Research

18 pages, 4642 KiB

Open AccessArticle

Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study

by Ali Khattib, Sanaa Musa, Majdi Halabi, Tony Hayek and Soliman Khatib

Antioxidants 2022, 11(10), 2058; https://doi.org/10.3390/antiox11102058 - 19 Oct 2022

Cited by 2 | Viewed by 1793

Abstract

Paraoxonase 1 (PON1) plays a role in regulating reverse cholesterol transport and has antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities. Scientists are currently focused on the modulation of PON1 expression using different pharmacological, nutritional, and lifestyle approaches. We previously isolated a novel active [...] Read more.

Paraoxonase 1 (PON1) plays a role in regulating reverse cholesterol transport and has antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities. Scientists are currently focused on the modulation of PON1 expression using different pharmacological, nutritional, and lifestyle approaches. We previously isolated a novel active compound from Nannochloropsis microalgae—lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS)—which increased PON1 activity, HDL-cholesterol efflux, and endothelial nitric oxide release. Here, to explore this important lipid moiety’s effect on PON1 activities, we examined the effect of synthesized lipid derivatives and endogenous analogs of lyso-DGTS on PON1 lactonase and arylesterase activities and LDL oxidation using structure–activity relationship (SAR) methods. Six lipids significantly elevated recombinant PON1 (rePON1) lactonase activity in a dose-dependent manner, and four lipids significantly increased rePON1 arylesterase activity. Using tryptophan fluorescence-quenching assay and a molecular docking method, lipid–PON1 interactions were characterized. An inverse correlation was obtained between the lactonase activity of PON1 and the docking energy of the lipid–PON1 complex. Furthermore, five of the lipids increased the LDL oxidation lag time and inhibited its propagation. Our findings suggest a beneficial effect of lyso-DGTS or lyso-DGTS derivatives through increased PON1 activity and prevention of LDL oxidation. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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9 pages, 631 KiB

Open AccessCommunication

Significance of Serum Oxidative and Antioxidative Status in Congenital Central Hypoventilation Syndrome (CCHS) Patients

by Elisabetta Bigagli, Maura Lodovici, Marzia Vasarri, Marta Peruzzi, Niccolò Nassi and Donatella Degl’Innocenti

Antioxidants 2022, 11(8), 1497; https://doi.org/10.3390/antiox11081497 - 30 Jul 2022

Cited by 1 | Viewed by 1240

Abstract

Congenital central hypoventilation syndrome (CCHS) is a rare neurological genetic disorder that affects sleep-related respiratory control. Currently, no drug therapy is available. In light of this, there is a need for lifelong ventilation support, at least during sleep, for these patients. The pathogenesis [...] Read more.

Congenital central hypoventilation syndrome (CCHS) is a rare neurological genetic disorder that affects sleep-related respiratory control. Currently, no drug therapy is available. In light of this, there is a need for lifelong ventilation support, at least during sleep, for these patients. The pathogenesis of several chronic diseases is influenced by oxidative stress. Thus, determining oxidative stress in CCHS may indicate further disorders in the course of this rare genetic disease. Liquid biopsies are widely used to assess circulating biomarkers of oxidative stress. In this study, ferric reducing ability of plasma, thiobarbituric acid-reactive substances, advanced oxidation protein products (AOPPs), and advanced glycation end-products were measured in the serum of CCHS patients to investigate the relationship between oxidative stress and CCHS and the significance of this balance in CCHS. Here, AOPPs were found to be the most relevant serum biomarker to monitor oxidative stress in CCHS patients. According to this communication, CCHS patients may suffer from other chronic pathophysiological processes because of the persistent levels of AOPPs. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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19 pages, 3619 KiB

Open AccessArticle

Unraveling the Effects of Carotenoids Accumulation in Human Papillary Thyroid Carcinoma

by Alessandra di Masi, Rosario Luigi Sessa, Ylenia Cerrato, Gianni Pastore, Barbara Guantario, Roberto Ambra, Michael Di Gioacchino, Armida Sodo, Martina Verri, Pierfilippo Crucitti, Filippo Longo, Anda Mihaela Naciu, Andrea Palermo, Chiara Taffon, Filippo Acconcia, Fabrizio Bianchi, Paolo Ascenzi, Maria Antonietta Ricci and Anna Crescenzi

Antioxidants 2022, 11(8), 1463; https://doi.org/10.3390/antiox11081463 - 27 Jul 2022

Cited by 4 | Viewed by 1841

Abstract

Among the thyroid cancers, papillary thyroid cancer (PTC) accounts for 90% of the cases. In addition to the necessity to identify new targets for PTC treatment, early diagnosis and management are highly demanded. Previous data indicated that the multivariate statistical analysis of the [...] Read more.

