Murat Alisik

How does thiol/disulfide homeostasis change in prediabetic patients?

AIMS Our aim was to examine thiol/disulfide homeostasis, which has a critical role in many cellular activities such as antioxidant protection, detoxification, cell growth and apoptosis, in prediabetic patients. METHODS The study population was formed of a total of 250 participants; 125 (54 males, 71 females) of which were newly diagnosed with prediabetes, aged over 18 and who had not received any prior treatment and 125 (52 males, 73 females) healthy volunteers. Prediabetic patients were diagnosed using a glucose tolerance test. In both groups, native thiol-disulfide exchanges were examined using the automated measurement method newly developed by Erel and Neselioglu. RESULTS When compared to the control group, the native thiol (p<0.001) and total thiol (p=0.008) levels, and the native thiol/total thiol (p=0.022) ratio was lower; while disulfide (p=0.001) level and, disulfide/native thiol (p=0.003) and disulfide/total thiol (p=0.022) ratios were higher in prediabetic patients. A positive correlation was determined between disulfide and the fasting blood glucose levels (r=0.394, p=0.017) and glycolysed hemoglobin (HbA1c) (r=0.307, p=0.011). On the other hand, a negative correlation was determined between native thiol and fasting blood glucose levels (r=-0.335, p=0.004). CONCLUSION With this study, we have shown for the first time that thiol oxidation increases in prediabetic patients and that there is a positive correlation between the disulfide and blood glucose and HbA1c levels.

Oxidative stress in children and adolescents with anxiety disorders

BACKGROUND Anxiety disorders are common in children and adolescents, and they can significantly impair quality of life. Genetic, neurobiological, neurochemical, and psychological factors are believed to play a role in the etiopathogenesis of anxiety disorders. Recent evidence suggests that the pathophysiology of anxiety disorders may be associated with oxidative stress. In this study, we investigated whether there are associations between children with anxiety disorders and total oxidant/antioxidant status. METHODS The experimental group consisted of 40 patients (children and adolescents) with anxiety disorders. An age- and gender-matched control group composed of 35 healthy subjects was also assessed. Venous blood samples were collected and total antioxidative status (TAS), total oxidative status (TOS), and the oxidative stress index (OSI) were determined. RESULTS Both the TOS and the OSI of the experimental group were significantly higher than those of the control group. There were no significant differences in TAS between the experimental and control groups. LIMITATIONS The main limitation of our study was the small sample size. CONCLUSIONS This study suggests that oxidative balance is impaired in children with anxiety disorders. Oxidative stress may play a role in the etiopathogenesis of anxiety disorders, and TOS may be a useful diagnostic tool in this context.

Attention Deficit Hyperactivity Disorder and oxidative stress: A short term follow up study.

In this study, we aimed to investigate total antioxidative status (TAS) and total oxidative status (TOS) of plasma and antioxidant enzymes such as paraoxonase (PON), stimulated paraoxonase (SPON), arylesterase (ARES) and thiols in plasma of children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD). In the second step. this study aimed to reveal the possible effects of ADHD treatment on these parameters. Fifty-six patients with ADHD and 52 healthy controls were involved in this study. Venous blood samples were collected and oxidative and antioxidative parameters were studied. In the second phase of the study, blood samples were taken from patients using medication. Pre-treatment oxidative stress index (OSI) values and the plasma TOS levels of the patients with ADHD were statistically higher than those of the control group. The plasma thiol levels of the patients with ADHD were significantly lower than the control group. The post-treatment plasma antioxidative parameters levels were significantly higher than the pre-treatment levels. The post-treatment oxidative stress index value was significantly lower than the pre-treatment value. Therefore, oxidative metabolism was found to be impaired in children and adolescents with ADHD. It was also determined that methylphenidate repairs the oxidative balance by increasing antioxidant defence mechanisms.

Impairment of thiol-disulfide homeostasis in preeclampsia

Abstract 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.

