{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T13:41:32Z","timestamp":1792330892578,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Sustained \u03b2\u2010adrenergic stimulation represents a pharmacologically relevant stressor capable of inducing systemic oxidative and inflammatory injury that extends to the central nervous system. Isoproterenol (ISO), a synthetic catecholamine, is widely used to model catecholaminergic injury in experimental settings. Dapagliflozin, a sodium\u2013glucose cotransporter\u20102 (SGLT2) inhibitor, exhibits pleiotropic antioxidant and anti\u2010inflammatory properties; however, its effects on catecholamine\u2010induced brain injury remain poorly defined. In the present study, we investigated the pharmacological effects of dapagliflozin and a bile salt\u2013stabilized dapagliflozin\u2010loaded nanovesicular formulation in an ISO\u2010induced model of catecholaminergic brain injury in rats. ISO administration resulted in marked oxidative imbalance, neuroinflammatory activation, behavioral dysfunction, and structural alterations in hippocampal and cortical regions. These changes were accompanied by reduced expression of stress\u2010responsive and neurotrophic proteins, including SIRT6, TRAP1, and BDNF, along with enhanced astroglial activation as indicated by increased GFAP immunoreactivity. Treatment with dapagliflozin attenuated these molecular, cellular, and functional alterations, while the nanovesicular formulation produced a more pronounced improvement of redox balance, suppression of inflammatory responses, normalization of protein expression, and preservation of neuronal architecture and behavior. Collectively, these findings demonstrate that dapagliflozin mitigates catecholaminergic brain injury through attenuation of oxidative and inflammatory stress, with enhanced efficacy achieved via formulation\u2010assisted drug delivery, without implying a distinct pharmacodynamic mechanism.<\/jats:p>","DOI":"10.1002\/jbt.71134","type":"journal-article","created":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T12:56:01Z","timestamp":1792328161000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological Modulation of Catecholaminergic Brain Injury by Dapagliflozin and Its Nanovesicular Formulation in an Isoproterenol Model"],"prefix":"10.1002","volume":"40","author":[{"given":"Faisal Ashraf","family":"Bhat","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Pharmaceutical Education and Research, Jamia Hamdard (SPER) New Delhi Delhi 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