Plasma Glutathione and Prodromal Parkinson's Disease Probability.

BACKGROUND: A decrease in glutathione (GSH) levels is considered one of the earliest biochemical changes in Parkinson's disease (PD). OBJECTIVE: The authors explored the potential role of plasma GSH as a risk/susceptibility biomarker for prodromal PD (pPD) by examining its longitudinal associations with pPD probability trajectories. METHODS: A total of 405 community-dwelling participants (median age [interquartile range] = 73.2 [7.41] years) without clinical features of parkinsonism were followed for a mean (standard deviation) of 3.0 (0.9) years. RESULTS: A 1 µmol/L increase in plasma GSH was associated with 0.4% (95% confidence interval [CI], 0.1%-0.7%; P = 0.017) less increase in pPD probability for 1 year of follow-up. Compared with participants in the lowest GSH tertile, participants in the highest GSH tertile had a 12.9% (95% CI, 22.4%-2.2%; P = 0.020) slower rate of increase of pPD probability for 1 year of follow-up. CONCLUSION: Plasma GSH was associated with pPD probability trajectories; therefore, it might assist in the identification of individuals who are likely to reach the threshold for pPD diagnosis more rapidly. © 2021 International Parkinson and Movement Disorder Society.

A Novel Swimming Performance Test in Rats.

Swimming is an advantageous exercise modality since it induces limited muscle damage. Performance is a crucial endpoint measurement of physiological relevance in exercise physiology and clinical settings alike. To our knowledge, the literature lacks a comprehensive and widely accepted swimming performance protocol without suffering from high variability in time to exhaustion. Thus, the present study presents an easily carried out, two-phased swimming performance incremental test exhibiting low variability in the time to exhaustion among rats. All nine rats managed to complete the first 12 min-part of the test (phase 1) with gradually increased loads attached at the base of their tails equal to 2%, 3.5% and 5% (for 4 min each). All rats reached exhaustion at the 10% final load (phase 2). The mean swimming time until exhaustion, as a measure for defining exercise performance, was 865 ± 59 s. In conclusion, we have presented in detail a novel protocol for practically and satisfactorily measuring swimming performance in rats characterized by low variability in the time to exhaustion. This protocol, with the appropriate modifications, can be applied to a wide spectrum of experimental treatments.

Spectrophotometric assays for measuring redox biomarkers in blood.

The assessment of redox status is most frequently performed by measuring redox biomarkers. The spectrophotometer is the most commonly used analytical instrument in biochemistry. There is a huge number of spectrophotometric redox biomarkers and assays, thus distinguishing the most appropriate biomarkers and protocols is overwhelming. The aim of the present review is to propose valid and reliable spectrophotometric assays for measuring redox biomarkers in blood. It is hoped that this work will help researchers to select the most suitable redox biomarkers and assays.

The rat closely mimics oxidative stress and inflammation in humans after exercise but not after exercise combined with vitamin C administration.

PURPOSE: The purpose of the present study was to directly compare oxidative stress and inflammation responses between rats and humans. METHODS: We contrasted rat and human oxidative stress and inflammatory responses to exercise (pro-oxidant stimulus) and/or vitamin C (anti-oxidant stimulus) administration. Vitamin C was administered orally in both species (16 mg kg(-1) of body weight). Twelve redox biomarkers and seven inflammatory biomarkers were determined in plasma and erythrocytes pre- and post-exercise or pre- and post-exercise combined with vitamin C administration. RESULTS: Exercise increased oxidative stress and induced an inflammatory state in rats and humans. There were only 1/19 significant species × exercise interactions (catalase), indicating similar responses to exercise between rats and humans in redox and inflammatory biomarkers. Vitamin C decreased oxidative stress and increased antioxidant capacity only in humans and did not affect the redox state of rats. In contrast, vitamin C induced an anti-inflammatory state only in rats and did not affect the inflammatory state of humans. There were 10/19 significant species × vitamin C interactions, indicating that rats poorly mimic human oxidative stress and inflammatory responses to vitamin C administration. Exercise after acute vitamin C administration altered redox state only in humans and did not affect the redox state of rats. On the contrary, inflammation biomarkers changed similarly after exercise combined with vitamin C in both rats and humans. CONCLUSIONS: The rat adequately mimics human responses to exercise in basic blood redox/inflammatory profile, yet this is not the case after exercise combined with vitamin C administration.

Blood reflects tissue oxidative stress: a systematic review.