Among the thyroid cancers, papillary thyroid cancer (PTC) accounts for 90% of the cases. In addition to the necessity to identify new targets for PTC treatment, early diagnosis and management are highly demanded. Previous data indicated that the multivariate statistical analysis of the Raman spectra allows the discrimination of healthy tissues from PTC ones; this is characterized by bands typical of carotenoids. Here, we dissected the molecular effects of carotenoid accumulation in PTC patients by analyzing whether they were required to provide increased retinoic acid (RA) synthesis and signaling and/or to sustain antioxidant functions. HPLC analysis revealed the lack of a significant difference in the overall content of carotenoids. For this reason, we wondered whether the carotenoid accumulation in PTC patients could be related to vitamin A derivative retinoic acid (RA) biosynthesis and, consequently, the RA-related pathway activation. The transcriptomic analysis performed using a dedicated PCR array revealed a significant downregulation of RA-related pathways in PTCs, suggesting that the carotenoid accumulation in PTC could be related to a lower metabolic conversion into RA compared to that of healthy tissues. In addition, the gene expression profile of 474 PTC cases previously published in the framework of the Cancer Genome Atlas (TGCA) project was examined by hierarchical clustering and heatmap analyses. This metanalysis study indicated that the RA-related pathways resulted in being significantly downregulated in PTCs and being associated with the follicular variant of PTC (FV-PTC). To assess whether the possible fate of the carotenoids accumulated in PTCs is associated with the oxidative stress response, the expression of enzymes involved in ROS scavenging was checked. An increased oxidative stress status and a reduced antioxidant defense response were observed in PTCs compared to matched healthy thyroids; this was possibly associated with the prooxidant effects of high levels of carotenoids. Finally, the DepMap datasets were used to profile the levels of 225 metabolites in 12 thyroid cancer cell lines. The results obtained suggested that the high carotenoid content in PTCs correlates with tryptophan metabolism. This pilot provided novel possible markers and possible therapeutic targets for PTC diagnosis and therapy. For the future, a larger study including a higher number of PTC patients will be necessary to further validate the molecular data reported here. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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13 pages, 2539 KiB

Open AccessArticle

Platinum Nanoparticles: The Potential Antioxidant in the Human Lung Cancer Cells

by Noor Akmal Shareela Ismail, Jun Xin Lee and Fatimah Yusof

Antioxidants 2022, 11(5), 986; https://doi.org/10.3390/antiox11050986 - 18 May 2022

Cited by 12 | Viewed by 2674

Abstract

Oxidative stress-related conditions associated with lung cells, specifically lung cancer, often lead to a poor prognosis. We hypothesized that platinum nanoparticles (PtNPs) can play a role in reversing oxidative stress in human lung adenocarcinoma A549 epithelial lung cell lines. Hydrogen peroxide (H₂ [...] Read more.

Oxidative stress-related conditions associated with lung cells, specifically lung cancer, often lead to a poor prognosis. We hypothesized that platinum nanoparticles (PtNPs) can play a role in reversing oxidative stress in human lung adenocarcinoma A549 epithelial lung cell lines. Hydrogen peroxide (H₂O₂) was used to induce oxidative stress in cells, and the ability of PtNPs to lower the oxidative stress in the H₂O₂ treated epithelial lung cell line was determined. The differential capacity of PtNPs to remove H₂O₂ was studied through cell viability, nanoparticle uptake, DNA damage, ROS production, and antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase). Results indicated that a higher concentration of PtNPs exhibited a higher antioxidant capacity and was able to reduce DNA damage and quench ROS production in the presence of 350 µM H₂O₂. All antioxidant enzymes’ activities also increased in the PtNPs treatment. Our data suggested that PtNPs could be a promising antioxidant in the treatment of lung cancer. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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12 pages, 863 KiB

Open AccessArticle

Human Milk Antioxidative Modifications in Mastitis: Further Beneficial Effects of Cranberry Supplementation

by Victoria Valls-Bellés, Cristina Abad, María Teresa Hernández-Aguilar, Amalia Nacher, Carlos Guerrero, Pablo Baliño, Francisco J. Romero and María Muriach

Antioxidants 2022, 11(1), 51; https://doi.org/10.3390/antiox11010051 - 27 Dec 2021

Cited by 3 | Viewed by 2654

Abstract

Mastitis is the inflammation of one or several mammal lobes which can be accompanied by a mammary gland infection, and is the leading cause of undesired early weaning in humans. However, little information exists regarding the changes that this disease may induce in [...] Read more.

