Free Radical Research最新文献

{"title":"Association between lipid peroxidation and risk of type 2 diabetes in women.","authors":"Yingya Zhao, Ginger L Milne, Qingxia Chen, Qi Dai, Xianglan Zhang, Marina S Nogueira, Hui Cai, Qing Lan, Nathaniel Rothman, Qiuyin Cai, Yu-Tang Gao, Xiao-Ou Shu, Wei Zheng, Gong Yang","doi":"10.1080/10715762.2022.2154667","DOIUrl":"10.1080/10715762.2022.2154667","url":null,"abstract":"<p><p><i>In-vitro</i> and animal studies demonstrate that lipid peroxidation plays an important role in the pathogenesis of type 2 diabetes (T2D). However, human data from prospective studies are limited and contradictory. We used data originally collected in two nested case-control studies of cancer to prospectively evaluate whether systemic levels of lipid peroxidation were associated with incidence of T2D in 1917 women who were 40-70 years old and diabetes-free at baseline. Lipid peroxidation was measured by urinary F₂-isoprostanes (F₂-IsoPs) and its major metabolite 2,3-dinor-5,6-dihydro-15-F_2t-IsoP (F₂-IsoP-M) with GC/NICI-MS assays. The Cox regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident T2D. After a median follow-up of 10.1 years, 187 women were diagnosed with T2D. Urinary concentrations of both F₂-IsoPs and F₂-IsoP-M were significantly higher in T2D cases than in non-cases. Both biomarkers were positively associated with subsequent risk of T2D in multivariable-adjusted Cox models. When further adjusted for body mass index (BMI), the positive association with F₂-IsoP-M was attenuated and no longer statistically significant, whereas the association with F₂-IsoPs remained (<i>P</i> for overall significance < 0.001). HR for T2D was 1.68 (95% CI: 1.13, 2.51) for the highest vs the lowest quartile of F₂-IsoPs. Moreover, this association appeared more pronounced among women with higher BMI. In summary, our study suggests that F₂-IsoPs could be of significance in T2D risk prediction among middle-aged and elderly women.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10243607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of ebselen on bleomycin-induced lung fibrosis: analysis of the molecular mechanism of lung fibrosis mediated by oxidized diacylglycerol.","authors":"Hidehiko Yagasaki,&nbsp;Susumu Takekoshi,&nbsp;Kanae Kitatani,&nbsp;Chikara Kato,&nbsp;Hiroyuki Yamasaki,&nbsp;Kie Shioyama,&nbsp;Takaaki Tsuboi,&nbsp;Tomohiko Matsuzaki,&nbsp;Yutaka Inagaki,&nbsp;Ryota Masuda,&nbsp;Masayuki Iwazaki","doi":"10.1080/10715762.2022.2092477","DOIUrl":"https://doi.org/10.1080/10715762.2022.2092477","url":null,"abstract":"<p><p>The molecular mechanisms underlying the development of pulmonary fibrosis remain unknown, and effective treatments have not yet been developed. It has been shown that oxidative stress is involved in lung fibrosis. Oxidized diacylglycerol (DAG) produced by oxidative stress is thought to play an important role in lung fibrosis. This study assessed the effect of oxidized DAG in an animal model of pulmonary fibrosis induced by aspiration of bleomycin (BLM) into the lungs. The inhibitory effect of ebselen on pulmonary fibrosis was also investigated. In lung fibrotic tissue induced by BLM, an increase in lipid peroxides and collagen accumulation was observed. Moreover, the levels of oxidized DAG, which has strong protein kinase C (PKC) activation activity, were significantly increased over time following the administration of BLM. Western blotting showed that phosphorylation of PKCα and δ isoforms was increased by BLM. Oral administration of ebselen significantly suppressed the increase in oxidized DAG induced by BLM and improved lung fibrosis. PKCα and δ phosphorylation were also significantly inhibited. The mRNA expression of α-smooth muscle actin and collagen I (marker molecules for fibrosis), as well as the production of transforming growth factor-β and tumor necrosis factor-α(a potentially important factor in the fibrotic process), were increased by BLM and significantly decreased by ebselen. The administration of BLM may induce lipid peroxidation in lung tissue, while the oxidized DAG produced by BLM may induce overactivation of PKCα and δ, resulting in the induction of lung fibrosis.