Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe最新文献

{"title":"Mitochondria-targeted derivative of pterostilbene, a dietary phytoestrogen, exhibits superior cancer cell cytotoxicity via mitochondrial superoxide mediated induction of autophagy","authors":"Mahin K. Ibrahim ,&nbsp;Shivani R. Nandha ,&nbsp;Ashwani S. Patil ,&nbsp;Sadhana Sathaye ,&nbsp;Mariam S. Degani ,&nbsp;Binita Kumar ,&nbsp;Rahul Checker ,&nbsp;Deepak Sharma ,&nbsp;Santosh K. Sandur","doi":"10.1016/j.arres.2023.100071","DOIUrl":"10.1016/j.arres.2023.100071","url":null,"abstract":"<div><p>Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene;PTS), a dimethyl ether analogue of resveratrol, has been shown to possess anti-bacterial, anti-cancer, anti-inflammatory and antioxidant properties. In the present study, we have synthesized a mitochondria targeted derivative of Pterostilbene (M-PTS) with aim to enhance its anti-cancer efficacy. M-PTS was synthesized by substituting the free hydroxyl group of PTS with a propyl linker and Triphenylphosphonium (TPP+, a membrane-permeable lipophilic cation that readily accumulates and penetrates through the mitochondrial membrane). We observed that mitochondrial uptake of M-PTS in A549 cells was higher (∼8.5-fold) as compared to PTS and M-PTS was more potent in killing human lung (A549) and breast (MCF-7) cancer cells as compared to PTS. IC₅₀ of M-PTS was found to be 0.17 µM and 0.76 µM, respectively, while IC₅₀ of PTS was found to be 40.45 µM and 53.15 µM in A549 and MCF-7 cells, respectively. M-PTS was superior in inhibiting the clonogenic potential of A549 and MCF-7 cell and M-PTS induced apoptosis in A549 cells. M-PTS specifically increased both cytosolic ROS and mitochondrial superoxide levels whereas PTS did not have any effect on mitochondrial superoxide. M-PTS treatment led to autophagy induction in cancer cells. M-PTS induced cytotoxicity was attenuated on pre-treatment with mitochondria-targeted antioxidant (mitoTEMPO) as well as inhibitor of autophagy (chloroquine) signifying the involvement of mitochondrial ROS and autophagy in the cytotoxic effects of M-PTS. In conclusion, the superior cytotoxic efficacy of M-PTS via specific induction of mitochondrial superoxide illustrates the application of mitochondria targeted redox-active natural products as potent anti-cancer drugs.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"8 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42118019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemopexin and albumin inhibit heme-induced macrophage activation while also enabling heme-LPS synergistic promotion of TNF production","authors":"Rafael Cardoso Maciel Costa Silva ,&nbsp;Luis Batista Tan ,&nbsp;Andreza Moreira dos Santos Gama ,&nbsp;Nuccia Nicole Theodoro De Cicco ,&nbsp;Nicolas S. Merle ,&nbsp;Lubka T. Roumenina ,&nbsp;Yi Zhang ,&nbsp;Gregory C. Henderson ,&nbsp;André N.A. Gonçalves ,&nbsp;Georgia C. Atella ,&nbsp;João Trindade Marques ,&nbsp;Leonardo Holanda Travassos ,&nbsp;Claudia N. Paiva ,&nbsp;Bénédicte Manoury ,&nbsp;Marcelo Torres Bozza","doi":"10.1016/j.arres.2023.100069","DOIUrl":"10.1016/j.arres.2023.100069","url":null,"abstract":"<div><p>Free heme released from hemoglobin contributes to exacerbated inflammation and tissue damage in hemolytic diseases. While a moderate level of free heme does not cause intravascular inflammation by itself, its presence during infection greatly enhances inflammation. Although specific serum proteins have been found to affect heme-induced inflammation, the selective contribution of serum proteins inhibiting macrophage activation by heme or, conversely, amplifying the production of cytokines by macrophages stimulated with heme and microbial molecules, is poorly defined. Here we identified a serum fraction containing proteins with &gt;50 KDa which was capable of inhibiting heme-stimulated TNF production and capable of enabling TNF production under conditions of a heme-LPS synergy. The inhibition of heme-induced TNF production was mimicked by Hemopexin (Hx), human serum albumin (HSA), serum from Hx-knockout mice, and less efficiently by serum from albumin-knockout mice, but not by serum LDL. Hx and HSA inhibited heme-induced ROS generation, MAPK/ Syk phosphorylation and cell death. However, Hx and HSA each also promoted the synergistic relationship between heme and LPS upon TNF production. Serum from Hx-knockout mice was fully capable of enabling this synergy, while serum from albumin-knockout mice was less efficient to promote TNF production under these conditions. Low concentrations of HSA mimicked the ability of serum to enable heme-stimulated IL-1β production after LPS priming, while high concentrations inhibited it. Together, our findings indicate how heme inflammatory effects are restrained in the blood upon sterile hemolysis, yet exacerbate inflammation in the presence of microbes. Moreover, it is interesting to note that opposing effects of serum proteins on heme-induced macrophage activation were selected through evolution, with both effects exerted by Hx and albumin.