Thiol-disulfide Homeostasis Research Articles

Thiol Disulfide Homeostasis in Pseudoexfoliation Syndrome

ABSTRACTPurpose: To determine the serum thiol disulfide homeostasis in patients with pseudoexfoliation (PEX) syndrome.Method: Thirty-five patients with PEX syndrome and forty healthy subjects were included in this observational case-control study. Serum native thiol, total thiol, disulfide, and native thiol/disulfide ratio were determined using a novel and automated assay.Results: The mean serum total thiol and native thiol levels were significantly lower in patients with PEX syndrome compared to healthy controls (p = 0.001). The mean serum disulfide level was significantly higher in patients with PEX syndrome compared to healthy controls (p = 0.023). The serum native thiol/disulfide ratio was lower in patients with PEX syndrome compared to healthy subjects (16 ± 10.1 vs 22.3 ± 11.5, respectively, p = 0.014).Conclusion: Our findings provide evidence that the dynamic native thiol/disulfide ratio is lower in PEX syndrome, which shows a reduction in the natural cell reductive capacity reservoir.

Investigation of Dynamic Thiol-Disulfide Homeostasis in Alopecia Areata Patients

Investigation of Dynamic Thiol-Disulfide Homeostasis in Alopecia Areata Patients

Impaired Thiol-Disulfide Balance in Acute Brucellosis

The objective of this study was to examine a novel profile: thiol-disulfide homeostasis in acute brucellosis. The study included 90 patients with acute brucellosis, and 27 healthy controls. Thiol-disulfide profile tests were analyzed by a recently developed method, and ceruloplasmin levels were determined. Native thiol levels were 256.72 ± 48.20 μmol/L in the acute brucellosis group and 461.13 ± 45.37 μmol/L in the healthy group, and total thiol levels were 298.58 ± 51.78 μmol/L in the acute brucellosis group and 504.83 ± 51.05 μmol/L in the healthy group (p < 0.001, for both). The disulfide/native thiol ratios and disulfide/total thiol ratios were significantly higher, and native thiol/total thiol ratios were significantly lower in patients with acute brucellosis than in the healthy controls (p < 0.001, for all ratios). There were either positive or negative relationships between ceruloplasmin levels and thiol-disulfide parameters. The thiol-disulfide homeostasis was impaired in acute brucellosis. The strong associations between thiol-disulfide parameters and a positive acute-phase reactant reflected the disruption of the balance between the antioxidant and oxidant systems. Since thiol groups act as anti-inflammatory mediators, the alteration in the thiol-disulfide homeostasis may be involved in brucellosis.

Dynamic thiol/disulfide homeostasis in patients with age-related macular degeneration.

We evaluated dynamic thiol/disulfide homeostasis (TDH), malondialdehyde (MDA) levels, and catalase (CAT) activity in patients with age-related macular degeneration (AMD). All analyzes were conducted on plasma samples. Thirty-two patients with AMD and 38 age-matched healthy controls were included. Native thiol, total thiol, and disulfide levels and TDH status were determined using a novel, automated assay. MDA levels and CAT activity were determined. Percentages were compared using the chi-squared test. The Student's t-test and Mann-Whitney U-test were used to compare quantitative variables. Native thiol levels were significantly lower (p=0.004) in patients with AMD (272.02 ± 52.41 µmol/l) than in healthy individuals (307.82 ± 47.18 µmol/l), whereas disulfide levels were significantly higher (p<0.001) in patients with AMD than in controls (21.64 ± 5.59 vs. 14.48 ± 5.37 µmol/L). Dynamic TDH was also significantly lower (p<0.001) in patients with AMD than in controls (13.41 ± 4.3 vs. 25.41 ± 14.52 µmol/l). No significant differences were evident in total thiol or MDA levels. Mean CAT activity was significantly higher (p=0.043) in patients with AMD compared with controls (0.035 vs. 0.018 k/ml). The antioxidant/oxidant balance demonstrated by dynamic TDH is shifted to the oxidative side in patients with AMD.

Clinical Utility of Thiol/Disulfide Homeostasis.

Recently, the usefulness of thiol/disulfide homeostasis (TDH) in various diseases is being widely investigated. In this mini-review, our aim is to clarify the role of TDH in clinical practice in the light of current literature. We performed a systematic review of the existing literature describing the clinical utility of TDH in the clinical setting. MEDLINE, EMBASE, and CINAHL were used as data sources. Two reviewers conducted independent screening and data extraction. Use of TDH in each system was investigated separately. A total of 35 studies were detected in this mini-review. Our results revealed the protective role of TDH and its utility as a diagnostic marker in many common diseases in clinical practice. Maintenance of TDH as a crucial part of antioxidant defense system is critical in diagnosis and prognosis of potentially lethal diseases.