Mastitis is the inflammation of one or several mammal lobes which can be accompanied by a mammary gland infection, and is the leading cause of undesired early weaning in humans. However, little information exists regarding the changes that this disease may induce in the biochemical composition of human milk, especially in terms of oxidative status. Given that newborns are subject to a significant increase in total ROS burden in their transition to neonatal life and that their antioxidant defense system is not completely developed, the aim of this study was to evaluate antioxidant defense (glutathione peroxidase (GPx), reduced glutathione (GSH), total polyphenol content (TPP), and total antioxidant capacity (TAC)) in milk samples from mothers suffering from mastitis and controls. We also measured the oxidative damage to lipids (malondyaldehyde (MDA)) and proteins (carbonyl group content (CGC)) in these samples. Finally, we tested whether dietary supplementation with cranberries (a product rich in antioxidants) in these breastfeeding mothers during 21 days could improve the oxidative status of milk. GPx activity, TPP, and TAC were increased in milk samples from mastitis-affected women, providing a protective mechanism to the newborn drinking mastitis milk. MDA concentrations were diminished in the mastitis group, confirming this proposal. Some oxidative damage might occur in the mammary gland since the CGC was increased in mastitis milk. Cranberries supplementation seems to strengthen the antioxidant system, further improving the antioxidative state of milk. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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16 pages, 3332 KiB

Open AccessArticle

The Protective Effect of Carotenoids, Polyphenols, and Estradiol on Dermal Fibroblasts under Oxidative Stress

by Aya Darawsha, Aviram Trachtenberg, Joseph Levy and Yoav Sharoni

Antioxidants 2021, 10(12), 2023; https://doi.org/10.3390/antiox10122023 - 20 Dec 2021

Cited by 13 | Viewed by 4990

Abstract

Skin ageing is influenced by several factors including environmental exposure and hormonal changes. Reactive oxygen species (ROS), which mediate many of the effects of these factors, induce inflammatory processes in the skin and increase the production of matrix metalloproteinases (MMPs) in dermal fibroblasts, [...] Read more.

Skin ageing is influenced by several factors including environmental exposure and hormonal changes. Reactive oxygen species (ROS), which mediate many of the effects of these factors, induce inflammatory processes in the skin and increase the production of matrix metalloproteinases (MMPs) in dermal fibroblasts, which leads to collagen degradation. Several studies have shown the protective role of estrogens and a diet rich in fruits and vegetables on skin physiology. Previous studies have shown that dietary carotenoids and polyphenols activate the cell’s antioxidant defense system by increasing antioxidant response element/Nrf2 (ARE/Nrf2) transcriptional activity and reducing the inflammatory response. The aim of the current study was to examine the protective effect of such dietary-derived compounds and estradiol on dermal fibroblasts under oxidative stress induced by H₂O₂. Human dermal fibroblasts were used to study the effect of H₂O₂ on cell number and apoptosis, MMP-1, and pro-collagen secretion as markers of skin damage. Treatment of cells with H₂O₂ led to cell death, increased secretion of MMP-1, and decreased pro-collagen secretion. Pre-treatment with tomato and rosemary extracts, and with estradiol, reversed the effects of the oxidative stress. This was associated with a reduction in intracellular ROS levels, probably through the measured increased activity of ARE/Nrf2. Conclusions: This study indicates that carotenoids, polyphenols, and estradiol protect dermal fibroblasts from oxidative stress-induced damage through a reduction in ROS levels. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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16 pages, 2591 KiB

Open AccessArticle

Aminoguanidine Prevents the Oxidative Stress, Inhibiting Elements of Inflammation, Endothelial Activation, Mesenchymal Markers, and Confers a Renoprotective Effect in Renal Ischemia and Reperfusion Injury

by Consuelo Pasten, Mauricio Lozano, Jocelyn Rocco, Flavio Carrión, Cristobal Alvarado, Jéssica Liberona, Luis Michea and Carlos E. Irarrázabal

Antioxidants 2021, 10(11), 1724; https://doi.org/10.3390/antiox10111724 - 28 Oct 2021

Cited by 10 | Viewed by 2502

Abstract

Oxidative stress produces macromolecules dysfunction and cellular damage. Renal ischemia-reperfusion injury (IRI) induces oxidative stress, inflammation, epithelium and endothelium damage, and cessation of renal function. The IRI is an inevitable process during kidney transplantation. Preliminary studies suggest that aminoguanidine (AG) is an antioxidant [...] Read more.

