Aging might augment reactive oxygen species (ROS) formation and affect reactive nitrogen species (RNS) level after myocardial ischemia/reperfusion in both humans and rats

Abstract

Previous studies indicate aging results in significantly decreased cardiac function and increased myocardial apoptosis after myocardial ischemia/reperfusion (MI/R) in humans or rats. The underlying mechanisms of aging-exacerbated effects remain unknown. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are known to play vital roles in aging-related MI/R injury. Heretofore, the effects of aging upon ROS and RNS formation were not investigated in humans, which is the focus of the current study. Due to experimental limitations with clinical trials, an additional animal experiment was performed. All enrolled acute myocardial infarction (AMI) patients received percutaneous coronary intervention (PCI) therapy. AMI patients were assigned into two groups: adult (age <65, n034) and elderly (age ≥65, n045) AMI patients. Blood samples were obtained from all study participants at 24 h and 3 days post-PCI. Plasma/white blood cell (WBC) ROS and RNS markers (malondialdehyde (MDA), myeloperoxidase (MPO), reduced glutathione (GSH), inducible nitric oxide synthase (iNOS) activity, NOx, and nitrotyrosine) were determined. The same markers were determined in rat cardiac tissue after 24 h MI/R. Compared to the adult group, elderly patients manifested increased plasma MDA and MPO and decreased plasma GSH concentrations. No significant differences in plasma NOx or nitrotyrosine concentration existed between adult and elderly patients. Furthermore, WBC iNOS activity in elderly patients was significantly decreased compared to the adult group. The measurement of ROS markers in the rat experiments was consistent and supported human study data. Surprisingly, RNS markers (NOx and nitrotyrosine) in blood and heart tissue increased from young to middle-aged rats but decreased from middle age to old age. Aging augments ROS, which might exacerbate MI/R injury. Additionally, our data

Role of thioredoxin-1 in ischemic preconditioning, postconditioning and aged ischemic hearts

“…This lack of studies in middle-aged is striking, since an ischemic episode in patients begins at that stage of life, and they are not exclusive of advanced age [90,91]. However, it is known that even though oxidation processes start when life begins; it is in middle-aged that they reach sufficient levels to trigger deleterious mechanisms on different cell components [92], and this ROS increase is able to modify expression and/or activity of several proteins [93][94][95]. In a recent paper from our lab, we showed that young mice overexpressing Trx-1 have a smaller infarct size compared to their corresponding Wt mice [96].…”

Thioredoxin Reductase Was Nitrated in the Aging Heart After Myocardial Ischemia/Reperfusion

“…In aging hearts, high levels of nitric oxide (NO) are converted to a number of more reactive derivatives, known collectively as reactive nitrogen species (RNS). 6 Peroxynitrite (ONOO -), an extremely important RNS, is a highly reactive species and oxidizes or nitrates (e.g., tyrosine nitration) a variety of molecules, and this has been shown to induce cardiomyocyte death. 7 The glutathione (GSH) anti-oxidant system has been demonstrated to be a defense against ONOO -.…”

Reducing Resistance to Acid Hemolysis by Iron-Contained Drug Increases the Level of Hemoglobin in the Erythrocytes of Aging Animals

“…рис.2,б). Окисний (як оксидативний, так і, особливо, нітрозативний) стрес, який спо-стерігається за умов старіння [2], є його першопричиною [18], і також мішенню дії препарату. На це вказує зафіксоване знижен-ня генерації *О 2 -в еритроцитах і пулів Н 2 О 2 як в еритроцитах, так і в плазмі (див.…”