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.

Total thiol can contribute to differentiating prostate cancer from BPH: Prostate Thiol Index as a new player.

To assess the distinctiveness of serum native thiol (NT), total thiol (TT) and disulfide (SS) levels in PCa patients, we created a new parameter, prostate thiol index (PTI) [tPSA (TTxPVxAge) -1/2 ]. We determined the performance of the PTI on PCa diagnosis. A total of 107 male patients (PCa:65; BPH:42) who were separated according to their Gleason scores, ISUP grades and EAU risk groups and 20 healthy subjects were included. The performances of the tests were determined. The PCa and BPH groups had lower NT and TT levels and higher SS levels than the control group. PCa patients had higher PTI, tPSA, fPSA, PSAD levels, lower fPSA%, PV and PSA-AV levels than BPH patients. TT, PTI, tPSA, fPSA, fPSA%, PSA-AV, PSAD and PV had significant diagnostic performances. PTI had the highest AUC value and accuracy, PSA-AV had the highest specificity, and fPSA had the lowest sensitivity. The performance of the PTI was the best in distinguishing PCa from BPH. PTI, tPSA and PSAD positively and PSA-AV negatively correlated with ISUP grades and EAU groups. TT can contribute to the discrimination of PCa from BPH and PTI may decrease unnecessary biopsies in clinical practice.

Serum total thiol levels and the risk of lung, colorectal, breast and prostate cancer: A prospective case-cohort study.

Free thiol groups of intra and extracellular molecules are considered to be antioxidative and to protect cells from damage caused by free radicals. However, the associations of serum total thiol levels (TTL) with the incidences of the four most frequent cancer sites have not yet been investigated in a large population-based, prospective study. TTL was measured in case-cohort design in a sample from the population-based, Norwegian Tromsø 3 study (cancer cases: n = 941; random subcohort: n = 1,000) and was repeatedly measured at Tromsø 5. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by weighted multivariable-adjusted Cox regression with time-dependent modeling of TTL for incident lung, colorectal, breast and prostate cancer. High serum TTL were associated with a reduced risk of all four major cancers. The associations with lung (top vs. bottom tertile: HR, 0.64; 95% CI, 0.41, 0.99) and breast cancer (top vs. bottom tertile: HR, 0.64; 95% CI, 0.42, 0.96) were statistically significant, whereas associations with colorectal (top vs. bottom tertile: HR, 0.79; 95% CI, 0.54, 1.16) and prostate cancer (top vs. bottom tertile: HR, 0.79; 95% CI, 0.53, 1.17) were not statistically significant but pointed in the same protective direction. These findings from a large, prospective Norwegian cohort study suggest a preventive role of thiols against the development of the four most frequent cancers. Whereas associations with breast and lung cancer could be shown with statistical significance, larger studies are needed to corroborate potential associations of TTL with colorectal and prostate cancer.

Brain-Derived Neurotrophic Factor and Oxidative Stress in Cannabis Dependence.

INTRODUCTION: Neurotrophin levels and oxidative stress markers such as ceruloplasmin and free thiols have been shown to contribute to pathophysiology in several psychiatric disorders. OBJECTIVE: Our aim is to evaluate whether those markers are altered in cannabis dependence. METHODS: Forty-five cannabis-dependent patients diagnosed according to the DSM-IV criteria and 45 healthy controls matched according to sex, age, BMI, and smoking status were enrolled. Brain-derived neurotrophic factor (BDNF), ceruloplasmin, lipid hydroperoxide, and total free thiols were measured in both groups. Those who had psychiatric comorbidities were excluded before sampling. RESULTS: We found significantly increased BDNF, ceruloplasmin, and lipid hydroperoxide, and decreased free thiol levels in patients with cannabis dependence. There is also a positive correlation between BDNF and lipid hydroperoxide (n = r = 0.472, p < 0.001) and a negative correlation between BDNF and total thiols (n = r = -0.412, p = 0.001). CONCLUSIONS: Increased BDNF might be a sign of impaired neuronal plasticity that is crucial for memory formation and adaptive response to drug addiction. Neuronal plasticity in the ventral tegmental area dopaminergic neurons was implied to play a role in substance addiction disorders, and these adaptations can be secondary to oxidative stress. Our findings, including increased lipid hydroperoxide, ceruloplasmin, and decreased free thiols, might support this hypothesis. In conclusion, cannabis dependency alters BDNF levels and increases oxidative stress.

