Antioxidant Therapy in Inflammatory Bowel Disease: A Systematic Review and a Meta-Analysis of Randomized Clinical Trials.

The objective of this study is to assess the effectiveness of treatment for inflammatory bowel diseases in modulating oxidative stress biomarkers and cytokine levels. A systematic review of clinical trials was conducted, searching electronic databases including PubMed, Science Direct, and Scopus. After excluding articles that did not meet the inclusion criteria, 19 studies were included in the systematic review and 8 in the meta-analysis (6 for antioxidant capacity, 6 for superoxide dismutase (SOD), and 5 for lipid peroxidation analyzed through malondialdehyde (MDA) levels). SOD was significantly modulated (RR = 0.3764, 95% CI [0.0262 to 0.7267], p = 0.035) but not antioxidant capacity (RR = 0.3424, 95% CI [0.0334 to 0.7183], p = 0.0742) or MDA (RR = -0.8534, 95% CI [-1.9333 to 0.2265], p = 0.1214). Nonetheless, studies investigating oxidative stress biomarkers and cytokines in the context of alternative therapies for IBD treatment are still scarce. This review highlights the potential of antioxidant supplementation in IBD management and underscores the need for further investigations into its effects on oxidative stress biomarkers and cytokines to improve therapeutic approaches for IBD patients.

Extraintestinal Manifestations in Induced Colitis: Controversial Effects of N-Acetylcysteine on Colon, Liver, and Kidney.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD) characterized by continuous inflammation in the colonic mucosa. Extraintestinal manifestations (EIM) occur due to the disruption of the intestinal barrier and increased permeability caused by redox imbalance, dysbiosis, and inflammation originating from the intestine and contribute to morbidity and mortality. The aim of this study is to investigate the effects of oral N-acetylcysteine (NAC) on colonic, hepatic, and renal tissues in mice with colitis induced by dextran sulfate sodium (DSS). Male Swiss mice received NAC (150 mg/kg/day) in the drinking water for 30 days before and during (DSS 5% v/v; for 7 days) colitis induction. On the 38th day, colon, liver, and kidney were collected and adequately prepared for the analysis of oxidative stress (superoxide dismutase (SOD), catalase (CAT), glutathione reduced (GSH), glutathione oxidized (GSSG), malondialdehyde (MDA), and hydrogen peroxide (H2O2)) and inflammatory biomarkers (myeloperoxidase (MPO) -, tumor necrosis factor alpha - (TNF-α, and interleukin-10 (IL-10)). In colon, NAC protected the histological architecture. However, NAC did not level up SOD, in contrast, it increased MDA and pro-inflammatory effect (increased of TNF-α and decreased of IL-10). In liver, colitis caused both oxidative (MDA, SOD, and GSH) and inflammatory damage (IL-10). NAC was able only to increase GSH and GSH/GSSG ratio. Kidney was not affected by colitis; however, NAC despite increasing CAT, GSH, and GSH/GSSG ratio promoted lipid peroxidation (increased MDA) and pro-inflammatory action (decreased IL-10). Despite some beneficial antioxidant effects of NAC, the negative outcomes concerning irreversible oxidative and inflammatory damage in the colon, liver, and kidney confirm the nonsafety of the prophylactic use of this antioxidant in models of induced colitis, suggesting that additional studies are needed, and its use in humans not yet recommended for the therapeutic routine of this disease.

Pain Assessment and Acute Phase Response in Donkeys Submitted to Inguinal Orchiectomy.

