Plasma thiol/disulphide homeostasis changes in patients with restless legs syndrome.

OBJECTIVES: Restless legs syndrome (RLS) is a common neurological condition. Oxidative stress plays an important role in its pathogenesis. Thiol-disulphide homeostasis (TDH) is a new biomarker of oxidative stress. We studied plasma TDH to determine whether TDH could be used as a new biomarker for RLS and evaluated correlations between TDH and various disease severity rating scales. METHODS: A total of 25 RLS patients and 25 healthy controls were included into the study. TDH status was determined using an automated spectrophotometric analysis method and correlations were analyzed between the TDH status and various disease rating scales in the RLS patients. RESULTS: Plasma total (401±27 µmol/L) and native thiol (354±30 µmol/L) levels were significantly lower, but disulphide level (24±6 µmol/L) was significantly (<0.0001) higher in the RLS patients compared to the controls (455±36, 424±37, 15±5 µmol/L, respectively). The disulphide/native thiol and disulphide/total thiol ratios increased, in contrast, native thiol/total thiol ratio decreased significantly in the RLS patients compared to the healthy controls (<0.0001). The disulphide levels correlated positively with age and various rating scores of the RLS patients. International Restless Legs Syndrome Study Group (IRLSSG) rating score and age correlated negatively with the total and native thiol levels. CONCLUSIONS: Our findings indicate increased oxidative stress in the RLS patients reflected by decreased native and total thiol, and increased disulphide levels and positive correlations between the disulphide levels and various rating scores. We suggest dynamic TDH status to be used as a novel biomarker for the diagnosis and follow-up of the RLS patients.

A novel marker in acute central serous chorioretinopathy: thiol/disulfide homeostasis.

PURPOSE: The aim of this study was to compare dynamic thiol/disulfide homeostatic status in acute central serous chorioretinopathy (CSCR) patients by using a novel and automated assay determining dynamic thiol/disulfide homeostasis. METHODS: Fifty-one patients with acute CSCR (study group) and 65 healthy individuals (control group) were enrolled in this study. Diagnosis of acute CSCR was made clinically and using spectral-domain RTVue OCT (optical coherence tomography) (Optovue, Fremont, CA). Fluorescein angiography confirmed the diagnosis of acute CSCR in all subjects. Total thiol, native thiol, disulfide amount, and native thiol/disulfide ratio (TDR) were calculated in the blood samples. RESULTS: Mean total thiol, native thiol, and native TDR values were lower in patients with acute CSCR (364.2 ± 14.1, 326.4 ± 13.2, 17.14 ± 1.9, respectively) than in healthy eyes (441.2 ± 16.3, 398.5 ± 16.4, 22.70 ± 2.15, respectively; mean total thiol, p = 0.017; native thiol, p = 0.011; native TDR, p = 0.031). CONCLUSIONS: Total thiol, native thiol, and native TDR were significantly lower statistically in patients with acute CSCR when compared with healthy controls.

A novel tool reflecting the role of oxidative stress in the cataracts: thiol/disulfide homeostasis.

We investigated serum and aqueous humor thiol/disulfide (T-D) homeostasis in patients with cataracts versus healthy controls. In total, 56 patients with cataracts and 49 healthy controls were enrolled in this case-control study. Serum total thiol (TT), native thiol (NT), and disulfide (DS) concentrations were determined using a novel automated measurement method. Additionally, DS/TT, DS/NT and NT/TT percentage ratios were compared between the groups. In comparison with the control group, serum NT levels and aqueous humor TT and NT levels were significantly lower (p < .05, p < .05 and p < .001, respectively), whereas serum and aqueous humor DS levels were significantly higher in cataract patients (p < .01 and p < .001). DS/TT and DS/NT ratios were significantly higher and the NT/TT ratio was lower in cataract patients in serum (p < .005) and aqueous humor samples (p < .001). In conclusion, serum T-D homeostasis may be useful as biochemical markers, indicating the role of oxidative stress in the development of cataracts. Further studies are needed to confirm the pathophysiological role of T-D homeostasis in cataractogenesis.

Comparison of serum thiol-disulphide homeostasis and total antioxidant-oxidant levels between exudative age-related macular degeneration patients and healthy subjects.