Thiol-Disulfide Homeostasis in Patients with Panic Disorder

Objective: To determine serum thiol/disulfide homeostasis in panic disorder (PD). Methods: Serum native thiol, total thiol, and disulfide levels were measured in the patients with 40 PD patients and 40 healthy subjects. Serum native thiol, total thiol, and disulfide levels were measured with a novel colorimetric, automated method. The thiol-disulfide ratio was also calculated. Results: The native thiol (p < 0.001) and total thiol (p < 0.001) levels, and the native thiol/total thiol (p < 0.001) ratio were significantly lower, whereas disulfide/native thiol (p < 0.001) and disulfide/total thiol (p < 0.001) ratio significantly increased in the PD patient group compared to the control group. The cut-off value was 92.26, 3.83 and 3.56 for native thiol/total thiol, disulfide/native thiol and disulfide/total thiol respectively. Conclusion: This is the first study in the literature to evaluate thiol-disulfide homeostasis in patients with PD. Our results suggest that the disulfide/thiol ratio is significantly greater in panic disorder patients.

Can the Thiol/Disulfide Imbalance Be a Predictor of Colchicine Resistance in Familial Mediterranean Fever?

Familial Mediterranean fever (FMF) is a chronic autoinflammatory condition characterized by fever attacks and recurrent polyserositis. Subclinical inflammation that persists during attack-free periods can result in oxidative stress (OS) damage. Thiol groups bind to reactive oxygen radicals and protect cells and tissues from OS damage. The aim of this study was to investigate the relationship between thiol-disulfide balance and colchicine resistance in FMF patients during an attack or attack-free period. A newly developed spectrophotometric method was used to measure native thiol (NT) and disulfide (DS) levels in FMF patients and an age-sex matched group of healthy controls. NT and DS levels were compared in FMF patients 1) with vs. without colchicine resistance; and 2) during an attack (FMF-AP) vs. attack-free period (FMF-AFP). A total of 118 FMF patients and 60 healthy controls were studied. NT (P < 0.001) and total thiol (TT) (P < 0.001) levels in FMF patients were significantly lower compared to healthy controls. NT (P = 0.030) and TT (P = 0.010) levels of FMF-AP patients were significantly lower than that of FMF-AFP patients. FMF-AP patients had significantly higher DS levels than FMF-AFP patients (P = 0.039). Compared to FMF patients without colchicine resistance, elevated levels of DS (P = 0.019) but not NT (P = 0.620) and TT (P = 0.718) were found in those with colchicine resistance. Thiol-disulfide homeostasis is altered in FMF patients during an attack period and this imbalance may be associated with colchicine resistance.

Association of Thiol Disulfide Homeostasis with Childhood Asthma

The aim of this study is to evaluate the oxidative stress level in asthmatic children in terms of the disulfide/thiol ratio, to research the role the disulfide/thiol ratio plays in the pathogenesis of the malady, and to determine the usefulness of the disulfide/thiol ratio as an indicator of the oxidation stress situations in patients with asthma. We report that the disulfide/thiol ratio and disulfide levels were significantly higher in the asthmatic group than in the control group. All in all, high levels of disulfide/thiol ratios in asthmatic children are thought to play roles in the pathogenesis of the disease.

The thiol-disulfide homeostasis and its role in the pathogenesis of the experimental alimentary obesity

