Oxidative Stress Biomarkers In Patients Research Articles

Novel Assay Assessment of Oxidative Stress Biomarkers in Patients with Keratoconus: Thiol–Disulfide Homeostasis

ABSTRACTPurpose: To investigate systemic oxidative stress by evaluating thiol–disulfide homeostasis using a novel automated homeostasis assay in keratoconus patients.Methods: Twenty-eight patients with keratoconus and 30 control subjects of a similar age and gender were enrolled in the present study. The native thiol, total thiol, and disulfide levels and the disulfide–native thiol, disulfide–total thiol, and native thiol–total thiol ratios were analyzed and compared between the keratoconus and control groups using a novel automatized spectrophotometric assay.Results: The median serum native thiol value was 441.5 (362.6–488.1) in the keratoconus group and 467.8 (401.8–564.6) in the control subjects. The median serum total thiol value was 467.9 (375–580.6) in the keratoconus group and 503.3 (437.7–578.5) in the control subjects. The median serum disulfide value was 20.1 (6.2–46.3) in the keratoconus patients and 16.7 (1.1–20.8) in the controls. There were significant differences between the native thiol, total thiol, and disulfide levels of the keratoconus patients and controls (p = 0.001, p = 0.04, and p = 0.03, respectively) and the disulfide–native thiol, disulfide–total thiol, and native thiol–total thiol ratios of these two groups (p = 0.02, p = 0.01, and p = 0.001, respectively). We found no significant correlation between age and any of the thiol–disulfide parameters (p > 0.05 for all values).Conclusions: There is an imbalance in the systemic thiol–disulfide homeostasis in KC patients. This metabolic imbalance may play an important role in the pathogenesis of keratoconus; thus, it can be discussed in terms of the prevention, diagnosis, and the possible treatment for keratoconus.

The contributions of fasting and postprandial blood glucose increments to oxidative stress and inflammation in dyslipidemic type 2 diabetic patients with stable ischemic heart disease

Background/objectivesContributions of fasting and postprandial blood glucose increments on level of inflammation and oxidative stress biomarkers in patients with stable ischemic heart disease (IHD) and diabetes mellitus type 2 (T2DM) was evaluated. MethodologyNinety T2DM patients (60 with IHD and 30 without IHD) treated with metformin and/or sulphonylurea were enrolled in cross-sectional nested case–control clinical study. The areas under the six-point daily glucose curve above the fasting glucose concentrations (AUCpp) and over 5.5mmol/L (AUCbg) were calculated to determine postprandial (AUCpp) and fasting (AUCbg-AUCpp) glucose increments. Malondialdehyde (MDA), protein carbonyl group (PCO), fibrinogen, C-reactive protein (hsCRP), leukocyte count and adhesion molecules ICAM-1 and VCAM-1 were determined. ResultsAUCbg-AUCpp 58.2 (95%CI 40.6–75.8) was higher in IHD group compared to non-IHD 36.9 (95%CI 23.5–50.2) mmol*h/L. They had significantly higher ICAM-1 (mean±SD) 72.70±30.6 vs. 60.22±22.6ng/mL and MDA 16.47±4.5 vs. 13.42±4.01μmol/g plasma proteins, but similar PCO, VCAM-1, fibrinogen, hsCRP concentration and leukocyte count. AUCpp positively correlated with MDA (r=0.45) and ICAM-1 (r=0.32) in the presence of IHD, and VCAM-1 (r=0.44) in the absence of IHD. AUCbg-AUCpp positively correlated with PCO (r=0.45) in the absence of IHD. The analysis revealed that AUCpp over turning point of 0mmol*h/L was associated with high MDA and ICAM-1 expression in diabetics with IHD. AUCbg-AUCpp over 30mmol*h/L leads to high oxidative protein modification in diabetics without IHD. ConclusionIn T2DM patients with stable IHD, AUCpp at any point, significantly contributes to increasing of MDA and ICAM-1 expression. Fasting blood glucose increment showed significant correlation with carbonyl content in diabetics without IHD.

