{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T14:35:51Z","timestamp":1769092551364,"version":"3.49.0"},"reference-count":109,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T00:00:00Z","timestamp":1631836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/MED-TOX\/30418\/2017"],"award-info":[{"award-number":["PTDC\/MED-TOX\/30418\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>We hypothesized that an interplay between aryl hydrocarbon receptor (AhR) and cysteine-related thiolome at the kidney cortex underlies the mechanisms of (mal)adaptation to chronic intermittent hypoxia (CIH), promoting arterial hypertension (HTN). Using a rat model of CIH-HTN, we investigated the impact of short-term (1 and 7 days), mid-term (14 and 21 days, pre-HTN), and long-term intermittent hypoxia (IH) (up to 60 days, established HTN) on CYP1A1 protein level (a sensitive hallmark of AhR activation) and cysteine-related thiol pools. We found that acute and chronic IH had opposite effects on CYP1A1 and the thiolome. While short-term IH decreased CYP1A1 and increased protein-S-thiolation, long-term IH increased CYP1A1 and free oxidized cysteine. In addition, an in vitro administration of cystine, but not cysteine, to human endothelial cells increased Cyp1a1 expression, supporting cystine as a putative AhR activator. This study supports CYP1A1 as a biomarker of obstructive sleep apnea (OSA) severity and oxidized pools of cysteine as risk indicator of OSA-HTN. This work contributes to a better understanding of the mechanisms underlying the phenotype of OSA-HTN, mimicked by this model, which is in line with precision medicine challenges in OSA.<\/jats:p>","DOI":"10.3390\/antiox10091484","type":"journal-article","created":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T21:23:29Z","timestamp":1631913809000},"page":"1484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex"],"prefix":"10.3390","volume":"10","author":[{"given":"Maria Jo\u00e3o","family":"Correia","sequence":"first","affiliation":[{"name":"CEDOC, NOVA Medical School, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6672-5747","authenticated-orcid":false,"given":"Ant\u00f3nio B.","family":"Pimp\u00e3o","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]},{"given":"Filipa","family":"Lopes-Coelho","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023 Lisboa, Portugal"}]},{"given":"Catarina O.","family":"Sequeira","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]},{"given":"Nuno R.","family":"Coelho","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]},{"given":"Clara","family":"Gon\u00e7alves-Dias","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]},{"given":"Robert","family":"Barouki","sequence":"additional","affiliation":[{"name":"INSERM UMR-S 1124, 3TS, Environmental Toxicity, Therapeutic Targets, Cellular Signaling and Biomarkers, Universit\u00e9 de Paris, 45 rue des Saints-P\u00e8res, 75006 Paris, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2928-9648","authenticated-orcid":false,"given":"Xavier","family":"Coumoul","sequence":"additional","affiliation":[{"name":"INSERM UMR-S 1124, 3TS, Environmental Toxicity, Therapeutic Targets, Cellular Signaling and Biomarkers, Universit\u00e9 de Paris, 45 rue des Saints-P\u00e8res, 75006 Paris, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1548-5907","authenticated-orcid":false,"given":"Jacinta","family":"Serpa","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023 Lisboa, Portugal"}]},{"given":"Judit","family":"Morello","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]},{"given":"Em\u00edlia C.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8456-9995","authenticated-orcid":false,"given":"Sofia A.","family":"Pereira","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.smrv.2016.07.002","article-title":"Prevalence of obstructive sleep apnea in the general population: A systematic review","volume":"34","author":"Senaratna","year":"2017","journal-title":"Sleep Med. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.21037\/jtd.2017.10.33","article-title":"Intermittent hypoxia, cardiovascular disease and obstructive sleep apnoea","volume":"10","author":"Turnbull","year":"2018","journal-title":"J. Thorac. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1007\/s11325-016-1321-4","article-title":"Adiponectin protects the kidney against chronic intermittent hypoxia-induced injury through inhibiting endoplasmic reticulum stress","volume":"20","author":"Ding","year":"2016","journal-title":"Sleep Breath."