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10642976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cold atmospheric plasma-induced oxidative stress and ensuing immunological response - a Neo-Vista in immunotherapy.","authors":"Sreedevi P R,&nbsp;Suresh K,&nbsp;Yugeswaran S","doi":"10.1080/10715762.2022.2139691","DOIUrl":"https://doi.org/10.1080/10715762.2022.2139691","url":null,"abstract":"<p><p>Plasma, the fourth state of matter could be artificially generated at room temperature under atmospheric pressure - termed as cold atmospheric plasma (CAP). The reactive oxygen and nitrogen radicals emanated during plasma discharge accord manifold applications in medicine and have proven clinical applications in cancer treatment, dentistry, and dermatology. Developments in the field termed \"Plasma medicine\" has inclined research toward its prospects in immunotherapy. Controlled generation of reactive oxygen and nitrogen radicals during plasma formation produces oxidative stress on tissue of concern, selectively and activates a number of cytological and molecular reactions, triggering immunological response. Plasma treatment induces immunogenic cell death (ICD) in tumor cells and elicits enhanced adaptive and systemic immune response with memory cells, conferring better defense to cancer. HIV inactivation, reduced viral replication, reversal of latency in HIV-infected cells, and augmented infected cell opsonization has been observed with CAP treatment. Plasma-treated medium has shown to deactivate <i>Herpes simplex</i> virus (HSV-1) in human corneal explants and epithelial cells, and lessen the severity of herpes simplex keratitis. Perception of cellular changes that triggers innate and adaptive immune response during CAP treatment is quintessential for understanding and expansion of research in this arena. This review mentions the inimitable properties of plasma that makes it a safe and sensitive immunotherapeutic tool. The methods of plasma generation relied for the purpose are elucidated. The cellular mechanism of immunological stimulation in cancer, HIV, and keratitis during CAP treatment is detailed. The future prospects and challenges are briefly addressed.HighlightsReactive oxygen and nitrogen radicals produced by cold atmospheric plasma (CAP) triggers oxidative stress in exposed cells.Cells in oxidative stress incite immunological response that could be suitably manipulated for immunotherapy.The role of reactive radicals and methods of plasma generation for immunotherapy is elucidated.The cellular and molecular cascade of reactions leading to immunological cell death in cancer cells is detailed.The mechanism of HIV inactivation and reduced infection; further, deactivation of HSV in Herpes keratitis in intact human corneal explants is also described.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10656218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron deficiency aggravates DMNQ-induced cytotoxicity via redox cycling in kidney-derived cells.","authors":"Daisaku Yoshihara,&nbsp;Noriko Fujiwara,&nbsp;Hironobu Eguchi,&nbsp;Haruhiko Sakiyama,&nbsp;Keiichiro Suzuki","doi":"10.1080/10715762.2022.2154668","DOIUrl":"https://doi.org/10.1080/10715762.2022.2154668","url":null,"abstract":"<p><p>Iron, an essential element for most of living organisms, participates in many biological functions. Since iron is redox-active transition metal, it is known that excessive levels stimulate the formation of reactive oxygen species (ROS) and exacerbate cytotoxicity. An iron deficiency is the most common nutritional deficiency disorder in the world (about 30% of the population) and is more common than cases of iron overload. However, the effects of iron deficiency on ROS-induced cytotoxicity and the maintenance of intracellular redox homeostasis are not fully understood. The present study reports on an evaluation of the effects of iron deficiency on cytotoxicity induced by several ROS generators. In contrast to hydrogen peroxide and erastin, the cytotoxicity of 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), a redox cycling agent that induces intracellular superoxide anion formation, was exacerbated by iron deficiency. Cytochrome b₅ reductase was identified as a candidate enzyme responsible for the redox cycling of DMNQ under conditions of iron depletion. Moreover, the DMNQ-induced intracellular accumulation of ROS and a decrease in NADH/NAD⁺ ratios were enhanced by an iron deficiency. These negative changes were found to be ameliorated by overexpressing NAD(P)H:quinone oxidoreductase 1 (NQO1) in kidney-derived cells that originally showed a very low expression of NQO1. These results indicate that NQO1 plays a protective role against redox cycling quinone-mediated cytotoxicity under iron-depleted conditions. This is because NQO1 generates less-toxic hydroquinones via the two-electron reduction of quinones. The collective findings reported herein demonstrate that not only an iron overload but also an iron deficiency exacerbates ROS-mediated cytotoxicity.