Asymmetric dimethylarginine and heart-type fatty acid-binding protein 3 are risk markers of cardiotoxicity in carbon monoxide poisoning cases in Zagazig university hospitals.

Carbon monoxide (CO) poisoning is a leading cause of toxicity-related mortality and morbidity worldwide. Recent studies focused on CO-induced cardiovascular toxicity. Oxidative stress plays an important role in the pathophysiology of CO toxicity. The aim of this study was to elucidate the relationship between cardiac damage biomarkers and oxidative stress biomarkers in patients with CO-induced cardiotoxicity. This study was carried out on 36 CO-poisoned patients admitted to Zagazig University Hospitals. Forty healthy individuals (age- and sex-matched) were selected as a control group. Clinical examination and electrocardiography (ECG) were performed for CO-poisoned patients. These patients have been investigated for carboxyhaemoglobin percent (COHB%) and cardiac damage biomarkers; cardiac troponin I (cTn-I), heart-type fatty acid-binding protein 3 (H-FABP3). Oxidative stress biomarkers comprising malondialdehyde (MDA), asymmetric dimethylarginine (ADMA), and total antioxidant capacity (TAC) have been also assessed. All biomarkers have been assessed on admission (0 h) and 6 h after treatment of CO-poisoned patients with high-flow oxygen and compared with those of the control groups. ECG findings were abnormal in 31 patients (86.11%), where sinus tachycardia was the commonest finding (58.33%). There was a statistically significant increase of COHB%, MDA, ADMA, and H-FABP3 levels, and a significant decrease of TAC level in CO-poisoned patients compared to controls with no significant changes in cTn-I. Six hours following treatment, all measured parameters were significantly improved except for cTn-I, which was significantly increased when compared with admission status (0 h). Furthermore, H-FABP3 showed a significant positive correlation with COHB%, MDA, ADMA, and a negative correlation with TAC, while cTn-I was significantly correlated with COHB% only. ADMA and MDA seem to be the strongest determinants for the prediction of H-FABP3 changes and hence cardiovascular toxicity. Thus, cardiac damage in patients with CO poisoning could be partially mediated by CO-induced oxidative stress, where H-FABP3 level was directly and strongly associated with MDA and ADMA levels.

Correlation of TGF-β1 and oxidative stress in the blood of patients with melanoma: a clue to understanding melanoma progression?

TGF-β1 and oxidative stress are involved in cancer progression, but in melanoma, their role is still controversial. Our aim was to correlate plasma TGF-β1 levels and systemic oxidative stress biomarkers in patients with melanoma, with or without disease metastasis, to understand their participation in melanoma progression. Thirty patients were recruited for melanoma surveillance, together with 30 healthy volunteers. Patients were divided into two groups: Non-metastasis, comprising patients with tumor removal and no metastatic episode for 3years; and Metastasis, comprising patients with a metastatic episode. The plasmatic cytokines TGF-β1, IL-1 β, and TNF-α were analyzed by ELISA. For oxidative stress, the following assays were performed: malondialdehyde (MDA), advanced oxidation protein products (AOPP) levels, total radical-trapping antioxidant parameter (TRAP) and thiol in plasma, and lipid peroxidation, SOD and catalase activity and GSH in erythrocytes. Patients with a metastatic episode had less circulating TGF-β1 and increased TRAP, thiol, AOPP and lipid peroxidation levels. MDA was increased in both melanoma groups, while catalase, GSH, and IL-1β was decreased in Non-metastasis patients. Significant negative correlations were observed between TGF-β1 levels and systemic MDA, and TGF-β1 levels and systemic AOPP, while a positive correlation was observed between TGF-β1 levels and erythrocyte GSH. Lower levels of TGF-β1 were related to increased oxidative stress in Metastasis patients, reinforcing new evidence that in melanoma TGF-β1 acts as a tumor suppressor, inhibiting tumor relapse. These findings provide new knowledge concerning this cancer pathophysiology, extending the possibilities of investigating new therapies based on this evidence.