Oxidative stress produces macromolecules dysfunction and cellular damage. Renal ischemia-reperfusion injury (IRI) induces oxidative stress, inflammation, epithelium and endothelium damage, and cessation of renal function. The IRI is an inevitable process during kidney transplantation. Preliminary studies suggest that aminoguanidine (AG) is an antioxidant compound. In this study, we investigated the antioxidant effects of AG (50 mg/kg, intraperitoneal) and its association with molecular pathways activated by IRI (30 min/48 h) in the kidney. The antioxidant effect of AG was studied measuring GSSH/GSSG ratio, GST activity, lipoperoxidation, iNOS, and Hsp27 levels. In addition, we examined the effect of AG on elements associated with cell survival, inflammation, endothelium, and mesenchymal transition during IRI. AG prevented lipid peroxidation, increased GSH levels, and recovered the GST activity impaired by IRI. AG was associated with inhibition of iNOS, Hsp27, endothelial activation (VE-cadherin, PECAM), mesenchymal markers (vimentin, fascin, and HSP47), and inflammation (IL-1β, IL-6, Foxp3, and IL-10) upregulation. In addition, AG reduced kidney injury (NGAL, clusterin, Arg-2, and TFG-β1) and improved kidney function (glomerular filtration rate) during IRI. In conclusion, we found new evidence of the antioxidant properties of AG as a renoprotective compound during IRI. Therefore, AG is a promising compound to treat the deleterious effect of renal IRI. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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17 pages, 23130 KiB

Open AccessArticle

Biochemical Evaluation of the Effects of Hydroxyurea in Vitro on Red Blood Cells

by Cristiane Oliveira Renó, Grazielle Aparecida Silva Maia, Leilismara Sousa Nogueira, Melina de Barros Pinheiro, Danyelle Romana Alves Rios, Vanessa Faria Cortes, Leandro Augusto de Oliveira Barbosa and Hérica de Lima Santos

Antioxidants 2021, 10(10), 1599; https://doi.org/10.3390/antiox10101599 - 12 Oct 2021

Cited by 1 | Viewed by 1904

Abstract

Hydroxyurea (HU) is a low-cost, low-toxicity drug that is often used in diseases, such as sickle cell anemia and different types of cancer. Its effects on the red blood cells (RBC) are still not fully understood. The in vitro effects of HU were [...] Read more.

Hydroxyurea (HU) is a low-cost, low-toxicity drug that is often used in diseases, such as sickle cell anemia and different types of cancer. Its effects on the red blood cells (RBC) are still not fully understood. The in vitro effects of HU were evaluated on the biochemical parameters of the RBC from healthy individuals that were treated with 0.6 mM or 0.8 mM HU for 30 min and 1 h. After 30 min, there was a significant increase in almost all of the parameters analyzed in the two concentrations of HU, except for the pyruvate kinase (PK) activity. A treatment with 0.8 mM HU for 1 h resulted in a reduction of the levels of lipid peroxidation, Fe³⁺, and in the activities of some of the enzymes, such as glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), and PK. After the incubation for 1 h, the levels of H₂O₂, lipid peroxidation, reduced glutathione (GSH), enzymatic activity (hexokinase, G6PD, and superoxide dismutase (SOD) were reduced with the treatment of 0.8 mM HU when compared with 0.6 mM. The results have suggested that a treatment with HU at a concentration of 0.8 mM seemed to be more efficient in protecting against the free radicals, as well as in treating diseases, such as sickle cell anemia. HU appears to preferentially stimulate the pentose pathway over the glycolytic pathway. Although this study was carried out with the RBC from healthy individuals, the changes described in this study may help to elucidate the mechanisms of action of HU when administered for therapeutic purposes. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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10 pages, 1551 KiB

Open AccessArticle

Salivary Oxidative Stress Markers’ Relation to Oral Diseases in Children and Adolescents

by Bahareh Nazemi Salman, Shayan Darvish, Ancuta Goriuc, Saeideh Mazloomzadeh, Maryam Hossein Poor Tehrani and Ionut Luchian

Antioxidants 2021, 10(10), 1540; https://doi.org/10.3390/antiox10101540 - 28 Sep 2021

Cited by 10 | Viewed by 2724

Abstract

Current evidence suggests that salivary markers of oxidative stress are indicative of clinical disease indices such as the papillary bleeding index (PBI) and the caries index (CI). The aim of this study was to assess the relation of oxidative stress markers with oral [...] Read more.