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.cmet.2005.05.001","article-title":"Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing","volume":"1","author":"Guzy","year":"2005","journal-title":"Cell Metab."},{"key":"ref_5","first-page":"385","article-title":"Intermittent hypoxia-induced renal antioxidants and oxidative damage in male mice: Hormetic dose response","volume":"11","author":"Sun","year":"2012","journal-title":"Dose Response"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e5594","DOI":"10.1590\/1414-431x20165594","article-title":"Angiotensin-(1-7) relieved renal injury induced by chronic intermittent hypoxia in rats by reducing inflammation, oxidative stress and fibrosis","volume":"50","author":"Lu","year":"2017","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/978-3-319-91137-3_10","article-title":"Cysteine Oxidative Dynamics Underlies Hypertension and Kidney Dysfunction Induced by Chronic Intermittent Hypoxia","volume":"Volume 1071","author":"Coelho","year":"2018","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"465","DOI":"10.3389\/fphys.2019.00465","article-title":"Is aberrant reno-renal reflex control of blood pressure a contributor to chronic intermittent hypoxia-induced hypertension?","volume":"10","author":"AlMarabeh","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1001\/jama.297.8.842","article-title":"Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: Systematic review and meta-analysis","volume":"297","author":"Bjelakovic","year":"2007","journal-title":"J. Am. Med. Assoc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1001\/jama.2008.600","article-title":"Vitamins E and C in the prevention of cardiovascular disease in men: The physicians\u2019 health study II randomized controlled trial","volume":"300","author":"Sesso","year":"2008","journal-title":"JAMA\u2014J. Am. Med. Assoc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1161\/CIRCULATIONAHA.115.019790","article-title":"Novel Biomarker of Oxidative Stress Is Associated with Risk of Death in Patients with Coronary Artery Disease","volume":"133","author":"Patel","year":"2016","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1146\/annurev.nutr.24.012003.132208","article-title":"Extracellular thiols and thiol\/disulfide redox in metabolism","volume":"24","author":"Jones","year":"2004","journal-title":"Annu. Rev. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1093\/gerona\/61.10.1030","article-title":"Age-related influence on thiol, disulfide, and protein-mixed disulfide levels in human plasma","volume":"61","author":"Giustarini","year":"2006","journal-title":"J. Gerontol.\u2014Ser. A Biol. Sci. Med. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.1111\/j.1582-4934.2008.00417.x","article-title":"Cysteinylation and homocysteinylation of plasma protein thiols during ageing of healthy human beings","volume":"13","author":"Rossi","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1042\/CS20180157","article-title":"Implications of plasma thiol redox in disease","volume":"132","author":"Oliveira","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_16","first-page":"862","article-title":"Cysteine metabolic circuitries: Druggable targets in cancer","volume":"124","author":"Pereira","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/s41598-018-35566-2","article-title":"Cysteine Disulfides (Cys-ss-X) as Sensitive Plasma Biomarkers of Oxidative Stress","volume":"9","author":"Fu","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/978-3-030-63908-2_8","article-title":"A Mechanistic-Based and Non-invasive Approach to Quantify the Capability of Kidney to Detoxify Cysteine-Disulfides","volume":"Volume 1306","author":"Sequeira","year":"2021","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1089\/ars.2006.8.1865","article-title":"Redefining oxidative stress","volume":"8","author":"Jones","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ejps.2017.05.010","article-title":"Unmasking efavirenz neurotoxicity: Time matters to the underlying mechanisms","volume":"105","author":"Grilo","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4936","DOI":"10.1016\/S0021-9258(17)33205-2","article-title":"Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase","volume":"251","author":"Poland","year":"1976","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.drudis.2012.11.014","article-title":"The AhR twist: Ligand-dependent AhR signaling and pharmaco-toxicological implications","volume":"18","author":"Guyot","year":"2013","journal-title":"Drug