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"8 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42205790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spectroelectrochemical testing of a proposed mechanism for a redox-based therapeutic intervention: Ascorbate treatment of severe paraquat poisoning","authors":"Zhiling Zhao ,&nbsp;Eunkyoung Kim ,&nbsp;William E. Bentley ,&nbsp;Gregory F. Payne","doi":"10.1016/j.arres.2023.100068","DOIUrl":"10.1016/j.arres.2023.100068","url":null,"abstract":"<div><p>The toxicity of paraquat is believed to involve a redox-cycling mechanism that can disrupt cellular redox homeostasis and, also, generate damaging free radicals. It has been suggested that for cases of severe paraquat poisoning the administration of ascorbate (i.e., vitamin C) can confer benefit by quenching the paraquat free radical (PQ^+·). Here, we used an electrochemical approach that abstracts-away many of the (bio)chemical complexities and isolates the redox-interactions between paraquat and ascorbate. Specifically, we used a series of experiments that coupled electrochemical measurements of electron flow with optical measurements of paraquat's redox-state switching. Our results demonstrate that the reduced absorbate cannot quench the PQ^+·-radical because they are both reductants. However, oxidation of ascorbate does allow PQ^+·-radical scavenging. More broadly, we believe this study demonstrates the potential for developing electrochemical approaches to complement existing experimental methods in redox biology.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"8 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42845763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of X-ray irradiation on the redox status of mouse colorectal tissues","authors":"Megumi Ueno ,&nbsp;Raj Kumar Parajuli ,&nbsp;Hiromu Ito ,&nbsp;Megumi Iiyama ,&nbsp;Saaya Suzuki ,&nbsp;Ken-ichiro Matsumoto ,&nbsp;Ikuo Nakanishi ,&nbsp;Ichio Aoki ,&nbsp;Akira Sumiyoshi","doi":"10.1016/j.arres.2023.100067","DOIUrl":"10.1016/j.arres.2023.100067","url":null,"abstract":"<div><p>The effects of X-ray irradiation on the redox status of colorectal tissues were investigated using magnetic resonance redox imaging.</p><p>The pyrrolidine-ring nitroxyl contrast agent, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-<em>N</em>-oxyl (CmP), was used as a suitable redox-sensitive contrast agent for colorectal tissues. The lower abdomen of an 8-week-old female C3H/HeSlc mouse was X-ray irradiated with a single 10-Gy dose under anesthesia. X-rays were collimated through a 19-mm slit made by a pair of 5-cm-thick lead blocks. MRI experiments using CmP as the contrast agent were conducted on mice irradiated by X-rays at different times, i.e., 2‒8 h, 1, 2, 4, 8, 12, and 16 day(s) after irradiation. Dynamic datasets of multi-slice T₁-weighted images were obtained by repeating scans every 20 s for 22 min. The time course of the CmP-induced T₁-weighted signal in colorectal tissues was analyzed. The relationship between mitochondrial damage and redox responses was also investigated.</p><p>The <em>k</em>₁ decay rate of CmP, which mainly reflects the biological reduction of nitroxyl radicals in tissue, was significantly suppressed on day 2, increased on day 8, and then recovered to the control level. The decrease in the <em>k</em>₁ value on day 2 indicated the inhibition of biological activity in injured tissue. Further animal studies are required to verify the relationship between the redox response of the colorectum tissue and the mitochondrial damages. This magnetic resonance redox imaging technique has the potential to visualize radio-biological responses in the tissues of living animals.