Protein Damage In Patients Research Articles

Evaluation of Oxidative Protein Damage in Patients with Type 1 and 2 Diabetes Mellitus in Bangladesh

Evaluation of Oxidative Protein Damage in Patients with Type 1 and 2 Diabetes Mellitus in Bangladesh

Plasma and cerebrospinal fluid nonenzymatic protein damage is sustained in Alzheimer's disease

BackgroundOxidative stress is considered to play an important role in the pathogenesis of Alzheimer's disease (AD). It has been observed that oxidative damage to specific protein targets affecting particular functional networks is one of the mechanisms by which oxidative stress contributes to neuronal failure and consequently loss of cognition and AD progression. Studies are lacking in which oxidative damage is measured at both systemic and central fluid levels and in the same cohort of patients. We aimed to determine the levels of both plasma and cerebrospinal fluid (CSF) nonenzymatic protein damage in patients in the continuum of AD and to evaluate the relation of this damage with clinical progression from mild cognitive impairment (MCI) to AD. MethodsDifferent markers of nonenzymatic post-translational protein modification, mostly from oxidative processes, were detected and quantified in plasma and CSF by isotope dilution gas chromatography‒mass spectrometry using selected ion monitoring (SIM-GC/MS) for 289 subjects: 103 AD, 92 MCI, and 94 control subjects. Characteristics of the study population such as age, sex, Mini-mental state examination, CSF AD biomarkers, and APOE ϵ4, were also considered. ResultsForty-seven (52.8%) MCI patients progressed to AD during follow-up (58 ± 12.5 months). After controlling for age, sex, and APOE ϵ4 allele, plasma and CSF concentrations of protein damage markers were not associated with either diagnosis of AD or MCI. The CSF levels of nonenzymatic protein damage markers were associated with none of the CSF AD biomarkers. In addition, neither in CSF nor in plasma were the levels of protein damage associated with the MCI to AD progression. ConclusionThe lack of association between both CSF and plasma concentrations of nonenzymatic protein damage markers and AD diagnosis and progression suggests that oxidative damage in AD is a pathogenic mechanism specifically expressed at the cell-tissue level, not in extracellular fluids.

Increased Oxidative Stress Markers in Acute Ischemic Stroke Patients Treated with Thrombolytics.

One of the most common neurological disorders involving oxidative stress is stroke. During a stroke, the balance of redox potential in the cell is disturbed, and, consequently, protein oxidation or other intracellular damage occurs, ultimately leading to apoptosis. The pineal gland hormone, melatonin, is one of the non-enzymatic antioxidants. It not only modulates the perianal rhythm but also has anti-inflammatory properties and protects against stress-induced changes. The focus of this research was to evaluate the concentration of the carbonyl groups and melatonin metabolite in time in patients with acute ischemic stroke that were treated with intravenous thrombolysis. This included a comparison of the functional status of patients assessed according to neurological scales with the control sample comprising healthy people. The studies showed that the serum concentrations of carbonyl groups, which were elevated in patients with ischemic stroke (AIS) in comparison to the control samples, had an impact on the patients' outcome. A urine concentration of the melatonin metabolite, which was lower in patients than controls, was related to functional status after 24 h from cerebral thrombolysis. It shows that determination of carbonyl groups at different time intervals may be an important potential marker of protein damage in patients with AIS treated with cerebral thrombolysis, and that impaired melatonin metabolism induces a low antioxidant protection. Thus, due to the neuroprotective effects of melatonin, attention should also be paid to the design and conduct of clinical trials and hormone supplementation in AIS patients to understand the interactions between exogenous melatonin and its endogenous rhythm, as well as how these relationships may affect patient outcomes.

Oxidative stress in colonic adenocarcinoma: An impact on the body’s antioxidative status and oxidative protein damage