Objective: According to WHO, about 30 % of people in the world are overweight that allows to characterize this disease as a new non-infection “epidemic” of the XXI century. More than 500 million people in the world are overweight and 250 million are obese. There is a clear tendency to increasing of alimentary obesity among people with different age, sex and nationality. The aim of the study is to investigate the thiol-disulfide homeostasis in liver tissue, adipose tissue and erythrocytes in the pathogenesis of experimental alimentary obesity.Materials and methods: 60 males, non-liner, white rats around 3 months of age with alimentary obesity were examined during the study. Experimental obesity was modeled by administering of sodium glutamate to the feed mixture in a ratio of 0.6:100.0 and adding high-calorie diet. The glutathione redox-system activity in erythrocytes, liver and adipose tissue were analyzed by the level of reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR) and glutathione peroxidase (GP) activity.Results and Discussion: The data indicate a decrease in GSH level within 14 days of the experiment in all investigated tissues. The same trend was observed in animals on 28th day of the experiment: GSH index decreased in blood, adipose tissue and liver (P&lt;0.05). The index of GSSG have increased on 28th day of the experiment in all investigated tissues vs control group (P&lt;0.05). The ratio of the reduced and oxidized forms of glutathione contents was much lower vs control group in all the studied tissues within 28 days of the experiment. During additional investigation of the activity of thiol-disulfide system enzymes it was found that reducing the concentration of GSH in rats with alimentary obesity was due to the lack of thiol-disulfide system enzymes activity: GP and GR, which take part in the regeneration of GSH from GSSG.Conclusion: experimental alimentary obesity is characterized by a reduced redox state in blood, adipose and liver tissues, which is determinative in increasing the free radical reactions and accumulation of highly toxic lipoperoxides in the tissue substrates.Bangladesh Journal of Medical Science Vol.15(3) 2016 p.419-423

Changes in Thiol-Disulfide Homeostasis of the Body to Surgical Trauma in Laparoscopic Cholecystectomy Patients.

We aimed to investigate the short-term effect of laparoscopic surgery on serum thiol-disulfide homeostasis levels as a marker of oxidant stress of surgical trauma in elective laparoscopic cholecystectomy patients. Venous blood samples were collected, and levels of native thiols, total thiols, and disulfides were determined with a novel automated assay. Total antioxidant capacity (measured as the ferric-reducing ability of plasma) and serum ischemia modified albumin, expressed as absorbance units assayed by the albumin cobalt binding test, were determined. The major findings of the present study were that native thiol (283 ± 45 versus 241 ± 61 μmol/L), total thiol (313 ± 49 versus 263 ± 67 μmol/L), and disulfide (14.9 ± 4.6 versus 11.0 ± 6.1 μmol/L) levels were decreased significantly during operation and although they increased, they did not return to preoperation levels 24 hours after laparoscopic surgery compared to the levels at baseline. Disulfide/native thiol and disulfide/total thiol levels did not change during laparoscopic surgery. The decrease in plasma level of native and total thiol groups suggests impairment of the antioxidant capacity of plasma; however, the delicate balance between the different redox forms of thiols was maintained during surgery.

Disulfide stress in carbon monoxide poisoning

ObjectivesCarbon monoxide (CO) remains the most common cause of lethal poisoning around the world. The purpose of this study was to investigate the homeostasis between thiol-disulfide couples and to evaluate oxidative status comprehensively in acute CO poisoning, using new parameters along with other well-known oxidant-antioxidant molecules. Design and methodsThis case study consisted of 43 subjects who were diagnosed with carbon monoxide poisoning and 35 healthy individuals who were used as controls. Thiol-disulfide paired tests were examined in both groups using the method developed recently. ResultsPatients with CO poisoning had significantly higher levels of serum disulfide than the control patients (20.7±5.03 versus 16.43±3.97, p=0.001). Native thiol and total thiol levels were lower in the CO patient group than in the control group (p<0.001, for each variable). The disulfide/native thiol ratios and disulfide/total thiol ratios were significantly higher, while native thiol/total thiol ratios were significantly lower, in patients with acute CO poisoning than in the healthy controls (p<0.001, for all ratios). The disulfide/native ratios were negatively correlated with both total antioxidant response and paraoxonase and arylesterase values and were positively correlated with total oxidant status and ceruloplasmin values (p<0.05, for all correlations). ConclusionsExcessive disulfide levels and their related ratios were found in CO poisoning patients. In particular, the disulfide/native thiol ratio was identified as an indicator for overall oxidative status. Among CO poisoning patients, the thiol-disulfide balance was found to be impaired. Therefore, the disruption of thiol-disulfide homeostasis might be involved in CO toxicity.