Discov. Today"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3608","DOI":"10.1016\/j.febslet.2007.03.046","article-title":"The aryl hydrocarbon receptor, more than a xenobiotic-interacting protein","volume":"581","author":"Barouki","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.plipres.2017.06.001","article-title":"Aryl hydrocarbon receptor (AHR): \u201cpioneer member\u201d of the basic-helix\/loop\/helix per-Arnt-sim (bHLH\/PAS) family of \u201csensors\u201d of foreign and endogenous signals","volume":"67","author":"Nebert","year":"2017","journal-title":"Prog. Lipid Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1124\/mol.106.032748","article-title":"Induction of Cyp1a1 Is a Nonspecific Biomarker of Aryl Hydrocarbon Receptor Activation: Results of Large Scale Screening of Pharmaceuticals and Toxicants in Vivo and in Vitro","volume":"71","author":"Hu","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"104869","DOI":"10.1016\/j.phrs.2020.104869","article-title":"First evidence of aryl hydrocarbon receptor as a druggable target in hypertension induced by chronic intermittent hypoxia","volume":"159","author":"Coelho","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105407","DOI":"10.1016\/j.phrs.2020.105407","article-title":"AHR canonical pathway: In vivo findings to support novel antihypertensive strategies","volume":"165","author":"Coelho","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101530","DOI":"10.1016\/j.redox.2020.101530","article-title":"The aryl hydrocarbon receptor as a target of environmental stressors\u2014Implications for pollution mediated stress and inflammatory responses","volume":"34","author":"Vogel","year":"2020","journal-title":"Redox Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7943495","DOI":"10.1155\/2016\/7943495","article-title":"Antioxidant Functions of the Aryl Hydrocarbon Receptor","volume":"2016","author":"Dietrich","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1203\/00006450-198711000-00025","article-title":"Cysteine and glutathione levels in developing rat kidney and liver","volume":"22","author":"States","year":"1987","journal-title":"Pediatr. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.freeradbiomed.2010.11.029","article-title":"Cysteine\/cystine redox signaling in cardiovascular disease","volume":"50","author":"Go","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1093\/aje\/kws342","article-title":"Increased Prevalence of Sleep-Disordered Breathing in Adults","volume":"177","author":"Peppard","year":"2013","journal-title":"Am. J. Epidemiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1177\/0023677213516312","article-title":"FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units","volume":"48","author":"Berar","year":"2014","journal-title":"Lab. Anim."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ejphar.2015.08.019","article-title":"Efficacy of carvedilol in reversing hypertension induced by chronic intermittent hypoxia in rats","volume":"765","author":"Diogo","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1152\/ajprenal.00254.2018","article-title":"Renal cortical oxygen tension is decreased following exposure to long-term but not short-term intermittent hypoxia in the rat","volume":"316","author":"Jasionek","year":"2019","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jchromb.2005.10.051","article-title":"Improved HPLC method for the simultaneous determination of allantoin, uric acid and creatinine in cattle urine","volume":"832","author":"George","year":"2006","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s11255-011-9905-1","article-title":"Total, free, and protein-bound thiols in plasma of peritoneal dialysis and predialysis patients","volume":"43","author":"Piotr","year":"2011","journal-title":"Int. Urol. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.freeradbiomed.2020.05.002","article-title":"Berry fruits modulate kidney dysfunction and urine metabolome in Dahl salt-sensitive rats","volume":"154","author":"Gomes","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"656229","DOI":"10.3389\/fonc.2021.656229","article-title":"The Activation of Endothelial Cells Relies on a Ferroptosis-Like Mechanism: Novel Perspectives in Management of Angiogenesis and Cancer Therapy","volume":"11","author":"Martins","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1152\/ajpcell.1992.262.1.C50","article-title":"Cystine uptake and glutathione level in endothelial cells exposed to oxidative stress","volume":"262","author":"Miura","year":"1992","journal-title":"Am. J. Physiol.