PURPOSE: The purpose of the study was to calculate serum total oxidant status (TOS), total antioxidant status (TAS), and dynamic thiol-disulphide (T-D) homeostasis in patients with age-related macular degeneration (AMD), and compare the results with healthy individuals. METHODS: Thirty-three exudative AMD patients and 33 healthy controls were included in this case-control study. Participants' serum TAS and TOS levels were measured. In addition, total thiol (TT), native thiol (NT), and disulphide (DS) concentrations were assessed using a novel automated method of measurement. RESULTS: In comparison with the control group, serum TAS, TT, and NT levels were found to be significantly lower (p < 0.0001, p = 0.004, p = 0.003, respectively) and TOS levels were detected higher (p = 0.032) in AMD patients. Serum DS levels were elevated in the AMD patient group, but the difference was not statistically significant (p = 0.219). DS/TT and DS/NT ratios were significantly higher (p = 0.012, p = 0.013, respectively) in AMD patients. A positive correlation was found between TT and NT (p < 0.0001) in AMD group. CONCLUSIONS: Serum TOS levels are higher, TAS levels are lower, and the T-D balance is shifted to the DS bond side in AMD patients. These results suggest that increased oxidative stress and decreased antioxidant levels may play a role in AMD progression. Further studies are needed to confirm the pathophysiologic role of T-D homeostasis in AMD.

Assessment of thiol/disulfide and ischemia modified albumin level and oxidative stress in pregnancies complicated by meconium.

OBJECTIVE: The purpose of this study is to evaluate antioxidant balance in pregnant women with meconium-stained amniotic fluid. METHODS: Forty pregnant women with meconium-stained amniotic fluid and 40 pregnant women with non-meconium-stained amniotic fluid were included in the study. By checking the ischemia modified albumin (IMA) level and thiol/disulfide homeostasis in the maternal blood during labor and in newborn umbilical cord blood at the first minute after birth, antioxidant/oxidant balance was evaluated. RESULTS: No statistically significant difference was found between the maternal albumin levels. Maternal IMA level was statistically significantly higher in the meconium group than in the control group (p = .045). Maternal native thiol (SH) and maternal total thiol levels were statistically significantly higher in the control group than in the meconium group (p = .042 and p = .009, respectively). No statistically significant difference was found between maternal disulfide/native thiol (p = .262), maternal disulfide/total thiol (p = .152), maternal native thiol/total thiol (p = .153) rates in both groups. No statistically significant difference was determined between the patients with meconium and the control group in terms of cord blood IMA (p = .474), Albumin levels (p = .664), cord blood Native thiol (p = .944), cord blood total thiol (p = .612) levels and cord blood disulfide/native thiol (p = .240), cord blood disulfide/total thiol (p = .276), cord blood native thiol/total thiol (p = .277) rates. CONCLUSION: Determination of a decrease in SH and Total Thiol levels in maternal serum and an increase in the meconium group's IMA level was interpreted as a shift of antioxidant balance toward oxidant in this group.

Thiol-disulfide balance and trace element levels in patients with seasonal allergic rhinitis.

Background: The prevalence of allergic diseases is gradually increasing worldwide. The most common such allergic disease is allergic rhinitis (AR). Objective: The present study investigated the possible relationship between seasonal AR and the thiol-disulfide balance and zinc and copper levels in adult individuals. Study Design and Methods: 130 male and female adults were included in the study. The participants' serum thiol-disulfide balance and zinc and copper levels were measured spectrophotometrically using commercial kits. Statistical significance was accepted as p < 0.05 between the groups. Results: The serum copper (p = 0.001), native thiol (p = 0.006), reduced thiol (p < 0.001), and thiol oxidation reduction ratio (p < 0.001) levels were significantly lower in the seasonal AR group than in the control group. Conclusion: In AR patients, the low level of copper, which is an important trace element, the deterioration of the thiol-disulfide balance, which represents a unique indicator of the oxidant-antioxidant balance, the increased disulfide level caused by oxidative stress, and the decreased native thiol level can all serve as important biochemical markers.

The relationship between adjuvant chemotherapy and thiol-disulfide compounds.

Aim: Thiols are the organic compounds of the antioxidant system. There is limited data in the literature concerning chemotherapy (CT) in cancer and thiol balance. In this study, we aimed to evaluate the possible changes of thiol/disulfide levels with the recurrent CT cycles and type of cancer. Materials and Methods: The 40 healthy individuals and 40 patients who had been newly diagnosed with early-stage breast, ovary and endometrium cancer receiving adjuvant CT. Blood samples were taken from all patients three times as basal and after the first and second CT sessions. Results: We compared preadjuvant treatment levels of thiol and disulfide parameters in the patients group with the control group. The median of native thiol and total thiol was found to be higher in the control group than in the study group (P < 0.001). In addition, disulfide/native thiol and disulfide/total thiol rates were found to be higher in the patient group (P = 0.001). When we look at the comparison before and after CT in the patient group, disulfide/native thiol and disulfide/total thiol rates, which represent increased oxidative stress (OS) levels were found to be higher after CT than before CT measurement (P < 0.016). Discussion: This is the first study, which has researched the relationship between cancer type and thiol compounds and changes of thiol compounds during CT therapy, by using the method designed by Erel and Neselioglu. In this study, we found that pre-CT thiol disulfide balance in cancer patients shifted toward disulfide direction and OS levels may increase after repetitive CT sessions.

