Se-modified gold nanorods for enhancing the efficiency of photothermal therapy: avoiding the off-target problem induced by biothiols.

Tumor-targeting gold nanorods (AuNRs) assembled through Au-S bonds have been widely used for photothermal therapy (PTT) via intravenous injection. However, with extended in vivo circulation times, biothiols can replace some S-modified targeting ligands on the surface of the AuNRs, which lowers their targeting efficacy towards cancer cells, resulting in a non-ideal PTT effect. To address this problem, herein, we utilized Se-modified AuNRs to establish a dual functional nanoprobe (Casp-RGD-Se-AuNRs) for improving the therapeutic effect and real-time monitoring of Caspase-9 levels to indicate the degree of cell apoptosis. The experiments demonstrated that the Casp-RGD-Se-AuNRs are better at avoiding interference from biothiols than the S-modified nanoprobe (Casp-RGD-S-AuNRs) for extended blood-circulation times after intravenous injection, significantly improving the PTT efficacy via more effectively targeting cancer cells. Simultaneously, the change of Caspase-9 levels visually shows the degree of apoptosis. Moreover, an in vivo study showed that, compared with the S-modified nanoprobe, the Se-modified nanoprobe exhibits a higher delivery efficiency to the tumor region after intravenous injection (accumulation in the tumor increased by 87%) and a better anticancer efficacy under NIR light irradiation (the tumor inhibition rate increased 6-fold). This work provides a valuable strategy to overcome the off-target problem, and new ideas for avoiding interference by biomolecules during blood circulation.

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.

The gut microbiome drives inter- and intra-individual differences in metabolism of bioactive small molecules.

The origin of inter-individual variability in the action of bioactive small molecules from the diet is poorly understood and poses a substantial obstacle to harnessing their potential for attenuating disease risk. Epidemiological studies show that coffee lowers the risk of developing type 2 diabetes, independently of caffeine, but since coffee is a complex matrix, consumption gives rise to different classes of metabolites in vivo which in turn can affect multiple related pathways in disease development. We quantified key urinary coffee phenolic acid metabolites repeated three times in 36 volunteers, and observed the highest inter- and intra-individual variation for metabolites produced by the colonic microbiome. Notably, a urinary phenolic metabolite not requiring the action of the microbiota was positively correlated with fasting plasma insulin. These data highlight the role of the gut microbiota as the main driver of both intra- and inter-individual variation in metabolism of dietary bioactive small molecules.

Antioxidant Activity with Increased Endogenous Levels of Vitamin C, E and A Following Dietary Supplementation with a Combination of Glutathione and Resveratrol Precursors.

The effects of two different dietary supplements on the redox status of healthy human participants were evaluated. The first supplement (GluS, Glutathione Synthesis) contains the precursors for the endogenous synthesis of glutathione and the second (GluReS, Glutathione and Resveratrol Synthesis) contains in addition polydatin, a precursor of resveratrol. To assess the influence of GluS and GluReS on the redox status, ten thiol species and three vitamins were measured before (t0) and after 8 weeks (t1) of dietary supplementation. An inflammatory marker, neopterin, was also assessed at the same time points. Both supplements were highly effective in improving the redox status by significantly increasing the reduced-glutathione (GSH) content and other reduced thiol species while significantly decreasing the oxidized species. The positive outcome of the redox status was most significant in the GluRes treatment group which also experienced a significant reduction in neopterin levels. Of note, the endogenous levels of vitamins C, E and A were significantly increased in both treatment groups, with best results in the GluReS group. While both dietary supplements significantly contributed to recognized antioxidant and anti-inflammatory outcomes, the effects of GluReS, the combination of glutathione and resveratrol precursors, were more pronounced. Thus, dietary supplementation with GluReS may represent a valuable strategy for maintaining a competent immune status and a healthy lifespan.

A Randomized, Doubled-Blind Clinical Trial on the Effect of Zataria multiflora on Clinical Symptoms, Oxidative Stress, and C-Reactive Protein in COPD Patients.