\u2014Cell Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"C803","DOI":"10.1152\/ajpcell.1999.276.4.C803","article-title":"Stimulation of cystine uptake by nitric oxide: Regulation of endothelial cell glutathione levels","volume":"276","author":"Li","year":"1999","journal-title":"Am. J. Physiol.\u2014Cell Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lopes-Coelho, F., Silva, F., Gouveia-Fernandes, S., Martins, C., Lopes, N., Domingues, G., Brito, C., Almeida, A.M., Pereira, S.A., and Serpa, J. (2020). Monocytes as Endothelial Progenitor Cells (EPCs), Another Brick in the Wall to Disentangle Tumor Angiogenesis. Cells, 9.","DOI":"10.3390\/cells9010107"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1021\/tx034212w","article-title":"Geometric trajectory analysis of metabolic responses to toxicity can define treatment specific profiles","volume":"17","author":"Keun","year":"2004","journal-title":"Chem. Res. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Sumayao, R., Newsholme, P., and McMorrow, T. (2018). The role of cystinosin in the intermediary thiol metabolism and redox homeostasis in kidney proximal tubular cells. Antioxidants, 7.","DOI":"10.3390\/antiox7120179"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1253\/circj.CJ-12-0647","article-title":"Activation of Aryl Hydrocarbon Receptor Mediates Indoxyl Sulfate-Induced Monocyte Chemoattractant Protein-1 Expression in Human Umbilical Vein Endothelial Cells","volume":"77","author":"Watanabe","year":"2013","journal-title":"Circ. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1093\/biolre\/ioaa128","article-title":"Roles of aryl hydrocarbon receptor in endothelial angiogenic responses","volume":"103","author":"Li","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1161\/CIRCULATIONAHA.104.515155","article-title":"Intracellular proatherogenic events and cell adhesion modulated by extracellular thiol\/disulfide redox state","volume":"111","author":"Go","year":"2005","journal-title":"Circulation"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.freeradbiomed.2009.10.050","article-title":"A key role for mitochondria in endothelial signaling by plasma cysteine\/cystine redox potential","volume":"48","author":"Go","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1152\/ajpregu.00208.2014","article-title":"Therapeutic potential of intermittent hypoxia: A matter of dose","volume":"307","author":"Mitchell","year":"2014","journal-title":"Am. J. Physiol.\u2014Regul. Integr. Comp. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1113\/JP272346","article-title":"Epigenetic regulation of redox state mediates persistent cardiorespiratory abnormalities after long-term intermittent hypoxia","volume":"595","author":"Nanduri","year":"2017","journal-title":"J. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1046\/j.1523-1755.2001.00483.x","article-title":"Nephron pO2 and renal oxygen usage in the hypertensive rat kidney","volume":"59","author":"Welch","year":"2001","journal-title":"Kidney Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"H22","DOI":"10.1152\/ajpheart.00626.2004","article-title":"Angiotensin-induced defects in renal oxygenation: Role of oxidative stress","volume":"288","author":"Welch","year":"2005","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"R1229","DOI":"10.1152\/ajpregu.00720.2010","article-title":"Renal oxidative stress, oxygenation, and hypertension","volume":"301","author":"Palm","year":"2011","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/s11906-010-0135-1","article-title":"The Impact of Obstructive Sleep Apnea on Chronic Kidney Disease","volume":"12","author":"Adeseun","year":"2010","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/hr.2014.80","article-title":"Obstructive sleep apnea syndrome as a cause of resistant hypertension","volume":"37","author":"Parati","year":"2014","journal-title":"Hypertens. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1089\/ars.2007.1716","article-title":"Molecular mechanisms and potential clinical significance of S-glutathionylation","volume":"10","author":"Milzani","year":"2008","journal-title":"Antioxid. Redox Signal."