Eprosartan: A closer insight into its neuroprotective activity in rats with focal cerebral ischemia-reperfusion injury
Autor: | Ahmed Abd El-Aziz Hegazy, Muhammad Y. Al-Shorbagy, Mohamed Ibrahim Mohamed Fahmy, Reham Abdelrahman Elnaggar, Muhammad Farag El-Yamany, Muhammad Abd El-Latif Saad, Rabab H. Sayed |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male Angiotensin receptor Health Toxicology and Mutagenesis Ischemia Nerve Tissue Proteins Thiophenes Pharmacology Toxicology medicine.disease_cause Biochemistry Neuroprotection 03 medical and health sciences 0302 clinical medicine medicine Hippocampus (mythology) Animals Rats Wistar Molecular Biology Angiotensin II receptor type 1 030102 biochemistry & molecular biology business.industry Imidazoles Brain General Medicine medicine.disease Rats Cerebrovascular Disorders Neuroprotective Agents Acrylates Apoptosis 030220 oncology & carcinogenesis Reperfusion Injury Molecular Medicine business Reperfusion injury Oxidative stress Signal Transduction |
Zdroj: | Journal of biochemical and molecular toxicologyREFERENCES. 35(7) |
ISSN: | 1099-0461 |
Popis: | Eprosartan (EPRO), an angiotensin receptor type-1 (AT-1) blocker, exhibited neuroprotective activities in ischemic stroke resulting from focal cerebral ischemia in rats. The current study aimed to clarify the neuroprotective role of EPRO in middle carotid artery occlusion (MCAO)-induced ischemic stroke in rats. Fifty-six male Wistar rats were divided into four groups (n = 14 per group): sham-operated group, sham receiving EPRO (60 mg/kg/day, po) group, ischemia-reperfusion (IR) group, and IR receiving EPRO (60 mg/kg/day, po) group. MCAO led to a remarkable impairment in motor function together with stimulation of inflammatory and apoptotic pathways in the hippocampus of rats. After MCAO, the AT1 receptor in the brain was stimulated, resulting in activation of Janus kinase 2/signal transducers and activators of transcription 3 signaling generating more neuroinflammatory milieu and destructive actions on the hippocampus. Augmentation of caspase-3 level by MCAO enhanced neuronal apoptosis synchronized with neurodegenerative effects of oxidative stress biomarkers. Pretreatment with EPRO opposed motor impairment and decreased oxidative and apoptotic mediators in the hippocampus of rats. The anti-inflammatory activity of EPRO was revealed by downregulation of nuclear factor-kappa B and tumor necrosis factor-β levels and (C-X-C motif) ligand 1 messenger RNA (mRNA) expression. Moreover, the study confirmed the role of EPRO against a unique pathway of hypoxia-inducible factor-1α and its subsequent inflammatory mediators. Furthermore, upregulation of caveolin-1 mRNA level was also observed along with decreased oxidative stress marker levels and brain edema. Therefore, EPRO showed neuroprotective effects in MCAO-induced cerebral ischemia in rats via attenuation of oxidative, apoptotic, and inflammatory pathways. |
Databáze: | OpenAIRE |
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