Study on changes of plasma levels of oxidative stress biomarkers and its relation with cognition function in patients with parkinson's disease

To study the changes of plasma levels of oxidative stress biomarkers in patients with parkinson's disease (PD), and to explore its association with cognition function. Seventy-two PD patients from June 2013 to May 2012 were enrolled. All of them were outpatients or inpatients at the First Affiliated Hospital of Nanjing Medical University. And forty-five age- and gender- matched healthy subjects were used as controls. The information including gender, age, illness duration, years of education and Hoehn & Yahr (H-Y) stage were recorded. Cognition function of all the patients with PD and the controls were measured by using Montreal Cognitive Assessment (MoCA) scale. Plasma levels of catalase (CAT), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), total glutathione (T-GSH) and malondialdehyde (MDA) were measured by ELISA . Then we compared and analyzed the results. Plasma levels of CAT, T-SOD and T-GSH in PD group were significantly lower than the control group [(159 ± 9) kU/L vs (170 ± 5) kU/L, P< 0.01; (97 ± 24) kU/L vs (124 ± 25) kU/L, P<0.01; (17 ± 10) µmol/L vs (60 ± 51) µmol/L, P< 0.01]. Plasma levels of CAT, T-GSH, GSH-Px and MDA were no differences between early PD group (H-Y stage I-II) and middle-late PD group (H-Y stage III or higher) of patients (P>0.05). Plasma levels of T-GSH in PD group with mild cognitive impairment (MCI) were obviously lower than PD group without MCI [(14 ± 7) µmol/L vs (19 ± 11) µmol/L, P< 0.05]. In PD patients, MoCA scores were positively correlated with years of education (β=0.634, P= 0.000) and plasma levels of T-GSH (β= 0.204, P= 0.014), and were negatively correlated with H-Y stage (β=-0.194, P=0.020). The damage of plasma antioxidant mechanism may be involved in the pathogenesis of patients with PD. Decrease in plasma levels of T-GSH may be associated with MCI in PD patients . Plasma levels of T-GSH may be a potential early predictive index in PD patients with cognitive dysfunction.

Oxidative/Nitrosative Stress in Patients With Modic Changes: Preliminary Controlled Study.

Oxidative/nitrosative stress in vertebral endplates of patients with low back pain and Modic changes (MCs) (types I, II, and III) endplate changes on magnetic resonance imaging. The aim of this study was to assess the levels of oxidative/nitrosative stress biomarkers in patients with MCs. Degenerated discs and endplate abnormalities is postulated as a possible source of low back pain. Oxidative/nitrosative stress plays an important the role in various human diseases. However, the presence of oxidative/nitrosative stress has not been studied in patients with low back pain and endplate changes on magnetic resonance imaging. Patients with MCI, II, and III (n = 32) and age- and sex-matched controls subjects (n = 15) were enrolled in this study. Also, 3-nitrotyrosine (3-NT) and nitric oxide levels as nitrosative stress biomarkers were measured with enzyme-linked immunosorbent assay. Also, the activities of catalase (CAT) and superoxide dismutase (SOD), and the levels of malondialdehyde (MDA) as oxidative stress biomarkers were determined on spectrophotometer. Oxidative/nitrosative stress was confirmed by the significant elevation in nitric oxide, 3-NT, MDA and decreased of CAT and SOD activities in MCI compared with other MCs and the control group (P < 0.05). The highest CAT and SOD activities were found in patients with MCII compared with the other MCs and the control group. However, the levels of nitric oxide, 3-NT, and MDA showed moderate increase in this group (P < 0.05). In addition, the levels of nitrosative stress biomarkers in patients with MCIII were approximated to the control values (P > 0.05). However, the levels of oxidative stress biomarkers in patients with MCIII were slightly higher than that of the control group (P < 0.05). Our findings indicated that oxidative/nitrosative stress in patients with MCI may be aggravated as a result of oxidant/antioxidant imbalance and it may cause formation of the lesion in these patients. However, the increased antioxidant activities and MDA, 3-NT levels in patients with MCII and MCIII may be an adaptative response to against oxidative/nitrosative stress. 4.