Evaluation of serum thiol-disulphide homeostasis parameters as oxidative stress markers in epilepsy patients.

The present study focuses on the investigation of the dynamic thiol-disulphide homeostasis in patients with epilepsy and understanding the effects of antiepileptic drugs on thiol levels. A total of 148 participants, 75 of whom had epilepsy and 73 were healthy volunteers, were included in the study. Total thiol and native thiol levels of all epilepsy patients and healthy volunteers were measured. Disulphide level, disulphide/native thiol, disulphide/total thiol and native/total thiol ratios were calculated from these values. The results were compared between epilepsy patients and healthy volunteers. A statistically significant difference was found between native thiol level, total thiol level, disulphide level, disulfide/total thiol, disulphide/native thiol and native/total thiol ratios between patients with epilepsy and healthy volunteers (p = 0.002, p = 0.035, p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). The drugs used had a significant effect on disulphide, disulphide/total thiol, native/total thiol levels (p values 0.004, 0.009, 0.009, respectively). Decreased levels of serum native, total thiol and increased disulfide levels as parameters of oxidative stress may be considered as parameters to explain the pathogenesis or consequences of epilepsy.

A useful and sensitive marker in the prediction of COVID-19 and disease severity: Thiol.

Thiol-disulphide homeostasis (TDH) is a new parameter indicating oxidative stress that plays a role in the pathogenesis of various clinical disorders. Our study planned to investigate TDH in COVID-19 patients. Age and gender-matched healthy subjects (n = 70) and COVID-19 patients (n = 144) were included in the study. In addition to the routine laboratory parameters of the groups, their native thiol (NT), total thiol (TT) and disulphide levels were measured. Primarily, we compared COVID-19 patients to the healthy control group for inflammatory parameters, NT, TT and disulphide levels. Then, COVID-19 patients were divided into two groups according to the severity of the disease as mild to moderate and severe COVID-19, and the three groups were compared with each other. Predictive value of thiol parameters in the diagnosis of COVID-19 and in the determining its severity, and its correlation with presence and duration of symptoms were investigated. Severe COVID-19 patients had lower NT and TT levels compared with healthy controls and mild to moderate patients (P < 0.001 for both). The results of ROC analysis show that the greatest AUC was IL-6 and NT (AUC = 0.97, AUC = 0.96, respectively) between control and COVID-19 patients, while it was CRP and NT (AUC = 0.85, AUC = 0.83) between mild to moderate and severe patients. A negative correlation was found between duration of symptoms of dyspnoea, cough, fever, and sore throat and NT (r = -0.45, P = 0.017, r = -0.418, P < 0.001, r = -0.131, P = 0.084, r = -0.452, P = 0.040, respectively). NT and TT levels have a strong predictive value in the diagnosis of COVID-19 and in determining disease severity. Our results support that changing TDH parameters appears to have an important role in disease pathogenesis and it can be used in clinical management of patients.

Comparison of serum human Klotho levels and thiol/disulfide homeostasis in women with polycystic ovary syndrome and in healthy women.

OBJECTIVES: Women with polycystic ovary syndrome (PCOS) have an increased cardiometabolic risk. Similarly, it was previously shown that atherosclerotic and cardiovascular risk is increased in the general population with lower serum Klotho levels. The aim of this study was to investigate the lotho and thiol/disulfide levels in women with non-obese PCOS compared to healthy controls and also to investigate the relationship of serum Klotho and thiol/disulfide homeostasis with cardiometabolic risk factors. MATERIALS AND METHODS: In this prospective case control study, human serum alpha Klotho levels and thiol/disulfide homeostasis of women with PCOS aged between 19-33 were compared to their age and BMI matched non - PCOS healthy controls. In addition, the correlation of these molecules with other metabolic markers/measurements were also investigated. RESULTS: Metabolic parameters such as mean waist circumference, lipid accumulation product, visceral adiposity index, fasting insulin, homeostasis model assessment of insulin resistance and triglyceride values were higher in the PCOS group (p = 0.038, p = 0.008, p = 0.001, p = 0.001, p = 0.002 and p = 0.002, respectively) compared to controls. However, mean serum Klotho and native thiol levels (respectively p < 0.0001 and p = 0.038) were lower compared to controls. Correlation analysis revealed that serum Klotho levels were negatively correlated with BMI, waist circumference, disulphide/total thiol, disulphide/native thiol, HOMA-IR and LAP-index. CONCLUSIONS: Findings of decreased serum Klotho and native thiol values of the PCOS group compared to controls and the negative correlation of serum Klotho levels with metabolic markers supports the idea that decreased Klotho may be another mechanism by which cardiovascular risk is increased in women with PCOS.