We examined whether the levels of oxidative stress biomarkers measured in blood reflect the tissue redox status. Data from studies that measured redox biomarkers in blood, heart, liver, kidney and skeletal muscle were analyzed. In seven out of nine investigated redox biomarkers (malondialdehyde, reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase, vitamin C and E) there was generally good qualitative and quantitative agreement between the blood and tissues. In contrast, oxidized glutathione and the reduced to oxidized glutathione ratio showed poor agreement between the blood and tissues. This study suggests that most redox biomarkers measured in blood adequately reflect tissue redox status.

The development and validation of the pandemic medication-assisted treatment questionnaire for the assessment of pandemic crises impact on medication management and administration for patients with opioid use disorders.

Pandemic and the globally applied restriction measures mainly affect vulnerable population groups, such as patients with opioid use disorders. Towards inhibiting SARS-Cov-2 spread, the medication-assisted treatment (MAT) programs follow strategies targeting the reduction of in-person psychosocial interventions and an increase of take-home doses. However, there is no available instrument to examine the impact of such modifications on diverse health aspects of patients under MAT. The aim of this study was to develop and validate the PANdemic Medication-Assisted Treatment Questionnaire (PANMAT/Q) to address the pandemic effect on the management and administration of MAT. In total, 463 patients under ΜΑΤ participated. Our findings indicate that PANMAT/Q has been successfully validated exerting reliability and validity. It can be completed within approximately 5 min, and its implementation in research settings is advocated. PANMAT/Q could serve as a useful tool to identify the needs of patients under MAT being at high risk of relapse and overdose.

Vineyard-mediated factors are still operative in spontaneous and commercial fermentations shaping the vinification microbial community and affecting the antioxidant and anticancer properties of wines.

The grapevine and vinification microbiota have a strong influence on the characteristics of the produced wine. Currently we have a good understanding of the role of vineyard-associated factors, like cultivar, vintage and terroir in shaping the grapevine microbiota. Notwithstanding, their endurance along the vinification process remains unknown. Thus, the main objective of our study was to determine how these factors influence (a) microbial succession during fermentation (i.e., bacterial and fungal) and (b) the antioxidant, antimutagenic and anticancer potential of the produced wines. These were evaluated under different vinification strategies (i.e., spontaneous V1, spontaneous with preservatives V2, commercial V3), employed at near full-scale level by local wineries, for two cultivars (Roditis and Sideritis), two terroir types, and two vintages. Cultivar and vintage were strong and persistent determinants of the vinification microbiota, unlike terroir whose effect became weaker from the vineyard, and early fermentation stages, where non-Saccharomyces yeasts, filamentous fungi (i.e., Aureobasidium, Cladosporium, Lachancea, Alternaria, Aspergillus, Torulaspora) and acetic acid bacteria (AAB) (Gluconobacter, Acetobacter, Komagataeibacter) dominated, to late fermentation stages where Saccharomyces and Oenococcus become prevalent. Besides vineyard-mediated factors, the vinification process employed was the strongest determinant of the fungal community compared to the bacterial community were effects varied per cultivar. Vintage and vinification type were the strongest determinants of the antioxidant, antimutagenic and anticancer potential of the produced wines. Further analysis identified significant positive correlations between members of the vinification microbiota like the yeasts Torulaspora debrueckii and Lachancea quebecensis with the anticancer and the antioxidant properties of wines in both cultivars. These findings could be exploited towards a microbiota-modulated vinification process to produce high-quality wines with desirable properties and enhanced regional identity.

Mathieu Joseph Bonaventure Orfila (1787-1853): The Founder of Modern Toxicology.

Mateu Joseph Bonaventura Orfila i Rotger was a prominent Spanish chemist and scholar of the 19th century whose experimental work has enormously contributed to the progress of toxicology. Being a pioneer with his research on the effects of toxins and antidotes on live animals, he established basic principles of modern medicine and pharmacology. Orfila improved the accuracy of several chemical techniques such as the Marsh test. He served as an expert and well-known scientific investigator in important legal trials involving alleged poisonings with arsenic and other chemical substances. In 1840, he was asked to investigate the notorious case of Charles Lafarge's death, whose wife had been accused with murder by poisoning his food with arsenic. After four failed chemical analyses, Orfila was finally able to detect arsenic in the victim's body, leading the court to convict Madame Lafarge. Due to his overall contribution to the field, Orfila is considered the father of modern toxicology.

A Mixture of Endocrine Disruptors and the Pesticide Roundup® Induce Oxidative Stress in Rabbit Liver When Administered under the Long-Term Low-Dose Regimen: Reinforcing the Notion of Real-Life Risk Simulation.