The effects of Zataria multiflora on clinical symptoms, pulmonary function tests, oxidative stress, and C-reactive protein levels in chronic obstructive pulmonary disease (COPD) patients were evaluated. Forty-five patients were allocated to 3 groups: placebo group and 2 groups that received 3 and 6 mg/kg/day Z. multiflora extract (Z3 and Z6) for 2 months. Clinical symptoms, pulmonary function tests, oxidative stress, and serum C-reactive protein levels were evaluated pretreatment (step 0) and 1 (step I) and 2 (step II) months after treatment. Clinical symptoms including breathlessness and chest wheeze in Z3- and Z6-treated groups and sputum production only in the Z6-treated group were significantly improved 1 and 2 months after treatment compared with baseline values (P < .01 to P < .001). The FEV1 was significantly increased after 2 months of treatment with Z3 and Z6 (P < .05 to P < .01). Malondialdehyde and nitrite levels were significantly decreased after a 2-month treatment with Z6 compared with step 0 (P < .05 to P < .01). The thiol contents in the Z6 group as well as superoxide dismutase and catalase activities in both groups treated with the extract were significantly increased in step II compared with step 0 (P < .05 to P < .01). The C-reactive protein level at the end of the study was significantly reduced compared with the step 0 in both treated groups (P < .05 for both cases). Two-month treatment with Z. multiflora improved clinical symptoms, pulmonary function tests, oxidative stress, and C-reactive protein in COPD patients. The results suggest that this herbal medicine could be of therapeutic value as a preventive drug for the treatment of COPD.

The thiol-disulphide homeostasis in patients with acute pancreatitis and its relation with other blood parameters.

BACKGROUND: Acute pancreatitis is a common disease seen in emergency departments because of abdominal pain. The present study aims to evaluate the relation between measurements of thiol-disulfide parameters in patients diagnosed with acute pancreatitis and other blood parameters. METHODS: A total of 56 (56%) patients, who were admitted to the emergency department, and 44 (44%) healthy volunteers participated in this study. A total of 100 samples were taken from the participants. Detailed blood samples were taken from the patients at the time of arrival at the hospital. The thiol-disulfide level in serum was examined using a brand new method that was developed by Erel and Neselioglu in the venous blood samples of the patients who were diagnosed with acute pancreatitis during the admission. The data were evaluated in the computer medium. RESULTS: Gallstones were defined as the etiology of AP in 41 patients (73.2%); in one patient, hypertriglyceridemia (1.7%); in four patients, alcohol use (7.1%), and idiopathic 10 patients (17.8%). While the blood thiol levels were low, the disulfide levels were high at a significant level. No statistically significant relations were detected between the amylase, lipase, neutrophil lymphocyte ratio (NLR), which are other blood parameters, and thiol-disulfide balance parameters. CONCLUSION: The disruption of the thiol-disulfide balance may play a role in the pathogenesis of acute pancreatitis. In acute pancreatitis, since the thiol level is decreased in the blood, administration of the complementary therapies for this thiol deficiency may contribute to the treatment of the disease.

Riboflavin Supplementation in Patients with Crohn's Disease [the RISE-UP study].

BACKGROUND AND AIMS: Crohn's disease [CD] is characterised by chronic intestinal inflammation and dysbiosis in the gut. Riboflavin [vitamin B2] has anti-inflammatory, antioxidant and microbiome-modulatory properties. Here, we analysed the effect of riboflavin on oxidative stress, markers of inflammation, clinical symptoms, and faecal microbiome in patients with CD. METHODS: In this prospective clinical intervention study, patients received 100 mg riboflavin [DSM, Nutritional Products Ltd] daily for 3 weeks. Clinical disease activity [Harvey-Bradshaw Index: HBI], serum biomarkers of inflammation and redox status [plasma free thiols], and faecal microbiome taxonomical composition and functionality [fluorescent in situ hybridisation: FISH; and metagenomic shotgun sequencing: MGS], were analysed before and after riboflavin intervention. RESULTS: In total, 70 patients with CD with varying disease activity were included. Riboflavin supplementation significantly decreased serum levels of inflammatory markers. In patients with low faecal calprotectin [FC] levels, IL-2 decreased, and in patients with high FC levels, C-reactive protein [CRP] was reduced and free thiols significantly increased after supplementation. Moreover, HBI was significantly decreased by riboflavin supplementation. Riboflavin supplementation led to decreased Enterobacteriaceae in patients with low FC levels as determined by FISH; however, MGS analysis showed no effects on diversity, taxonomy, or metabolic pathways of the faecal microbiome. CONCLUSIONS: Three weeks of riboflavin supplementation resulted in a reduction in systemic oxidative stress, mixed anti-inflammatory effects, and a reduction in clinical symptoms [HBI]. FISH analysis showed decreased Enterobacteriaceae in patients with CD with low FC levels, though this was not observed in MGS analysis. Our data demonstrate that riboflavin supplementation has a number of anti-inflammatory and anti-oxidant effects in CD.