In most animals, pain can compromise physiological functions and delay healing so, rapid detection of pain through behavior and inflammatory reaction with biomarkers are necessary. This study aimed to evaluate pain, physiological variations and Acute Phase Proteins (APP) in donkeys undergoing orchiectomy technique by inguinal access. For this research, 15 male northeastern donkeys kept in extensive management were selected, with a mean age of 4.5±3.1 years. All animals had the same anesthetic protocol, using dissociative anesthesia and local block with lidocaine, followed by orchiectomy by inguinal access. Due to their predisposition to complications, the inguinal technique is the most indicated to minimize complications and excessive inflammation in donkeys' orchiectomy, the donkeys were evaluated regarding behavioral assessment of pain, hematological parameters, APP and the surgical wound, during 0 hour, 24 hours, 48 hours and 72 hours. As for the physiological parameters and APP, no significant differences were observed between times, due to the use of nonsteroidal antiinflammatory drugs. In the macroscopic evaluation of the surgical wound, it was observed that there were no significant differences between the times, with animals presenting mean scores of 1.8±0.414, in 48 hours 1.6 ± 0.507, and in 72 hours 1.6 ± 0.507. Most animals had mild to moderate edema in the scrotum and foreskin regions. As for pain assessment, the average scores were between 2 and 3, representing mild and moderate pain, not requiring intervention. However, further research is needed to elucidate the behavior of PFAs in the face of variables and the creation of new pain scales for animals raised in an extensive system.

Gestational Diabetes Mellitus: The Crosslink among Inflammation, Nitroxidative Stress, Intestinal Microbiota and Alternative Therapies.

Gestational diabetes mellitus (GDM) is characterized by a set of metabolic complications arising from adaptive failures to the pregnancy period. Estimates point to a prevalence of 3 to 15% of pregnancies. Its etiology includes intrinsic and extrinsic aspects of the progenitress, which may contribute to the pathophysiogenesis of GDM. Recently, researchers have identified that inflammation, oxidative stress, and the gut microbiota participate in the development of the disease, with potentially harmful effects on the health of the maternal-fetal binomial, in the short and long terms. In this context, alternative therapies were investigated from two perspectives: the modulation of the intestinal microbiota, with probiotics and prebiotics, and the use of natural products with antioxidant and anti-inflammatory properties, which may mitigate the endogenous processes of the GDM, favoring the health of the mother and her offspring, and in a future perspective, alleviating this critical public health problem.

Lack of Concordance among Nutritional Diagnostic Methods in Newly Diagnosed Colorectal Cancer Patients.

This study aimed to investigate the concordance of different nutritional assessment methods and the prevalence of inadequate nutritional status in newly diagnosed Colorectal cancer (CRC) patients. Cross sectional study was conducted in a public hospital in Alagoas, Brazil. Clinical, nutritional (patient-generated subjective global assessment [PG-SGA], body mass index [BMI], arm circumference [AC], triceps skinfold [TSF], arm muscle circumference [AMC]) and functional (handgrip strength [HGS]) data were collected from July 2017-January 2019. Of the 31 CRC patients with a mean age of 58.97 ± 14.96 years, 48.4% were elderly and 51.6% were female. TSF adequacy (80.8%) and PG-SGA (80.0%) revealed the highest prevalence of malnutrition. BMI identified the same prevalence of malnutrition and excess weight (30.0%). The concordance between PG-SGA and BMI (kappa = 0.086; p = 0.426) was slight, with fair HGS (kappa = 0.268; p = 0.124). PG-SGA and AC (kappa = 0.015; p = 0.99), TSF (kappa = 0.195; p = 0.558) and AMC adequacy (kappa = 0.142; p = 0.380) were poor. PG-SGA can diagnose malnutrition, even in those who are eutrophic/overweight, by other methods. Various methods do not show concordance with PG-SGA, confirming the need for both objective and subjective methods for better diagnosis of CRC patients.

The impact on colostrum oxidative stress, cytokines, and immune cells composition after SARS-CoV-2 infection during pregnancy.