High-intensity exercise-induced oxidative stress in sedentary pre-pubertal & post-pubertal boys: A comparative study.

Background & objectives: High-intensity exercise results in oxidative stress in adult population. Impact of pubertal attainment on high-intensity exercise-induced oxidative stress in sedentary paediatric population has not been investigated in detail. The present study was conducted to investigate the extent of high-intensity exercise-induced oxidative stress in sedentary pre- and post-pubertal boys through estimation of serum thiobarbituric acid reactive substances (TBARS), total thiol content and activities of superoxide dismutase (SOD) and catalase (CAT). Methods: Sixty four sedentary pre-pubertal (n=32, age = 10.21±0.67 yr) and post-pubertal (n=32, age = 15.58±0.47 yr) boys performed incremental treadmill running exercise at 80 per cent of the age predicted maximum heart rate till volitional exhaustion. Blood sample (5 ml) was drawn from each individual before and after the exercise for estimation of oxidative stress markers. Results: Pre-exercise SOD activity and total thiol level showed significant positive relationship with age and were significantly higher in post-pubertal boys. Serum TBARS level, SOD and CAT activities increased while total thiol content decreased in both the groups following exercise. Post-exercise percentage change in TBARS, SOD activity and total thiol level was significantly higher in post-pubertal boys, and these variables had significant positive relationship with age. No significant intergroup variations were noted in CAT activity before or after exercise. Interpretation & conclusions: Extent of post-exercise oxidative stress increased significantly with attainment of puberty. However, baseline and post-exercise antioxidation status also increased significantly as a function of age with pubertal maturation allowing the post-pubertal boys to counter relatively higher oxidative stress more efficiently than their pre-pubertal counterparts. Post-exercise upregulation in CAT activity might not be influenced by age or pubertal maturation in this age group.

Biomarkers of oxidative stress in blood of workers exposed to non-cholinesterase inhibiting pesticides.

In occupational settings workers are often exposed to pesticides at relatively high doses compared to environmental exposures. Long-term exposure to pesticides has been associated with numerous adverse health effects in epidemiological studies, and oxidative stress is often claimed as one of the underlying mechanisms. In fact, different pesticides have been reported to induce oxidative stress due to the generation of free radicals and/or alteration in antioxidant defense enzymes. The present study examined greenhouse workers regularly exposed to diverse pesticides under integrated production system, and a group of controls of the same geographic area without any chemical exposure. Two different periods of the same crop season were assessed, one of high exposure (with greater use of pesticides) and other of low exposure (in which a less use of these compounds was made). Non-specific biomarkers of oxidative stress, e.g. thiobarbituric acid reactive substances (TBARS), ferric reducing ability of serum (FRAS), total thiol groups (SHT), gamma-glutamyl transpeptidase (GGT) and paraoxonase-1 (PON1) were measured in serum samples from all study subjects, alongside erythrocyte acetylcholinesterase (AChE). Results are suggestive of a mild increase in oxidative stress associated with pesticide exposure, which was compensated by an adaptive response to raise the antioxidant defenses and thus counter the detrimental effects of sustained oxidative stress. This response led to significantly increased levels of FRAS, SHT and PON1 in greenhouse workers relative to controls. Furthermore, AChE was decreased likely as a result of oxidative stress as workers did not use organophosphate insecticides.

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.

Oxidative injury associated with stenting of asymptomatic carotid artery stenosis.

