Disulfide Levels Research Articles

New Oxidative Stress Markers Useful in the Diagnosis of Acute Appendicitis in Children: Thiol/Disulfide Homeostasis and the Asymmetric Dimethylarginine Level.

The aim of this study was to evaluate 2 new oxidative stress markers, thiol/disulfide homeostasis status and the asymmetric dimethylarginine (ADMA) level, in children with acute appendicitis (AA) and to evaluate their diagnostic utility. This case-control study included 45 patients with AA and 35 healthy children. Age, sex, white blood cell count, neutrophil-to-lymphocyte ratio, high-sensitivity C-reactive protein (hs-CRP) level, ultrasonographic findings, thiol/disulfide homeostasis parameters (native and total thiol levels, native thiol/total thiol ratios [antioxidant parameters], and disulfide, disulfide/native thiol, and disulfide/total thiol ratios [oxidant parameters]), and the ADMA level were compared between the 2 groups. The native and total thiol levels, and the native thiol/total thiol ratio, were significantly lower, and the disulfide level and disulfide/native thiol and disulfide/total thiol ratios significantly higher, in the AA compared with the control group (all P < 0.001). The ADMA level was significantly higher in a perforated versus nonperforated subgroup of AA patients, but the thiol/disulfide homeostasis parameters did not differ significantly between the two subgroups. In addition, the hs-CRP level and appendiceal wall thickness were higher in the perforated subgroup. The thiol/disulfide antioxidant parameters and ADMA level correlated negatively with the white blood cell count, the neutrophil-to-lymphocyte ratio, and the hs-CRP level, in the AA group, but correlated positively with oxidant parameters. The sensitivity and specificity of the disulfide/native thiol and disulfide/total thiol ratios were high when used to diagnose AA, whereas the sensitivity of the ADMA level was high when used to diagnose perforated appendicitis. Thiol/disulfide homeostasis and the ADMA level, together with certain other parameters, may be useful biomarkers of AA in children.

93 - Protein S-Nitrosylation: Possible Links between Psychophysiological Stress and Neurodegeneration

Psychophysiological stress has long been recognized as a risk factor for diverse pathologies including cardiovascular disease, psychiatric illnesses, and aging-related neurodegenerative disorders but molecular events linking stress to disease remain ill-defined. Mounting evidence supports a role for nitro-oxidative modifications of protein thiols in cellular signaling and toxicity. In light of numerous reports that acute stress can increase the activities and/or expression levels of multiple nitric oxide synthase isoforms in the brains of rodent models, we investigated the possibility that subjecting rats to acute restraint stress may promote S-nitrosylation of proteins from the brain measured by the classical biotin-switch method. Our results indeed show that restraint stress increased S-nitrosylation of brain proteins albeit transiently. S-nitrosylation was highest following 2 hours of restraint but returned to levels at or below the control by six hours. Among the S-nitrosylated proteins identified by LC-MS/MS were, from highest to lowest abundance, glyceraldehyde-3-phosphate dehydrogenase, peroxiredoxin-2, protein phosphatase 2B, and the ADP/ATP translocase all of which have immediate implications for cellular pathology. As protein nitrosthiols are generally unstable and readily convert to disulfides, efforts were also made to measure the impacts of restraint stress on disulfides involving proteins. Levels of protein-glutathione mixed disulfides appeared to be inversely related to S-nitrosylation but changes across groups were not statistically-significant. In addition, unique challenges to the trapping of the in vivo redox states of protein vicinal thiols and the determination of the effects of restraint stress on oxidations of these, resulting in protein disulfides, were noted and linked to the very high reactivity of the catalytic thiols of peroxiredoxins. These findings provide initial support for the notion that protein S-nitrosylation may link psychophysiological stress to neural insults and open the door for further investigations of nitro-oxidative modifications of protein thiols as potential links between life stresses and disease.

