DAPAGLIFLOZIN/ CARVEOL COMBINATION AMELIORATES PENTYLENETETRAZOLE INDUCED EPILEPSY IN RATS: ANTIOXIDANT, ANTI-INFLAMMATORY AND ANTI-APOPTOTIC EFFECTS: TARGETING TLR4/MIR-181B/NFKB

Seleem, Monira; Eltantawy, Asmaa F.; Almeldin, Ahmed; Ibrahim, Hoda A.; El-Gohary, Rehab; Azzam, Asmaa; Ibrahim, Sarah; Elkordy, Alaa; Faheem, Heba

doi:10.21608/bfsa.2024.316010.2256

	DAPAGLIFLOZIN/ CARVEOL COMBINATION AMELIORATES PENTYLENETETRAZOLE INDUCED EPILEPSY IN RATS: ANTIOXIDANT, ANTI-INFLAMMATORY AND ANTI-APOPTOTIC EFFECTS: TARGETING TLR4/MIR-181B/NFKB
Bulletin of Pharmaceutical Sciences Assiut University
Volume 48, Issue 1, June 2025, Page 665-680 PDF (1.45 MB)
Document Type: Original Article
DOI: 10.21608/bfsa.2024.316010.2256
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Authors
Monira Seleem¹; Asmaa F. Eltantawy¹; Ahmed Almeldin ²; Hoda A. Ibrahim³; Rehab El-Gohary³; Asmaa Azzam⁴; Sarah Ibrahim⁴; Alaa Elkordy⁵; Heba Faheem²
¹Medical Pharmacology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
²Medical Physiology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
³Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta31527, Egypt
⁴Anatomy and Embryology Department, Faculty of Medicine, Tanta University, Tanta31527, Egypt
⁵Neuropsychiatry Department, Faculty of Medicine, Tanta University, Tanta31527, Egypt
Abstract
Background: Epilepsy is a significant public health problem, which encompasses socio-cultural, psychological, and economic dimensions. Dapagliflozin is an SGLT2 inhibitor that has antiseizure activity. Carveol is a naturally occurring monocyclic monoterpenoid compound with antioxidant properties. This study examines the impacts of Dapagliflozin and Carveol, either monotherapy or in combination, on PTZ-induced epilepsy in rats. Methods: 45 Male Wistar rats were randomly categorized in 5 equal groups: Group I: Control Group, Group II: PTZ Group, Group III: Dapagliflozin-Treated Group, Group IV: Carveol-Treated Group and Group V: Dapagliflozin + Carveol Treated Group. Hippocampal tissues were obtained for assay of tissue biomarkers including, SOD, MDA, NFκB, IL-6, TNF-alpha, Beclin-1, GABA, glutamate, gene expression of TLR4, miR-181b, NKCC1 and KCC2, immunohistochemical analysis of caspase 3 and histopathological analysis. Results: Dapagliflozin and Carveol treated group (Group V) ameliorated PTZ induced epilepsy evidenced by increased GABA, decreased glutamate, improvement of histopathology and oxidative stress via upregulation of SOD and downregulation of MDA, improved inflammation via significant reduction of NFκB, IL-6, TNF-α. Moreover, modulation of apoptosis and autophagy process via significant reduction of caspase3, TLR4 gene expression and up regulation of miR-181b gene expression and beclin-1, a significant increase in GABA and gene expression of KCC2 accompanied with a significant decrease in glutamate and gene expression of NKCC1, compared to other groups. Conclusion: The combination of Dapagliflozin and Carveol exhibited significantly better antioxidant, anti-inflammatory and anti-apoptotic effects than monotherapy by either of each of both drugs against PTZ induced epilepsy.
Keywords
Dapagliflozin; Carveol; Pentylenetetrazol; Epilepsy; Experimental Model


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