Biomarkers of Oxidative Stress in Syndrome Metabolic Patients, a Case Control Study

Abstract Background: Owing to the proposal of the increase of oxidative stress (OxS) as an early event in the development of the metabolic syndrome (MetS), the aim of the present study was to evaluate certain OxS biomarkers in patients with MetS compared to healthy people age-matched and younger to assess the relevance of aging in OxS and MetS. Methods: A total of 72 patients, 32 who fulfilled the Adult Treatment Panel III criteria for the MetS and 40 individuals without MetS, 20 age-matched to the MetS patients (Control I) and 20 younger subjects (Control II) were studied. We measured several anthropometric and serum parameters and two kinds of molecules related to OxS: modified molecules by reactive oxygen species (ROS) such as oxidized LDL (oxLDLc), and consumed or inducted molecules (enzymes or antioxidants such as Glutathione reductase GR,) associated with ROS metabolism. The statistical analysis was performed using SPSS v18.0. Results: Only significant differences were observed in the values of GR between the MetS patients and Control I (50.31 ± 8.15 U/L vs 59.50 ± 9.98 U/L). We found significantly higher levels in the MetS patients compared to Control II of oxLDLc (96.77 ± 23.05 U/L vs 60.17 ± 16.28 U/L), F2 -isoprostanes (3.17 ± 1.78 µg/g creatinine vs 2.04 ± 0.80 µg/g creatinine) and protein cabonils (PC) (0.56 ± 0.26 nmol/mg vs 0.29 ± 0.13 nmol/mg). Conclusions: Results have shown that MetS patients don’t present a superior OxS in comparison to age-related healthy individuals. Finally, aging is more relevant to OxS than MetS per se.

Effects of vitamin C, vitamin E, zinc gluconate, and selenomethionine supplementation on muscle function and oxidative stress biomarkers in patients with facioscapulohumeral dystrophy: A double-blind randomized controlled clinical trial

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by progressive weakness and atrophy of specific skeletal muscles. As growing evidence suggests that oxidative stress may contribute to FSHD pathology, antioxidants that might modulate or delay oxidative insults could help in maintaining FSHD muscle function. Our primary objective was to test whether oral administration of vitamin C, vitamin E, zinc gluconate, and selenomethionine could improve the physical performance of patients with FSHD. Adult patients with FSHD (n=53) were enrolled at Montpellier University Hospital (France) in a randomized, double-blind, placebo-controlled pilot clinical trial. Patients were randomly assigned to receive 500mg vitamin C, 400mg vitamin E, 25mg zinc gluconate and 200μg selenomethionine (n=26), or matching placebo (n=27) once a day for 17 weeks. Primary outcomes were changes in the two-minute walking test (2-MWT), maximal voluntary contraction, and endurance limit time of the dominant and nondominant quadriceps (MVCQD, MVCQND, TlimQD, and TlimQND, respectively) after 17 weeks of treatment. Secondary outcomes were changes in the antioxidant status and oxidative stress markers. Although 2-MWT, MVCQ, and TlimQ were all significantly improved in the supplemented group at the end of the treatment compared to baseline, only MVCQ and TlimQ variations were significantly different between groups (MVCQD: P=0.011; MVCQND: P=0.004; TlimQD: P=0.028; TlimQND: P=0.011). Similarly, the vitamin C (P<0.001), vitamin E as α-tocopherol (P<0.001), vitamin C/vitamin E ratio (P=0.017), vitamin E γ/α ratio (P=0.022) and lipid peroxides (P<0.001) variations were significantly different between groups. In conclusion, vitamin E, vitamin C, zinc, and selenium supplementation has no significant effect on the 2-MWT, but improves MVCQ and TlimQ of both quadriceps by enhancing the antioxidant defenses and reducing oxidative stress. This trial was registered at clinicaltrials.gov (number: NCT01596803).

Effects of sesame seed supplementation on lipid profile and oxidative stress biomarkers in patients with knee osteoarthritis.