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Lermant, A., and Murdoch, C.E. (2019). Cysteine glutathionylation acts as a redox switch in endothelial cells. Antioxidants, 8.","DOI":"10.3390\/antiox8080315"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.freeradbiomed.2014.01.009","article-title":"Disulfide stress: A novel type of oxidative stress in acute pancreatitis","volume":"70","author":"Moreno","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3389\/fcell.2015.00030","article-title":"Novel roles for protein disulphide isomerase in disease states: A double edged sword?","volume":"3","author":"Parakh","year":"2015","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/j.1365-2443.2010.01473.x","article-title":"Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution","volume":"16","author":"Taguchi","year":"2011","journal-title":"Genes Cells"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.freeradbiomed.2014.03.025","article-title":"Redox regulation of antioxidants, autophagy, and the response to stress: Implications for electrophile therapeutics","volume":"71","author":"Levonen","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.freeradbiomed.2014.11.013","article-title":"The basics of thiols and cysteines in redox biology and chemistry","volume":"80","author":"Poole","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"627","DOI":"10.3181\/0710-MR-267","article-title":"Intermittent hypoxia: Cause of or therapy for systemic hypertension?","volume":"233","author":"Serebrovskaya","year":"2008","journal-title":"Exp. Biol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Abuyassin, B., Badran, M., Ayas, N.T., and Laher, I. (2018). Intermittent hypoxia causes histological kidney damage and increases growth factor expression in a mouse model of obstructive sleep apnea. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192084"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"118500","DOI":"10.1016\/j.lfs.2020.118500","article-title":"Renal denervation improves chronic intermittent hypoxia induced hypertension and cardiac fibrosis and balances gut microbiota","volume":"262","author":"Lu","year":"2020","journal-title":"Life Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.toxlet.2014.11.015","article-title":"Metallothionein deletion exacerbates intermittent hypoxia-induced renal injury in mice","volume":"232","author":"Wu","year":"2015","journal-title":"Toxicol. Lett."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1015390","DOI":"10.1155\/2016\/1015390","article-title":"Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via P38\/JNK Signaling Pathways","volume":"2016","author":"Wu","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Zhao, L., Liu, T., Dou, Z.J., Wang, M.T., Hu, Z.X., and Wang, B. (2021). CB1 receptor antagonist rimonabant protects against chronic intermittent hypoxia-induced renal injury in rats. BMC Nephrol., 22.","DOI":"10.1186\/s12882-021-02362-6"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s11325-017-1587-1","article-title":"Chronic intermittent hypoxia exposure induces kidney injury in growing rats","volume":"22","author":"Poonit","year":"2018","journal-title":"Sleep Breath."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"F1","DOI":"10.1152\/ajprenal.00377.2020","article-title":"Chronic intermittent hypoxia impairs diuretic and natriuretic responses to volume expansion in rats with preserved low-pressure baroreflex control of the kidney","volume":"320","author":"AlMarabeh","year":"2021","journal-title":"Am. J. Physiol.\u2014Ren. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/sleep\/30.7.923","article-title":"Obstructive sleep apnea is associated with increased urinary albumin excretion","volume":"30","author":"Faulx","year":"2007","journal-title":"Sleep"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1053\/j.ajkd.2008.05.001","article-title":"Association of Obstructive Sleep Apnea With Urinary Albumin Excretion in Essential Hypertension: A Cross-sectional Study","volume":"52","author":"Tsioufis","year":"2008","journal-title":"Am. J. Kidney Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4130","DOI":"10.1038\/s41467-019-11576-0","article-title":"Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria","volume":"10","author":"Teumer","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/j.kint.2018.12.017","article-title":"Identification of 22 novel loci associated with urinary biomarkers of albumin, sodium, and potassium excretion","volume":"95","author":"Zanetti","year":"2019","journal-title":"Kidney Int."