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10706549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In memoriam: Emeritus Professor Robin L. Willson.","authors":"","doi":"10.1080/10715762.2022.2140273","DOIUrl":"https://doi.org/10.1080/10715762.2022.2140273","url":null,"abstract":"It is with great sadness that we announce the passing of one of the ‘founding fathers’ of the free radical and redox fields, Professor Robin Linhope Willson. He died peacefully at his home in Puerto Madryn, Patagonia, Argentina, where he had lived since retiring from Brunel University. He was 81 and leaves behind a wife Vicky, and two children, Emma and Suzy, from his first marriage to Hester Bowen who died in 1996. In thinking about what highlights to include of the many discoveries associated with Robin Willson, and particularly those of the widest and most-enduring interest to the field of free radical chemistry and biology, the direct observation of the ‘repair’ of radicals formed from the antioxidants, vitamin E and thiols, by ascorbate (vitamin C) immediately springs to mind [1,2]. These observations were reported in a paper with John Packer and Trevor Slater in Nature in 1979 [3] and is Robin’s most cited work ( 2000 citations). However, glancing through the list of Robin’s publications presents a great problem: where to start? This is because Robin led the way in so many different areas, and not just as a scientist, but also as a communicator, educator and inspiration behind the ‘Magic Pennies’ project, which opened the eyes of many children and young adults to the field of magnetism. Robin was born in 1941 in Lytham St Annes, Lancashire, and his scientific career began as a radiation chemist in the mid-1960s in the laboratory of ‘Joe’ Weiss (of Haber-Weiss fame) at the University of Newcastle, UK, after having completed his undergraduate training at King’s College, Durham University. Joe Weiss had, more or less, invented the field of radiation chemistry of biomolecules with his paper in Nature in 1944. With George Scholes, Elie Hayon, Gabriel Stein and Alastair Johnson, the Newcastle group ‘spawned’ a large number of the radiation chemists who went on to have a major international impact in free-radical and radiation biology, including John Ward, Les Redpath and, of course, Robin. The Newcastle group focused on reactions of radicals produced on radiolysis of aqueous solutions of nucleic acids, and Robin’s first papers were in this area; he was awarded his PhD in 1966. After the Cortina International Congress of Radiation Research in 1966, Robin took up a postdoc with Larry Myers at the Laboratory of Nuclear Medicine and Radiation Biology, University of California Los Angeles. While there, he played a major role in developing a nanosecond pulse radiolysis facility at General Atomics, San Diego [4]. He also initiated the use of an early programmable Olivetti calculator for handling the data. After his post-doctoral position in California, Robin was recruited by Ged Adams to strengthen the radiation chemistry group in the Gray Laboratory at Mount Vernon Hospital, Northwood, near London. In 1960, radiation chemistry was revolutionized by the development of kinetic spectrophotometry methods that allowed direct observation and monitoring of ra","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10654230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thermodynamic and kinetic studies on antioxidant capacity of amentoflavone: a DFT (density functional theory) computational approach.","authors":"Phan Thi Thuy,&nbsp;Ninh The Son","doi":"10.1080/10715762.2022.2146584","DOIUrl":"https://doi.org/10.1080/10715762.2022.2146584","url":null,"abstract":"<p><p>Density functional theory (DFT) at the theoretical M06-2X/6-311G(d,p) level was used to assess thermodynamics and kinetics in the antioxidative action of amentoflavone (AF). The antioxidative HAT pathway (H-atom transfer) is assigned to this compound in gas, but the SPL-ET (sequential proton loss-electron transfer) is the main route in polar solvents methanol and water. In all four mediums gas, benzene, methanol, and water, 4‴-OH is the most active site in free radical quenching with the lowest BDE (bond dissociation enthalpy) values of 81.8-84.8 kcal/mol, as well as it exerted the PA (proton affinity) values of 29.8-33.0 kcal/mol in methanol and water. Regarding kinetics, when interacted with ^•OOH and ^•NO₂ in gas and methanol, 4‴-OH group is also responsible for the lowest <i>ΔG</i>^# values (Gibbs free energy of activation), and the highest rate constant <i>K</i> values. Acidic assessment also indicated that 4‴-OH is associated with the strongest acidity (the lowest pK_a). Two favorable oriented 4‴-OH and 7-OH groups further exhibited antioxidative activity since they prevented metal ions Zn²⁺ and Fe²⁺ from participating in free radical producing processes, in which the most stable complex [FeAF(H₂O)₄] generated the lowest IE value of -206.2 kcal/mol, and <i>E</i>_gap value of 3.491 kcal/mol, but the highest MIA values of 184.6 kcal/mol in methanol.