This study was designed to assess the effect of sesame seed on lipid profile and oxidative stress biomarkers in knee osteoarthritis (OA) patients. Fifty patients with knee OA were allocated into two groups receiving 40 g of sesame seed daily along with standard medical therapy (n=25) or stan-dard treatment (n=25) for two months. Serum total antioxidant capacity, ma-londialdehyde (MDA) and lipid profile (total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, triglycerides) were measured. After the intervention period two months of study, serum TC, LDL-cholesterol and MDA decreased significantly in the sesame group (P<0.05), while no significant difference in serum values of lipid profile and oxidative stress parameters was seen in the control group (P>0.05). There was no signifi-cant difference in pre and post-treatment values of lipid profile and oxidative parameters between the two groups (P>0.05). Current study showed a positive effect of sesame seed in improv-ing lipid profile and oxidative stress in patients with knee OA and indicated the fact that sesame seed might be of help to reduce oxidative stress in OA patients.

Evaluation of oxidative stress biomarkers in patients with fixed orthodontic appliances.

Aim. The aim of this study was to examine the changes in the levels of interleukine-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxydeoxyguanosine (8-OHdG) in saliva and IL-1β, TNF-α, and NO in gingival crevicular fluid (GCF) samples of patients with fixed orthodontic appliances. Material and Method. The subject population consisted of 50 volunteers who were in need of orthodontic treatment with fixed orthodontic appliances. GCF and saliva samples were obtained from all individuals before treatment, at 1st month of treatment and at 6th month of treatment. Periodontal clinical parameters were measured. Samples were investigated to detect IL-1β, TNF-α, and 8-OHdG levels using ELISA method and NO and MDA levels using spectrophotometric method. Results. Since IL-1β level detected in GCF at the 6th month of orthodontic treatment is statistically significant according to baseline (P < 0.05), all other biochemical parameters detected both in saliva and in GCF did not show any significant change at any measurement periods. Conclusion. Orthodontic tooth movement and orthodontic materials used in orthodontic treatment do not lead to a change above the physiological limits that is suggestive of oxidative damage in both GCF and saliva.

Circulating levels of linoleic acid and HDL-cholesterol are major determinants of 4-hydroxynonenal protein adducts in patients with heart failure

ObjectiveMeasurements of oxidative stress biomarkers in patients with heart failure (HF) have yielded controversial results. This study aimed at testing the hypothesis that circulating levels of the lipid peroxidation product 4-hydroxynonenal bound to thiol proteins (4HNE-P) are strongly associated with those of its potential precursors, namely n-6 polyunsaturated fatty acids (PUFA). Methods and resultsCirculating levels of 4HNE-P were evaluated by gas chromatography-mass spectrometry in 71 control subjects and 61 ambulatory symptomatic HF patients along with various other clinically- and biochemically-relevant parameters, including other oxidative stress markers, and total levels of fatty acids from all classes, which reflect both free and bound to cholesterol, phospholipids and triglycerides. All HF patients had severe systolic functional impairment despite receiving optimal evidence-based therapies. Compared to controls, HF patients displayed markedly lower circulating levels of HDL- and LDL-cholesterol, which are major PUFA carriers, as well as of PUFA of the n-6 series, specifically linoleic acid (LA; P=0.001). Circulating 4HNE-P in HF patients was similar to controls, albeit multiple regression analysis revealed that LA was the only factor that was significantly associated with circulating 4HNE-P in the entire population (R2=0.086; P=0.02). In HF patients only, 4HNE-P was even more strongly associated with LA (P=0.003) and HDL-cholesterol (p<0.0002). Our results demonstrate that 4HNE-P levels, expressed relative to HDL-cholesterol, increase as HDL-cholesterol plasma levels decrease in the HF group only. ConclusionResults from this study emphasize the importance of considering changes in lipids and lipoproteins in the interpretation of measurements of lipid peroxidation products. Further studies appear warranted to explore the possibility that HDL-cholesterol particles may be a carrier of 4HNE adducts.