The Effects of Bilirubin and Phototherapy on Neonatal Thiol-Disulfide Homeostasis.

OBJECTIVE: To determinate the effects of bilirubin and phototherapy on oxidative stress in newborns. STUDY DESIGN: A case-control study. PLACE AND DURATION OF STUDY: Third level Newborn Intensive Care Unit, Ankara Etlik Zubeyde Hanim Women's Health Teaching and Research Hospital, Turkey, from May to August 2017. METHODOLOGY: Blood samples of 62 term newborns were grouped as control, before and after phototherapy. Total and native thiol, disulfide and ischemia modified albumin values in expressed blood samples were measured. Disulfide-native thiol ratio, disulfide-total thiol ratio and native thiol-total thiol ratio values were computed. RESULTS: Bilirubin levels were positively correlated with native and total thiol levels and negatively correlated with ischemia modified albumin levels (r=0.409 p= 0.001, r= 0.328 p<0.009, r=-0.503 p<0.001). Native and total thiol levels of the control group were lower (p<0.001) and ischemia modified albumin levels were higher than those before and after phototherapy (p<0.001). In jaundiced newborns, native and total thiol values reduced after phototherapy, while IMA levels increased (p=0.001, p<0.001, p<0.001). CONCLUSION: Bilirubin showed antioxidant effect without increasing oxidative stress. Oxidative stress increased after phototherapy. This result was associated with decrease in bilirubin rather than oxidative effect of phototherapy.

Effects of diphenyl diselenide diet on a model of mercury poisoning.

This work investigated the preventive effect of diphenyl diselenide [(PhSe)2] against the toxic effects of mercury in silver catfish (Rhamdia quelen). The animals were treated during 30 consecutive days with a (PhSe)2 supplemented feed (3.0 mg kg-1) or commercial feed. During the last 5 days the animals received a daily intraperitoneal dose of HgCl2 (1.7 mg kg-1) or Saline (0.9%). Twenty-four hours after the last HgCl2 injection, the animals were euthanized by spinal cord section to biological material obtainment. Hepatic (AST and ALT) and renal (ammonia and creatinine) toxicity biomarkers, δ-ALA-D activity, TBARS, total and non-protein thiols levels and hepatic, renal and blood mercury (Hg) and zinc (Zn) content were evaluated. Considering renal parameters, HgCl2 exposition increased serum creatinine levels and decreased δ-ALA-D activity, total and non-protein thiols and TBARS levels. HgCl2 exposure also decreased blood δ-ALA-D activity. With exception of blood δ-ALA-D activity and total thiols levels, (PhSe)2 supplementation partially prevented mercury induced alterations. Animals exposed to HgCl2 presented an increase in liver and kidney Hg content and a decrease in liver and blood Zn content. The alteration in blood Zn content was partially prevented with (PhSe)2 supplementation. With the exception of mercury and zinc content, no effects of HgCl2 exposure on hepatic tissue were observed. These results show that (PhSe)2 supplementation can represent a promising alternative to prevent the toxic effects presented by Hg exposure.

Vitamin D supplementation does not improve plasma thiol/disulfide homeostasis.

BACKGROUND: Impairment of thiol/disulfide homeostasis, as well as vitamin D deficiency, are responsible for the pathophysiology of many acute and chronic diseases. This study examined the relationship between thiol/disulfide homeostasis and vitamin D level and supplementation. METHODS: A total of 203 healthy children were included in the study. The participants were divided into four groups according to 25-hydroxyvitamin D (25(OH)D) level: group 1, severe deficiency (<10 ng/mL); group 2, deficiency (10-20 ng/mL); group 3, insufficiency (20-30 ng/mL); and group 4, sufficiency (≥30 ng/mL). Furthermore, group 5 was defined as being on vitamin D supplementation. RESULT: Native thiol was lower in group 5 than in groups 2-4 (P = 0.003). Disulfide was higher in groups 1, 4 and 5 than groups 2 and 3 (P < 0.001). Total thiol was lower in group 5 than in group 4 (P = 0.032). The ratio of native thiol/total thiol was lower in groups 1 and 5 compared with groups 2 and 3, and in group 4 compared with group 3 (P < 0.001). The ratios of disulfide/total thiol and disulfide/native thiol were higher in groups 1 and 5 than in groups 2 and 3 whereas only the disulfide/total thiol ratio was higher in group 4 than in group 3 (P < 0.001). CONCLUSIONS: In healthy children, severe deficiency of vitamin D causes impairment of thiol/disulfide homeostasis and increases protein oxidation, which cannot be reversed by external vitamin D supplementation.