Background: Limited data are available regarding the differences between immunological, biochemical, and cellular contents of human colostrum following maternal infection during pregnancy with coronavirus 2 disease (COVID-19). Objective: To investigate whether maternal COVID-19 infection may affect immunological, biochemical, and cellular contents of human colostrum. Methods: Using a case-control study design, we collected colostrum from 14 lactating women with a previous diagnosis of COVID-19 during pregnancy and 12 without a clear diagnosis during September 2020 to May 2021. Colostrum samples were analysed for some enzymes and non-enzymatic oxidative stress markers (SOD, CAT, GPx, MDA, GSH, GSSG, H2O2, MPO) and for IL-1ß, IL-6, tumour necrosis factor (TNF)-α, protein induced by interferon gamma (IP)-10, IL-8, IFN-λ1, IL12p70, IFN-α2, IFN-λ2/3, granulocyte macrophage colony stimulating factor (GM-CSF), IFN-ß, IL-10 and IFN-γ, along with IgA and IgG for the SARS-CoV-2 S protein. We perform immunophenotyping to assess the frequency of different cell types in the colostrum. Results: Colostrum from the COVID-19 symptomatic group in pregnancy contained reduced levels of H2O2, IFN-α2, and GM-CSF. This group had higher levels of GSH, and both NK cell subtypes CD3-CD56brightCD16-CD27+IFN-γ+ and CD3-CD56dimCD16+CD27- were also increased. Conclusion: The present results reinforce the protective role of colostrum even in the case of mild SARS-Cov-2 infection, in addition to demonstrating how adaptive the composition of colostrum is after infections. It also supports the recommendation to encourage lactating women to continue breastfeeding after COVID-19 illness.

Biomarkers of Inflammation and Redox Imbalance in Umbilical Cord in Pregnancies with and without Preeclampsia and Consequent Perinatal Outcomes.

OBJECTIVE: To compare redox imbalance and inflammation biomarkers in umbilical cords from pregnancies with and without preeclampsia (PE) and to analyse their relationships with perinatal outcomes. METHODS: A controlled cross-sectional study was conducted in Maceió, Alagoas, Brazil, that involved pregnant women with PE and a group of women without the disease, through the application of a standardized questionnaire. After delivery, umbilical cord samples were collected to measure antioxidant defense, products from oxidative damage, and inflammation biomarkers such as myeloperoxidase (MPO), interleukin- (IL-) 6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α). Statistical analyses were performed using Stata version 13.0 software and IBM Statistical Package for the Social Sciences (SPSS) 20.0, adopting a 95% confidence level (α = 0.05), with the chi-square test, the Wilcoxon-Mann-Whitney test, and the multinomial and Poisson regression tests. RESULTS: One hundred PE pregnant women and 50 women without the disease were studied. The umbilical cords from PE pregnancies showed higher levels of reduced glutathione (GSH) (p ≤ 0.001), glutathione peroxidase (GPx) (p = 0.016), and malondialdehyde (MDA) (p = 0.028) and lower levels of IL-6 (p = 0.030) and TNF-α (p ≤ 0.001) than the other group, with some associations among these biomarkers with perinatal outcomes. CONCLUSION: The higher levels of GSH and GPx, in addition to the lower levels of IL-6 and TNF-α, found in the PE umbilical cord, may result from adaptive mechanisms to maintain the oxidative and inflammatory balance; however, despite these changes, the damage to the cell membranes was not minimized, as the MDA level was higher in women with PE than in women without the disease. This implies that a redox imbalance is present, confirming that other physiological and adaptive mechanisms are being activated to preserve foetal health. Therefore, the present work unveils an important role of the umbilical cord in controlling redox imbalance and inflammation in PE pregnancies. Our results reinforce the necessity for continuous research on GSH as a protective compound for the perinatal outcome, especially in PE women.

N-Acetylcysteine (NAC): Impacts on Human Health.

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1ß) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC's relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence.

Interleukin-6 and triceps skinfold are associated with severity/cancer stage in newly-diagnosed colorectal cancer patients.

INTRODUCTION: Introduction: colorectal cancer (CRC) has an important impact on morbidity and mortality globally, and nitroxidative stress, inflammation, and nutritional status are linked with its progression. Aim: to analyze the association of inflammatory, anthropometric, functional, and oxidative markers with tumor stage in newly-diagnosed CRC patients at a public reference center in Maceió, Alagoas, Brazil. Methods: patient-generated subjective global assessment was applied, and weight, height, arm circumference, triceps skinfold (TSF), arm muscle circumference, and handgrip strength were obtained. A fasting blood sample was collected, centrifuged, and the serum was stored at -80 °C until the analysis. Malonaldehyde levels were quantified by HPLC (high-performance liquid chromatography) and cytokines, namely tumor necrosis factor-alpha, and interleukins IL-6, IL-8, and IL-17 were analyzed by ELISA. Patients were grouped according to cancer stage into group 1 (stage 0-III) and group 2 (stage IV). A binary logistic regression analysis was performed, adjusted for sex and age, to assess the relationships between the variables studied and cancer stage. Significance was considered when p < 0.05. Results: twenty-eight CRC patients were included, twenty (71.4 %) from group 1 and eight (28.6 %) from group 2. The binary logistic regression revealed that lower TSF adequacy (OR = 0.929; CI 95 % = 0.870-0.993; p = 0.029) and higher IL-6 levels (OR = 1.001; CI 95 % = 1.000-1.002; p = 0.012) increased the chance of patients having tumor stage IV. Conclusion: These data support that IL-6 and TSF may help in cancer stage assessment in clinical practice. Modulation of inflammation by IL-6 levels may be a target in CRC treatment.