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1056\/NEJM199701163360306","article-title":"Melatonin in humans","volume":"336","author":"Brzezinski","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1177\/0748233712472521","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced hypertension: The beneficial effects of melatonin","volume":"31","author":"Mutlu","year":"2015","journal-title":"Toxicol. Ind. Health"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1600-079X.2007.00436.x","article-title":"Melatonin as a potential antihypertensive treatment","volume":"42","author":"Simko","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/bcp.12902","article-title":"Nutraceuticals with a clinically detectable blood pressure-lowering effect: A review of available randomized clinical trials and their meta-analyses","volume":"83","author":"Borghi","year":"2017","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Lopes-Coelho, F., Martins, F., Pereira, S.A., and Serpa, J. (2021). Anti-angiogenic therapy: Current challenges and future perspectives. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073765"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1111\/bph.14389","article-title":"Monocytes as immune targets in arterial hypertension","volume":"176","author":"Wenzel","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1161\/HYPERTENSIONAHA.107.097386","article-title":"Endothelial function and aminothiol biomarkers of oxidative stress in healthy adults","volume":"52","author":"Ashfaq","year":"2008","journal-title":"Hypertension"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Boneberg, R., Pardun, A., Hannemann, L., Hildebrandt, O., Koehler, U., Kinscherf, R., and Hildebrandt, W. (2021). High Plasma Cystine Levels Are Associated with Blood Pressure and Reversed by CPAP in Patients with Obstructive Sleep Apnea. J. Clin. Med., 10.","DOI":"10.3390\/jcm10071387"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/j.1523-1755.2004.00399.x","article-title":"The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation and wound repair","volume":"65","author":"Dou","year":"2004","journal-title":"Kidney Int."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejphar.2005.11.023","article-title":"Sen Antiproliferative and antiangiogenic effects of 3-methylcholanthrene, an aryl-hydrocarbon receptor agonist, in human umbilical vascular endothelial cells","volume":"530","author":"Juan","year":"2006","journal-title":"Eur. J. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.bbrc.2011.05.084","article-title":"Nitric oxide counters the inhibitory effects of uremic toxin indoxyl sulfate on endothelial cells by governing ERK MAP kinase and myosin light chain activation","volume":"409","author":"Kharait","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"30","DOI":"10.2215\/CJN.05340610","article-title":"Indoxyl sulfate-induced endothelial dysfunction in patients with chronic kidney disease via an induction of oxidative stress","volume":"6","author":"Yu","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.tox.2011.04.003","article-title":"Effects of PCB126 and 17\u03b2-oestradiol on endothelium-derived vasoactive factors in human endothelial cells","volume":"285","author":"Andersson","year":"2011","journal-title":"Toxicology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s12012-008-9027-x","article-title":"Hypertension, cardiac hypertrophy, and impaired vascular relaxation induced by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin are associated with increased superoxide","volume":"8","author":"Kopf","year":"2008","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1093\/toxsci\/kfq218","article-title":"Cytochrome P4501A1 is required for vascular dysfunction and hypertension induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"117","author":"Kopf","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000476074","article-title":"Aryl Hydrocarbon Receptor Activation in Chronic Kidney Disease: Role of Uremic Toxins","volume":"137","author":"Brito","year":"2017","journal-title":"Nephron"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.kint.2020.02.026","article-title":"Accumulation of protein-bound uremic toxins: The kidney remains the leading culprit in the gut-liver-kidney axis","volume":"97","author":"Burtey","year":"2020","journal-title":"Kidney Int."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Ng, H.-Y., Yisireyili, M., Saito, S., Lee, C.