Effects of ZnO nanoparticles on rat glioma C6 cells

Zinc oxide nanoparticles(ZnO NPs) are among the most commonly utilized nanomaterials. They are used in a wide range of applications, including medicine, sunscreens, cosmetics, paints, catalysis, electronics, as well as biosensors, and hence, it is crucial to illustrate their biological effects and risks. In the present study, the effects and mechanism of ZnO NPs(⩽5 nm) were investigated in rat glioma C6 cells in vitro. The results of transmission electron microscopy(TEM) and X-ray diffraction(XRD) show that ZnO NPs are pure with a uniform diameter of ca. 5 nm. 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide(MTT) assays on C6 cells show that ZnO NPs, at different concentrations(0―5 μg/mL), can induce significant cytotoxicity in C6 cells in a dose-dependent manner. An increased level of reactive oxygen species(ROS), a decreased level of glutathione(GSH), and an elevated level of glutathione disulfide(GSSG) and the toxicity mechanism are primarily attributed to the induced cellular oxidative stress. 4′,6-Diamidino-2-phenylindole(DAPI) staining was used to observe the apoptosis. The results show that C6 cells treated with the ZnO NPs at various concentrations(0, 1.25, 2.5 and 5 μg/mL) can induce apoptosis in a dose-dependent manner. These results suggest that ZnO NPs are the killers of the rat glioma C6 cells, and oxidative stress is the underlying mechanism of this process.

Ameliorative effect of black ginseng extract against oxidative stress-induced cellular damages in mouse hepatocytes

BackgroundOxidative stress induces the production of reactive oxygen species (ROS), which play important causative roles in various pathological conditions. Black ginseng (BG), a type of steam-processed ginseng, has drawn significant attention due to its biological activity, and is more potent than white ginseng (WG) or red ginseng (RG). MethodsWe evaluated the protective effects of BG extract (BGE) against oxidative stress-induced cellular damage, in comparison with WG extract (WGE) and RG extract (RGE) in a cell culture model. Ethanolic extracts of WG, RG, and BG were used to evaluate ginsenoside profiles, total polyphenols, flavonoid contents, and antioxidant activity. Using AML-12 cells treated with H2O2, the protective effects of WGE, RGE, and BGE on cellular redox status, DNA, protein, lipid damage, and apoptosis levels were investigated. ResultsBGE exhibited significantly enhanced antioxidant potential, as well as total flavonoid and polyphenol contents. ATP levels were significantly higher in BGE-treated cells than in control; ROS generation and glutathione disulfide levels were lower but glutathione (GSH) and NADPH levels were higher in BGE-treated cells than in other groups. Pretreatment with BGE inhibited apoptosis and therefore protected cells from oxidative stress-induced cellular damage, probably through ROS scavenging. ConclusionCollectively, our results demonstrate that BGE protects AML-12 cells from oxidative stress-induced cellular damages more effectively than WGE or RGE, through ROS scavenging, maintenance of redox status, and activation of the antioxidant defense system.

Nigella Sativa Oil Protects the Rat Ovary from Oxidative Injury Due to Ischemia-Reperfusion.

BackgroundThe aim of this study was to evaluate the effects of Nigella sativa (N. sativa) oil (NSO) on ovarian oxidative damage following ischemia-reperfusion injury, using a rat model of ovarian torsion.Material/MethodsForty-eight female albino Wistar rats were divided into six groups: (Group 1) laparotomy only; (Group 2) intraperitoneal NSO (2 ml/kg), 1 hour following laparotomy; (Group 3) 3 hours of ovarian ischemia; (Group 4) 3 hours of ovarian ischemia followed by 3 hours of reperfusion; (Group 5) 3 hours of ovarian ischemia and 2 ml/kg of NSO 1 hour before laparotomy; (Group 6) 3 hours of reperfusion after 3 hours of ovarian ischemia and 2 ml/mg of NSO 1 hour before laparotomy.ResultsThe antioxidant status, ceruloplasmin level, native thiol, total thiol, and disulfide levels of the control group (Group 1) were significantly increased compared with the ovarian ischemia-reperfusion group treated with NSO (Group 6) (p=0.003, p=0.002, p=0.006, p=0.001 and p=0.003, respectively); these levels in the ovarian ischemia group (Group 3) and ischemia-reperfusion group (Group 4) were statistically similar to those of the ovarian ischemia + NSO group (Group 5) and ovarian ischemia-reperfusion + NSO group (Group 6).ConclusionsIn this preliminary rat study, administration of NSO shortly after the onset of ovarian ischemia-reperfusion injury, did not significantly reduce levels of markers of oxidative injury. Further studies are required to evaluate the ovarian changes at the tissue level, and to determine the optimum dose of NSO.