Humans are exposed to xenobiotic mixtures daily through the long-term, low-dose regimen. Investigations designed to simulate this exposure profile approach the real-life risk simulation (RLRS) idea of modern toxicology. The purpose of the present study was to investigate the effects of 12-month exposure of New Zealand rabbits to a xenobiotic mixture comprising seven endocrine disruptors (EDs), which are chemical substances raising great concerns for human health, as well as the herbicide glyphosate, and its commercial formulation Roundup®, on blood and tissues redox status. It is reported herein that at the systemic level, the administration of the EDs mixture induced perturbations of blood redox homeostasis at 3 months, whereas at 6 and 12 months, it activated redox adaptations. Contrariwise, exposure to glyphosate and Roundup®, individually, caused mainly disturbances of blood redox equilibrium. At the tissue level, particularly in the liver, the administration of both the EDs mixture and Roundup® induced oxidative stress, whereas glyphosate did not affect it. The RLRS notion appears to be confirmed through these findings. Indeed, the administration of the EDs mixture and Roundup®, under the long-term, low-dose regimen, elicited detrimental effects on the redox status of the liver, a crucial tissue with a valuable biological role in the detoxification of organisms from xenobiotics.

The sesquiterpenoid valerenic acid protects neuronal cells from the detrimental effects of the fungicide benomyl on apoptosis and DNA oxidation.

BACKGROUND: Valerenic acid (VA), a sesquiterpenoid of the plant Valeriana officinalis, has attracted attention of the research community due to its potential positive role against neurodegenerative diseases induced by chemicals. However, the relevant evidence in the literature is scarce. Therefore, this study aimed to examine the putative protective role of VA on the toxic effects of the fungicide benomyl on SH-SY5Y neural cells. METHODS: Cell viability was determined via the MTT and NRU assays, DNA damage was assessed via comet assay and apoptosis was evaluated through the expression of relevant genes. RESULTS: According to the results, exposure of the cells to benomyl enhanced viability inhibition and promoted DNA damage and apoptosis since the expression levels of the genes coding for MAPK8, NF-kB, Bax, Caspase-9 and Caspase-3 were increased. Treatment of the cells with VA ameliorated these effects in a concentration dependent manner. CONCLUSION: It is concluded that the molecular mechanism through which benomyl exerts its toxic action appears to depend on DNA oxidation and apoptosis induction. Furthermore, VA, a plant-derived compound is a protective antioxidant against pesticide-induced toxicity. Therefore, herbs, extracts and compounds of plant origin could be used as nutritional supplements that back up the beneficial role of medicine in neurodegenerative diseases.

The Significance of Redox Biomarkers in the Evaluation of the Antioxidant Profile In Vitro and In Vivo.

The present Special Issue of Antioxidants, entitled The Significance of Redox Biomarkers in the Evaluation of the Antioxidant Profile In Vitro and In Vivo, ten research articles emphasize the significance of adopting reliable redox biomarkers to determine the antioxidant activities of bioactive compounds in vitro and to assess blood and tissue redox status in vivo [...].

Ameliorative Effects of the Sesquiterpenoid Valerenic Acid on Oxidative Stress Induced in HepG2 Cells after Exposure to the Fungicide Benomyl.

Valerenic acid (VA) is a sesquiterpenoid and a phytoconstituent of the plant valerian used for sleeping disorders and anxiety. The frequency of using herbal components as therapeutic nutritional agents has increased lately. Their ability to improve redox homeostasis makes them a valuable approach against harmful xenobiotics. The purpose of this study was to evaluate the putative beneficial role of VA against the redox-perturbating role of the fungicide benomyl in HepG2 human liver cells in terms of oxidative stress in the cellular environment and in endoplasmic reticulum (ER). Benomyl increased cell total oxidant status and reactive oxygen species production and decreased total antioxidant status. The expression of genes coding for antioxidant molecules, namely, heme oxygenase-1, alpha glutathione s-transferase, NF-ĸB, and liver fatty acid binding protein, were decreased due to benomyl. VA ameliorated these effects. Benomyl also increased ER-stress-related molecules such as endoplasmic reticulum to nucleus signaling 1 protein, glucose-regulated protein 78, and caspase-12 levels, and VA acted also as a preventive agent. These results indicate that VA exerts ameliorative effects after benomyl-induced oxidative stress. VA, a widely used nutritional supplement, is a compound with potent antioxidant properties, which are valuable for the protection of cells against xenobiotic-induced oxidative damage.