Plasma thiols and thiol-disulfide homeostasis in patients with isolated coronary artery ectasia

Background and aimsThiol/disulfide homeostasis has an important role in the antioxidant defense system. Oxidative stress may contribute to the pathogenesis of coronary artery ectasia. The aim of this study was to evaluate plasma thiol levels and thiol/disulfide homeostasis in patients with isolated coronary artery ectasia. MethodsForty-one patients with isolated coronary artery ectasia and 72 patients with normal coronary arteries were included in the study. Markis classification and number of ectatic coronary arteries were recorded. Plasma total thiol levels, native thiol levels and disulfide levels were measured. Thiol/disulfide homeostasis was appraised by calculating thiol/disulfide ratio. ResultsPlasma native thiol levels were significantly lower (336.9 (252.9–374.1) vs. 353.1 (327.0–380.0), p = 0.041) and disulfide levels were significantly higher (18.9 ± 6.3 vs. 16.6 ± 3.4, p = 0.014) in patients with coronary artery ectasia than control patients. Both native thiol/disulfide and total thiol/disulfide ratio was significantly lower in the coronary artery ectasia group (p < 0.001). Multivariate logistic regression analysis revealed that native thiol levels, disulfide levels and native thiol/disulfide ratio were independently associated with the presence of coronary artery ectasia. Thiol/disulfide ratio was not different according to number of ectatic coronary arteries and there was no association between thiol/disulfide ratio and Markis classification. ConclusionsPlasma thiol/disulfide homeostasis is altered in patients with coronary artery ectasia.

A retrospective controlled study of thiol disulfide homeostasis as a novel marker in Crimean Congo hemorrhagic fever

Objectives: Crimean Congo hemorrhagic fever (CCHF) is the second most common hemorrhagic fever worldwide. This study aimed to evaluate the oxidant–antioxidant balance of patients with CCHF by detecting dynamic thiol disulfide homeostasis (TDH), which is a novel oxidative stress marker, and other molecules, including paraoxonase (PON), arylesterase (ARES), ceruloplasmin (CLP), myeloperoxidase (MPO), and catalase.Methods: This retrospective, cross-sectional, controlled study, which involved patients with CCHF and healthy volunteers, measured dynamic TDH using a novel automated method developed by Erel.Results: We recruited 69 adult patients with CCHF (31 females, 38 males, median age 46 years). The case fatality rate was 1.49% (1/69). Increased disulfide/native thiol and disulfide/total thiol ratios, decreased total antioxidant status (TAS), and increased total oxidant status (TOS) were found in patients with CCHF. TAS, PON, and ARES values were found to be positively correlated with both native and total thiol levels, whereas TOS and CLP were negatively correlated with both, at a significant level. MPO activity was similar in both groups.Discussion: This is the first study in the literature to evaluate dynamic TDH in CCHF. TDH shifts to the oxidative side in patients with CCHF, leading to an increase in TOS.

Association of thiol disulfide homeostasis with slow coronary flow

Objective The aim of this study was to investigate the role of thiol disulfide homeostasis in the presence of slow coronary flow. Material and methods In this cross-sectional study, a total of 110 patients who admitted to our hospital between March 2014 and December 2015 were included in the study. There were 65 patients in the slow coronary flow, and 45 patients in the normal flow groups. Results We found significant differences between slow coronary flow and the normal flow groups for thiol disulfide homeostasis, and the results of our study indicated that hsCRP, and thiol disulfide ratio were independently associated with slow coronary flow. Conclusion Our study showed that thiol disulfide homeostasis was significantly and independently related to the presence of slow coronary flow.

Impairment of thiol-disulfide homeostasis in preeclampsia

Aim: To investigate the effects of severity of preeclampsia on thiol-disulfide homeostasis (TDH).Material and methods: A total of 108 participants were divided into three groups: Group 1 was composed of pregnant women with no obstetric complications, Group 2 included pregnant women with mild preeclampsia, and Group 3 consisted of pregnant women with severe preeclampsia. TDH parameters were determined, and comparisons of clinical and routine laboratory test findings were made in all groups.Results: The serum native thiol level was 347.9 ± 27.4 in the control group, 237.2 ± 44.2 in the mild preeclampsia group, and 227.9 ± 53.1 in the severe preeclampsia group (p < 0.001). The serum total thiol level was 376.1 ± 31.9 in the control group, 261.8 ± 49.4 in the mild preeclampsia group, and 248.3 ± 57.4 in the severe preeclampsia group (p < 0.001). The disulfide level was 14.1 ± 5.6 in the control group, 12.3 ± 5.1 in the mild preeclampsia group, and 10.2 ± 4.8 in the severe preeclampsia group (p = 0.001). A significant correlation between impairment in degree of TDH and severity of preeclampsia was observed.Conclusion: TDH was impaired in women with preeclampsia, and this impairment increased with disease severity. Therefore, impaired TDH may have a role in the etiopathogenesis of the disease.