INTRODUCCIÓN: Introducción: el cáncer colorrectal (CCR) tiene un impacto importante en la morbilidad y mortalidad a nivel mundial, y el estrés nitroxidativo, la inflamación y el estado nutricional están relacionados con su progresión. Objetivos: analizar la asociación de los marcadores inflamatorios, antropométricos, funcionales y oxidativos con el estadio tumoral de pacientes con CCR recién diagnosticados en un centro público de referencia de Maceió, Alagoas, Brasil. Métodos: se aplicó la valoración global subjetiva generada por el paciente y se obtuvieron el peso, la altura, la circunferencia del brazo, el pliegue cutáneo del tríceps (PCT), la circunferencia del músculo del brazo y la fuerza de prensión. Se tomó una muestra de sangre en ayunas, se centrifugó y el suero se almacenó a -80 °C hasta el momento del análisis. Los niveles de malonaldehído se cuantificaron por CLAR (cromatografía líquida de alta resolución) y las citocinas, representadas por el factor de necrosis tumoral alfa y las interleucinas IL-6, IL-8 e IL-17, se analizaron mediante ELISA. Los pacientes se agruparon según el estadio del cáncer en grupo 1 (estadio 0-III) y grupo 2 (estadio IV). Se realizó una regresión logística binaria, ajustada por sexo y edad, para evaluar las relaciones entre las variables estudiadas y el estadio del cáncer. Se consideró la significancia cuando p < 0,05. Resultados: se incluyeron veintiocho pacientes con CCR, de los cuales veinte (71,4 %) eran del grupo 1 y ocho (28,6 %) del grupo 2. La regresión logística binaria reveló que una menor adecuación de PCT (OR = 0,929; IC 95 % = 0,870-0,993; p = 0,029) y los niveles más altos de IL-6 (OR = 1,001; IC 95 % = 1,000-1,002; p = 0,012) aumentaban la probabilidad de que los pacientes tuvieran un tumor en estadio IV. Conclusiones: estos datos señalan que la IL-6 y el PCT pueden ayudar en la evaluación del estadio del cáncer en la práctica clínica. La modulación de la inflamación por los niveles de IL-6 podría ser una diana en el tratamiento del CCR.

Electrochemical evidence of nitrate release from the nitrooxy compound 4-((nitrooxy) methyl)-3-nitrobenzoic acid and its antinociceptive and anti-inflammatory activities in mice.

Considering the many biological activities of nitric oxide (NO), some lines of research focused on the modulation of these activities through the provision of this mediator by designing and synthesizing compounds coupled with an NO donor group. Thus, the objectives of the present study were to carry out an electrochemical investigation of the nitrooxy compound 4-((nitrooxy) methyl)-3-nitrobenzoic acid (1) and evaluate its activities and putative mechanisms in experimental models of pain and inflammation. Voltammetric studies performed in aprotic medium (mimetic of membranes) showed important electrochemical reduction mechanisms: nitroaromatic reduction, self-protonation, and finally reductive elimination, which leads to nitrate release. Systemic administration of the nitrooxy compound (1) inhibited the nociceptive response induced by heat and the tactile hypersensitivity and paw edema induced by carrageenan in mice. The activities in the models of inflammatory pain and edema were associated with reduced neutrophil recruitment and production of inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, tumor necrosis factor-α and CXCL-1, and increased production of IL-10. Concluding, electrochemical analysis revealed unequivocally that electron transfer at the nitro group of the nitrooxy compound (1) results in the cleavage of the organic nitrate, potentially resulting in the generation of NO. This electrochemical mechanism may be compared to a biochemical electron-transfer mediated nitrate release that, by appropriate in vivo bioreduction (enzymatic or not) would lead to NO production. Compound (1) exhibits activities in models of inflammatory pain and edema that may be due to reduced recruitment of neutrophils and production of inflammatory cytokines and increased production of IL-10. These results reinforce the interest in the investigation of NO donor compounds as candidates for analgesic and anti-inflammatory drugs.