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"8 ","pages":"Article 100067"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45464680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manganese abated indomethacin-induced gastrohepatorenal toxicities in Rats via suppression of oxidative stress, polyamine catabolism, inflammation and activation of Caspase-3","authors":"Abiola S. Tijani ,&nbsp;David O. Olori ,&nbsp;Ebenezer O. Farombi","doi":"10.1016/j.arres.2023.100070","DOIUrl":"10.1016/j.arres.2023.100070","url":null,"abstract":"<div><p>Indomethacin (IND) is a non-steroidal anti-inflammatory drug with many therapeutic benefits and multi-organ toxicities. Manganese (Mn) is a trace metal essential in many biological processes. However, there is dearth of information concerning the effect of Mn on IND-induced gastrohepatorenal damage in rats. This study investigated the mitigating effect of manganese on IND-induced gastrohepatorenal damage in rats. Adult male rats were assigned into four groups of eight rats each and were treated once daily for 14 days. Group 1 served as control; group 2 received IND alone (5 mg/kg); group 3 received IND (5 mg/kg) and Mn alone (10 mg/kg) and group 4 received Mn alone Mn alone (10 mg/kg). Administration of IND significantly increased ulcer score, ulcer index, titrable acidity and peptic activity and decreased pH, mucus content, hexosamine and sialic acid levels. IND also increased hepatorenal markers, myeloperoxidase (MPO), nitric oxide (•NO), malondialdehyde (MDA), lipid hydroperoxide (LOOH), protein carbonyl (PCO), spermine oxidase (SpmOX), putrescine Oxidase (PutOX), tumor necrosis factor-<em>α</em> (TNF-α) interleukin-1β (IL-1β), caspase-3 and decreased the activities of superoxide dismutase (SOD), catalase, glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione (GSH) level relative to control. Co-administration of IND and Mn significantly decreased ulcerogenic parameters, hepatorenal markers, MPO, •NO, MDA, LOOH, PCO, SpmOX, PutOX, TNF-α, IL-1β, caspase-3 and increased antioxidant status relative to IND alone group.</p><p>Histological examination showed that injuries induced by IND were ameliorated by Mn rats.</p><p>Mn suppressed IND-induced oxidative stress, inflammation, polyamine catabolism and caspase-3 activation in the liver and kidney of the rats.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"8 ","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44712664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the relationship between selenium and cadmium in diseased human lungs","authors":"Matthew Ryan Smith ,&nbsp;Xin Hu ,&nbsp;Zachery R Jarrell ,&nbsp;Xiaojia He ,&nbsp;Michael Orr ,&nbsp;Jolyn Fernandes ,&nbsp;Joshua D. Chandler ,&nbsp;Douglas I. Walker ,&nbsp;Annette Esper ,&nbsp;Lucian Marts ,&nbsp;David C. Neujahr ,&nbsp;Dean P. Jones ,&nbsp;Young-Mi Go","doi":"10.1016/j.arres.2023.100065","DOIUrl":"10.1016/j.arres.2023.100065","url":null,"abstract":"<div><p>Cadmium (Cd) is a toxic environmental metal that interacts with selenium (Se) and contributes to many lung diseases. Humans have widespread exposures to Cd through diet and cigarette smoking, and studies in rodent models show that Se can protect against Cd toxicities. We sought to identify whether an antagonistic relationship existed between Se and Cd burdens and determine whether this relationship may associate with metabolic variation within human lungs. We performed metabolomics of 31 human lungs, including 25 with end-stage lung disease due to idiopathic pulmonary fibrosis, cystic fibrosis, chronic obstructive lung disease (COPD)/emphysema and other causes, and 6 non-diseased lungs. Results showed pathway associations with Cd including amino acid, lipid and energy-related pathways. Metabolic pathways varying with Se had considerable overlap with these pathways. Hierarchical cluster analysis (HCA) of individuals according to metabolites associated with Cd showed partial separation of disease types, with COPD/emphysema in the cluster with highest Cd, and non-diseased lungs in the cluster with the lowest Cd. When compared to HCA of metabolites associated with Se, the results showed that the cluster containing COPD/emphysema had the lowest Se, and the non-diseased lungs had the highest Se. A greater number of pathway associations occurred for Cd to Se ratio than either Cd or Se alone, indicating that metabolic patterns were more dependent on Cd to Se ratio than on either alone. Network analysis of interactions of Cd and Se showed network centrality was associated with pathways linked to polyunsaturated fatty acids involved in inflammatory signaling. Overall, the data show that metabolic pathway responses in human lung vary with Cd and Se in a pattern suggesting that Se is antagonistic to Cd toxicity in humans.