Isoproterenol Case Study

With all living organisms, a process known as cell respiration is integral in order to provide the body with an essential form of energy, adenosine triphosphate (ATP). Oxygen, although an essential part of this process, can form reactants from colliding with electrons associated with carrier molecules. (pb101.rcsb.org, 2017). Hydrogen peroxide is an integral product of this reaction but is known to impose negative effects on the body if high levels are introduced. Explicitly, this reaction is caused “If oxygen runs into (one of these) carrier molecules, the electron may be accidentally transferred to it. This converts oxygen into dangerous compounds such as superoxide radicals and hydrogen peroxide, which can attack the delicate sulphur atoms and metal ions in proteins.” (pdbh101.rcb.org, 2017). Research has suggested that the hydrogen peroxide can be converted into hydroxyl radicals, known to mutate DNA, which can potentially cause bodily harm due to DNA’s role in the synthesis of proteins. These radicals can cause detrimental effects on the human body, and studies have suggested a link to ageing. Due to the harmful effects of these H2o2, it is important that the body finds a way to dispose of hydrogen peroxide before concentrations are too great.

Similarly, an increase in the levels of lipid peroxidation was observed in Aβ-induced rat hippocampal cells, confirming previous reports [17]. Enzymatic antioxidants such as SOD, catalase, and GPX act as the cellular antioxidant defense mechanism against free radicals. Since NADPH is required for the regeneration of catalase from its inactive form, catalase activity might be decreased in Aβ induced toxicity due to reduced NADPH levels. In this study, we have reported that Honokiol treatment significantly increased the enzymatic antioxidant activities in APP-CHO cells. In addition, non-enzymatic antioxidants like GSH also exhibited beneficial neuroprotective effects against oxidative stress. GSH is an endogenous nonenzymatic antioxidant that prevents damage to cellular components caused by ROS such as free radicals and peroxides. GSH is oxidized to glutathione disulfide (GSSG) by ROS, thereby causing a reduction in the level of GSH. GR reduces GSSG to GSH via NADPH, which in turn is released by glucose-6-phosphate dehydrogenase [18]. Honokiol treatment upregulated the activity of these antioxidants in APP-CHO cells. In addition to oxidative stress, a strong association between insulin resistance and the development of AD has been demonstrated. Several studies have reported that insulin resistance (IR), an underlying characteristic of type 2 diabetes, is an important risk factor for AD

As well as this, Nox2 affects the level of HIF-2a, which is responsible for anti-oxidative activity, and decreases it that lead to increased oxidative responses and neuronal

Urate hydroperoxide inactivated GAPDH in a dose-dependent manner. The ratio of urate hydroperoxide to inactivated GAPDH was ~6:1. When I reduced GAPDH with DTT I recovered half of the activity. In comparison, taurine chloramine inactivated GAPDH at ratio ~10:1 and all the activity was recovered with DTT. My results suggest urate hydroperoxide permanently inactivates GAPDH. Future work will investigate urate hydroperoxide inactivation of other thiol-dependent enzymes. My research furthers our understanding of the pro-oxidant effects of urate. Urate hydroperoxide links hyperuricemia, oxidative stress and inflammatory

Twenty healthy, age-matched (36 years of age, on average) subjects were randomized to either receive 200 mg of Polygonum cuspidatum extract (PCE) (containing 40 mg of resveratrol) or a placebo daily for 6 weeks. Blood samples were collected at baseline and at 1, 3 and 6 weeks. Oxidative stress was determined by analyzing blood for reactive oxygen species (ROS) generation. Inflammatory state was determined by assessing nuclear NFKB DNA binding activity (via gel shift assay) and TNFα mRNA expression (via PCR testing). Resveratrol supplementation was found to significantly reduce ROS generation, NFKB DNA binding activity, and TNFα mRNA expression compared to both baseline and the placebo group at 3 and 6 weeks. (see figure 1). The authors therefore concluded that 6 weeks of a resveratrol-containing supplement could reduce both oxidative stress and inflammation. A major weakness of the study is that the authors failed to report the sex of the subjects making it challenging to compare these findings with other studies. Furthermore, this study used a PCE supplement, which contains several other antioxidants in addition to resveratrol. The possibility therefore remains that these other compounds or an interaction effect could have been responsible for some of changes that were observed.

Nitrates are powerful vasodilators, which act in the epicardial vessels. They act to lower the blood pressure, and increase blood flow to ischaemic tissue.