BACKGROUND: After carotid artery stenting (CAS), neurological complications that cannot be explained with imaging methods may develop. In our study we aimed to show, using oxidative stress markers, isolated oxidative damage and resulting neurological findings following CAS in patients with asymptomatic carotid artery stenosis. PATIENTS AND METHODS: We included 131 neurologically asymptomatic patients requiring CAS. The neurological findings were evaluated using the modified Rankin Scale (mRS) prior to the procedure, one hour post-procedure, and two days after. Patients with elevated mRS scores but with or without typical hyperintense lesions observed on an MRI and with changes of oxidative stress marker levels at the time (Δtotal-thiol, Δtotal antioxidative status [TAS], and Δtotal oxidant status [TOS]) were evaluated. RESULTS: In the neurological examination carried out one hour prior to the procedure, there were 92 patients with mRS = 0, 20 with mRS = 1, and 12 with mRS = 2. When Δtotal-thiol, ΔTAS, and ΔTOS values and the mRS were compared, it was observed that as the difference in oxidative parameters increased, clinical deterioration also increased proportionally (p = 0.001). CONCLUSIONS: We demonstrate a possible correlation between oxidative damage and neurological findings after CAS which could not be explained by routine imaging methods.

Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat.

PURPOSE: Clinical use of cisplatin is limited by its nephrotoxicity. Cisplatin-induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to kidney dysfunction. The aim of this study was to investigate the effect of pomegranate seed oil against nephrotoxicity induced by cisplatin in adult rats. METHODS: Animals were divided into four groups. Group I received corn oil (1 mL/kg). Group II received cisplatin (8 mg/kg). Group III and IV received pomegranate seed oil (PSO) 0.4 mL/kg and 0.8 mL/kg one hour before cisplatin injection for 3 days, respectively. Blood samples were collected by cardiac puncture and used for measuring urea and creatinine concentration. Twenty-hour urine samples were collected to measure protein and glucose concentration. The right kidney fixed in formalin for histological examination and the left kidney was homogenized for measurement of malondialdehyde and total sulfhydryl groups. RESULTS: A significant elevation of serum creatinine, urea, urinary glucose, protein concentrations, and non-significant decrease in total thiol content and increase in MDA level in kidney homogenates were observed in cisplatin-treated rats. Also cisplatin reduced animal's body weight. Mild-to-moderate tubular cell necrosis, hyaline casts, and vascular congestion were observed in group II. PSO pre-treatment significantly decreased urinary protein, glucose, and serum creatinine concentration. PSO also caused a decrease in serum urea, renal MDA, and increase in thiol content, but the level of these parameters were not significant. CONCLUSION: The present results suggest that PSO is an effective agent for the prevention of cisplatin-induced renal dysfunction and oxidative damage in rat.

Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat.

PURPOSE: Clinical use of cisplatin is limited by its nephrotoxicity. Cisplatin-induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to kidney dysfunction. The aim of this study was to investigate the effect of pomegranate seed oil against nephrotoxicity induced by cisplatin in adult rats. METHODS: Animals were divided into four groups. Group I received corn oil (1 mL/kg). Group II received cisplatin (8 mg/kg). Group III and IV received pomegranate seed oil (PSO) 0.4 mL/kg and 0.8 mL/kg one hour before cisplatin injection for 3 days, respectively. Blood samples were collected by cardiac puncture and used for measuring urea and creatinine concentration. Twenty-hour urine samples were collected to measure protein and glucose concentration. The right kidney fixed in formalin for histological examination and the left kidney was homogenized for measurement of malondialdehyde and total sulfhydryl groups. RESULTS: A significant elevation of serum creatinine, urea, urinary glucose, protein concentrations, and non-significant decrease in total thiol content and increase in MDA level in kidney homogenates were observed in cisplatin-treated rats. Also cisplatin reduced animal's body weight. Mild-to-moderate tubular cell necrosis, hyaline casts, and vascular congestion were observed in group II. PSO pre-treatment significantly decreased urinary protein, glucose, and serum creatinine concentration. PSO also caused a decrease in serum urea, renal MDA, and increase in thiol content, but the level of these parameters were not significant. CONCLUSION: The present results suggest that PSO is an effective agent for the prevention of cisplatin-induced renal dysfunction and oxidative damage in rat.