The effect of Zataria multiflora on pulmonary function tests, hematological and oxidant/antioxidant parameters in sulfur mustard exposed veterans, a randomized doubled-blind clinical trial.

BACKGROUND: Sulfur mustard is an alkylating agent which cause to short and long term incapacitations on various organs including lung. There is no definite treatment for lung disorders induced by SM exposure. In the present study, the preventive effect of Zataria multiflora (Z. multiflora) on hematological parameters, oxidant/antioxidant markers and pulmonary function tests (PFT) in veterans, 27-30 years after exposed to SM were studied. MATERIALS AND METHODS: Forty seven veterans allocated to three groups included: placebo group (P) and two groups treated with 5 and 10 mg/kg/day of Z. multiflora (Zat 5 and Zat 10). Drugs were prescribed in a double-blind manner for two months. Total and different WBC, hematological indices, oxidant/antioxidant markers and PFT values included; force vital capacity (FVC) and peak expiratory flow (PEF) were assessed at the beginning (step 0), one and two month (step I and II, respectively) after starting treatment. RESULTS: Total and different white blood cell in Zat 5 and 10 mg/kg treated groups in Step I and II were significantly decreased compared to Step 0 (p < 0.05 to p < 0.001). The levels of thiol, superoxide dismutase (SOD) and catalase (CAT) in Zat 5 and 10 mg/kg treated groups in step I and II were significantly increased (p < 0.05 to p < 0.001) but the level of malondialdehyde (MDA) significantly decreased in two treatment groups compared to Step 0 (p < 0.05 and p < 0.001 respectively). FVC and PEF values were significant increase in Zat 5 and 10 mg/kg treated groups in step I and II compared to step 0 (p < 0.05 to p < 0.001). Furthermore, FVC and PEF values in Zat 5 mg/kg were also increased in step II compared to step I (p < 0.01 for both). The percentage improvement of total and differential WBC, oxidant/antioxidant markers, FVC and PEF values during two moth treatment period significantly improved in the treated groups compared to the placebo group. CONCLUSION: Z. multiflora reduces inflammatory cells and oxidant biomarkers, while increase antioxidant biomarkers and improved PFT tests in SM exposed patients in a two moth treatment period.

Renoprotective effect of Nigella sativa against cisplatin-induced nephrotoxicity and oxidative stress in rat.

Cisplatin is one of the important antineoplastic drugs. Its clinical use has been restricted due to severe kidney toxicity. Nigella sativa (N. sativa) is an herbaceous plant with many pharmacologic effects. In the present study, we evaluated the protective effects of aqueous-ethanolic extract of N. sativa and Vitamin E on cisplatin-induced nephrotoxicity in rats. Eighty male rats were divided into eight groups: control, cisplatin (6 mg/kg; ip), preventive Vitamin E (100 mg/kg), preventive N. sativa (100,200 mg/kg), preventive + treatment Vitamin E, and preventive + treatment N. sativa (100, 200 mg/kg). Duration of this study was 11 days and cisplatin was injected on the 6th day of the experiment. Tissue damage in all groups that received N. sativa extract and Vitamin E showed a significant improvement compared with the cisplatin group. In addition, serum and tissue total thiol content in preventive and preventive + treatment N. sativa groups showed significant increase compared with cisplatin group. There was no significant difference in serum malondialdehyde concentration of the control rats compared with the preventive and preventive + treatment N. sativa groups. N. sativa extract and viamin E improved the pathology and oxidative stress in the rat kidney. However, more studies are needed to determine the mechanism of action of N. sativa on cisplatin-induced kidney toxicity.

Exploring the Lean Phenotype of Glutathione-Depleted Mice: Thiol, Amino Acid and Fatty Acid Profiles.