Current evidence suggests that salivary markers of oxidative stress are indicative of clinical disease indices such as the papillary bleeding index (PBI) and the caries index (CI). The aim of this study was to assess the relation of oxidative stress markers with oral dental caries and periodontal problems in a pediatric population. In our case-control study, unstimulated whole saliva was collected from individuals aged 3–18 years (n = 177); 14 individuals were excluded. Study subjects were divided into those with caries (CI = 2, n = 78) and those who were caries-free (n = 85). These groups were then divided into another subset consisting of children (mean age 7.3 years, n = 121) and adolescents (mean age 16.1 years, n = 42). The PBI was determined in all groups. We then assessed salivary levels of oxidative stress markers. Our results showed that, the total antioxidant capacity (TAC) level increased in patients with more gingival bleeding (p < 0.05) in the study group aged 3–18 years. In addition, TAC showed a significant decrease in samples with caries when compared to the caries-free group in adolescents (p = 0.008). In conclusion, TAC levels may be a marker of both gingival bleeding and dental caries in young adult populations. We hope that in the near future, prophylaxis, control, follow up and even possible therapeutic use of oxidative stress markers in a chairside way will become possible as antioxidants have been shown to be effective against oral diseases. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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14 pages, 3952 KiB

Open AccessArticle

Verbascoside Protects Gingival Cells against High Glucose-Induced Oxidative Stress via PKC/HMGB1/RAGE/NFκB Pathway

by Pei-Fang Hsieh, Cheng-Chia Yu, Pei-Ming Chu and Pei-Ling Hsieh

Antioxidants 2021, 10(9), 1445; https://doi.org/10.3390/antiox10091445 - 12 Sep 2021

Cited by 8 | Viewed by 2710

Abstract

Impaired wound healing often occurs in patients with diabetes and causes great inconvenience to them. Aside from the presence of prolonged inflammation, the accumulation of oxidative stress is also implicated in the delayed wound healing. In the present study, we tested the effect [...] Read more.

Impaired wound healing often occurs in patients with diabetes and causes great inconvenience to them. Aside from the presence of prolonged inflammation, the accumulation of oxidative stress is also implicated in the delayed wound healing. In the present study, we tested the effect of verbascoside, a caffeoyl phenylethanoid glycoside, on the improvement of cell viability and wound healing capacity of gingival epithelial cells under high glucose condition. We showed that verbascoside attenuated the high glucose-induced cytotoxicity and impaired healing, which may be associated with the downregulation of oxidative stress. Our results demonstrated that verbascoside increased the activity of the antioxidant enzyme SOD and reduced the oxidative stress indicator, 8-OHdG, as well as apoptosis. Moreover, verbascoside upregulated the PGC1-α and NRF1 expression and promoted mitochondrial biogenesis, which was mediated by suppression of PKC/HMGB1/RAGE/NFκB signaling. Likewise, we showed the inhibitory effect of verbascoside on oxidative stress was via repression of PKC/HMGB1/RAGE/NFκB activation. Also, our data suggested that the PKC-mediated oxidative stress may lead to the elevated production of inflammatory cytokines, IL-6 and IL-1β. Collectively, we demonstrated that verbascoside may be beneficial to ameliorate impaired oral wound healing for diabetic patients. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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11 pages, 1483 KiB

Open AccessArticle

Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting

by Aranzazu Santiago-Hernandez, Paula J. Martinez, Marta Agudiez, Angeles Heredero, Laura Gonzalez-Calero, Alma Yuste-Montalvo, Vanesa Esteban, Gonzalo Aldamiz-Echevarria, Marta Martin-Lorenzo and Gloria Alvarez-Llamas

Antioxidants 2021, 10(9), 1369; https://doi.org/10.3390/antiox10091369 - 27 Aug 2021

Cited by 1 | Viewed by 2077

Abstract

Atherosclerosis is the predominant pathology associated to premature deaths due to cardiovascular disease. However, early intervention based on a personalized diagnosis of cardiovascular risk is very limited. We have previously identified metabolic alterations during atherosclerosis development in a rabbit model and in subjects [...] Read more.