The dynamic thiol/disulphide homeostasis in inflammatory bowel disease and its relation with disease activity and pathogenesis

Dear Editor: Inflammatory bowel disease (IBD) is an idiopathic and chronic inflammatory disease of the gastrointestinal tract. It is characterized by crohns disease (CD), that holds the entire gastrointestinal tract by hopping and transmural lesions and ulcerative colitis (UC), that only holds the colon in a mucosal and continuous way. Although microbial, genetical, environmental and immunological factors are thought to play a role in its ethiopathogenesis, there are still major uncertainties on this subject. Therefore, in recent studies, the importance of oxidative stress in the etiopathogenesis of IBD is often being questioned. After it is understood that there are major contributions of oxidative stress in IBD, researchers have lately started seeking answers for questions by which mechanisms of oxidative stress occur in IBD and how it can be prevented. Therefore, recently, thiol/disulphide homeostasis in IBD is being emphasized. As is known, thiol/disulphide homeostasis plays a critical role in several vital functions such as programmed cell death, detoxification, antioxidant protection and regulation of cellular enzymatic activity. Therefore when thiol/disulphide homeostasis shifts towards the disulphide formation, these vital activities are adversely affected and pathologies occur in the structure and functions of many organs. Until 2014, only thiol and disulphide amounts of low molecular weight thiol compounds such as cysteine (Cys), cystine (CySS), glutathione and glutathione disulphide (GSG and GSSG) had been measured in studies evaluating thiol/disulphide homeostasis. A new fully automated colorimetric method that gives an idea about a general balance of thiol and oxide thiol reserve in the body was developed in 2014 by Erel and Neselioglu. However we have not found any study in which thiol/disulphide homeostasis in IBD patients is determined with this new method. Therefore, for the first time in this study, we aimed to determine thiol/disulphide homeostasis in two subgroups of IBD patients, such as UC and CD with this new method and to examine the relation of disulphide/thiol balance with disease activity. Total of 125 adult participants, consisting of 61 IBD patients (UC/CD: 36/25) and 64 healthy volunteers for the control group were included in the study. Participants with known documented acute and chronic disease, users of vitamin supplements and antioxidant drugs, smokers and alcohol users were excluded from the study. Indexes that are formed with clinical and endoscopic parameters were used for disease activity. Rachmilewitz scoring system (endoscopic activity index (EAI)) was used to determine UC activity, as for CD activity, CD activity index (CDAI) scoring was used. To measure thiol/disulphide hemostasis parameters of all participants who were included in the study, venous blood samples were drawn in the morning between 08:00–10:00 A.M. after 8 of fasting. After blood samples were quickly centrifuged at 1500 rpm for 10 min, plasma and serum samples were separated. Serum samples have been stored at −80 °C until all samples were collected. Then thiol/ disulphide hemostasis parameters were studied in the same * Ihsan Ates dr.ihsanates@hotmail.com

Is disulphide/thiol ratio related to blood pressure in masked hypertension?

Abstract Dynamic thiol/disulphide homeostasis plays a critical role in numerous intracellular enzymatic pathways including antioxidant defence and detoxification. In this study, we sought to investigate dynamic thiol/disulphide homeostasis in patients with masked hypertension (MHT) and its relationship with blood pressure. Forty patients (23 men, 17 women) with newly diagnosed MHT and not yet on medical therapy, and 40 healthy volunteers (21 men, 19 women) were enrolled. Blood thiol/disulphide homeostasis was measured in both groups. Serum native and total thiol levels were measured using the novel, fully automated colorimetric method developed by Erel et al. Serum disulphide level was calculated as (serum total thiol − serum native thiol)/2. Native and total thiol levels (p = 0.001) and native thiol/total thiol ratio (p = 0.023) were found to be lower in patients with MHT when compared to those of the control group. Disulphide level and ratios of disulphide/native thiol and disulphide/total thiol were higher in patients with MHT than in the control group (p = 0.001). A positive correlation of systolic blood pressure (SBP) and diastolic blood pressure (DBP) was observed with disulphide/native thiol ratio (p < 0.001). Stepwise multivariable regression analysis showed disulphide/native thiol ratio to be an independent risk factor of SBP and DBP, and SBP to be an independent risk factor of disulphide/thiol ratio (p = 0.001). In this study, we found that dynamic thiol/disulphide homeostasis shifted towards disulphide formation due to thiol oxidation in patients with MHT. Prospective randomised controlled studies are required to elucidate whether abnormal thiol/disulphide status lies in the pathogenesis of MHT or is a consequence of MHT.