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10652039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Lactobacillus brevis</i> MTCC 1750 enhances oxidative stress resistance and lifespan extension with improved physiological and functional capacity in <i>Caenorhabditis elegans</i> via the DAF-16 pathway.","authors":"Sandeep Kumar,&nbsp;Nalla Sai Praneet,&nbsp;Kitlangki Suchiang","doi":"10.1080/10715762.2022.2155518","DOIUrl":"https://doi.org/10.1080/10715762.2022.2155518","url":null,"abstract":"<p><p>Redox imbalance plays a crucial role in the development of age-related diseases, and resistance to oxidative stress is crucial for optimum longevity and healthy aging. Using the wild-type, mutant and transgenic strains, this study explored the antioxidative potential and lifespan extension benefits of different <i>Lactobacillus strains</i> in <i>Caenorhabditis elegans</i> (<i>C. elegans</i>). We observed that <i>Lactobacillus brevis</i> MTCC 1750 could enhance the resistance of <i>C. elegans</i> against juglone induced oxidative stress by reducing its intracellular reactive oxygen species (ROS) accumulation. Also, live <i>L. brevis</i> MTCC 1750 could prolong the worm's lifespan. These effects are dependent on transcription factor DAF-16 evident with significant upregulation of its target gene <i>sod-3</i>. This also explained the significant improvements in different age-associated changes in physiological and mechanical parameters of the worm by <i>L. brevis</i> MTCC 1750. Further investigations revealed that DAF-16 activation and, its enhanced translocation in the nucleus is independent of DAF-2 or JNK pathway. These findings highlighted <i>L. brevis</i> MTCC 1750 as a potent anti-oxidant source for complementing current antioxidant therapeutic strategies. Nonetheless, the findings showed how different signaling events are regulated based on an organism's diet component, and their consequences on the aging process in multiple species.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9203775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum and cecal metabolic profile of the insulin resistant and dyslipidemic p47^phox knockout mice.","authors":"Hobby Aggarwal,&nbsp;Priya Pathak,&nbsp;Sonu Kumar Gupta,&nbsp;Yashwant Kumar,&nbsp;Kumaravelu Jagavelu,&nbsp;Madhu Dikshit","doi":"10.1080/10715762.2022.2133705","DOIUrl":"https://doi.org/10.1080/10715762.2022.2133705","url":null,"abstract":"<p><p>Involvement of NOX-dependent oxidative stress in the pathophysiology of metabolic disorders as well as in the maintenance of metabolic homeostasis has been demonstrated previously. In the present study, the metabolic profile in p47^phox-/- and WT mice fed on a chow diet was evaluated to assess the role of metabolites in glucose intolerance and dyslipidemia under altered oxidative stress conditions. p47^phox-/- mice displayed glucose intolerance, dyslipidemia, hyperglycemia, insulin resistance (IR), hyperinsulinemia, and altered energy homeostasis without any significant change in gluconeogenesis. The expression of genes involved in lipid synthesis and uptake was enhanced in the liver, adipose tissue, and intestine tissues. Similarly, the expression of genes associated with lipid efflux in the liver and intestine was also enhanced. Enhanced gut permeability, inflammation, and shortening of the gut was evident in p47^phox-/- mice. Circulating levels of pyrimidines, phosphatidylglycerol lipids, and 3-methyl-2-oxindole were augmented, while level of purine was reduced in the serum. Moreover, the cecal metabolome was also altered, as was evident with the increase in indole-3-acetamide, N-acetyl galactosamine, glycocholate, and a decrease in hippurate, indoxyl sulfate, and indigestible sugars (raffinose and melezitose). Treatment of p47^phox-/- mice with pioglitazone, marginally improved glucose intolerance, and dyslipidemia, with an increase in PUFAs (linoleate, docosahexaenoic acid, and arachidonic acid). Overall, the results obtained in p47^phox-/- mice indicate an association of IR and dyslipidemia with altered serum and cecal metabolites (both host and bacterial-derived), implying a critical role of NOX-derived ROS in metabolic homeostasis.