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"7 ","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cf/3c/nihms-1882601.PMC10078579.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9272323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indirect Antioxidant Effects of the Nitrite Anion: Focus on Xanthine Oxidase","authors":"Xena M. Williams ,&nbsp;Alec T. Bossert ,&nbsp;Evan Devalance ,&nbsp;Sara E. Lewis ,&nbsp;Michael R. Gunther ,&nbsp;Eric E. Kelley","doi":"10.1016/j.arres.2022.100058","DOIUrl":"10.1016/j.arres.2022.100058","url":null,"abstract":"<div><p>One electron reduction of nitrite (NO₂⁻) has been determined to be a significant, noncanonical source of nitric oxide (NO) with molybdopterin enzymes being identified as critical to this process. Of the molybdopterin enzymes identified as NO₂⁻ reductases, xanthine oxidoreductase (XOR) is the most extensively studied. Paradoxically, XOR generates oxidants and thus can contribute to oxidative stress under inflammatory conditions when the oxidase form (XO) of XOR is abundant. However, under similar inflammatory conditions XO has been associated with NO generation, especially when NO₂⁻ levels are elevated which begs the question: if reaction of nitrite with XO consumes electrons, then does it subsequently reduce oxidant generation? To address this question, electron paramagnetic resonance (EPR) was used, under controlled O₂ tensions, to assess superoxide (O₂^·⁻) generation by endothelial-bound XO plus xanthine and the resultant impact of introducing NO₂⁻. Nitrite diminished XO-derived O₂^·− under hypoxia (1% O₂) whereas at 21% O₂, it had no impact. To confirm these results and discount contributions from the reaction of NO with O₂^·−, molecular O₂ consumption was assessed. The presence of NO₂⁻ decreased the rate of XO/xanthine-dependent O₂ consumption in a concentration-dependent manner with greater impact under hypoxic conditions (1% O₂) compared to 21% O₂. In a more biologic setting, NO₂⁻ also diminished XO-dependent H₂O₂ formation in murine liver homogenates supplemented with xanthine. Interestingly, nitrate (NO₃⁻) did not alter XO-dependent O₂ consumption at either 21% or 1% O₂; yet it did slightly impact nitrite-mediated effects when present at 2:1 ratio vs. NO₂⁻. When combined, these data: 1) show a significant indirect antioxidant function for NO₂⁻ by decreasing oxidant generation from XO, 2) demonstrate that both XO-derived H₂O₂ and O₂^·− production are diminished by the presence of NO₂⁻ and 3) incentivize further exploration of the difference between XO reaction with NO₂⁻ vs. NO₃⁻.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"7 ","pages":"Article 100058"},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/af/nihms-1882598.PMC10100591.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9316689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical control of the mitochondrial protein MitoNEET by biological thiols and lipid-derived electrophiles","authors":"R.A. Skolik ,&nbsp;C. Noud ,&nbsp;S. Oliver ,&nbsp;J. Markitan ,&nbsp;L. Salazar ,&nbsp;M Asante ,&nbsp;W.J. Geldenhuys ,&nbsp;M.E. Konkle ,&nbsp;M.A. Menze","doi":"10.1016/j.arres.2022.100059","DOIUrl":"10.1016/j.arres.2022.100059","url":null,"abstract":"<div><p>MitoNEET is a mitochondrial [2Fe-2S]-containing protein known for its involvement in cellular metabolism, iron regulation, and oxidative stress. The protein has been associated with diseases ranging from diabetes to Parkinson's disease, prompting the development of compounds designed to target mitoNEET selectively. Unfortunately, drug development is limited due to a lack of mechanistic understanding of how mitoNEET integrates into pathophysiological processes, and biological compounds that govern mitoNEET function are still ill-defined. We demonstrate an oxygen-dependent reaction with biological thiols catalyzed by mitoNEET. Specifically, we observed that mitoNEET converts L-cysteine to cystine. Finally, we showed that reduced glutathione (L-GSH) regulates the reactivity of two lipid-derived biomarkers of oxidative stress, 4-HNE and 4-ONE, towards mitoNEET. We found that exposure to L-GSH before treatment with either of the electrophilic aldehydes prevents the formation of a covalently linked mitoNEET dimer. Meanwhile, adding L-GSH after electrophile treatment recovers mitoNEET from the 4-HNE induced modification but not from the modification induced by 4-ONE. These results indicate a possible role for mitoNEET in thiol-mediated oxidative stress and may facilitate the development of drugs designed to modulate mitoNEET activity to improve pathophysiological states.