Pharmacological Modulation of Catecholaminergic Brain Injury by Dapagliflozin and Its Nanovesicular Formulation in an Isoproterenol Model.
- 1Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard (SPER), New Delhi, Delhi, India.
- 2Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, Delhi, India.
Abstract
Sustained β-adrenergic 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-glucose cotransporter-2 (SGLT2) inhibitor, exhibits pleiotropic antioxidant and anti-inflammatory properties; however, its effects on catecholamine-induced brain injury remain poorly defined. In the present study, we investigated the pharmacological effects of dapagliflozin and a bile salt-stabilized dapagliflozin-loaded nanovesicular formulation in an ISO-induced 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-responsive 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-assisted drug delivery, without implying a distinct pharmacodynamic mechanism.
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BibTeX
@article{bhat2026pharmacological,
title = {{Pharmacological Modulation of Catecholaminergic Brain Injury by Dapagliflozin and Its Nanovesicular Formulation in an Isoproterenol Model.}},
author = {Faisal Ashraf Bhat and Syed Ehtaishamul Haque and Mohammed Aqil and Mohd Akhtar and Abul Kalam Najmi},
journal = {Journal of biochemical and molecular toxicology},
year = {2026},
month = oct,
doi = {10.1002/jbt.71134},
url = {https://europepmc.org/article/MED/42893416},
note = {CC BY},
}
RIS
TY - JOUR
TI - Pharmacological Modulation of Catecholaminergic Brain Injury by Dapagliflozin and Its Nanovesicular Formulation in an Isoproterenol Model.
AU - Faisal Ashraf Bhat
AU - Syed Ehtaishamul Haque
AU - Mohammed Aqil
AU - Mohd Akhtar
AU - Abul Kalam Najmi
PY - 2026
DA - 2026/10/30
JO - Journal of biochemical and molecular toxicology
DO - 10.1002/jbt.71134
UR - https://europepmc.org/article/MED/42893416
AB - Sustained β-adrenergic 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-glucose cotransporter-2 (SGLT2) inhibitor, exhibits pleiotropic antioxidant and anti-inflammatory properties; however, its effects on catecholamine-induced brain injury remain poorly defined. In the present study, we investigated the pharmacological effects of dapagliflozin and a bile salt-stabilized dapagliflozin-loaded nanovesicular formulation in an ISO-induced 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-responsive 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-assisted drug delivery, without implying a distinct pharmacodynamic mechanism.
SN - 1095-6670
SN - 1099-0461
ER -