Photoluminescent nanoprobes based on thiols capped CdTe quantum dots for direct determination of thimerosal in vaccines.

CdTe quantum dots (CdTe QD) have been produced at different times of synthesis (1, 2, and 4 h) using thiols as capping agents: mercaptopropionic acid (MPA), mercaptosuccinic acid (MSA) and N-acetyl-l-cysteine (NAC) using water as a solvent. The produced CdTe QD were characterized by UV-vis and photoluminescence (PL) spectroscopy and showed a relationship among reflux time, size, and spectroscopic properties. CdTe QD were shown to interact with thimerosal (TM), an organic mercury compound, and the PL intensity was effectively quenched, characterizing an ON-OFF process. However, the NAC capped CdTe (CdTe-NAC) at 1 h presented the best sensitivity for TM determination. Under optimized conditions, a linear range from 0.1 to 1.0 µg mL-1 (0.25-2.5 µM) and a LOD of 26.6 µg L-1 (66.7 nM) were achieved. The influence of different mercuric species [Hg(II), methylmercury, ethylmercury, and phenylmercury], along with thiosalicylic acid (TSA), and other ionic species on the sensitivity of the method and the interaction mechanism between TM and CdTe-NAC have been discussed. The method was successfully applied for direct quantification of TM in vaccines, and the results were validated by cold vapor atomic fluorescence spectroscopy (CV AFS). Finally, the proposed method proved to be fast, sensitive, and simple for suitable use in vaccine quality control.

Pre-eclampsia is associated with later kidney chronic disease and end-stage renal disease: Systematic review and meta-analysis of observational studies.

OBJECTIVES: To assess whether there is a risk of kidney disease during the postpartum period of women who had preeclampsia (PE). STUDY DESIGN: Observational trials were searched in the PubMed, Science Direct, Clinical trials, Cochrane, LILACS and Web of Science databases. The data extracted from the studies were systematized, and the risk of bias was evaluated for each of them. Meta-analyses were performed with studies that evaluated chronic kidney disease (CKD) and end-stage renal disease (ESRD), pooling the natural logarithms of the adjusted risk measures and the confidence intervals of each study in a random effects model. RESULTS: Of the 4149 studies evaluated, 35 articles were included in the review, of which 3 of the CKD and 6 of the ESRD presented the necessary outcomes to compose the meta-analysis. A formal registration protocol was included in the PROSPERO database (number: CRD42019111821). There was a statistically significant difference between the development of CKD (hazard ratio (HR): 1.82, confidence interval to 95% (95% CI): 1.27-2.62, P < 0.01) and ESRD (HR: 3.01, confidence interval to 95% (95% CI): 1.92-4.70, P < 0.01) in postpartum women affected by PE. CONCLUSIONS: PE was considered a risk factor for the onset of CKD and ESRD in the postpartum period. Thus, more research is needed to clarify the underlying mechanisms of this association, and to assist in determining the most appropriate and effective clinical conduct to prevent and/or treat such complications.

Oxidative stress markers in preeclamptic placentas: A systematic review with meta-analysis.