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"7 ","pages":"Article 100059"},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43654493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of liver regeneration by the nuclear factor erythroid 2-related factor 2","authors":"Francesco Bellanti,&nbsp;Gaetano Serviddio,&nbsp;Gianluigi Vendemiale","doi":"10.1016/j.arres.2023.100066","DOIUrl":"10.1016/j.arres.2023.100066","url":null,"abstract":"<div><p>The liver is provided with peculiar regenerative features, initiated by resection or acute/chronic injuries. Preservation of cell phenotype (“phenotypic fidelity”) characterizes liver regeneration triggered by resection and acute damage. On the contrary, this mechanism is defective during chronic liver injury, in which regeneration can be supported by activation of facultative progenitors or trans-differentiation of parenchymal cells.</p><p>Both resection and acute/chronic damages may alter hepatic redox homeostasis. This modification may impact the regulation of pathways involved in liver regeneration, including proliferation and trans-differentiation of parenchymal cells, as well as activation of facultative progenitors. The regenerative process of the liver may be modulated by several redox-dependent transcription factors. Among them, the nuclear factor erythroid 2-related factor 2 (NRF2) plays a determinant role. After hepatic resection, NRF2 contributes to the regulation of parenchymal proliferation, maintaining newly regenerated hepatocytes completely differentiated. NRF2 deactivation induces oxidative stress-related insulin resistance and impairs regeneration by blocking pro-mitogenic and anti-apoptotic pathways.</p><p>This review summarizes evidence on the commitment of NRF2 in several mechanisms involved in liver regeneration. Pharmacological stimulation of NRF2 boosts liver mass recovery after partial hepatectomy. Furthermore, when p21 overexpression inhibits hepatocellular proliferation, NRF2 modulates trans-differentiation of cholangiocytes toward hepatocytes. Of interest, activation and differentiation of hepatic progenitors is associated with NRF2 inhibition. Current reports suggest that NRF2 modulation could pave the way for viable therapies to be tested in clinical trials.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"7 ","pages":"Article 100066"},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43763101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico targeting of lipoxygenase, CYP2C9, and NAD(P)H oxidase by major green tea polyphenols to subvert oxidative stress","authors":"Prem Rajak ,&nbsp;Abhratanu Ganguly ,&nbsp;Moutushi Mandi ,&nbsp;Anik Dutta ,&nbsp;Saurabh Sarkar ,&nbsp;Sayantani Nanda ,&nbsp;Kanchana Das ,&nbsp;Siddhartha Ghanty ,&nbsp;Gopal Biswas","doi":"10.1016/j.arres.2023.100061","DOIUrl":"https://doi.org/10.1016/j.arres.2023.100061","url":null,"abstract":"<div><p>Oxidative stress (OS) is a phenomenon caused by an imbalance between free-radical production and antioxidant activity within the body. Status of endogenous antioxidants is not always sufficient to mitigate the oxidative damage. In this case, exogenous antioxidants could help to minimize free-radical production and subsequent OS. Green tea is rich in several phenolic compounds that have strong antioxidant properties. However, their mechanism of action is still unclear. Hence, the present study aims to investigate binding affinities of six green tea polyphenols such as catechin, epicatechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, and gallocatechin for common ROS producers such as Lipoxygenase (LOX), CYP2C9, and NAD(P)H oxidase (NOX). Results indicated that polyphenols interacted with binding pockets of these enzymes through hydrogen bonds and other stable interactions such as van der waals, Pi-Pi, Pi-alkyl, and alkyl. All polyphenols showed varied binding affinities. Among them, epigallocatechin gallate and epigallocatechin showed the highest binding affinities for the ROS producers. Findings of the present study suggest that, apart from free radical scavenging activity, green tea polyphenols may directly interact with binding pockets of LOX, CYP2C9, and NOX to dampen ROS production and OS. However, studies involving animal models are required for additional validation of results.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"7 ","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49773753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}