Inhalation exposure of nano diamond induced oxidative stress in lung, heart and brain

1. Today, diamond nanoparticles have several industrial applications. Nano diamond (ND) as a carbon allotrope diffuses in the air easily during producing and processing procedures.2. In this study, we investigated sub-acute exposed to ND at the exposure chamber in mice. The animals were divided into two groups (control and exposed group to ND at the concentration of 3 µg/m3 for 3 h/day, 5 days/week for 30 days) in a whole-body inhalation chamber.3. Our results showed that exposure to ND induced the hematological and biochemical changes. The target organs for ND were the lungs, brain and heart in the mice, respectively. Also, ND increased reactive oxygen species (ROS) generation, lipid peroxidation (LPO), the collapse of mitochondrial membrane potential (MMP), decreased a level of reduced glutathione (GSH) and finally increased a level of glutathione disulfide (GSSG) in lung, brain and heart tissues. Our results suggest that exposure to ND can induce oxidative stress in the tissue mentioned.4. These results suggest that exposure of researchers and workers with diamond nanoparticles probably increase a risk of respiratory, cardiovascular and cerebral disorders through oxidative stress. However, good ventilation, appropriate personal protective equipment and using of anti-oxidant compounds in daily diet of worker are suggested.

Thiol/disulfide homeostasis as a novel indicator of oxidative stress in children with simple febrile seizures.

Simple febrile seizures are generally benign, but during the seizure, elevated levels of glutamate and high levels of oxygen use due to the high metabolic brain activity result in oxidative stress. However, the relationship between febrile seizures and oxidative stress remains unclear. In this study, we investigated thiol/disulfide homeostasis as a new oxidative stress parameter in patients with simple febrile seizures. This study was performed between February 2016 and May 2016 at the Pediatric Emergency Unit. The study population consisted of 40 patients with a diagnosis of simple febrile seizure and 30 control participants aged 8-59months. Total thiol, native thiol and disulfide levels, disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios were used as thiol/disulfide homeostasis parameters and were quantified in patient and control groups. Furthermore, correlations with seizure duration were investigated. In the patient group, native and total thiol levels and native thiol/total thiol ratios were low, and disulfide levels, disulfide/native thiol, and disulfide/total thiol ratios were significantly higher than in the control group. Negative correlations were observed between seizure duration, total and native thiol levels, and native thiol/total thiol ratio, whereas positive correlations were observed between seizure duration and disulfide/native thiol and disulfide/total thiol ratio. The sensitivities of both disulfide/native thiol and disulfide/total thiol ratios were high for simple febrile seizures. Simple febrile seizures may cause impairment in favor of disulfide bonds in thiol/disulfide homeostasis. Overall, these changes may contribute to neuronal cell damage after simple febrile seizures.

Headache in children and dynamic thiol/disulfide balance evaluation with a new method.

Headache is one of the most common causes of presentation to the physician in children. We aimed to evaluate the dynamic thiol/disulfide homeostasis with a new method in children with headache and also to investigate the relationship between the headache type, pain severity and duration in our study. We included 40 patients diagnosed with migraine, 40 patients diagnosed with tension-type headache (TTH) and 40 healthy children in the study. No significant difference was found between the total thiol, native thiol, and disulfide levels of the patient and control groups. However, the disulfide/native thiol and disulfide/total thiol ratios were higher in the migraine group than in the TTH and control groups. No correlation was found between the Pediatric Migraine Disability Assessment (PedMIDAS) score and the headache duration and any of the thiol/disulfide parameters. A negative correlation was found between the total thiol and native thiol levels and the PedMIDAS score in the TTH group. Migraine and TTH patients have different effect to thiol/disulfide homeostasis.

Does oxidative stress play any role in diabetic cataract formation? ----Re-evaluation using a thioltransferase gene knockout mouse model

