On the other hand key enzymes also involved

On the other hand, key Capsaicin also involved in NO metabolism are nNOS and eNOS. Apparently, during acute ischemia, eNOS activity and NO concentration surge for a short period of time (Schulz et al., 2004) but eventually the expression and activity of the synthase and consequently NO concentration decrease rapidly as the injury evolves and acidosis develops. With reperfusion, NOS activity and NO concentration increase again, for a short period of time and then decline (Giraldez et al., 1997: Tsui et al., 2007). However, during late reperfusion (> 24h), NOS levels and activity increase again (Nikitaki et al., 2015). Our results are in agreement with those reported by Tsui (Tsui et al., 2007), in that during a longer post-reperfusion period (48h) nNOS protein levels significantly increase and as we report, this can prevented by EPI pre-treatment. In contrast, while eNOS protein levels modestly increased with ischemia, EPI pretreatment was able to notably increase their phosphorylation levels. It has been established that the physiology and pathophysiology of NO is complex. It is believed that a significant proportion of NO generated during I/R comes from all three NOS isoforms. A pathological excess of NO can also be harmful particularly to the heart. High levels of NO if present in a pro-oxidant milieu (as seen in the ischemic reperfused myocardium), can be easily oxidized and converted into peroxynitrite leading to the generation of NO2 and OH free radicals, which are highly reactive and harmful to biomolecules (Nikitaki et al., 2015; Kelley, 2015). It is important to note that EPI-induced actions are not “class” effects. We have analyzed the effects of EPI isomers without significant results. As an example, the EPI stereoisomer (+)-catechin is only partially able to stimulate NO production in endothelial cells. In fact, catechin displaced the EPI concentration–response curve to the right, suggesting that it has an antagonist-like effect (Ramirez-Sanchez et al., 2010). On the other hand, to determine if EPI-induced actions on mitochondrial swelling follow a general class effect, we evaluated the effects of epigallocatechin, epigallocatechin gallate (both of which have no significant effects) and quercetin, which only induced a partial reduction of mitochondrial swelling (Ortiz-Vilchis et al., 2014). In conclusion, results provide evidence for the modulation of Ar protein and activity levels as a possible mechanism by which EPI may reduce infarct size in I/R. This, in turn, may augment intracellular L-arginine concentrations, thereby shifting substrate availability for NOS. EPI may also limit tissue damage by selectively limiting pathological increases in NOS protein levels.
Introduction The importance of monitoring ions of heavy and transitional metals spans all areas of science and technology. A system that can provide selective detection of these ions in aqueous solutions will find numerous applications in such fields as environmental monitoring, biomedical research, clinical chemistry and pharmacology. Ions of heavy and transitional metals in trace quantities are essential mineral components for the human body and all other living organisms, but they exhibit the high level of toxicity at higher concentrations [1], [2]. Manganese (Mn) and cobalt (Co) are considered as the most abundant trace elements in the biosphere, being widely distributed in soil, sediment, water and live organisms [3], [4], [5], [6]. In human, chronic manganese excess affects the central nervous system, with the symptoms resembling those of Parkinson's disease and autism [7], [8], [9], [10], [11]. The mean total content of Mn in human adult is about 15mg (typically seen in nucleic acids), and the requirement of in this element is about 2–5mg/day [6]. Mn acts as an activator of enzymes and as a component of metalloenzymes, taking part in oxidative phosphorylation, fatty acids and cholesterol metabolism, mucopolysaccharide metabolism, and urea cycle [6].