Patients Undergoing Surgery for Hip Fractures Suffer from Severe Oxidative Stress as Compared to Patients with Hip Osteoarthritis Undergoing Total Hip Arthroplasty.

Hip fractures are associated with the highest degree of morbidity and mortality of all fractures in elderly patients and pose a major risk for subsequent fractures. Patients with hip fractures also present accelerated bone turnover despite early stable fracture fixation and early mobilization. We aimed to evaluate oxidative stress in two groups of patients (25 patients each, matched for age, side, and BMI) who underwent internal fixation of hip fractures and total hip arthroplasty for hip osteoarthritis. Blood samples were taken from all patients during admission, the day of surgery, the 4th postoperative day, and the 15th postoperative day. Reduced (GSH) and oxidized (GSSG) glutathione, GSH/GSSG, catalase (CAT), thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), and total antioxidant capacity (TAC) as a widely used battery of redox biomarkers were recorded from blood samples. Patients with hip fractures who undergo fixation surgery, compared to those with hip osteoarthritis, suffer significant oxidative stress with an active but insufficient first line of oxidative defense, an intensive first line reaction, a very active second line of oxidative defense, and a low plasma antioxidant capacity. Surgery worsened already present lipid- and protein-related tissue damage. The severe oxidative stress observed may explain high morbidity and mortality rates and high bone turnover status, as well as the high incidence of refractures. Furthermore, the question of whether antioxidant therapy measures should be introduced in the management of hip fracture patients is raised.

Redox Biomarker Baseline Levels in Cattle Tissues and Their Relationships with Meat Quality.

Cattle breeds or crossbreds with high productivity traits have been developed to meet a growing demand for food. When intensive farming practices are followed, animals face several challenges which can result in poor performance, compromised welfare and the reduced quality of their products. Our study aims to highlight the resting values of the physiological oxidative stress that three cattle breeds exhibit, and their potential relationship with meat quality. For this purpose, we determined the levels of five common redox biomarkers (glutathione (GSH), catalase (CAT), total antioxidant capacity (TAC), thiobarbituric reactive substances (TBARS) and protein carbonyls (CARBS)) in the tissues of three commonly used beef cattle breeds (Charolais (CHA), Limousin (LIM) and Simmental (SIM)) and their association with specific meat quality traits that depend on color, pH and texture. The results revealed that LIM cattle breed animals have elevated intrinsic antioxidant defense systems in comparison to CHA and SIM cattle breed animals. In addition, the meat quality parameters were associated with the redox biomarkers. We propose that the determination of specific antioxidant parameters in the blood might be used as potential biomarkers to predict meat quality. This would allow farmers to nutritionally intervene to improve the quality of their products.

Position Statement on Exercise Dosage in Rheumatic and Musculoskeletal Diseases: The Role of the IMPACT-RMD Toolkit.

There is convincing evidence to suggest that exercise interventions can significantly improve disease-related outcomes as well as comorbidities in rheumatic and musculoskeletal diseases (RMDs). All exercise interventions should be appropriately defined by their dose, which comprises of two components: a) the FITT (frequency, intensity, time and type) and b) the training (ie, specificity, overload, progression, initial values, reversibility, and diminishing returns) principles. In the published RMD literature, exercise dosage is often misreported, which in "pharmaceutical treatment terms", this would be the equivalent of receiving the wrong medication dosage. Lack of appropriately reporting exercise dosage in RMDs, therefore, results in limited clarity on the effects of exercise interventions on different outcomes while it also hinders reproducibility, generalisability and accuracy of research findings. Based on the collective but limited current knowledge, the main purpose of the present Position Statement is to provide specific guidance for RMD researchers to help improve the reporting of exercise dosage and help advance research into this important field of investigation. We also propose the use of the IMPACT-RMD toolkit, a tool that can be used in the design and reporting phase of every trial.

Approaching reactive species in the frame of their clinical significance: A toxicological appraisal.