Thus far, the pathogenesis of these intestinal tumors has not been fully explained. However, the analysis of risk factors and research regarding their formation that have continued for 3 decades have allowed us to demonstrate a significant role of oxidative stress in the processes leading to the development of cancer in the large intestine as well as in some other organs. The aim of the study was to examine the level of anti-oxidative status and the degree of oxidative protein damage in patients with varying severity of colonic adenocarcinoma (CAC) in relation to healthy individuals. The study involved 4 groups (A-D) of patients with increasing severity of CAC stages according to Dukes' classification and a control group of healthy volunteers. Total antioxidant capacity (TAC) of blood plasma, as well as carbonyl (C=O) group contents in blood plasma proteins as a product of their oxidative damage, were estimated in all participants. Both parameters were determined by spectrophotometric methods using commercial kit to test TAC and 2,4-dinitrophenylhydrazine to assay the contents of C=O groups. In each of the studied groups, A-D, a statistically significant reduction in the TAC values was noted relative to the control group, which progressed with increased severity of CAC stages: 1.783 mmol/L vs 1.191 mmol/L (group A), 1.07 mmol/L (group B), 0.931 mmol/L (group C), and 0.899 mmol/L (group D). At the same time, significantly increased contents of protein C=O groups were observed compared to the controls, also progressive in the course of growing CAC severity: 0.496 nmol/mg protein vs 0.57 nmol/mg protein (group A), 0.689 nmol/mg protein (group B), 0.804 nmol/mg protein (group C), and 1.054 nmol/mg protein (group D). The CAC-related oxidative stress considerably reduces the systemic anti-oxidative status and increases the protein damage; both those changes become worse in parallel with the progression of this cancer.

PS-234 Advanced Oxidation Protein Products In Children With Nephrotic Syndrome

<h3>Background and aims</h3> Advanced oxidation protein products (AOPP) represent an exquisite marker of oxidative stress, their role in the pathophysiology of chronic renal failure might be of great importance. The aim of the study was to determine serum and urinary levels of AOPP in children with nephrotic syndrome (NS). <h3>Methods</h3> The study included 40 children, aged 12 to 18 years, of whom 25 were diagnosed with acute NS, 8 children with chronic NS and 7 children with chronic kidney disease (CKD) stage 3–5. The control group consisted of 20 healthy children. Assessment of the serum and urinary excretion of AOPP was based on spectrophotometric detection method (Kalousova M. <i>et al</i>., 2002). <h3>Results</h3> Serum AOPP level in children with acute NS constituted 24,40 ± 4,27 mM/l compared to controls (36,91 ± 3,86 mM/l), however urinary excretion of AOPP was significantly higher (31,1 ± 4,6 mM/l vs. 12,14 ± 2,7 mM/l in controls; p &lt; 0,05). In the group of children with chronic NS serum and urinary levels were higher but not significantly as compared to controls (54,70 ± 7,6 mM/l and 22,46 ± 3,2 mM/l, accordingly; p &gt; 0,05). A remarkable increase of the serum excretion of AOPP in CKD stage 3–5 was noted (130,5 ± 22,83 mM/l; p &lt; 0,05). <h3>Conclusions</h3> The determination of AOPP in serum and urine is a reliable marker to estimate the degree of oxidant mediated protein damage in patients with nephrotic syndrome and to assess the progression of chronic kidney disease.

The Role of Xanthine Oxidase in Hemodialysis-Induced Oxidative Injury: Relationship with Nutritional Status

The role of xanthine oxidase (XOD) in patients undergoing chronic hemodialysis treatment (HD) is poorly understood. Geriatric nutritional risk index (GNRI) ≤ 90 could be linked with malnutrition-inflammation complex syndrome. This study measured XOD, myeloperoxidase (MPO), superoxide dismutase (SOD), lipid hydroperoxides, total free thiol groups, and advanced oxidation protein products (AOPP) in 50 HD patients before commencing (pre-HD) and immediately after completion of HD session (post-HD) and in 22 healthy controls. Pre-HD serum hydroperoxides, AOPP, XOD, and SOD were higher and total thiol groups were lower in patients than in controls (P < 0.05, resp.). Compared to baseline values, serum MPO activity was increased irrespective of GNRI status. Serum XOD activity was increasing during HD treatment in the group with GNRI ≤ 90 (P = 0.030) whilst decreasing in the group with GNRI > 90 (P = 0.002). In a multiple regression analysis, post-HD serum XOD activity was independently associated with GNRI ≤ 90 (β ± SE: 0.398 ± 0.151; P = 0.012) and HD vintage (β ± SE: −0.349 ± 0.139; P = 0.016). These results indicate that an upregulated XOD may be implicated in HD-induced oxidative injury contributing to accelerated protein damage in patients with GNRI ≤ 90.