Atherosclerosis is the predominant pathology associated to premature deaths due to cardiovascular disease. However, early intervention based on a personalized diagnosis of cardiovascular risk is very limited. We have previously identified metabolic alterations during atherosclerosis development in a rabbit model and in subjects suffering from an acute coronary syndrome. Here we aim to identify specific metabolic signatures which may set the basis for novel tools aiding cardiovascular risk diagnosis in clinical practice. In a cohort of subjects with programmed coronary artery bypass grafting (CABG), we have performed liquid chromatography and targeted mass spectrometry analysis in urine and plasma. The role of vascular smooth muscle cells from human aorta (HA-VSMCs) was also investigated by analyzing the intra and extracellular metabolites in response to a pro-atherosclerotic stimulus. Statistically significant variation was considered if p value < 0.05 (Mann-Whitney test). Urinary trimethylamine N-oxide (TMAO), arabitol and spermidine showed higher levels in the CVrisk group compared with a control group; while glutamine and pantothenate showed lower levels. The same trend was found for plasma TMAO and glutamine. Plasma choline, acetylcholine and valine were also decreased in CVrisk group, while pyruvate was found increased. In the secretome of HA-VSMCs, TMAO, pantothenate, glycerophosphocholine, glutathion, spermidine and acetylcholine increased after pro-atherosclerotic stimulus, while secreted glutamine decreased. At intracellular level, TMAO, pantothenate and glycerophosphocholine increased with stimulation. Observed metabolic deregulations pointed to an inflammatory response together with a deregulation of oxidative stress counteraction. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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12 pages, 2874 KiB

Open AccessCommunication

Antioxidant-Based Therapy Reduces Early-Stage Intestinal Ischemia-Reperfusion Injury in Rats

by Gaizka Gutiérrez-Sánchez, Ignacio García-Alonso, Jorge Gutiérrez Sáenz de Santa María, Ana Alonso-Varona and Borja Herrero de la Parte

Antioxidants 2021, 10(6), 853; https://doi.org/10.3390/antiox10060853 - 27 May 2021

Cited by 13 | Viewed by 3127

Abstract

Intestinal ischemia-reperfusion injury (i-IRI) is a rare disorder with a high mortality rate, resulting from the loss of blood flow to an intestinal segment. Most of the damage is triggered by the restoration of flow and the arrival of cytokines and reactive oxygen [...] Read more.

Intestinal ischemia-reperfusion injury (i-IRI) is a rare disorder with a high mortality rate, resulting from the loss of blood flow to an intestinal segment. Most of the damage is triggered by the restoration of flow and the arrival of cytokines and reactive oxygen species (ROS), among others. Inactivation of these molecules before tissue reperfusion could reduce intestinal damage. The aim of this work was to analyze the preventive effect of allopurinol and nitroindazole on intestinal mucosal damage after i-IRI. Wag/RijHsd rats were subjected to i-IRI by clamping the superior mesenteric artery (for 1 or 2 h) followed by a 30 min period of reperfusion. Histopathological intestinal damage (HID) was assessed by microscopic examination of histological sections obtained from injured intestine. HID was increased by almost 20% by doubling the ischemia time (from 1 to 2 h). Nitroindazole reduced HID in both the 1 and 2 h period of ischemia by approximately 30% and 60%, respectively (p < 0.001). Our preliminary results demonstrate that nitroindazole has a preventive/protective effect against tissue damage in the early stages of i-IRI. However, to better understand the molecular mechanisms underlying this phenomenon, further studies are needed. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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17 pages, 4865 KiB

Open AccessArticle

Antioxidant Ascorbic Acid Modulates NLRP3 Inflammasome in LPS-G Treated Oral Stem Cells through NFκB/Caspase-1/IL-1β Pathway

by Jacopo Pizzicannella, Luigia Fonticoli, Simone Guarnieri, Guya D. Marconi, Thangavelu Soundara Rajan, Oriana Trubiani and Francesca Diomede

Antioxidants 2021, 10(5), 797; https://doi.org/10.3390/antiox10050797 - 18 May 2021

Cited by 18 | Viewed by 2923

Abstract

Human gingival mesenchymal stem cells (hGMSCs) and endothelial committed hGMSCs (e-hGMSCs) have considerable potential to serve as an in vitro model to replicate the inflammation sustained by Porphyromonas gingivalis in periodontal and cardiovascular diseases. The present study aimed to investigate the effect of [...] Read more.