-T., Adelibieke, Y., Nishijima, F., and Niwa, T. (2014). Indoxyl Sulfate Downregulates Expression of Mas Receptor via OAT3\/AhR\/Stat3 Pathway in Proximal Tubular Cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091517"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"16105","DOI":"10.1073\/pnas.1821809116","article-title":"Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion","volume":"116","author":"Jansen","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1681\/ASN.2011121175","article-title":"Normal and pathologic concentrations of uremic toxins","volume":"23","author":"Duranton","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1159\/000447096","article-title":"Indoxyl Sulfate Downregulates Mas Receptor via Aryl Hydrocarbon Receptor\/Nuclear Factor-kappa B, and Induces Cell Proliferation and Tissue Factor Expression in Vascular Smooth Muscle Cells","volume":"133","author":"Ng","year":"2016","journal-title":"Nephron"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1159\/000494390","article-title":"Mercapturate pathway in the tubulocentric perspective of diabetic kidney disease","volume":"143","author":"Morello","year":"2019","journal-title":"Nephron"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/s41467-021-21301-5","article-title":"Renal metabolism and hypertension","volume":"12","author":"Tian","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S1382-6689(01)00065-5","article-title":"Interactions between aryl hydrocarbon receptor (AhR) and hypoxia signaling pathways","volume":"10","author":"Nie","year":"2001","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1159\/000354487","article-title":"The Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT\/HIF-1\u03b2) is Influenced by Hypoxia and Hypoxia-Mimetics","volume":"32","author":"Wolff","year":"2013","journal-title":"Cell Physiol. Biochem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.cbi.2014.05.001","article-title":"Regulatory crosstalk and interference between the and hypoxia sensing pathways at the AhR-ARNT-HIF1\u03b1 signaling node","volume":"218","author":"Vorrink","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2942","DOI":"10.2337\/db17-0186","article-title":"Chronic intermittent hypoxia impairs insulin sensitivity but improves whole-body glucose tolerance by activating skeletal muscle AMPK","volume":"66","author":"Thomas","year":"2017","journal-title":"Diabetes"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1164\/rccm.200702-238OC","article-title":"Intermittent Hypoxia Induces Early Functional Cardiovascular Remodeling in Mice","volume":"177","author":"Dematteis","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3389\/fneur.2012.00051","article-title":"Glucoregulatory consequences and cardiorespiratory parameters in rats exposed to chronic-intermittent hypoxia: Effects of the duration of exposure and losartan","volume":"3","author":"Fenik","year":"2012","journal-title":"Front. Neurol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1152\/ajpregu.00258.2012","article-title":"Metabolic effects of intermittent hypoxia in mice: Steady versus high-frequency applied hypoxia daily during the rest period","volume":"303","author":"Carreras","year":"2012","journal-title":"Am. J. Physiol.\u2014Regul. Integr. Comp. Physiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1210\/en.2014-1706","article-title":"Resveratrol attenuates intermittent hypoxia-induced macrophage migration to visceral white adipose tissue and insulin resistance in male mice","volume":"156","author":"Carreras","year":"2015","journal-title":"Endocrinology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1038\/ijo.2015.63","article-title":"Aryl hydrocarbon receptor deficiency protects mice from diet-induced adiposity and metabolic disorders through increased energy expenditure","volume":"39","author":"Xu","year":"2015","journal-title":"Int. J. Obes."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.jnutbio.2010.12.009","article-title":"Dietary cystine level affects metabolic rate and glycaemic control in adult mice","volume":"23","author":"Elshorbagy","year":"2012","journal-title":"J. Nutr. Biochem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1702616","DOI":"10.1183\/13993003.02616-2017","article-title":"Challenges and perspectives in obstructive sleep apnoea","volume":"52","author":"Randerath","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s11030-014-9534-6","article-title":"Predicting drug metabolism by CYP1A1, CYP1A2, and CYP1B1: Insights from MetaSite, molecular docking and quantum chemical calculations","volume":"18","author":"Pragyan","year":"2014","journal-title":"Mol. Divers."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/9\/1484\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:01:10Z","timestamp":1760166070000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/9\/1484"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,17]]},"references-count":109,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["antiox10091484"],"URL":"https:\/\/doi.org\/10.3390\/antiox10091484","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,17]]}}}