Protective effect of pomegranate seed oil against mercuric chloride-induced nephrotoxicity in rat.

PURPOSE: Heavy metals such as mercury can induce the generation of free radicals and oxidative stress which are associated with tissue injury. The present study was designed to evaluate the protective effect of pomegranate seed oil against HgCl2-induced nephrotoxicity. METHODS: Twenty-four W/A adult rats were randomly divided into four groups. Group I received corn oil (1 mL/kg). Group II received HgCl2 (5 mg/kg) for 3 days. Group III and IV received PSO 0.4 mL/kg and 0.8 mL/kg, respectively one hour before HgCl2 administration for 3 days. Blood samples were taken by cardiac puncture and used for the measurement of urea and creatinine concentration. Twenty-hour-hour urine samples were collected to measure protein and glucose. The right kidney was fixed in formalin for histological examination and the left kidney was homogenized for measuring malondialdehyde (MDA) and total sulfhydryl groups. RESULTS: Significant elevation of serum creatinine and urea levels as well as urine glucose and protein concentrations, a significant decrease in total thiol content and a significant increase in MDA levels in kidney homogenate samples were observed after administration of HgCl2 as compared with control group. PSO pretreatment resulted in a significant decrease in serum creatinine and urea levels as well as urine glucose and protein concentrations when compared with HgCl2 treated (group II). PSO also significantly reversed the HgCl2-induced depletion in thiol content and elevation in MDA content. Histological studies revealed milder kidney lesions in PSO treated groups (groups III and IV) compared to HgCl2 treated group. CONCLUSION: Our results suggest that PSO has a protective effect against HgCl2-induced nephrotoxicity in rats.

Changes in Novel Biomarkers for Protein Oxidation in Pork Patties under Different Cooking Methods.

The aim of this study was to assess the effectiveness of different biomarkers to identify the levels of protein oxidation in pork patties induced by assorted cooking methods. To achieve this purpose, pork patties prepared from longissimus dorsi were cooked using three methods (frying, steaming, and roasting) at different internal temperatures (60, 70, 80, and 90 °C). Traditional biomarkers including total carbonyl and total thiol and novel biomarkers including α-aminoadipic semialdehyde (AAS) and lysinonorleucine (LNL) were determined. Results demonstrated that total thiol and AAS were the most successful biomarkers in distinguishing the three cooking methods in relation to protein oxidation, with AAS being the most sensitive. Moreover, as indicated by the biomarkers of total thiol and AAS, frying caused the highest level of protein oxidation, while steaming resulted in the lowest level when pork patties were cooked to the internal temperatures of 70 or 80 °C.

Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats.

It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/antioxidative status, and Cd and Zn were determined in the distal femur of the rats administered Zn (30 and 60mg/l) or/and Cd (5 and 50mg/l) for 6months. Soluble RANKL (sRANKL) and OPG were measured in the bone and serum. Zn supplementation importantly protected from Cd-induced oxidative stress preventing protein, DNA, and lipid oxidation in the bone. Moreover, Zn protected from the Cd-induced increase in sRANKL concentration and the sRANKL/OPG ratio, and decrease in OPG concentration in the bone and serum. Numerous correlations were noted between indices of the oxidative/antioxidative bone status, concentrations of sRANKL and OPG in the bone and serum, as well as the bone concentrations of Zn and Cd, and previously reported by us in these animals (Brzóska et al., 2007) indices of bone turnover and bone mineral density. The results allow us to conclude that the ability of Zn to prevent from oxidative stress and the RANK/RANKL/OPG system imbalance may be implicated in the mechanisms of its protective impact against Cd-induced bone damage. This paper is the first report from an in vivo study providing evidence that beneficial Zn impact on the skeleton under exposure to Cd is related to the improvement of the bone tissue oxidative/antioxidative status and mediating the RANK/RANKL/OPG system.