INTRODUCTION: Oxidative stress (OS) is the basis of several diseases. Preeclampsia (PE) is a multisystemic syndrome, considered one of the major causes of maternal and fetal mortality. The placenta is considered the main anatomical pathogenetic substrate for the disease, being the placental OS a likely critical pathway in the pathogenesis of PE. This meta-analysis aimed to verify whether there is OS in the preeclamptic placenta and which markers are altered in this condition. METHODS: The search was conducted in the following databases: MEDLINE (via PubMed), Lilacs and Scopus. Relevant studies were identified until May 2020. The quality of the studies was evaluated according to the Newcastle-Ottawa scale. RESULTS: From the 3998 screened records, 43 were finally included in the systematic review, and 23 in the meta-analysis. The biomarkers evaluated were related to cell and macromolecules' damage, such as malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OH-dG), lipid peroxides, isoprostane, total oxidant status (TOS), carbonylated proteins and some of the reactive oxygen and nitrogen species (RONS), like hydrogen peroxide and nitric oxide. It was also related to antioxidant activity, both enzymatic, including superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione S-transferase and total antioxidant status, and non-enzymatic, through quantification of reduced glutathione, vitamin C and E, zinc and copper. CONCLUSION: It was observed that there was OS in the preeclamptic placentas, based on results, like lower activity of some of the enzymes of the antioxidant system (SOD and GPx) as well as the increase in oxidative damage markers (MDA and lipid peroxide), corroborating literature data.

Biomarkers of placental redox imbalance in pregnancies with preeclampsia and consequent perinatal outcomes.

OBJECTIVE: To compare redox and inflammatory markers between normal and PE-derived placentas and to evaluate the relationship between placental redox imbalance markers and perinatal outcomes in pregnancies with PE. METHODS: This was a cross-sectional study conducted at the maternity hospital of a university hospital in Maceio-Alagoas, Brazil, in 2017, including women diagnosed with PE and healthy pregnant women and their conceptuses. After screening, standardized questionnaires containing socioeconomic, clinical, obstetric and anthropometric data were applied. After delivery, placental samples were collected for quantification of biomarkers of redox imbalance (catalase - CAT; malondialdehyde - MDA; hydrogen peroxide - H2O2; superoxide dismutase - SOD; reduced glutathione - GSH; oxidized glutathione - GSSG; and their ratio - GSH/GSSG) and inflammation (myeloperoxidase - MPO; interleukin (IL)-6; IL-8; IL-10; and tumor necrosis factor-alpha - TNF-α). All biomarkers were evaluated via linear regression with adjustments of variables with measures of weight, length, head circumference (HC), chest circumference (CC) and gestational age of newborns at birth, considering p < 0.05 as significant. RESULTS: A total of 100 pregnant women with PE and 50 healthy pregnant women were studied. Higher placental levels of catalase (p = 0.018), SOD (p = 0.031), the GSH/GSSG ratio (p = 0.019) and IL-6 (p = 0.010) and lower GSSG (p = 0.001) were observed in pregnant women with PE than in the control group. Positive associations between placental GSH levels and body weight, HC, CC and gestational age at birth (p < 0.05) were identified. CONCLUSION: PE-derived placentas had high concentrations of some antioxidants (enzymes and thiols), which might be a compensation mechanism against oxidative stress. Placental GSH levels were the only biomarker, among the studied ones, related positively with beneficial perinatal outcomes, suggesting that this endogenous antioxidant plays an important role in maintaining the health of the conceptus and women with PE.

Toxicity of thimerosal in biological systems: Conformational changes in human hemoglobin, decrease of oxygen binding capacity, increase of protein glycation and amyloid's formation.

Thimerosal (TH), an organomercurial compound, is used as a preservative in vaccines and cosmetics. Its interaction with human hemoglobin (Hb) was investigated under physiological conditions using biophysical and biological assays, aiming to evaluate hazardous effects. TH interacts spontaneously with Hb (stoichiometry 2:1, ligand-protein), preferably by electrostatic forces, with a binding constant of 1.41 × 106 M-1. Spectroscopic data allows to proposing that TH induces structural changes in Hg, through ethylmercury transfer to human Hb-Cys93 residues, forming thiosalicylic acid, which, in turn, interacts with the positive side of the amino acid in the Hb-HgEt adduct chain. As a consequence, inhibition of Hb-O2 binding capacity up to 72% (human Hb), and 50% (human erythrocytes), was verified. Dose-dependent induction of TH forming advanced glycation end products (AGE) and protein aggregates (amyloids) was additionally observed. Finally, these results highlight the toxic potential of the use of TH in biological systems, with a consequent risk to human health.