Oxidative stress is a known risk factor in senile cataract formation. In recent years, it has been suggested that oxidation may also be associated with cataract induced by hyperglycemia, but this concept has not been well examined or validated. Since thioltransferase (TTase) is one of the key enzymes that regulates redox homeostasis and protects against oxidative stress in the lens, we have used TTase gene knockout (KO) mice as a model to examine this new concept. Lenses from 4 months old TTase KO and wild-type (WT) mice were incubated in TC199 culture medium containing 30 mM glucose for 48 h. Each lens was assessed for opacity, graded by LOCSII system, and the wet weight was recorded after which it was homogenized in lysis buffer and analyzed for water-soluble protein and free glutathione (GSH). In vivo studies were carried out using 4 months old TTase KO and WT mouse groups. Each mouse received two consecutive days of intraperitoneal streptozotozin (STZ) injections to induce diabetes. The lenses were examined weekly for 4 weeks using a slit-lamp biomicroscope, and then extracted and analyzed for levels of GSH, water-soluble protein, ATP and protein-GSH mixed disulfide (PSSG). TTase KO lenses cultured in high glucose developed a mild cortical opacity but slightly more than that of the WT lenses. Both groups had similar contents of soluble proteins and GSH. Exposure to high glucose did not change the soluble protein level but did suppress GSH by 20% in lenses with or without TTase. STZ-induced diabetic KO mice also developed a higher degree of mild cortical lens opacity compared to that of the diabetic WT controls. Similar 15–20% losses in lens GSH and ATP were found after one-month induced diabetes in WT and KO mice. There was a 20% greater amount of PSSG in the lenses of TTase KO than the WT control. Under diabetic condition, both groups displayed more glutathionylated proteins in the beta-actin (42 kDa) and lens crystallin proteins (18–22 kDa) regions, and some additional modified proteins at 15–17 kDa and 60–70 kDa, with a total 20–30% PSSG increment in both groups. In conclusion, we have found that hyperglycemia induced some oxidative stress-associated biochemical changes with mild lens opacity in both WT and KO mice. However, these changes were only marginally higher in the TTase KO mouse than that of the WT control, suggesting that TTase deletion may only play a minor role in the early stage of hyperglycemia-induced cataract formation in the mice.

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.

Real-Time Imaging of the Bacillithiol Redox Potential in the Human Pathogen Staphylococcus aureus Using a Genetically Encoded Bacilliredoxin-Fused Redox Biosensor.

Aims: Bacillithiol (BSH) is utilized as a major thiol-redox buffer in the human pathogen Staphylococcus aureus. Under oxidative stress, BSH forms mixed disulfides with proteins, termed as S-bacillithiolation, which can be reversed by bacilliredoxins (Brx). In eukaryotes, glutaredoxin-fused roGFP2 biosensors have been applied for dynamic live imaging of the glutathione redox potential. Here, we have constructed a genetically encoded bacilliredoxin-fused redox biosensor (Brx-roGFP2) to monitor dynamic changes in the BSH redox potential in S. aureus.Results: The Brx-roGFP2 biosensor showed a specific and rapid response to low levels of bacillithiol disulfide (BSSB) in vitro that required the active-site Cys of Brx. Dynamic live imaging in two methicillin-resistant S. aureus (MRSA) USA300 and COL strains revealed fast and dynamic responses of the Brx-roGFP2 biosensor under hypochlorite and hydrogen peroxide (H2O2) stress and constitutive oxidation of the probe in different BSH-deficient mutants. Furthermore, we found that the Brx-roGFP2 expression level and the dynamic range are higher in S. aureus COL compared with the USA300 strain. In phagocytosis assays with THP-1 macrophages, the biosensor was 87% oxidized in S. aureus COL. However, no changes in the BSH redox potential were measured after treatment with different antibiotics classes, indicating that antibiotics do not cause oxidative stress in S. aureus.Conclusion and Innovation: This Brx-roGFP2 biosensor catalyzes specific equilibration between the BSH and roGFP2 redox couples and can be applied for dynamic live imaging of redox changes in S. aureus and other BSH-producing Firmicutes. Antioxid. Redox Signal. 26, 835–848.

Parameter Fisikokimia dan Analisis Kadar Allyl Disulfide dalam Ekstrak Etanol 70% Bawang Putih (Allium sativum L.) dengan Perbandingan Daerah Tempat Tumbuh

Garlic (Allium sativum L.) is one of the medicinal plants that has a potential to be developed to become a traditional medicine. Traditional medicinal products and medicinal plants which have good quality are determined by the quality and safety of the extract. One of many factors that can affect the quality is the growing area. This research aimed to compare the value of physicochemical parameters as well as the levels of compounds responsible for pharmacological activity in ethanol 70% extract of garlic obtained from two growing areas, Bogor and Wonosobo. The test results obtained from garlic extract of Bogor were: compound contents dissolved in water was 62.5684%, compound contents dissolved in ethanol was 10.0779%, essential oils contents was 0.7477%, levels of allyl disulfide was 1.8322%, total ash content was 2.3529%, ash content insoluble in acid was 0.1115%. While the test results obtained from garlic extract of Wonosobo: compound contents dissolved in water was 59.0007%, compound contents dissolved in ethanol was 8.9230%, essential oils contents was 0.3400%, levels of allyl disulfide was 1.6542%, total ash content was 3.0196%, ash content insoluble in acid was 0.4974%. Based on those results, the best quality extract was garlic from Bogor with higher specific parameter values and lower non-specific parameter values.