BACKGROUND: Although reduced glutathione (rGSH) is decreased in obese mice and humans, block of GSH synthesis by buthionine sulfoximine (BSO) results in a lean, insulin-sensitive phenotype. Data is lacking about the effect of BSO on GSH precursors, cysteine and glutamate. Plasma total cysteine (tCys) is positively associated with stearoyl-coenzyme A desaturase (SCD) activity and adiposity in humans and animal models. OBJECTIVE: To explore the phenotype, amino acid and fatty acid profiles in BSO-treated mice. DESIGN: Male C3H/HeH mice aged 11 weeks were fed a high-fat diet with or without BSO in drinking water (30 mmol/L) for 8 weeks. Amino acid and fatty acid changes were assessed, as well as food consumption, energy expenditure, locomotor activity, body composition and liver vacuolation (steatosis). RESULTS: Despite higher food intake, BSO decreased particularly fat mass but also lean mass (both P<0.001), and prevented fatty liver vacuolation. Physical activity increased during the dark phase. BSO decreased plasma free fatty acids and enhanced insulin sensitivity. BSO did not alter liver rGSH, but decreased plasma total GSH (tGSH) and rGSH (by ~70%), and liver tGSH (by 82%). Glutamate accumulated in plasma and liver. Urine excretion of cysteine and its precursors was increased by BSO. tCys, rCys and cystine decreased in plasma (by 23-45%, P<0.001 for all), but were maintained in liver, at the expense of decreased taurine. Free and total plasma concentrations of the SCD products, oleic and palmitoleic acids were decreased (by 27-38%, P <0.001 for all). CONCLUSION: Counterintuitively, block of GSH synthesis decreases circulating tCys, raising the question of whether the BSO-induced obesity-resistance is linked to cysteine depletion. Cysteine-supplementation of BSO-treated mice is warranted to dissect the effects of cysteine and GSH depletion on energy metabolism.

A new oxidative stress marker for thiol-disulphide homeostasis in seasonal allergic rhinitis.

BACKGROUND: Reactive oxygen species has a crucial role in the pathogenesis of many diseases. Reactive oxygen species has been effectively documented in patients with asthma, but very little research has been reported in subjects with allergic rhinitis. OBJECTIVES: To investigate thiol (SH)-disulfide (SS) homeostasis, a new oxidative stress marker present in patients with seasonal allergic rhinitis (SAR). METHODS: A total of 64 subjects, including 32 patients with SAR and 32 healthy controls, were included in the study. We measured the SH levels as a marker of antioxidant protection and SS as a marker related to oxidant stress. Sera specimens were taken from patients with SAR during exacerbation and during asymptomatic time periods. In addition, sera samples from the control group were also obtained during the pollen season to compare with those from patients with SAR. RESULTS: In patients with SAR, during exacerbation periods, SH, SS, % SS/SH, % SS to total SH (TT), and % SH/TT were significantly different (p < 0.05) than in patients with SAR during asymptomatic periods. Although SS was significantly higher in patents with SAR during exacerbation periods, SH was significantly higher in patients with SAR during asymptomatic periods. Patients with SAR during asymptomatic periods and the control group did not significantly differ (p > 0.05) regarding SH, SS, TT, % SS/SH, % SS/TT, and % SH/TT. CONCLUSION: SAR is a disorder that elevates systemic oxidative stress and reduces antioxidant enzyme activities. Our results shed light on the etiopathogenesis of the disease and can help develop new therapeutic approaches.

Effect of Omega-3 and Vitamins E + C Supplements on the Concentration of Serum B-Vitamins and Plasma Redox Aminothiol Antioxidant Status in Elderly Men after Strength Training for Three Months.

BACKGROUND: Data on redox plasma aminothiol status in individuals on strength training are very limited. Therefore, we studied the effect of omega-3 and vitamins E + C supplementation on the concentration of B-vitamins and redox aminothiol status in elderly men after strength training for 3 months. METHODS: Healthy men, age 60 ± 6 (mean ± SD) were randomly divided into 3 groups: group I received placebo (n = 17), group II consumed omega-3 (700 mg, n = 17), and group III consumed vitamins E + C (235 mg +1 g, n = 16) daily for 3 months. All participants completed a strength training program for the same period. RESULTS: The concentration of serum vitamin B12 decreased and the concentration of serum folate increased in group I after the intervention (p = 0.01, p = 0.009). The concentration of plasma 5-pyridoxal phosphate decreased in groups II and III (p = 0.03 and p = 0.01), whereas the concentration of serum uric acid decreased only in group II (p = 0.02). We detected an increase in the concentration of reduced form of aminothiols in all groups (p < 0.001). The red/ox plasma aminothiol status was significantly changed in all groups after the intervention (p < 0.05). CONCLUSION: Omega-3 and vitamins E + C supplementation affect the concentrations of serum B-vitamins and redox plasma aminothiol status in healthy elderly men on strength training.