The Close Interplay of Nitro-Oxidative Stress, Advanced Glycation end Products and Inflammation in Inflammatory Bowel Diseases.

BACKGROUND: Inflammatory Bowel Disease (IBD) exhibits no defined aetiology. However, factors such as genetic and nitro-oxidative stress are associated with chronic inflammation and IBD progression to Colorectal Cancer (CRC). The present review discusses the association of nitro-oxidative stress, inflammation and Advanced Glycation End products (AGE) and their corresponding receptor (RAGE) in IBD and examines the connection between these factors and nuclear factors, such as Nuclear Factor Kappa B (NF-κB), factorerythroid 2-related factor-2 (Nrf2), and p53 Mutant (p53M). METHODS: We searched the PubMed, ScienceDirect and Web of Science databases using a combination of the following terms: IBD, CRC, oxidative stress, inflammation, NF-κB, Nrf2, p53M, AGE and RAGE. RESULTS: Oxidative stress and inflammation activated two cellular pathways, the nuclear expression of pro-inflammatory, pro-oxidant and pro-oncogenic genes based on NF-κB and p53M, which is associated with NF-κB activation, Deoxyribonucleic acid (DNA) damage and the expression of pro-oncogenic genes. Nrf2 stimulates the nuclear expression of enzymatic and non-enzymatic antioxidant systems and anti-inflammatory genes, and is inhibited by chronic oxidative stress, NF-κB and p53M. AGE/RAGE are involved in inflammation progression because RAGE polymorphisms and increased RAGE levels are found in IBD patients. Alterations of these pathways in combination with oxidative damage are responsible for IBD symptoms and the progression to CRC. CONCLUSION: IBD is an inflammatory and nitro-oxidative stress-based bowel disease. Achieving a molecular understanding of the biochemical events and their complicated interactions will impact basic and applied research, animal models, and clinical trials.

Cross-Talk between Oxidative Stress and Inflammation in Preeclampsia.

The occurrence of hypertensive syndromes during pregnancy leads to high rates of maternal-fetal morbidity and mortality. Amongst them, preeclampsia (PE) is one of the most common. This review aims to describe the relationship between oxidative stress and inflammation in PE, aiming to reinforce its importance in the context of the disease and to discuss perspectives on clinical and nutritional treatment, in this line of research. Despite the still incomplete understanding of the pathophysiology of PE, it is well accepted that there are placental changes in pregnancy, associated with an imbalance between the production of reactive oxygen species and the antioxidant defence system, characterizing the placental oxidative stress that leads to an increase in the production of proinflammatory cytokines. Hence, a generalized inflammatory process occurs, besides the presence of progressive vascular endothelial damage, leading to the dysfunction of the placenta. There is no consensus in the literature on the best strategies for prevention and treatment of the disease, especially for the control of oxidative stress and inflammation. In view of the above, it is evident the important connection between oxidative stress and inflammatory process in the pathogenesis of PE, being that this disease is capable of causing serious implications on both maternal and fetal health. Reports on the use of anti-inflammatory and antioxidant compounds are analysed and still considered controversial. As such, the field is open for new basic and clinical research, aiming the development of innovative therapeutic approaches to prevent and to treat PE.

Oxidative Stress in Rheumatoid Arthritis: What the Future Might Hold regarding Novel Biomarkers and Add-On Therapies.

