, suggesting that the agents that inhibit NF-κB activation could be effective in CRC prevention and therapy [811].…”

“…The blots were then exposed to X-Omat Film (Kodak), and the molecular weights of the detected bands were compared against a high molecular weight marker. Each band concentration was calculated using Image J Launcher (National Institutes of Health, Bethesda, MD, USA), imaging programs [15]. …”

<p>Postconditioning Protection Against Myocardiocyte Anoxia/Reoxygenation Injury From Penehyclidine Hydrochloride</p>

“…Our previous investigation showed that Penehyclidine Hydrochloride offered this protective effect via limiting calcium overload, decreasing formation of reactive oxygen species, restraining mitochondrial MPTP opening and reducing inflammatory response in vitro and in vivo. 5,6 The most effective dose of Penehyclidine Hydrochloride on H9c2 cell against anoxia/reoxygenation injury was determined to be 0.1 μm/L in our research group. 9 In 2012, Barrere-Lemaire et al found out the effective time window for delayed postconditioning treatment in rats model was 30 mins, 27 and our previous animal study determined the protective time window of PHC postcondition was within 10 mins after the reperfusion stage began.…”

“…We previously determined that the most effective concentration was 0.1 μm/L. 5,6 This current investigation focused on the effect of timing that PHC had on postconditioning. We also designed this in vitro experiment to further elucidate the mechanism of A/R injury in the early reoxygenation period.…”

Ginsenoside Rg3 Improves Cardiac Function after Myocardial Ischemia/Reperfusion via Attenuating Apoptosis and Inflammation

“…Studies have demonstrated that myocardial I/R injury may induce the changes of cardiac hemodynamic parameters and then affect cardiac function [13]. Echocardiography and hemodynamic analyzing system are widely used for measuring cardiac function in myocardial ischemic animal model [14, 15].…”