Cranberry extract-enriched diets increase NAD(P)H:quinone oxidoreductase and catalase activities in obese but not in nonobese mice.

Consumption of antioxidant-enriched diets is 1 method of addressing obesity, which is associated with chronic oxidative stress and changes in the activity/expression of various enzymes. In this study, we hypothesized that the modulation of antioxidant enzymes and redox status through a cranberry extract (CBE)-enriched diet would differ between obese and nonobese mice. The CBE used in this study was obtained from the American cranberry (Vaccinium macrocarpon, Ericaceae), a popular constituent of dietary supplements that is a particularly rich source of (poly)phenols and has strong antioxidant properties. The present study was designed to test and compare the in vivo effects of 28-day consumption of a CBE-enriched diet (2%) on the antioxidant status of nonobese mice and mice with monosodium glutamate-induced obesity. Plasma, erythrocytes, liver, and small intestine were studied concurrently to obtain more complex information. The specific activities, protein, and messenger RNA expression levels of antioxidant enzymes as well as the levels of malondialdehyde and thiol (SH) groups were analyzed. Cranberry extract treatment increased the SH group content in plasma and the glutathione S-transferase activity in the erythrocytes of the obese and nonobese mice. In addition, in the obese animals, the CBE treatment reduced the malondialdehyde content in erythrocytes and increased NAD(P)H: quinone oxidoreductase (liver) and catalase (erythrocytes and small intestine) activities. The elevation of hepatic NAD(P)H: quinone oxidoreductase activity was accompanied by an increase in the corresponding messenger RNA levels. The effects of CBE on the activity of antioxidant enzymes and redox status were more pronounced in the obese mice compared with the nonobese mice.

Oxidative stress and menopause-related hot flashes may be independent events.

OBJECTIVE: At present, there is growing demand for alternative, or additional, treatments to hormone replacement therapy for menopause-related hot flashes (HF). Antioxidant supplements have been recently proposed as possible candidates for this purpose, regardless of the absence of clear evidence in support of a link between these vasomotor symptoms and oxidative stress (OxS). The aim of our study was to evaluate the association between HF and OxS serum markers in a large sample of middle-aged women. MATERIALS AND METHODS: We conducted a cross-sectional study on 245 perimenopausal and early postmenopausal women (age 45-60 years). The variables examined were presence of self-reported HF and levels of 8-iso-prostaglandin F2α, 8-OH-deoxy-2'-guanosine, advanced oxidation protein products, total antioxidant power, uric acid, thiols, and paroxonase-1. RESULTS: Seventy-six women (31%) reported to suffer from HF (either medium or high intensity). None of the peripheral markers of OxS examined was found to be significantly associated with the presence of HF. CONCLUSION: Taken together, our data suggest that systemic OxS might not be implicated with the onset of the climacteric vasomotor symptoms that most commonly affect women experiencing perimenopause and early postmenopause.

The impact of intensified training with a high or moderate carbohydrate feeding strategy on resting and exercise-induced oxidative stress.