Human gingival mesenchymal stem cells (hGMSCs) and endothelial committed hGMSCs (e-hGMSCs) have considerable potential to serve as an in vitro model to replicate the inflammation sustained by Porphyromonas gingivalis in periodontal and cardiovascular diseases. The present study aimed to investigate the effect of ascorbic acid (AA) on the inflammatory reverting action of lipopolysaccharide (LPS-G) on the cell metabolic activity, inflammation pathway and reactive oxygen species (ROS) generation in hGMSCs and e-hGMSCs. Cells were treated with LPS-G (5 μg mL⁻¹) or AA (50 μg mL⁻¹) and analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay, immunofluorescence and Western blot methods. The rate of cell metabolic activity was decreased significantly in LPS-G-treated groups, while groups co-treated with LPS-G and AA showed a logarithmic cell metabolic activity rate similar to untreated cells. AA treatment attenuated the inflammatory effect of LPS-G by reducing the expression of TLR4/MyD88/NFκB/NLRP3/Caspase-1/IL-1β, as demonstrated by Western blot analysis and immunofluorescence acquisition. LPS-G-induced cells displayed an increase in ROS production, while AA co-treated cells showed a protective effect. In summary, our work suggests that AA attenuated LPS-G-mediated inflammation and ROS generation in hGMSCs and e-hGMSCs via suppressing the NFκB/Caspase-1/IL-1β pathway. These findings indicate that AA may be considered as a potential factor involved in the modulation of the inflammatory pathway triggered by LPS-G in an vitro cellular model. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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Review

Jump to: Research, Other

17 pages, 358 KiB

Open AccessReview

Risk Assessment of Oxidative Stress Induced by Metal Ions Released from Fixed Orthodontic Appliances during Treatment and Indications for Supportive Antioxidant Therapy: A Narrative Review

by Jasmina Primožič, Borut Poljšak, Polona Jamnik, Vito Kovač, Gordana Čanadi Jurešić and Stjepan Spalj

Antioxidants 2021, 10(9), 1359; https://doi.org/10.3390/antiox10091359 - 26 Aug 2021

Cited by 9 | Viewed by 3148

Abstract

The treatment with fixed orthodontic appliances could have an important role in the induction of oxidative stress and associated negative consequences. Because of the simultaneous effects of corrosion, deformation, friction, and mechanical stress on fixed orthodontic appliances during treatment, degradation of orthodontic brackets [...] Read more.

The treatment with fixed orthodontic appliances could have an important role in the induction of oxidative stress and associated negative consequences. Because of the simultaneous effects of corrosion, deformation, friction, and mechanical stress on fixed orthodontic appliances during treatment, degradation of orthodontic brackets and archwires occurs, causing higher concentrations of metal ions in the oral cavity. Corroded appliances cause the release of metal ions, which may lead to the increased values of reactive oxygen species (ROS) due to metal-catalyzed free radical reactions. Chromium, iron, nickel, cobalt, titanium, and molybdenum all belong to the group of transition metals that can be subjected to redox reactions to form ROS. The estimation of health risk due to the amount of heavy metals released and the level of selected parameters of oxidative stress generated for the time of treatment with fixed orthodontic appliances is presented. Approaches to avoid oxidative stress and recommendations for the preventive use of topical or systemic antioxidants during orthodontic treatment are discussed. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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15 pages, 863 KiB

Open AccessReview

Flavonoids-Macromolecules Interactions in Human Diseases with Focus on Alzheimer, Atherosclerosis and Cancer

by Dana Atrahimovich, Dorit Avni and Soliman Khatib

Antioxidants 2021, 10(3), 423; https://doi.org/10.3390/antiox10030423 - 10 Mar 2021

Cited by 30 | Viewed by 3649

Abstract

Flavonoids, a class of polyphenols, consumed daily in our diet, are associated with a reduced risk for oxidative stress (OS)-related chronic diseases, such as cardiovascular disease, neurodegenerative diseases, cancer, and inflammation. The involvement of flavonoids with OS-related chronic diseases have been traditionally attributed [...] Read more.

Flavonoids, a class of polyphenols, consumed daily in our diet, are associated with a reduced risk for oxidative stress (OS)-related chronic diseases, such as cardiovascular disease, neurodegenerative diseases, cancer, and inflammation. The involvement of flavonoids with OS-related chronic diseases have been traditionally attributed to their antioxidant activity. However, evidence from recent studies indicate that flavonoids’ beneficial impact may be assigned to their interaction with cellular macromolecules, rather than exerting a direct antioxidant effect. This review provides an overview of the recent evolving research on interactions between the flavonoids and lipoproteins, proteins, chromatin, DNA, and cell-signaling molecules that are involved in the OS-related chronic diseases; it focuses on the mechanisms by which flavonoids attenuate the development of the aforementioned chronic diseases via direct and indirect effects on gene expression and cellular functions. The current review summarizes data from the literature and from our recent research and then compares specific flavonoids’ interactions with their targets, focusing on flavonoid structure–activity relationships. In addition, the various methods of evaluating flavonoid–protein and flavonoid–DNA interactions are presented. Our aim is to shed light on flavonoids action in the body, beyond their well-established, direct antioxidant activity, and to provide insights into the mechanisms by which these small molecules, consumed daily, influence cellular functions. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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Other