Dynamic thiol-disulfide homeostasis in acute ischemic stroke patients.

Dynamic thiol-disulfide homeostasis plays a critical role in the cellular protection provided by antioxidation. The aim of this study was to investigate whether there is a change in thiol-disulfide homeostasis in acute ischemic stroke patients. Patients diagnosed with acute ischemic stroke that had undergone magnetic resonance diffusion-weighted imaging within the first 24h were prospectively included in this study. The thiol, disulfide, and total thiol levels were measured during the first 24 and 72h, and the National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) of the patients were recorded. Overall, the relationships between the thiol-disulfide levels of the patients and the infarct volumes, NIHSS, mRS, and BI scores were investigated. In this study, 54 patients and 53 healthy controls were included. The mean of the native thiol levels in the stroke group was 356.572±61.659μmol/L (min/max 228.00/546.40), while it was 415.453±39.436μmol/L (min/max 323.50/488.70) in the control group (p<0.001). A negative, significant correlation was observed between the infarct volumes and native thiol levels (ρ=-0.378; p=0.005), and the disulfide levels were similar between the groups (Z=0.774; p=0.439). Significant difference was found between the thiol levels of the mild and moderate-severe NIHSS groups (p=0.026). The changes in the thiol levels under oxidative stress may be associated with the severity of the stroke. Substitution of thiol deficiency and correction of thiol-disulfide imbalance may be beneficial in ischemic stroke.

Dynamic thiol-disulfide homeostasis in hyperemesis gravidarum.

To determine serum thiol-disulfide homeostasis in hyperemesis gravidarum. Twenty-six pregnant women with hyperemesis gravidarum and 37 healthy pregnant women were included in the study. Native thiol, disulfide and total thiol concentrations were measured with a novel automated method. Serum disulfide levels were 15.68±4.41 μmol l(-1) in the hyperemesis gravidarum group and 13.49±2.81 μmol l(-1) in the healthy group (P=0.031). Native thiol levels were 213.86±26.29 μmol l(-1) in the hyperemesis gravidarum group and 232.18±19.21 μmol l(-1) in healthy group (P=0.004), and total thiol levels were 245.23±28.58 μmol l(-1) in the hyperemesis gravidarum group and 259.17±19.94 μmol l(-1) in the healthy group (P=0.038). Native and total thiol were deficient in the hyperemesis gravidarum group and this deficiency was correlated with the severity of the disease. The thiol-disulfide balance has shifted to the oxidative side. This metabolic disturbance may have a role in the pathogenesis of hyperemesis gravidarum.

PP-046 Plasma Thiol-disulfide Homeostasis in Patients with and without Critical Epicardial Coronary Artery Disease

A B S T R A C T S versus 10.80 7.04 mmol/L; p1⁄40.477, respectively). ROCcurve analysis revealed that thiol levels over 260 mmol/L predicted ACS with 65% sensitivity and 62% specificity (area under the curve1⁄40.702; 95% CI 0.626-0.778). Conclusions: These findings indicate that SH and SHHS level decrease in patients with ACS and SA. Decreased SH and SHHS level may be related with pathogenesis of coronary atherosclerosis.

PP-045 The Investigation of the Dynamic Thiol-disulfide Homeostasis in Acute Coronary Syndromes

PP-045 The Investigation of the Dynamic Thiol-disulfide Homeostasis in Acute Coronary Syndromes

Molecular and biochemical aspects of the neuroprotective effect of the selective estrogen receptor modulator tamoxifen in a model of acute cerebral ischemia

We studied the neurochemical aspects of the neuroprotective action of a selective modulator of the estrogen receptors, tamoxifen citrate, in a model of acute cerebral ischemia (ACI). It was shown that modeling of cerebral ischemia is followed by pathobiochemical changes in the brain tissue: a rapid shift of thioldisulfide homeostasis, intensification of free radical oxidation, and impaired synthesis of the cytoprotective protein Hsp70. A course of the 1 mg/kg tamoxifen citrate led to the normalization of the thiol-disulfide system due to an increase of the glutathione level in the brain tissue which, in turn, restricted the development of oxidative and nitrosative stress. In addition, Western blot analysis showed that treatment with tamoxifen citrate increased the Hsp70 level in the brain tissue, which resulted from genomic and non-genomic actions. The neuroprotective profile of tamoxifen citrate that we found here opens the future perspective of the studies in this field for introduction of this agent as a neuroprotective drug into clinical practice.