Oxidative Stress as an Underlying Contributor in the Development of Chronic Complications in Diabetes Mellitus

The high prevalence of diabetes mellitus and its increasing incidence worldwide, coupled with several complications observed in its carriers, have become a public health issue of great relevance. Chronic hyperglycemia is the main feature of such a disease, being considered the responsible for the establishment of micro and macrovascular complications observed in diabetes. Several efforts have been directed in order to better comprehend the pathophysiological mechanisms involved in the course of this endocrine disease. Recently, numerous authors have suggested that excess generation of highly reactive oxygen and nitrogen species is a key component in the development of complications invoked by hyperglycemia. Overproduction and/or insufficient removal of these reactive species result in vascular dysfunction, damage to cellular proteins, membrane lipids and nucleic acids, leading different research groups to search for biomarkers which would be capable of a proper and accurate measurement of the oxidative stress (OS) in diabetic patients, especially in the presence of chronic complications. In the face of this scenario, the present review briefly addresses the role of hyperglycemia in OS, considering basic mechanisms and their effects in diabetes mellitus, describes some of the more commonly used biomarkers of oxidative/nitrosative damage and includes selected examples of studies which evaluated OS biomarkers in patients with diabetes, pointing to the relevance of such biological components in general oxidative stress status of diabetes mellitus carriers.

Local oxidative stress in interdigital tinea pedis

Several skin diseases are believed to be associated with oxidative stress. Tinea pedis is an infection of the feet caused by fungi. The infectious diseases caused by dermatophytes are mainly related to the enzymes produced by these fungi. The cutaneous oxidative stress status of tinea pedis has not been demonstrated in the published work up to now. The aim of the present study was to evaluate the role of oxidative stress in affected skin areas in a group of patients with interdigital tinea pedis. Thirty-one consecutive patients with a diagnosis of unilateral interdigital tinea pedis were enrolled. The samples were obtained by scraping the skin surface. Oxidative stress biomarkers such as superoxide dismutase, catalase and malondialdehyde levels were measured spectrophotometrically. The activities of superoxide dismutase and catalase and the levels of malondialdehyde were significantly higher on the lesional area than the non-lesional area (P<0.001). According to sex and fungal subtypes, there was no significant difference in the levels of oxidative stress biomarkers in patients with tinea pedis (P>0.05). Our results suggested that antioxidant defense of lesional skin surface was higher compared to non-lesional skin. This is possibly due to a compensatory response to various fungal infections and thereby protects the cells against oxidative damage.

Oxidative stress biomarkers in patients with endometriosis: systematic review

Since the first description about oxygen toxicity made by Joseph Priestley, the oxidative stress has been enrolled as a key factor in the pathogenesis of endometriosis. Our aim was to review oxidative stress biomarkers measured in patients with endometriosis. Relevant studies were identified by searches of the MEDLINE database from 1990 to March 2011 using endometriosis, free radical and oxidative stress as mesh terms. We only included manuscripts in English, and review articles were excluded. In addition, free radical chemistry and oxidative stress history were discussed. After inclusion and exclusion criteria, 19 articles were selected to be included in this systematic review. A total of 36 oxidative stress biomarkers (20 different markers) were measured in patients with endometriosis. Some of the markers were measured in more than one manuscript. They were arranged in five subgroups: Enzymatic activity (n = 3), Anions/free radicals (n = 5), Lipoperoxidation markers (n = 7), DNA Damage markers (n = 1), and Protein oxidation (n = 4). Of those 36 markers, 23 were found to be significantly higher in patients with endometriosis comparing with control patients. Oxidative stress plays an important role in the pathogenesis and progression of endometriosis.