Redox biology and toxicology are interrelated fields that have produced valuable evidence regarding the role and clinical significance of reactive species. These issues are analyzed herein by presenting 6 arguments, as follows: Argument 1: There is no direct connection of redox-related pathologies with specific reactive species; Argument 2: The measurement of reactive species concentration is a major challenge due to their very short half lives; Argument 3: There is an interplay between reactive species generation and fundamental biological processes, such as energy metabolism; Argument 4: Reactive species exert beneficial biological action; Argument 5: Reactive species follow the hormesis phenomenon; Argument 6: Oxidative modifications of redox-related molecules are not necessarily interpreted as oxidative damage. We conclude that reactive species do not seem to exert clinical significance, which means that they lack a measurable cause-effect relation with chronic diseases. Unpredictable results could, nevertheless, arise through novel experimental setups applied in the field of toxicology. These are related to the real-life exposure scenario via the regimen of long-term low-dose (far below NOAEL) exposure to mixtures of xenobiotics and can potentially offer perspectives in order to investigate in depth whether or not reactive species can be introduced as clinically significant redox biomarkers.

Erratum: Nutritional habits and free grazing regimen of productive animals along with specific ingredients are influential factors for the antioxidant properties of milk: From farm to market.

[This corrects the article DOI: 10.3892/br.2020.1301.].

Nutritional habits and free grazing regimen of productive animals along with specific ingredients are influential factors for the antioxidant properties of milk: From farm to market.

Milk is a fundamental product of animal origin for human health and well-being. It possesses crucial biological properties, which depend on its composition and production methodology. To this end, one of the aims of the present study was to assess the impact of the nutritional and dwelling patterns of productive animals on the antioxidant potency of their generated milk. Thus, samples of sheep milk were collected for 30 consecutive days during the spring months from 5 different farms with different traits and its antioxidant activity was measured. Furthermore, this study aimed to evaluate the antioxidant capacity of 15 commercially available milk samples of different animal origin (i.e., cow and buffalo) and type (i.e., full-fat, light and chocolate) derived from 5 different companies. For all the experiments, the assay that examines the ability of the milk samples to reduce the DPPH• radical was used. It was thus found that the free-grazing regimen of the farm sheep dwelling at high altitude resulted in the production of milk with a greater antioxidant potential. On the other hand, it was also found that the samples of chocolate milk exhibited notably mote potent antioxidant activity than the full-fat and light samples, obviously due to the excessively high composition in antioxidant molecules present in cocoa. From this study that holistically examined the antioxidant properties of milk derived from three different productive animal species, it becomes evident that the nutritional and grazing practices, as well as specific ingredients (i.e., cocoa) lead to the generation of milk with high added biological value.

Whey protein boosts the antioxidant profile of rats by enhancing the activities of crucial antioxidant enzymes in a tissue-specific manner.

Whey protein, a by-product of cheese industry, is harmful for the environment (i.e., surface and subterranean waters, soil) and, therefore, for humans due to its high polluting burden. Concomitantly, it has been reported that it is a mixture with potent antioxidant action since it is rich in cysteine residues, which are necessary for glutathione synthesis in vivo. On this basis, this study intended to examine the role of whey protein on the intensification of tissue antioxidant arsenal. To this end, a dose of sheep/goat whey protein equal to 1 g/kg of body weight/day dissolved in drinking water was administered to rats for 28 consecutive days. According to our findings, whey protein improved the antioxidant profile of liver, small intestine, lung and muscle whereas it did not affect the redox state of kidney. Our results were based on the alterations found in the protein expression of glutamate cysteine ligase, catalase and superoxide dismutase-1 measured in all tissues and the activity of glutathione S-transferase evaluated in muscle. Although tissue-specific, it is obvious that the action of whey protein is biologically beneficial and could serve as a biofunctional constituent for foods able to improve redox profile when administered against redox-related diseases.

Benomyl, a benzimidazole fungicide, induces oxidative stress and apoptosis in neural cells.

Fungicides are used in the agricultural sector against the harmful action of fungi, however they are potential toxic agents for the environment and the living organisms. Benomyl is a widely encountered benzimidazole fungicide that exerts its toxicity via inhibiting microtubule formation in the nervous system and the male reproductive and endocrine systems, whilst it is a known teratogen. Since toxic effects of benomyl and its molecular mechanisms are not fully understood, we aimed to detect its neurotoxic potential via evaluating cytotoxicity, oxidative stress and apoptosis in SH-SY5Y cell line. The cells were incubated with benomyl in a concentration range between 1 and 6 µM for 24 h. Our results indicated a concentration-dependent enhancement of reactive oxygen species measured through flow cytometry and DNA damage evaluated via the comet assay. Additionally, it induced apoptosis in all tested concentrations. According to the findings of the present study, benomyl is a xenobiotic, which it appears to exert its toxic action via a redox-related mechanism that, finally, induces cell apoptosis and death. We believe that this study will offer further insight in the toxicity mechanism of benomyl, although further studies are recommended in order to elucidate these mechanisms in the molecular level.