{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:30:33Z","timestamp":1790857833790,"version":"4.1.0"},"reference-count":73,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Innovation and Technological Development of the Republic of Serbia","award":["451-03-66\/2024-03\/200007"],"award-info":[{"award-number":["451-03-66\/2024-03\/200007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oxidative stress and inflammation are significant causes of aging. At the same time, citrus flavanones, naringenin (NAR), and hesperetin (HES) are bioactives with proven antioxidant and anti-inflammatory properties. Nevertheless, there are still no data about flavanone\u2019s influence and its potential effects on the healthy aging process and improving pituitary functioning. Thus, using qPCR, immunoblot, histological techniques, and biochemical assays, our study aimed to elucidate how citrus flavanones (15 mg\/kg b.m. per os) affect antioxidant defense, inflammation, and stress hormone output in the old rat model. Our results showed that HES restores the redox environment in the pituitary by down-regulating the nuclear factor erythroid 2-related factor 2 (Nrf2) protein while increasing kelch-like ECH-associated protein 1 (Keap1), thioredoxin reductase (TrxR1), and superoxide dismutase 2 (SOD2) protein expression. Immunofluorescent analysis confirmed Nrf2 and Keap1 down- and up-regulation, respectively. Supplementation with NAR increased Keap1, Trxr1, glutathione peroxidase (Gpx), and glutathione reductase (Gr) mRNA expression. Decreased oxidative stress aligned with NLRP3 decrement after both flavanones and glycogen synthase kinase-3 (GSK3) only after HES. The signal intensity of adrenocorticotropic hormone (ACTH) cells did not change, while corticosterone levels in serum decreased after both flavanones. HES showed higher potential than NAR in affecting a redox environment without increasing the inflammatory response, while a decrease in corticosterone level has a solid link to longevity. Our findings suggest that HES could improve and facilitate redox and inflammatory dysregulation in the rat\u2019s old pituitary.<\/jats:p>","DOI":"10.3390\/ijms25168918","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T06:23:20Z","timestamp":1723789400000},"page":"8918","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Citrus Flavanone Effects on the Nrf2-Keap1\/GSK3\/NF-\u03baB\/NLRP3 Regulation and Corticotroph-Stress Hormone Loop in the Old Pituitary"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8366-3138","authenticated-orcid":false,"given":"Marko","family":"Miler","sequence":"first","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmina","family":"\u017divanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9854-1934","authenticated-orcid":false,"given":"Sanja","family":"Kova\u010devi\u0107","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6931-3695","authenticated-orcid":false,"given":"Nevena","family":"Vidovi\u0107","sequence":"additional","affiliation":[{"name":"Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7042-1631","authenticated-orcid":false,"given":"Ana","family":"Djordjevic","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branko","family":"Filipovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6540-9603","authenticated-orcid":false,"given":"Vladimir","family":"Ajd\u017eanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/path.2110","article-title":"The endocrine system and ageing","volume":"211","author":"Chahal","year":"2007","journal-title":"J. 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