Numerous rheumatologic autoimmune diseases, among which rheumatoid arthritis, are chronic inflammatory diseases capable of inducing multiple cumulative articular and extra-articular damage, if not properly treated. Nevertheless, benign conditions may, similarly, exhibit arthritis as their major clinical finding, but with short-term duration instead, and evolve to spontaneous resolution in a few days to weeks, without permanent articular damage. Such distinction-self-limited arthritis with no need of immunosuppressive treatment or chronic arthritis at early stages?-represents one of the greatest challenges in clinical practice, once many metabolic, endocrine, neoplastic, granulomatous, infectious diseases and other autoimmune conditions may mimic rheumatoid arthritis. Indeed, the diagnosis of rheumatoid arthritis at early stages is a crucial step to a more effective mitigation of the disease-related damage. As a prototype of chronic inflammatory autoimmune disease, rheumatoid arthritis has been linked to oxidative stress, a condition in which the pool of reactive oxygen species increases over time, either by their augmented production, the reduction in antioxidant defenses, or the combination of both, ultimately implying compromise in the redox signaling. The exact mechanisms through which oxidative stress may contribute to the initiation and perpetuation of local (in the articular milieu) and systemic inflammation in rheumatoid arthritis, particularly at early stages, still remain to be determined. Furthermore, the role of antioxidants as therapeutic adjuvants in the control of disease activity seems to be overlooked, as a little number of short studies addressing this issue is currently found. Thus, the present review focuses on the binomial rheumatoid arthritis-oxidative stress, bringing insights into their pathophysiological relationships, as well as the implications of potential diagnostic oxidative stress biomarkers and therapeutic interventions directed to the oxidative status in patients with rheumatoid arthritis.

Polyphenol profile by UHPLC-MS/MS, anti-glycation, antioxidant and cytotoxic activities of several samples of propolis from the northeastern semi-arid region of Brazil.

CONTEXT: Propolis has promising biological activities. Propolis samples from the Northeast of Bahia, Brazil - sample A from Ribeira do Pombal and B, from Tucano - were investigated, with new information regarding their biological activities. OBJECTIVE: This paper describes the chemical profile, antioxidant, anti-glycation and cytotoxic activities of these propolis samples. MATERIAL AND METHODS: Ethanol extracts of these propolis samples (EEP) and their fractions were analyzed to determine total phenolic content (TPC); antioxidant capacity through DPPH•, FRAP and lipid peroxidation; anti-glycation activity, by an in vitro glucose (10 mg/mL) bovine serum albumine (1 mg/mL) assay, during 7 d; cytotoxic activity on cancer (SF295, HCT-116, OVCAR-8, MDA-MB435, MX-1, MCF7, HL60, JURKAT, MOLT-4, K562, PC3, DU145) and normal cell lines (V79) at 0.04-25 µg/mL concentrations, for 72 h. The determination of primary phenols by ultra high-pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) and volatile organic compounds content by gas chromatography-mass spectrometry (GC-MS) were also performed. RESULTS: The EEP polar fractions exhibited up to 90% protection against lipid peroxidation. The IC50 value for anti-glycation activity of EEP was between 16.5 and 19.2 µg/mL, close to aminoguanidine (IC50 = 7.7 µg/mL). The use of UHPLC-MS/MS and GC-MS allowed the identification of 12 bioactive phenols in the EEP and 24 volatile compounds, all already reported. CONCLUSIONS: The samples present good antioxidant/anti-glycation/cytotoxic activities and a plethora of biologically active compounds. These results suggest a potential role of propolis in targeting ageing and diseases associated with oxidative and carbonylic stress, aggregating value to them.

Colonic and Hepatic Modulation by Lipoic Acid and/or N-Acetylcysteine Supplementation in Mild Ulcerative Colitis Induced by Dextran Sodium Sulfate in Rats.

Lipoic acid (LA) and N-acetylcysteine (NAC) are antioxidant and anti-inflammatory agents that have not yet been tested on mild ulcerative colitis (UC). This study aims to evaluate the action of LA and/or NAC, on oxidative stress and inflammation markers in colonic and hepatic rat tissues with mild UC, induced by dextran sodium sulfate (DSS) (2% w/v). LA and/or NAC (100 mg·kg·day-1, each) were given, once a day, in the diet, in a pretreatment phase (7 days) and during UC induction (5 days). Colitis induction was confirmed by histological and biochemical analyses (high performance liquid chromatography, spectrophotometry, and Multiplex®). A redox imbalance occurred before an immunological disruption in the colon. NAC led to a decrease in hydrogen peroxide (H2O2), malondialdehyde (MDA) levels, and myeloperoxidase activity. In the liver, DSS did not cause damage but treatments with both antioxidants were potentially harmful, with LA increasing MDA and LA + NAC increasing H2O2, tumor necrosis factor alpha, interferon gamma, and transaminases. In summary, NAC exhibited the highest colonic antioxidant and anti-inflammatory activity, while LA + NAC caused hepatic damage.