Unravelling copper effect on the production of varietal thiols during Colombard and Gros Manseng grape juices fermentation by Saccharomyces cerevisiae.

Nowadays the rapidly increasing organic vineyard management with the utilization of copper as sole fungal control pesticide against downy mildew raises once again the question of copper impact on varietal thiols in wine. For this purpose, Colombard and Gros Manseng grape juices were fermented under different copper levels (from 0.2 to 3.88 mg/l) to mimic the consequences in must of organic practices. The consumption of thiol precursors and the release of varietal thiols (both free and oxidized forms of 3-sulfanylhexanol and 3-sulfanylhexyl acetate) were monitored by LC-MS/MS. It was found that the highest copper level (3.6 and 3.88 mg/l for Colombard and Gros Manseng respectively) significantly increased yeast consumption of precursors (by 9.0 and 7.6% for Colombard and Gros Manseng respectively). For both grape varieties, free thiol content in wine significantly decreased (by 84 and 47% for Colombard and Gros Manseng respectively) with the increase of copper in the starting must as already described in the literature. However, the total thiol content produced throughout fermentation was constant regardless of copper conditions for the Colombard must, meaning that the effect of copper was only oxidative for this variety. Meanwhile, in Gros Manseng fermentation, the total thiol content increased along with copper content, resulting in an increase up to 90%; this suggests that copper may modify the regulation of the production pathways of varietal thiols, also underlining the key role of oxidation. These results complement our knowledge on copper effect during thiol-oriented fermentation and the importance of considering the total thiol production (reduced+oxidized) to better understand the effect of studied parameters and differenciate chemical from biological effects.

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.

The association of vitamin D with survival in colorectal cancer patients depends on antioxidant capacity.

BACKGROUND: Vitamin D plays a role in detoxifying free radicals, which might explain the previously reported lower mortality in colorectal cancer (CRC) patients with higher vitamin D concentrations. OBJECTIVES: We aimed to assess whether the associations of 25-hydroxyvitamin D [25(OH)D] with prognosis in CRC patients differ by total thiol concentration (TTC), a biomarker of antioxidant capacity. METHODS: CRC patients who were diagnosed from 2003 to 2010 and recruited into a population-based study in southern Germany (n = 2,592) were followed over a period of 6 y. 25(OH)D and TTC were evaluated from blood samples collected shortly after CRC diagnosis. Associations of 25(OH)D with all-cause and CRC mortality according to TTC were estimated using multivariable Cox proportional hazards regression. RESULTS: There was a weak positive correlation between 25(OH)D and TTC (r = 0.26, P < 0.001). 25(OH)D was inversely associated with mortality among patients in the lowest and middle TTC tertiles, but no associations were found among patients in the highest TTC tertile (P-interaction = 0.01). Among patients in the lowest/middle TTC tertiles, those in the middle and highest (compared with lowest) 25(OH)D tertiles had 31% and 44% lower all-cause mortality (P < 0.001) and 25% and 45% lower CRC mortality (P < 0.001), respectively. However, in the highest TTC tertile, 25(OH)D was not associated with all-cause (P = 0.638) or CRC mortality (P = 0.395). CONCLUSIONS: The survival advantages in CRC patients with adequate vitamin D strongly depend on antioxidant capacity and are most pronounced in cases of low antioxidant capacity. These findings suggest that TTC and other biomarkers of antioxidant status may be useful as the basis for enhanced selection criteria of patients for vitamin D supplementation, in addition to the conventional judgment based on blood 25(OH)D concentrations, and also for refining selection of patients for clinical trials aiming to estimate the effect of vitamin D supplementation.

Acute Lung Injury Biomarkers in the Prediction of COVID-19 Severity: Total Thiol, Ferritin and Lactate Dehydrogenase.