The maternal thiol/disulfide homeostasis does not change in pregnancies complicated by preterm prelabor rupture of membranes

Purpose: To evaluate the maternal thiol/disulfide homeostasis in pregnant women complicated by preterm prelabor rupture of membranes (PPROM) and to compare the results with healthy pregnancies.Materials and methods: This cohort study consisted of thirty-nine pregnancies complicated by PPROM and 44 gestational age-matched healthy pregnancies in the third trimester of gestation. Maternal serum samples were obtained at the day of diagnosis, and thiol/disulfide profiles were measured by using an automated assay method. The patients were followed till delivery, and perinatal outcomes were noted.Results: The maternal native thiol (319.9 ± 30.5 μmol/L versus 305.1 ± 49.2 μmol/L, p: .100), total thiol (379.2 ± 38.8 μmol/L versus 363.6 ± 56.4 μmol/L, p: .142) and disulfide (29.7 ± 11.7 μmol/L versus 29.3 ± 10.1 μmol/L, p: .864) levels were similar between the groups. Maternal disulfide/native thiol, disulfide/total thiol and native thiol/total thiol ratios were similar between the groups (p: .610, p: .565 and .562, respectively). The maternal serum thiol/disulfide profiles were not significantly correlated with maternal serum C-reactive protein, white blood cell count values and ongoing pregnancy outcomes (p > .05).Conclusions: The current study demonstrated that there was not any disturbance in maternal thiol/disulfide homeostasis in pregnancies complicated by PPROM at the time of initial diagnosis. Follow-up studies with larger sample size are needed to confirm our results.

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.

Alteration of thiol-disulfide homeostasis in workers occupationally exposed to arsenic

ABSTRACTThis study evaluates the redox state in occupationally arsenic-exposed workers (n = 71) by assessing the dynamic serum thiol-disulfide homeostasis. We determined the serum thiol-disulfide homeostasis parameters of exposed workers and controls (n = 43) using a novel automated colorimetric assay. Median urinary As and 8-isoprostane levels of exposed group were significantly higher than control group (16.40 μg/L vs 2μg/L, p < .001 and 2.28 ng/ml vs 0.54 ng/ml, p < .001, respectively). Disulfide level, disulfide/native thiol ratio, and disulfide/total thiol ratio were significantly higher in exposed group. The mean ceruloplasmine and myeloperoxidase activities of As-exposed group were significantly higher than control group (117.15 U/L vs 87.02 U/L, p = .035 and 148.53 U/L vs 97.75 U/L, p = .000, respectively). The median catalase activity did not differ in the two groups. Our findings revealed that As disrupts the thiol-disulfide homeostasis in favor of disulfide.

Thiol/disulfide homeostasis in untreated schizophrenia patients

BackroundThe aim of the study was to investigate dynamic thiol/disulfide (SH/SS) homeostasis in untreated schizophrenia. MethodsBlood thiol/disulfide homeostasis status, which reflects native thiol-disulfide exchanges, was investigated in 87 untreated patients (52 males, 35 females), and the obtained results were compared with 86 healthy controls. Blood serum native thiol and total thiol (ToSH) concentrations were measured in a paired test. The half value of the difference between native thiol and ToSH concentrations was calculated as the disulfide bond amount. ResultsSH and ToSH concentrations were found to be significantly lower (p<0.001 for both) in patients with untreated schizophrenia compared with the control group, whereas disulfide levels were significantly higher (p<0.001). Schizophrenia patients had significantly higher SS/ToSH and SS/SH ratios and a significantly lower SH/ToSH ratio compared to those of healthy individuals. ConclusionsSH and ToSH amounts were found to be insufficient in untreated schizophrenia patients. Additionally, according to the results of the study, thiol/disulfide homeostasis was also disturbed by a shift to the disulfide bond formation side. This might affect the neurotransmission processes, which are known to be related with many symptoms observed in schizophrenia. The replacement of the thiol gap and the reduction of excess SS amounts might have a positive effect in supporting therapy for schizophrenia patients.

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.

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.

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.

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.