Jump to: Research, Review

14 pages, 1578 KiB

Open AccessSystematic Review

Meta-Analysis and Systematic Review of the Association between a Hypoactive NCF1 Variant and Various Autoimmune Diseases

by Liang Zhang, Jacqueline Wax, Renliang Huang, Frank Petersen and Xinhua Yu

Antioxidants 2022, 11(8), 1589; https://doi.org/10.3390/antiox11081589 - 16 Aug 2022

Viewed by 1998

Abstract

Genetic association studies have discovered the GTF2I-NCF1 intergenic region as a strong susceptibility locus for multiple autoimmune disorders, with the missense mutation NCF1 rs201802880 as the causal polymorphism. In this work, we aimed to perform a comprehensive meta-analysis of the association of the [...] Read more.

Genetic association studies have discovered the GTF2I-NCF1 intergenic region as a strong susceptibility locus for multiple autoimmune disorders, with the missense mutation NCF1 rs201802880 as the causal polymorphism. In this work, we aimed to perform a comprehensive meta-analysis of the association of the GTF2I-NCF1 locus with various autoimmune diseases and to provide a systemic review on potential mechanisms underlying the effect of the causal NCF1 risk variants. The frequencies of the two most extensively investigated polymorphisms within the locus, GTF2I rs117026326 and NCF1 rs201802880, vary remarkably across the world, with the highest frequencies in East Asian populations. Meta-analysis showed that the GTF2I-NCF1 locus is significantly associated with primary Sjögren’s syndrome, systemic lupus erythematosus, systemic sclerosis, and neuromyelitis optica spectrum disorder. The causal NCF1 rs201802880 polymorphism leads to an amino acid substitution of p.Arg90His in the p47phox subunit of the phagocyte NADPH oxidase. The autoimmune disease risk His90 variant results in a reduced ROS production in phagocytes. Clinical and experimental evidence shows that the hypoactive His90 variant might contribute to the development of autoimmune disorders via multiple mechanisms, including impairing the clearance of apoptotic cells, regulating the mitochondria ROS-associated formation of neutrophil extracellular traps, promoting the activation and differentiation of autoreactive T cells, and enhancing type I IFN responses. In conclusion, the identification of the association of NCF1 with autoimmune disorders demonstrates that ROS is an essential regulator of immune tolerance and autoimmunity mediated disease manifestations. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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11 pages, 1090 KiB

Open AccessPerspective

The Influence of Oxidative Stress on Thyroid Diseases

by Joanna Kochman, Karolina Jakubczyk, Piotr Bargiel and Katarzyna Janda-Milczarek

Antioxidants 2021, 10(9), 1442; https://doi.org/10.3390/antiox10091442 - 10 Sep 2021

Cited by 45 | Viewed by 7433

Abstract

Thyroid diseases, including neoplasms, autoimmune diseases and thyroid dysfunctions, are becoming a serious social problem with rapidly increasing prevalence. The latter is increasingly linked to oxidative stress. There are many methods for determining the biomarkers of oxidative stress, making it possible to evaluate [...] Read more.

Thyroid diseases, including neoplasms, autoimmune diseases and thyroid dysfunctions, are becoming a serious social problem with rapidly increasing prevalence. The latter is increasingly linked to oxidative stress. There are many methods for determining the biomarkers of oxidative stress, making it possible to evaluate the oxidative profile in patients with thyroid diseases compared to the healthy population. This opens up a new perspective for investigating the role of elevated parameters of oxidative stress and damage in people with thyroid diseases, especially of neoplastic nature. An imbalance between oxidants and antioxidants is observed at different stages and in different types of thyroid diseases. The organ, which is part of the endocrine system, uses free radicals (reactive oxygen species, ROS) to produce hormones. Thyroid cells release enzymes that catalyse ROS generation; therefore, a key role is played by the internal defence system and non-enzymatic antioxidants that counteract excess ROS not utilised to produce thyroid hormones, acting as a buffer to neutralise free radicals and ensure whole-body homeostasis. An excess of free radicals causes structural cell damage, undermining genomic stability. Looking at the negative effects of ROS accumulation, oxidative stress appears to be implicated in both the initiation and progression of carcinogenesis. The aim of this review is to investigate the oxidation background of thyroid diseases and to summarise the links between redox imbalance and thyroid dysfunction and disease. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases)

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