{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:06:39Z","timestamp":1789470399599,"version":"build-2803163510"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Studies of redox status and bioenergetics in cardiac tissue during unpredictable chronic mild stress (UCMS) are scarce. The present study examined the effect of candesartan, an angiotensin II type 1 receptor (AT1R) blocker primarily used to treat hypertension and congestive heart failure, on the antioxidant capacity and energy homeostasis of cardiac tissue in UCMS-subjected rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Forty-eight male Wistar rats were randomly assigned to four groups (n = 12\/group): undosed normal controls (NC), UCMS-subjected rats (UCMS), unstressed candesartan-treated rats (Can), and stressed candesartan-treated rats (UCMS + Can). Enzyme activities and mRNA transcripts of key antioxidant enzymes, tricarboxylic acid cycle enzymes, and respiratory chain complexes were measured in myocardial tissue, together with oxidative-phosphorylation (OXPHOS) markers, redox state, and the energy-homeostasis ratios GSH\/GSSG, NAD\n                      <jats:sup>+<\/jats:sup>\n                      \/NADH, and ATP\/ADP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The UCMS group showed marked elevations in oxidative-stress markers, accompanied by significantly reduced antioxidant enzyme activities and downregulated antioxidant gene expression. In parallel, all TCA-cycle and OXPHOS enzyme activities were significantly decreased, and their relative gene transcripts were markedly downregulated. The cellular GSH\/GSSG and ATP\/ADP ratios were significantly lowered, whereas the NAD\n                      <jats:sup>+<\/jats:sup>\n                      \/NADH ratio was increased. Each of these changes was either fully reversed or significantly attenuated in unstressed and stressed rats receiving candesartan.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Candesartan clearly mitigates cellular oxidative stress and the disruption of energy metabolism in the myocardial tissue of UCMS-subjected rats. Because blood pressure, cardiac function and systemic haemodynamics were not measured, these findings should be interpreted as biochemical evidence of a cytoprotective action of AT1R blockade in myocardial tissue, and they provide a preliminary rationale for further evaluation of candesartan in stress-related cardiovascular disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1876050","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:42:58Z","timestamp":1789468978000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of candesartan on cellular redox status and bioenergetics of cardiac tissue in normal and chronically stressed rats"],"prefix":"10.3389","volume":"17","author":[{"given":"Mahmoud M. A.","family":"Abulmeaty","sequence":"first","affiliation":[{"name":"Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazem K.","family":"Ghneim","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dara","family":"Aldisi","sequence":"additional","affiliation":[{"name":"Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reham M.","family":"Wahid","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, Zagazig University","place":["Zagazig, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesam M. 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