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Hesperidin was methylated to increase its solubility, generating hesperidin methyl chalcone (HMC), an emerging flavonoid that possess anti-inflammatory and antioxidant properties. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a powerful regulator of cellular resistance to oxidant products. Previous data evidenced HMC can activate Nrf2 signaling, providing antioxidant protection against diverse pathological conditions. However, its effects on kidney damage caused by non-steroidal anti-inflammatory drugs (NSAIDs) have not been evaluated so far. Mice received a nephrotoxic dose of diclofenac (200 mg\/kg) orally followed by intra-peritoneal (i.p.) administration of HMC (0.03\u20133 mg\/kg) or vehicle. Plasmatic levels of urea, creatinine, oxidative stress, and cytokines were assessed. Regarding the kidneys, oxidative parameters, cytokine production, kidney swelling, urine NGAL, histopathology, and Nrf2 mRNA expression and downstream targets were evaluated. HMC dose-dependently targeted diclofenac systemic alterations by decreasing urea and creatinine levels, and lipid peroxidation, as well as IL-6, IFN-\u03b3, and IL-33 production, and restored antioxidant properties in plasma samples. In kidney samples, HMC re-established antioxidant defenses, inhibited lipid peroxidation and pro-inflammatory cytokines and upregulated IL-10, reduced kidney swelling, urine NGAL, and histopathological alterations. Additionally, HMC induced mRNA expression of Nrf2 and its downstream effectors HO-1 and Nqo1, as well as reduced the levels of Keap1 protein detected in renal tissue. The present data demonstrate HMC is a potential compound for the treatment of acute renal damage caused by diclofenac, a routinely prescribed non-steroidal anti-inflammatory drug.<\/jats:p>","DOI":"10.3390\/antiox11071261","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T22:31:14Z","timestamp":1656369074000},"page":"1261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The Flavonoid Hesperidin Methyl Chalcone Targets Cytokines and Oxidative Stress to Reduce Diclofenac-Induced Acute Renal Injury: Contribution of the Nrf2 Redox-Sensitive Pathway"],"prefix":"10.3390","volume":"11","author":[{"given":"Allan J. C.","family":"Bussmann","sequence":"first","affiliation":[{"name":"Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina 86057-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago H.","family":"Zaninelli","sequence":"additional","affiliation":[{"name":"Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina 86057-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Telma","family":"Saraiva-Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina 86057-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4565-7706","authenticated-orcid":false,"given":"Victor","family":"Fattori","sequence":"additional","affiliation":[{"name":"Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina 86057-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla F. S.","family":"Guazelli","sequence":"additional","affiliation":[{"name":"Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina 86057-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana M.","family":"Bertozzi","sequence":"additional","affiliation":[{"name":"Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina 86057-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketlem C.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina 86057-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-0773","authenticated-orcid":false,"given":"Camila R.","family":"Ferraz","sequence":"additional","affiliation":[{"name":"Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina 86057-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1986-658X","authenticated-orcid":false,"given":"Doumit","family":"Camilios-Neto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, Center of Exact Sciences, Londrina State University, Londrina 86057-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f4nio M. B.","family":"Casella","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Center of Health Sciences, Londrina State University, Londrina 86039-440, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2296-1668","authenticated-orcid":false,"given":"Rubia","family":"Casagrande","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Center of Health Sciences, Londrina State University, Londrina 86039-440, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6978-7505","authenticated-orcid":false,"given":"Sergio M.","family":"Borghi","sequence":"additional","affiliation":[{"name":"Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina 86057-970, Brazil"},{"name":"Center for Research in Health Sciences, University of Northern Paran\u00e1, Londrina 86041-140, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2756-9283","authenticated-orcid":false,"suffix":"Jr.","given":"Waldiceu A.","family":"Verri","sequence":"additional","affiliation":[{"name":"Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Pathology, Londrina