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 diseases progress during the treatment.

Lipid peroxidation markers in children with anxiety disorders and their diagnostic implications

Abstract Objective Numerous factors, including genetic, neurobiological, neurochemical, and psychological factors, are thought to be involved in the development of anxiety disorders. The latest findings show that the pathophysiology of anxiety disorders might be associated with oxidative stress and lipid peroxidation; however, no studies have so far investigated lipid peroxidation markers in children with anxiety disorders. Serum levels of lipid hydroperoxide (LOOH) are a reliable marker of lipid peroxidation. Paraoxonase and arylesterase are two enzymes that protect against such peroxidation, and might also be diagnostic markers. In this study, we investigated whether there are associations between anxiety disorders and lipid peroxidation markers in children, and assessed the diagnostic performance of these markers. Methods The study group consisted of 37 patients (children and adolescents) with anxiety disorders. A control group, matched for age and gender, was composed of 36 healthy subjects. Venous blood samples were collected, and LOOH levels and paraoxonase and arylesterase activity were measured. Results LOOH levels were significantly higher in the anxiety disorders group than in the control group. There were no significant differences in paraoxonase or arylesterase activities between the patient and the control groups. Discussion Lipid peroxidation or oxidative damage might play a role in the aetiopathogenesis of anxiety disorders. LOOH may be a potential biological marker for anxiety disorders in children.

Dynamic thiol/disulphide homeostasis before and after radical prostatectomy in patients with prostate cancer

Abstract Thiol groups are important anti-oxidants and essential molecules protecting organism against the harmful effects of reactive oxygen species (ROS). The aim of our study is to evaluate thiol–disulphide homeostasis with a novel recent automated method in patients with localized prostate cancer (PC) before and six months after radical prostatectomy (RP). 18 patients with PC and 17 healthy control subjects were enrolled into the study. Blood samples were collected from the controls subjects and patients before and six months after RP. Thiol–disulphide homeostasis was determined using a recently developed novel method. Prostate-specific antigen (PSA), albumin, total protein, total thiol, native thiol, disulphide and total antioxidant status (TAS) were measured and compared between the groups. Native thiol, total thiol and TAS levels were significantly higher in the control group than the patients before RP (p < .001). There was a non-significant increase in the native thiol, total thiol and TAS levels in the patients six months after RP in comparison to the levels before RP (p values .3, .3 and .09, respectively). We found a significant negative correlation between PSA and thiol levels. Our study demonstrated that the decreased thiol and TAS levels weakened anti-oxidant defence mechanism in the patients with PC as indicated. Increased oxidative stress in prostate cancer patients may cause metabolic disturbance and have a role in the aetiopathogenesis of prostate cancer.

Increased levels of serum neopterin in attention deficit/hyperactivity disorder (ADHD).

Attention deficit/hyperactivity disorder (ADHD) is the most frequently occurring neuropsychiatric disorder in childhood with an etiology that is not fully understood. A number of reviews that have addressed the neurobiology of ADHD have focused on imaging and genetics. Relatively little attention has been given to factors/mechanisms involved in the brain dysfunction. We suggest that changes in cellular immunity may be involved. Neopterin is a good indicator of cellular immunity, and we evaluated serum levels of neopterin in patients with ADHD. The study group consisted of 49 patients with ADHD. An age- and gender-matched control group was composed of 31 healthy subjects. Venous blood samples were collected, and the levels of neopterin were measured. The levels of neopterin were significantly higher in ADHD than in the comparison subjects. Cellular immunity may have a role in the etiopathogenesis of ADHD.