SARS-CoV-2 (COVID-19) patients who develop acute respiratory distress syndrome (ARDS) can suffer acute lung injury, or even death. Early identification of severe disease is essential in order to control COVID-19 and improve prognosis. Oxidative stress (OS) appears to play an important role in COVID-19 pathogenesis; we therefore conceived a study of the potential discriminative ability of serum biomarkers in patients with ARDS and those with mild to moderate disease (non-ARDS). 60 subjects were enrolled in a single-centre, prospective cohort study of consecutively admitted patients: 29 ARDS/31 non-ARDS. Blood samples were drawn and marker levels analysed by spectrophotometry and immunoassay techniques. C-reactive protein (CRP), lactate dehydrogenase (LDH), and ferritin were significantly higher in ARDS versus non-ARDS cases at hospital admission. Leukocytes, LDH, ferritin, interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were also significantly elevated in ARDS compared to non-ARDS patients during the hospital stay. Total thiol (TT) was found to be significantly lower in ARDS. Conversely, D-dimer, matrix metalloproteinase-9 (MMP-9) and advanced glycosylated end products (AGE) were elevated. Leukocytes, LDH, CRP, ferritin and IL-6 were found to be significantly higher in non-survivors. However, lymphocyte, tumour necrosis factor beta (TGF-ß), and TT were lower. In summary, our results support the potential value of TT, ferritin and LDH as prognostic biomarkers for ARDS development in COVID-19 patients, distinguishing non-ARDS from ARDS (AUCs = 0.92; 0.91; 0.89) in a fast and cost-effective manner. These oxidative/inflammatory parameters appear to play an important role in COVID-19 monitoring and can be used in the clinical management of patients.

Protective Effects of Astaxanthin on Nephrotoxicity in Rats with Induced Renovascular Occlusion.

BACKGROUND: Various effects of Astaxanthin were shown in the studies, including its antioxidant, anti-inflammatory, anti-tumor and immunoregulatory effects. OBJECTIVE: The aim of this study was to evaluate the beneficial effects of Astaxanthin on renovascular occlusion induced renal injury and to investigate the possible mechanisms. METHODS: The rats were randomly assigned into three groups as follows: Group 1: control group (n=12), Group 2: renal ischemia-reperfusion injury group (n=12), Group 3: renal ischemia-reperfusion + asthaxantine treated group (n=12). The control group and the renal ischemia-reperfusion group were given 2cc/kg/g olive oil for 7 days before establishing ischemia to renal tissue. Astaxanthin dissolved in olive oil was given orally to the renal ischemia+astaxanthin group for 7 days before inducing renal ischemia. Caspase-(3, 8, 9), GSH, SOD, Total Thiol, TNF-α, IL-6, 8-OHdG were evaluated in each group. RESULTS: Renal IRI was verified by analysing the pathological changes of renal tissues and the renal functions after renal reperfusion. Much less renal tubular damage was determined in the IRI+ASX group in comparison to the IRI group. Caspase-8, -9 and -3 immunoreactivity was observed to be minimal in the control group. Apoptosis was observed to be significantly reduced in the IRI + ASX group with respect to the IRI group and close to the level of the control group (p <0.05). Caspase-3 levels of tissue samples were significantly increased in the IRI group compared to the other groups, but significantly lower in the IRI+ASX group with respect to the IRI group (p<0.05). The TOS and OSI levels, indicating increased oxidative stress, were significantly lower in the IRI+ASX group with respect to the IRI group (p <0.001), but still higher than the control group (p <0.001). In addition to GSH, SOD and Total Thiol levels, TAS levels were also significantly higher in the IRI + ASX group in comparison to the IRI group (p <0.05). TNF-α, IL-6, lipid hydroperoxide, AOPP and 8-OHdG levels were lower in the IRI+ASX group than the IRI group (p <0.001). MPO, IL-6, TNF-α levels, representing the parameters indicating neutrophil infiltration and inflammation of the renal tissues, significantly increased in the IRI group with respect to the other groups (p <0.005). CONCLUSION: When all the data obtained in our study were evaluated, ASX was determined to prevent renal damage due to renovascular occlusion to a great extent, through complex mechanisms involving antioxidant, anti-inflammatory and antiapoptotic effects. Biochemical, histological and oxidative stress parameters were improved due to ASX.