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10648596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD36 down regulation by the macrophage antioxidant 7,8-dihydroneopterin through modulation of PPAR-γ activity.","authors":"Nooshin Ghodsian,&nbsp;Anthony Yeandle,&nbsp;Barry D Hock,&nbsp;Steven P Gieseg","doi":"10.1080/10715762.2022.2114904","DOIUrl":"https://doi.org/10.1080/10715762.2022.2114904","url":null,"abstract":"<p><p>CD36 is the key scavenger receptor driving the formation of cholesterol-loaded foam cells, the principal cellular component of atherosclerotic plaques. CD36 is down regulated by 7,8-dihydroneopterin, a potent superoxide and hypochlorite scavenging antioxidant generated by interferon-γ stimulated macrophages. 7,8-dihydroneopterin downregulates CD36 mRNA and protein levels so inhibiting macrophage foam cell formation <i>in vitro</i>. We examined the mechanism of 7,8-dihydroneopterin downregulation of CD36 by measuring CD36 and PPAR-γ levels by Western blot analysis, in the monocyte-like U937 cells with a range of PPAR-γ stimulants and inhibitors. Lipoxygenase activity was measured by monitoring linoleic acid oxidation at 234 nm for diene formation. Between 100 and 200 μM, 7,8-dihydroneopterin decreased CD36 levels by 50% within 12 h with levels dropping below 25% by 24 h. CD36 levels returned to basal levels after 24 h. Inhibition of protein synthesis by cycloheximide shows 7,8-dihydroneopterin had no effect on CD36 degradation rates. PPAR-γ levels were not altered by the addition of 7,8-dihydroneopterin. MAP Kinase, P38 and NF-κB pathways inhibitors SP600125, PD98059, SB202190 and BAY 11-7082, respectively, did not restore the CD36 levels in the presence of 7,8-dihydroneopterin. The addition of the lipophilic PPAR-γ activators rosiglitazone and azelaoyl-PAF prevented the CD36 downregulation by 7,8-dihydroneopterin. 7,8-dihydroneopterin inhibited soybean lipoxygenase and reduced U937 cell basal levels of cellular lipid oxides as measured by HPLC-TBARS analysis. The data show 7,8-dihydroneopterin down regulates CD36 expression by decreasing the level of lipid oxide stimulation of PPAR-γ promotor activity, potentially through lipoxygenase inhibition.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33438613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Near-infrared Nrf2 activator IR-61 dye alleviates radiation-induced lung injury.","authors":"Jiancheng Zheng,&nbsp;Yang Wang,&nbsp;Ziwen Wang,&nbsp;Wanchao Chen,&nbsp;Min Luo,&nbsp;Can Zhang,&nbsp;Yawei Wang,&nbsp;Long Chen,&nbsp;Feng Wu,&nbsp;Wei Yang,&nbsp;Zeyu Yang,&nbsp;Yu Wang,&nbsp;Chunmeng Shi","doi":"10.1080/10715762.2022.2132942","DOIUrl":"https://doi.org/10.1080/10715762.2022.2132942","url":null,"abstract":"<p><p>Oxidative stress injury and subsequent inflammatory response are considered to play critical roles in radiation-induced lung injury (RILI). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that regulates oxidative stress response and represses inflammation, but its therapeutic value in RILI remains elusive. Our previous studies have shown that the near-infrared (NIR) IR-61 dye evokes intracellular antioxidant defense by enhancing Nrf2 signaling and promoting anti-inflammatory effects. We established a model of RILI in mice exposed to whole-thoracic irradiation. The results showed that IR-61 treatment notably improved pulmonary functions by decreasing lung density and diminishing airway resistance. In addition, IR-61 significantly ameliorated radiation-induced inflammatory cell infiltration and proinflammatory cytokine (IL-1β, IL-6, and TNF-α) release, thereby mitigating inflammatory response. Furthermore, IR-61 mitigated radiation-induced lung fibrosis by decreasing the collagen deposition and the levels of fibrogenesis-related factors (collagen I, collagen III, α-SMA, and fibronectin). More importantly, IR-61 was found to accumulate in the mitochondria of macrophages in irradiated lung tissues. Therefore, the functions of IR-61 in macrophages were further studied in irradiated macrophage cell lines, MH-s and RAW 264.7 <i>in vitro</i>. The results indicated that IR-61 upregulated the expression of Nrf2 and heme oxygenase-1 (HO-1) and decreased the levels of reactive oxygen species (ROS) and pro-inflammatory cytokines (IL-1β and IL-6) in macrophages after radiation. In summary, our study suggests that IR-61 effectively mitigates RILI by activating Nrf2 signaling in irradiated lung tissues. In particular, Nrf2-mediated anti-inflammatory and antioxidant effects in irradiated lung tissue macrophages play critical roles in protecting against RILI.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33490813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}