Pathogenesis of cardiac injury caused by doxorubicin is multifactorial and it is in direct relationship with metabolism and antitumor activity of the drug . Free radical stress, calcium overloading and mitochondrial dysfunction are main triggers in doxorubicin-induced cardiotoxicity. Subsequent gene expression changes and activation of the ubiquitin-proteasome system, cell death, as well as innate immunity activation all contribute to the toxicity (Shi et al., 2011). The level of the doxorubicin-induced oxidative stress is up to 10 times greater in the heart than in the other tissues (liver, kidney, spleen( Mukherjee et al., 2003) and therefore oxidative injury of the heart is widely accepted theory presumed as a primary mechanism of the DOX-induced cardiotoxicity. Formation of reactive oxygen species (ROS) has a leading role in promoting the oxidative myocardial

Based from observations made in the early 1950s, Denham Harman proposed that functional decline in cells and tissues was due to cumulative effects of macromolecular damage caused by oxygen radicals produced by respiratory enzymes (Harman 1956). This theory proposes that superoxide and other free radicals cause damage to the macromolecular components of the cell, resulting in accumulated damage to cause cells, and eventually organs, to stop functioning, leading to the aging phenotype (Sohal and Weindruch 1996, Clancy and Birdsall 2013). Oxidative damage is thought to occur from an imbalance when the antioxidant systems are unable to counter all the free radicals continuously generated during the life of the cell.

Superoxide is a free radical that can induce endothelial dysfunction by scavenging the endogenous endothelium-derived vasodilator nitric oxide (NO). Endothelium-dependent vasodilation relies on NO for normal function. Therefore, vascular superoxide concentrations will be measured by exposing isolated mesenteric arteries to a fluorescent indicator of superoxide, dihydroethidium (DHE; Life Technologies, Grand Island, NY), which in the presence of superoxide becomes oxidized to form ethidium bromide [1]. Paired isolated mesenteric arteries from each animal will be incubated at 37°C for 1 hour in a HEPES buffered saline solution (in mM: 143.3 NaCl, 6KCl, 1MgCl2, 1.8CaCl2, 10 HEPES, 10 glucose, pH 7.4 with NaOH) containing either vehicle or the superoxide dismutase mimetic tiron (10mM). The vessels will then be transferred to a HEPES-filled microcentrifuge tube containing 10 μM/mL dihydroethidium (Molecular Probes, Invitrogen, Grand Island, NY) for 10 mins at 37°C.Subsequent to a five minute wash with HEPES, arteries will be embedded in optimal cutting temperature (OCT) compound and snap-frozen in isopropyl alcohol cooled by dry ice and stored at -80°C until sectioning. Cryosections (12 μm) will be mounted onto polylysine coated glass microscope slides followed by fixation for 30 min in 4% formaldehyde and a 10 min rinse in phosphate buffered saline (PBS;

The enhancing influence of OLE may possibly be associated to its multifunctional radical scavenging and anti-inflammatory

During ischemia, the intracellular and extracellular adenosine and three phosphate (ATP) is depleted, leading to increased ATP degradation products, such as adenosine, hypoxanthine, xanthine and a shift towards anaerobic metabolism [3]. However, on reperfusion, the initial increase in oxygen delivery amount exceeds the amount needed for cellular metabolism from anaerobic pathways back to aerobic pathways. The whole process would lead to generation of damaging free radicals and a wide variety of reactive oxygen species (ROS) are generated, including superoxide radical, hydrogen peroxide and hydroxyl radical. Even though hepatocyte can directly produce ROS, physiologically Kupffer cells are thought to be the main source of ROS in the early stages of live ischemia-reperfusion injury followed by natural killer T-cells generating ROS and neutrophils being the main source in the very later stages [4, 5].

A recent study investigated the effect of H2S deficiency on endothelial NO synthase (eNOS) function, NO production, and ischemia / reperfusion injury by on CSE- knocked out mice and control [12]. Significant Lower H2S levels among CSE- knocked out mice was confirmed by gas chromatography. From oxidative stress perspective; their results revealed significant higher levels of malondialdehyde (indicator for lipid peroxidation) in heart muscle among CSE- knocked out mice compared to

Free radicals in the body are responsible for destroying healthy cells and they lead to degenerative diseases and premature aging. It is thought that free radicals come from many different substances, including UV rays, X-rays, pesticides, tobacco smoke, alcohol,

The use of a free radical scavenger is a helpful strategy for finding whether or not a free radical is involved in the degradation reaction mechanism. The reaction was explored in the presence of isopropanol, a well-known radical scavenger. That has been used in peroxide reactions to trap a wide range of radical species. The experiment was carried out by the addition of isopropyl alcohol (0.02M) as a radical scavenger. The rate constant decreased remarkably from 0.035 to 0.009 min-1.The decrease in the rate constant is due to the consumption of the generated OH radical by a scavenger. This experiment has clearly confirmed the participation of hydroxyl radical as a powerful oxidant in the oxidative degradation of the dye with the synthesized

The involvement of intracellular Ca2+ may be the underlying mechanism of these functional disorders. It is likely that endoplasmic reticulum disturbances are partially responsible for increasing the risk of cell death. Oxygen radicals play a part in the microvascular and parenchymal cell injury which are affiliated with organ preservation. Oxygen radicals seem to create large leakages mainly in the small venules and thus increase microvascular permeability. The hydroxyl radical, which is highly reactive, seems to be the cause of the oxygen radical production-associated microvascular alterations. While many other similar types of cell injury are triggered by an enhanced released of 02- (superoxide anion radical) or H2O2 (hydrogen peroxide), cold-induced cell injury is not. Rather, an increase in the redox-active, cellular chelatable iron pool that transforms species with low reactivity into those that are highly