State University, Londrina 86057-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.lfs.2018.07.038","article-title":"Pyrrolidine dithiocarbamate inhibits mouse acute kidney injury induced by diclofenac by targeting oxidative damage, cytokines and NF-kappaB activity","volume":"208","author":"Borghi","year":"2018","journal-title":"Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhang, X., Donnan, P.T., Bell, S., and Guthrie, B. (2017). Non-steroidal anti-inflammatory drug induced acute kidney injury in the community dwelling general population and people with chronic kidney disease: Systematic review and meta-analysis. BMC Nephrol., 18.","DOI":"10.1186\/s12882-017-0673-8"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ejim.2015.03.008","article-title":"Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury: A systematic review and meta-analysis of observational studies","volume":"26","author":"Ungprasert","year":"2015","journal-title":"Eur. J. Intern. Med."},{"key":"ref_4","first-page":"632","article-title":"NSAIDs and kidney","volume":"52","author":"Ejaz","year":"2004","journal-title":"J. Assoc. Physicians India"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1590\/2175-8239-jbn-2018-0107","article-title":"Pathophysiological aspects of nephropathy caused by non-steroidal anti-inflammatory drugs","volume":"41","author":"Lucas","year":"2019","journal-title":"J. Bras. Nefrol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"McGettigan, P., and Henry, D. (2013). Use of non-steroidal anti-inflammatory drugs that elevate cardiovascular risk: An examination of sales and essential medicines lists in low-, middle-, and high-income countries. PLoS Med., 10.","DOI":"10.1371\/journal.pmed.1001388"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s40265-015-0392-z","article-title":"Advances in NSAID development: Evolution of diclofenac products using pharmaceutical technology","volume":"75","author":"Altman","year":"2015","journal-title":"Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.clinthera.2008.01.016","article-title":"Analgesic effectiveness of celecoxib and diclofenac in patients with osteoarthritis of the hip requiring joint replacement surgery: A 12-week, multicenter, randomized, double-blind, parallel-group, double-dummy, noninferiority study","volume":"30","author":"Emery","year":"2008","journal-title":"Clin. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.phrs.2016.12.039","article-title":"Vinpocetine reduces diclofenac-induced acute kidney injury through inhibition of oxidative stress, apoptosis, cytokine production, and NF-kappaB activation in mice","volume":"120","author":"Fattori","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"375","DOI":"10.5414\/CPP41375","article-title":"Relief of acute low back pain with diclofenac-K 12.5 mg tablets: A flexible dose, ibuprofen 200 mg and placebo-controlled clinical trial","volume":"41","author":"Dreiser","year":"2003","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"k3426","DOI":"10.1136\/bmj.k3426","article-title":"Diclofenac use and cardiovascular risks: Series of nationwide cohort studies","volume":"362","author":"Schmidt","year":"2018","journal-title":"BMJ"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1161\/01.HYP.0000116221.27079.ea","article-title":"Cyclooxygenases, the kidney, and hypertension","volume":"43","author":"Cheng","year":"2004","journal-title":"Hypertension"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1185\/03007995.2010.486301","article-title":"Diclofenac: An update on its mechanism of action and safety profile","volume":"26","author":"Gan","year":"2010","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_14","first-page":"44","article-title":"Diclofenac-Induced Kidney Damage in Wistar Rats: Involvement of Antioxidant Mechanism","volume":"7","author":"Abiola","year":"2019","journal-title":"J. Biosci. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"140","DOI":"10.22317\/jcms.v5i3.607","article-title":"Diclofenac-induced acute kidney injury is linked with oxidative stress and pro-inflammatory changes in sprague-dawley rats","volume":"5","author":"Alkuraishy","year":"2019","journal-title":"J. Contemp. Med. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0891-5849(01)00560-3","article-title":"Diclofenac induced in vivo nephrotoxicity may involve oxidative stress-mediated massive genomic DNA fragmentation and apoptotic cell death","volume":"31","author":"Hickey","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.intimp.2008.01.011","article-title":"Hesperidin, hesperidin methyl chalone and phellopterin from Poncirus trifoliata (Rutaceae) differentially regulate the expression of adhesion molecules in tumor necrosis factor-alpha-stimulated human umbilical vein endothelial cells","volume":"8","author":"Nizamutdinova","year":"2008","journal-title":"Int. Immunopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ferraz, C.R., Carvalho, T.T., Manchope, M.F., Artero, N.A., Rasquel-Oliveira, F.S., Fattori, V., Casagrande, R., and Verri, W.A. (2020). Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development. Molecules, 25.","DOI":"10.3390\/molecules25030762"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.cbi.2015.01.011","article-title":"Protective effects of the flavonoid hesperidin methyl chalcone in inflammation and pain in mice: Role of TRPV1, oxidative stress, cytokines and NF-kappaB","volume":"228","author":"Hohmann","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/BF03189486","article-title":"Absorption and elimination of (14C) hesperidin methylchalcone in the rat","volume":"6","author":"Chanal","year":"1981","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0021-9673(01)87191-0","article-title":"Analysis of commercial hesperidin methylchlcone by high performance liquid chromatography","volume":"555","author":"Gastillo","year":"1991","journal-title":"J. Chromatogr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s10787-020-00686-7","article-title":"Hesperidin methyl chalcone interacts with NFkappaB Ser276 and inhibits zymosan-induced joint pain and inflammation, and RAW 264.7 macrophage activation","volume":"28","author":"Manchope","year":"2020","journal-title":"Inflammopharmacology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1039\/c5pp00467e","article-title":"Topical formulation containing hesperidin methyl chalcone inhibits skin oxidative stress and inflammation induced by ultraviolet B irradiation","volume":"15","author":"Martinez","year":"2016","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6269","DOI":"10.1021\/acs.jafc.8b00959","article-title":"Hesperidin Methylchalcone Suppresses Experimental Gout Arthritis in Mice by Inhibiting NF-kappaB Activation","volume":"66","author":"Borghi","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.23736\/S0392-9590.16.03788-3","article-title":"The place of Ruscus extract, hesperidin methyl chalcone, and vitamin C in the management of chronic venous disease","volume":"36","author":"Jawien","year":"2017","journal-title":"Int. Angiol."},{"key":"ref_26","first-page":"1536","article-title":"Contribution of Nrf2 Modulation to the Mechanism of Action of Analgesic and Anti-inflammatory Drugs in Pre-clinical and Clinical Stages","volume":"9","author":"Hohmann","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.redox.2018.05.002","article-title":"Antioxidant response elements: Discovery, classes, regulation and potential applications","volume":"17","author":"Raghunath","year":"2018","journal-title":"Redox Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"85","DOI":"10.23736\/S0392-9590.17.03935-9","article-title":"New data on chronic venous disease: A new place for Cyclo 3\u00ae Fort","volume":"37","author":"Kakkos","year":"2018","journal-title":"Int. Angiol."},{"key":"ref_29","first-page":"272","article-title":"Correlation between improvement in functional signs and plethysmographic parameters during venoactive treatment (Cyclo 3 Fort)","volume":"30","author":"Allaert","year":"2011","journal-title":"Int. Angiol."},{"key":"ref_30","first-page":"78","article-title":"Cyclo 3 fort\u2014Alternative in chronic venous insufficiency","volume":"45","author":"Stoianova","year":"2006","journal-title":"Akush. Ginekol. (Sofiia)"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1177\/000331970005100702","article-title":"An open-label, randomized multicenter study comparing the efficacy and safety of Cyclo 3 Fort versus hydroxyethyl rutoside in chronic venous lymphatic insufficiency","volume":"51","author":"Beltramino","year":"2000","journal-title":"Angiology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1097\/00000441-194807000-00010","article-title":"Administration of massive doses of vitamin P hesperidin methyl chalcone","volume":"216","author":"Kirtley","year":"1948","journal-title":"Am. J. Med. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ejphar.2013.10.035","article-title":"Effects of rebamipide on nephrotoxicity associated with selected NSAIDs in rats","volume":"720","author":"Wood","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"114708","DOI":"10.1016\/j.jep.2021.114708","article-title":"Sphagneticola trilobata (L.) Pruski-derived kaurenoic acid prevents ovalbumin-induced asthma in mice: Effect on Th2 cytokines, STAT6\/GATA-3 signaling, NFkappaB\/Nrf2 redox sensitive pathways, and regulatory T cell phenotype markers","volume":"283","author":"Borghi","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"184","DOI":"10.2165\/00003088-199733030-00003","article-title":"Clinical pharmacokinetics of diclofenac. Therapeutic insights and pitfalls","volume":"33","author":"Davies","year":"1997","journal-title":"Clin. Pharmacokinet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1111\/bph.14957","article-title":"Protective effect of cilastatin against diclofenac-induced nephrotoxicity through interaction with diclofenac acyl glucuronide via organic anion transporters","volume":"177","author":"Huo","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"640","DOI":"10.18203\/2319-2003.ijbcp20181162","article-title":"Diclofenac-induced biochemical changes in nephrotoxicity among male Albino rats","volume":"7","author":"Sivaraj","year":"2018","journal-title":"Int. J. Basic Clin. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1111\/hiv.12072","article-title":"Acute kidney injury caused by tenofovir disoproxil fumarate and diclofenac co-administration","volume":"14","author":"Bickel","year":"2013","journal-title":"HIV Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"129","DOI":"10.5530\/ijopp.12.2.27","article-title":"A Case Report on Diclofenac Induced Chronic Kidney Disease","volume":"12","author":"Babladi","year":"2019","journal-title":"Indian J. Pharm. Pract."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mohammad, R.S., Lokhandwala, M.F., and Banday, A.A. (2022). Age-Related Mitochondrial Impairment and Renal Injury Is Ameliorated by Sulforaphane via Activation of Transcription Factor NRF2. Antioxidants, 11.","DOI":"10.3390\/antiox11010156"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"16474","DOI":"10.1038\/srep16474","article-title":"Obesity-induced chronic inflammation in high fat diet challenged C57BL\/6J mice is associated with acceleration of age-dependent renal amyloidosis","volume":"5","author":"Bijzet","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"109315","DOI":"10.1016\/j.cbi.2020.109315","article-title":"Antioxidant and anti-inflammatory effects of hesperidin methyl chalcone in experimental ulcerative colitis","volume":"333","author":"Guazelli","year":"2021","journal-title":"Chem. Biol. Interact."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/cphy.c110041","article-title":"Pathophysiology of acute kidney injury","volume":"2","author":"Basile","year":"2012","journal-title":"Compr. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1053\/j.ackd.2008.04.003","article-title":"Biomarkers of acute kidney injury","volume":"15","author":"Edelstein","year":"2008","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/00365510802150158","article-title":"Neutrophil gelatinase-associated lipocalin (NGAL): A new marker of kidney disease","volume":"241","author":"Devarajan","year":"2008","journal-title":"Scand. J. Clin. Lab. Investig. Suppl."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.advms.2015.01.001","article-title":"High expression of neutrophil gelatinase-associated lipocalin (NGAL) in the kidney proximal tubules of diabetic rats","volume":"60","author":"Liu","year":"2015","journal-title":"Adv. Med. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/ki.2008.499","article-title":"Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons","volume":"75","author":"Kuwabara","year":"2009","journal-title":"Kidney Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"113939","DOI":"10.1016\/j.jep.2021.113939","article-title":"Nephroprotective activity of Aframomum melegueta seeds extract against diclofenac-induced acute kidney injury: A mechanistic study","volume":"273","author":"Abdou","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"165","DOI":"10.5414\/CN106921","article-title":"Cytokines in acute kidney injury (AKI)","volume":"76","author":"Lee","year":"2011","journal-title":"Clin. Nephrol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/cc11228","article-title":"Role of leukocytes in the pathogenesis of acute kidney injury","volume":"16","author":"Kinsey","year":"2012","journal-title":"Crit. Care"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.abb.2014.09.005","article-title":"Heme oxygenase-1 and anti-inflammatory M2 macrophages","volume":"564","author":"Naito","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1089\/ars.2016.6665","article-title":"Oxidant Mechanisms in Renal Injury and Disease","volume":"25","author":"Ratliff","year":"2016","journal-title":"Antioxid. Redox Signal."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"F800","DOI":"10.1152\/ajprenal.00111.2015","article-title":"Acute reactive oxygen species (ROS)-dependent effects of IL-1beta, TNF-alpha, and IL-6 on the glomerular filtration barrier (GFB) in vivo","volume":"309","author":"Sverrisson","year":"2015","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jphotobiol.2015.03.030","article-title":"Hesperidin methyl chalcone inhibits oxidative stress and inflammation in a mouse model of ultraviolet B irradiation-induced skin damage","volume":"148","author":"Martinez","year":"2015","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1073\/pnas.0400282101","article-title":"Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid","volume":"101","author":"Suh","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Deng, H. (2020). Nrf2 in Immune Responses during Inflammation. Nrf2 and Its Modulation in Inflammation, Springer.","DOI":"10.1007\/978-3-030-44599-7"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.4049\/jimmunol.1101712","article-title":"Th2 skewing by activation of Nrf2 in CD4+ T cells","volume":"188","author":"Rockwell","year":"2012","journal-title":"J. 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