Ozone oxidative post-conditioning reduces oxidative protein damage in patients with disc hernia

Introduction/objectives: Although inflammation in disc hernia (DH) has been recognized and it is a well-known process mediated by loss of the cellular redox balance, only a few studies about the impact of chronic oxidative stress on this neurological disorder have been made. Ozone therapy has been widely used with clinical efficacy in DH. This work aimed at characterizing the systemic redox status of patients with low back pain and neck pain as well as studying if ozone oxidative post-conditioning modified the pathological oxidative stress and protected against oxidative protein damage and if there is any relationship between oxidative changes and pain in both DH.Methods: Redox status of 33 patients with diagnosis of DH by computerized axial tomography, nuclear magnetic resonance, and clinical evaluations was studied. Ozone was administered by paravertebral way. After ozone treatment, plasmatic levels of antioxidant/pro-oxidant markers, pain, and life quality disability parameters were evaluated.Results: One hundred percent of patients showed a severe oxidative stress. Major changes in superoxide dismutase activity, total hydroperoxides, advanced oxidation protein products, fructolysine content, and malondialdehyde were observed. After ozone oxidative post-conditioning, there was a re-establishment of patients’ cellular redox balance as well as a decrease in pain in both DH. A relationship between indicators of oxidative protein damage and pain was demonstrated.Conclusions: Ozone therapy protected against oxidation of proteins and reduced the pain. Relationship between markers of oxidative protein damage, disability parameters, and pain suggests the role of oxidative stress in the pathological processes involved in DH.

Effect of Irbesartan treatment on plasma and urinary markers of protein damage in patients with type 2 diabetes and microalbuminuria

The aim of this study was to assess the effect of the angiotensin II receptor blocker Irbesartan on protein damage by glycation, oxidation and nitration in patients with type 2 diabetes and microalbuminuria. In a double-masked randomised crossover trial of 52 hypertensive type 2 diabetic patients, antihypertensive treatment was replaced with bendroflumethiazide. After 2-months wash-out, patients were treated randomly with Irbesartan 300, 600, and 900 mg o.d., each dose for 2 months in a three-way crossover study. Glycation, oxidation and nitration adduct residues in plasma protein and related urinary free adducts were determined by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. Treatment with Irbesartan decreased urinary excretion of advanced glycation endproducts (AGEs)--methylglyoxal- and glyoxal-derived hydroimidazolones, MG-H1 and G-H1. Urinary AGEs were decreased by 30-32%. In plasma protein, treatment with Irbesartan increased content of glycation adducts Nε-fructosyl-lysine, AGEs Nε-carboxymethyl-lysine, Nε-carboxyethyl-lysine and pentosidine, and also increased content of oxidation markers N-formylkynurenine and dityrosine. This was attributed to decreased clearance of plasma protein modified by Nε-fructosyl-lysine and oxidative markers through the glomerular filter tightened by Irbesartan treatment. Treatment of patients with type 2 diabetes with Irbesartan decreased urinary excretion of MG-H1, G-H1 and 3-NT, which may result from decreased exposure to these AGEs. This is likely achieved by blocking angiotensin II signalling and related down-regulation of glyoxalase 1 and may contribute to health benefits of Irbesartan therapy.

Reduction of lipid and protein damage in patients with disorders of propionate metabolism under treatment: a possible protective role of l-carnitine supplementation

Disorders of propionate metabolism are autosomal recessive diseases clinically characterized by acute metabolic crises in the neonatal period and long-term neurological deficits whose pathophysiology is not completely established. There are increasing evidences demonstrating antioxidant properties for l-carnitine, which is used in the treatment of propionic and methylmalonic acidemias to increase the excretion of organic acids accumulated in tissues and biological fluids of the affected patients. In this work we aimed to evaluate lipid (malondialdehyde content) and protein (carbonyl formation and sulfhydryl oxidation) oxidative damage in plasma from patients with propionic and methylmalonic acidemias at the moment of diagnosis and during treatment with l-carnitine. We also correlated the parameters of oxidative damage with plasma total, free and esterified l-carnitine levels. We found a significant increase of malondialdehyde and carbonyl groups, as well as a reduction of sulfhydryl groups in plasma of these patients at diagnosis compared to controls. Furthermore, patients under treatment presented a marked reduction of the content of protein carbonyl groups, similar to controls, and malondialdehyde content in relation to patients at diagnosis. In addition, plasma total and free l-carnitine concentrations were negatively correlated with malondialdehyde levels. Taken together, the present data indicate that treatment significantly reduces oxidative damage in patients affected by disorders of propionate metabolism and that l-carnitine supplementation may be involved in this protection.

Oxidative protein damage in patients with colorectal cancer

Oxidative protein damage in patients with colorectal cancer

749 Byproducts of oxidative lipid and protein damage in patients with chronic ischemic heart failure: relationship to disease severity

749 Byproducts of oxidative lipid and protein damage in patients with chronic ischemic heart failure: relationship to disease severity