Oxidative stress biomarkers in patients with untreated obstructive sleep apnea syndrome

The pathogenic role of oxidative stress in obstructive sleep apnea syndrome (OSAS) is still a matter of debate, with different studies obtaining contrasting results. The aim of the present study was to evaluate three well-known markers of oxidative stress (advanced oxidation protein products [AOPP], ferric reducing antioxidant power [FRAP], and total glutathione [GSH]) in a cohort of 41 untreated patients with a new diagnosis of OSAS. We observed that OSAS patients showed increased protein oxidative damage and impaired antioxidant defenses. Patients with more severe OSAS had a lower total antioxidant capability. Preliminary data on a subgroup of patients (n=7) treated with CPAP show a significant increment of the FRAP values (P<0.005). Our findings indicate that such oxidative stress markers may be useful to detect and monitor redox imbalance in OSAS. Moreover, FRAP might be a new useful biomarker to monitor in vivo the oxidative response to CPAP therapy.

Heme Oxygenase-1 mRNA Expression in Egyptian Patients With Chronic Liver Disease

: Background: Chronic liver disease (CLD) is a global medical problem. This disease is associated with increased hepatic oxidative stress. One of the antioxidant enzymes that protect cells against this stress is heme oxygenase-1 (HO-1).Objectives: This study aimed to investigate the mRNA expression of HO-1 in Egyptian patients with CLD and its relation to oxidative stress biomarkers.Patients and Methods: Levels of serum ferritin, carboxyhemoglobin, malondialdehyde (MDA), and erythrocyte-reduced glutathione (GSH) were measured, and HO-1 mRNA expression was detected in 45 CLD patients (15 with nonalcoholic steatohepatitis [NASH], 15 with chronic hepatitis C, and 15 with liver cirrhosis) and 15 healthy controls.Results: HO-1 mRNA expression was increased in patients with NASH, chronic hepatitis C, and liver cirrhosis compared to controls. The expression in cirrhotic patients was significantly higher than that in patients with NASH and chronic hepatitis C. Compared to controls, patients with NASH, chronic hepatitis C, and liver cirrhosis had higher levels of ferritin, carboxyhemoglobin, and MDA and lower levels of GSH. HO-1 mRNA expression was positively correlated with levels of carboxyhemoglobin, serum ferritin, and serum MDA and negatively correlated with levels of erythrocyte GSH in CLD patients.Conclusions: HO-1 mRNA expression was significantly increased in CLD patients, and the increase reflected the severity of the disease. The significant relationship between the increased HO-1 expression and oxidative stress biomarkers in patients with CLD suggests that HO-1 may play an important role in protecting the liver from oxidative stress-dependent damage. Therefore, induction of HO-1 could be a novel therapeutic option for CLD. Implication for health policy/practice/research/medical education:The significant relations between the increased HO-1 expression and oxidative stress biomarkers in patients with CLD suggest that HO-1 may play an important role to protect the liver from oxidative stress-dependent damage. Reading this article is recommended to all internists and hepatologists. Please cite this paper as:Bessa SS, Mohamed Ali EM, Abd El-Wahab AE, Nor El-Din SA. Heme Oxygenase-1 mRNA Expression in Egyptian Patients With Chronic Liver Disease. Hepat Mon. 2012;12(4):278-85. DOI: 10.5812/hepatmon.846 Copyright © 2012 Kowsar Corp. All rights reserved.

Heme Oxygenase-1 mRNA Expression in Egyptian Patients With Chronic Liver Disease

Chronic liver disease (CLD) is a global medical problem. This disease is associated with increased hepatic oxidative stress. One of the antioxidant enzymes that protect cells against this stress is heme oxygenase-1 (HO-1). This study aimed to investigate the mRNA expression of HO-1 in Egyptian patients with CLD and its relation to oxidative stress biomarkers. Levels of serum ferritin, carboxyhemoglobin, malondialdehyde (MDA), and erythrocyte-reduced glutathione (GSH) were measured, and HO-1 mRNA expression was detected in 45 CLD patients (15 with nonalcoholic steatohepatitis [NASH], 15 with chronic hepatitis C, and 15 with liver cirrhosis) and 15 healthy controls. HO-1 mRNA expression was increased in patients with NASH, chronic hepatitis C, and liver cirrhosis compared to controls. The expression in cirrhotic patients was significantly higher than that in patients with NASH and chronic hepatitis C. Compared to controls, patients with NASH, chronic hepatitis C, and liver cirrhosis had higher levels of ferritin, carboxyhemoglobin, and MDA and lower levels of GSH. HO-1 mRNA expression was positively correlated with levels of carboxyhemoglobin, serum ferritin, and serum MDA and negatively correlated with levels of erythrocyte GSH in CLD patients. HO-1 mRNA expression was significantly increased in CLD patients, and the increase reflected the severity of the disease. The significant relationship between the increased HO-1 expression and oxidative stress biomarkers in patients with CLD suggests that HO-1 may play an important role in protecting the liver from oxidative stress-dependent damage. Therefore, induction of HO-1 could be a novel therapeutic option for CLD.