PURPOSE: This study investigated the impact of intensified training (IT) and carbohydrate (CHO) supplementation on resting and exercise-induced oxidative stress. METHODS: Male cyclists (n = 13, mean ± SD: age 25 ± 6 years; [Formula: see text] 72 ± 5 ml/kg/min) undertook two 9 day periods of endurance-based IT. In a counter-balanced, crossover and double-blinded study design, participants completed IT whilst ingesting high (H-CHO) or moderate (M-CHO) CHO beverages before (H-CHO: 24 g vs. M-CHO: 2 g), during (H-CHO: 60 g/h vs. M-CHO: 20 g/h) and after training sessions (H-CHO: 44 g vs. M-CHO: 10 g). Participants completed fasted performance trials without CHO on days 2, 6 and 10. Blood samples were taken before and immediately after exercise to assess plasma oxidative stress. RESULTS: Resting thiol (-SH) and catalase (CAT) activities decreased following 6 days of IT, independent of CHO condition [-SH (µM oxidised NADPH): H-CHO-14.0 ± 18.8, M-CHO-20.4 ± 20.3 and CAT (nmol/min/ml): H-CHO 12.5 ± 12.5, M-CHO 6.0 ± 4.5; all p < 0.05]. Resting total antioxidant capacity (TAC) was reduced after IT in M-CHO. All exercise bouts elicited significant increases in CAT, TAC, protein carbonylation (PC) and lipid hydroperoxides (LOOH), independent of CHO condition (p < 0.05). The magnitude of increase in PC and LOOH was greater on days 6 and 10 compared to day 2 in both conditions. CONCLUSIONS: Short-term IT caused reductions in resting antioxidant capacity in trained cyclists. Exercise-induced increases in PC and LOOH were exaggerated as a result of IT; however, these responses were independent of carbohydrate intake before, during and after the preceding IT sessions.

Plasma thiols levels in Alzheimer's disease mice under diet-induced hyperhomocysteinemia: effect of S-adenosylmethionine and superoxide-dismutase supplementation.

Widely confirmed reports were published on association between hyperhomocysteinemia, B vitamin deficiency, oxidative stress, and amyloid-ß in Alzheimer's disease (AD). Homocysteine, cysteine, cysteinylglycine and glutathione are metabolically interrelated thiols that may be potential indicators of health status and disease risk; they all participate in the metabolic pathway of homocysteine. Previous data obtained in one of our laboratories showed that B vitamin deficiency induced exacerbation of AD-like features in TgCRND8 AD mice; these effects were counteracted by S-adenosylmethionine (SAM) supplementation, through the modulation of DNA methylation and antioxidant pathways. Since the cellular response to oxidative stress typically involves alteration in thiols content, a rapid and sensitive HPLC method with fluorescence detection was here used to evaluate the effect of SAM and superoxide-dismutase (SOD) supplementation on thiols level in plasma, in TgCRND8 mice. The quantitative data obtained from HPLC analysis of mice plasma samples showed significant decrease of thiols level when the B vitamin deficient diet was supplemented with SAM + SOD and SOD alone, the latter showing the greatest effect. All these considerations point out the measurement of plasma thiols concentration as a powerful tool of relevance for all clinical purposes involving the evaluation of oxidative stress. The coupling of HPLC with fluorimetric detection, here used, provided a strong method sensitivity allowing thiols determination at very low levels.

Protective Effect of Lavandula stoechas and Rosmarinus officinalis essential oils against reproductive damage and oxidative stress in alloxan-induced diabetic rats.

The authors aimed in the present study to assess the protective effect of Rosmarinus officinalis essential oils (ROEO) and Lavandula stoechas essential oils (LSEO) against reproductive damage and oxidative stress in alloxan-induced diabetic male rats. Essential oil samples were obtained from the aerial parts of the plants by hydrodistillation and analyzed by the gas chromatography-mass spectrometry (GC-MS). Rats were divided into four groups: healthy control (HC); diabetic control (DC); healthy+ROEO (H+ROEO), healthy+LSEO (H+LSEO), diabetic+ROEO (D+ROEO), and diabetic+LSEO (D+LSEO). The use of GC-MS allowed to the identification of 15 and 22 compounds in ROEO and LSEO, respectively. In addition, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test showed that ROEO and LSEO had an important antioxidant capacity. In vivo, we initially found that ROEO and LSEO treatment protected against the decrease in alloxan-induced body weight gain, relative reproductive organ weights, testosterone level, as well as sperm quality decline. On the other hand, we showed that alloxan administration was accompanied by an oxidative stress status assessed by an increase of malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels, as well as a depletion of sulfhydril group content (-SH) and antioxidant enzyme activities as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in testis, epididymis, and sperm. More importantly, ROEO and LSEO treatment significantly protected against oxidative damage of the male reproductive organ systems in alloxan-induced diabetic rats. These findings suggested that ROEO and LSEO exerted a potential protective effect against alloxan-induced reproductive function damage and oxidative stress in male rat. The beneficial effect of ROEO and LSEO might be related, in part, to their antioxidant properties.