Dynamic thiol-disulphide homeostasis in low-grade gliomas: Preliminary results in serum.

OBJECTIVE: Maintaining of precise balance between oxidation and anti-oxidation is important in both physiological and pathological states. Knowledge about this balance may give an idea about the process of the disease. The aim of this study was to investigate dynamic thiol-disulfide homeostasis in patients with low-grade gliomas. PATIENTS AND METHODS: Serial serum samples were collected in 13 patients operated on low-grade gliomas before and after surgery. Control serum samples were obtained from venous cord blood from 13 healthy women during cesarean section. Total thiol, native thiol, and disulfide bond formation were measured and compared with the controls. RESULTS: Total thiols, native thiols, and disulfide bond formation were significantly elevated in patients before the surgery compared to the controls (p<0.05). Even after the surgery, these three parameters were still high in patients, and the differences were significant (p<0.05). Although no significant difference was found between patients and controls regarding the ratios of disulfide/total thiol, disulfide/native thiol, and native thiol/total thiol (p>0.05), the balance seemed to shift to oxidative side. CONCLUSIONS: Thiol-disulfide homeostasis was disrupted in patients with low-grade gliomas, and oxidation may play a role in the process of this disease. Supplementation with antioxidants before and after surgery may be taken into consideration.

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

PURPOSE: 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.

Evaluation of oxidative stress markers and intra-extracellular antioxidant activities in patients with endometriosis.

OBJECTIVE: The aim of the study is to evaluate alterations in intracellular and extracellular antioxidant enzymes activities and serum oxidative stress markers in patients with endometriosis. STUDY DESIGN: The current prospective study consisted of 31 female patients with endometriosis and 27 healthy controls. Serum total thiol, native thiol, disulphide, catalase, myeloperoxidase, and ceruloplasmin concentrations were measured. Laboratory and clinical data of all participants were recorded to compare the differences between the study and the control groups. RESULTS: Serum native thiol and total thiol levels in the study group were significantly lower than those in the control group [(p=0.009, p=0.03, respectively)]. Serum catalase levels are significantly higher in patients with endometriosis comparing to the control group (p=0.009). CONCLUSIONS: The finding that significant differences in serum total thiol, native thiol, and catalase levels observed in endometriotic patients supports that oxidative stress carries weigh in the pathophysiological aspects of endometriosis. Also significantly low levels of extracellular antioxidants and significantly high levels of intracellular antioxidants in endometriotic patients may arise from differences of free radicals in endometriosis and the activity levels of endometriosis. These non-invasive serum markers might give us an opportunity to monitor the disease's progress during the treatment.

An evaluation of the relationship between vitamin D level and CTRP-9, tumor necrosis factor-alpha, thiol-disulfide hemostasis in women

SUMMARY OBJECTIVE: Many chronic diseases such as malignancy, cardiovascular diseases, endothelial dysfunction, and autoimmune diseases, which have been shown to be related to vitamin D in various studies; have similar relations with CTRP-9, TNFα, and thiol-disulfide hemostasis. We aimed to contribute to the literature by evaluating the relationship between CTRP-9, TNFα, and thiol-disulfide hemostasis and vitamin D levels, which we thought may have some effects on the pathogenesis of vitamin D deficiency. METHODS: In our study, 78 female volunteers older than 18 years were included. Volunteers were divided into three groups according to the reference values of vitamin D levels. Biochemical parameters, CTRP-9, TNFα, and thiol/disulfide hemostasis tests taken from all volunteers were studied. RESULTS: In this study, there was a significant difference in CTRP-9, TNFα, total thiol (TT), native thiol (NT), DIS (disulfide), TT/DIS, and NT/DIS levels in vitamin D groups (p<0.05). There was a significant negative correlation between vitamin D and TNFα and DIS, while a significant positive correlation was found with CTRP-9, TT, NT, TT/DIS, and NT/DIS (p<0.05). CONCLUSIONS: It was determined that vitamin D deficiency causes a significant decrease in CTRP-9 level and a significant increase in TNFα level, as well as an increase in thiol/disulfide hemostasis in favor of disulfide, which may be a risk factor for increased oxidative stress. We considered that these changes may play mediator roles for many chronic diseases and metabolic disorders that are increasing in frequency due to vitamin D deficiency.