Association of Lipids with Oxidative Stress Biomarkers in Subclinical Hypothyroidism

Objective. The aim of the present study was to evaluate the oxidative stress biomarkers in patients with subclinical hypothyroidism (n = 20) and health controls (n = 20). Subjects and Methods. Total cholesterol (TC), triglycerides (TGs), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), thiobarbituric acid reactive substances (TBARSs), catalase (CAT), superoxide dismutase (SOD), and arylesterase (ARE) were analyzed. Results. TC, LDL-C, TBARS, and CAT were higher in subclinical hypothyroidism patients, whereas SOD did not change. Arylesterase activity was significantly lower in the SH group, compared with the control group. Correlation analyses revealed the association of lipids (TC and LDL-C) with both oxidative stress biomarkers and thyrotropin (TSH). Thyroid hormones were correlated only with triglyceride levels. In addition, TSH was significantly correlated with TBARS, CAT, and SOD. However, no significant correlations were observed after controlling TC levels. Conclusions. We found that SH patients are under increased oxidative stress manifested by reduced ARE activity and elevated lipoperoxidation and CAT activity. Secondary hypercholesterolemia to thyroid dysfunction and not hypothyroidism per se appears to be associated with oxidative stress in subclinical hypothyroidism.

Plasma Biomarkers of Oxidative Stress and Genetic Variants in Age-Related Macular Degeneration

To compare plasma levels of oxidative stress biomarkers in patients with age-related macular degeneration (AMD) and controls and to evaluate a potential relationship between biochemical markers of oxidative stress and AMD susceptibility genotypes. Prospective case-control study. Plasma levels of oxidative stress biomarkers were determined in 77 AMD patients and 75 controls recruited from a clinical practice. Cysteine, cystine (CySS), glutathione, isoprostane, and isofuran were measured, and participants were genotyped for polymorphisms in the complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genes. CySS was elevated in cases compared with controls (P = .013). After adjustment for age, sex, and smoking, this association was not significant. In all participants, CySS levels were associated with the CFH polymorphism rs3753394 (P = .028) as well as an 8-allele CFH haplotype (P = .029) after correction for age, gender, and smoking. None of the other plasma markers was related to AMD status in our cohort. Our investigation of the gene-environment interaction involved in AMD revealed a relationship between a plasma biomarker of oxidative stress, CySS, and CFH genotype. These data suggest a potential association between inflammatory regulators and redox status in AMD pathogenesis.

Tetracycline treatment in patients with progressive external ophthalmoplegia

Tetracyclines could have neuroprotective effects in neuromuscular and neurodegenerative disorders. AIMS OF THE STUDY AND METHODS: Objective of this double-blind randomized pilot study (followed by an adjunctive open-label phase) was to evaluate whether tetracycline (500 mg/day × 14 days/month × 3 months) could be useful in patients (n = 16) with progressive external ophthalmoplegia (PEO). Our results do not formally support any effect of tetracycline on eye motility in PEO. However, some possible protective effects could not be completely ruled out, i.e. a further analysis suggests a possible difference between the tetracycline group and the placebo group, significant at least for oblique motility, when comparing the ratio between the end of the double-blind phase and baseline. Tetracycline could modify some oxidative stress biomarkers in patients with PEO. Further studies are needed to confirm such effects of tetracycline in patients with PEO, if any, and to clarify the mechanisms of action for antioxidant effects of tetracyclines in mitochondrial disorders and other diseases.