Ezetimibe Attenuates Oxidative Stress and Neuroinflammation via the AMPK/Nrf2/TXNIP Pathway after MCAO in Rats. 2020

Jing Yu, and Wen-Na Wang, and Nathanael Matei, and Xue Li, and Jin-Wei Pang, and Jun Mo, and Sheng-Pan Chen, and Ji-Ping Tang, and Min Yan, and John H Zhang
Department of Anesthesiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.

Oxidative stress and neuroinflammation play essential roles in ischemic stroke-induced brain injury. Previous studies have reported that Ezetimibe (Eze) exerts antioxidative stress and anti-inflammatory properties in hepatocytes. In the present study, we investigated the effects of Eze on oxidative stress and neuroinflammation in a rat middle cerebral artery occlusion (MCAO) model. One hundred and ninety-eight male Sprague-Dawley rats were used. Animals assigned to MCAO were given either Eze or its control. To explore the downstream signaling of Eze, the following interventions were given: AMPK inhibitor dorsomorphin and nuclear factor erythroid 2-related factor 2 (Nrf2) siRNA. Intranasal administration of Eze, 1 h post-MCAO, further increased the endogenous p-AMPK expression, reducing brain infarction, neurologic deficits, neutrophil infiltration, microglia/macrophage activation, number of dihydroethidium- (DHE-) positive cells, and malonaldehyde (MDA) levels. Specifically, treatment with Eze increased the expression of p-AMPK, Nrf2, and HO-1; Romo-1, thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), Cleaved Caspase-1, and IL-1β were reduced. Dorsomorphin and Nrf2 siRNA reversed the protective effects of Eze. In summary, Eze decreases oxidative stress and subsequent neuroinflammation via activation of the AMPK/Nrf2/TXNIP pathway after MCAO in rats. Therefore, Eze may be a potential therapeutic approach for ischemic stroke patients.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008297 Male Males
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000069438 Ezetimibe An azetidine derivative and ANTICHOLESTEREMIC AGENT that inhibits intestinal STEROL absorption. It is used to reduce total CHOLESTEROL; LDL CHOLESTEROL, and APOLIPOPROTEINS B in the treatment of HYPERLIPIDEMIAS. (1-(4-fluorophenyl)-(3R)-(3-(4-fluorophenyl)-(3S)-hydroxypropyl)-(4S)-(4-hydroxyphenyl)-2-azetidinone),Ezetimib,Ezetrol,SCH 58235,SCH-58235,SCH58235,Zetia,58235, SCH
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051267 NF-E2-Related Factor 2 A basic-leucine zipper transcription factor that was originally described as a transcriptional regulator controlling expression of the BETA-GLOBIN gene. It may regulate the expression of a wide variety of genes that play a role in protecting cells from oxidative damage. Nfe2l2 Protein,Nuclear Factor (Erythroid-Derived 2)-Like 2 Protein,Nuclear Factor E2-Related Factor 2,NF E2 Related Factor 2,Nuclear Factor E2 Related Factor 2
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D055372 AMP-Activated Protein Kinases Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP. 5'-AMP-Activated Protein Kinase,AMP-Activated Kinase,AMP-Activated Protein Kinase,AMP-Activated Protein Kinase alpha Subunit,AMP-Activated Protein Kinase alpha Subunits,AMP-Activated Protein Kinase beta Subunit,AMP-Activated Protein Kinase beta Subunits,AMP-Activated Protein Kinase gamma Subunit,AMP-Activated Protein Kinase gamma Subunits,PRKAA,5' AMP Activated Protein Kinase,AMP Activated Kinase,AMP Activated Protein Kinase,AMP Activated Protein Kinase alpha Subunit,AMP Activated Protein Kinase alpha Subunits,AMP Activated Protein Kinase beta Subunit,AMP Activated Protein Kinase beta Subunits,AMP Activated Protein Kinase gamma Subunit,AMP Activated Protein Kinase gamma Subunits,AMP Activated Protein Kinases
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative

Related Publications

Jing Yu, and Wen-Na Wang, and Nathanael Matei, and Xue Li, and Jin-Wei Pang, and Jun Mo, and Sheng-Pan Chen, and Ji-Ping Tang, and Min Yan, and John H Zhang
June 2022, Antioxidants (Basel, Switzerland),
Jing Yu, and Wen-Na Wang, and Nathanael Matei, and Xue Li, and Jin-Wei Pang, and Jun Mo, and Sheng-Pan Chen, and Ji-Ping Tang, and Min Yan, and John H Zhang
October 2023, Redox biology,
Jing Yu, and Wen-Na Wang, and Nathanael Matei, and Xue Li, and Jin-Wei Pang, and Jun Mo, and Sheng-Pan Chen, and Ji-Ping Tang, and Min Yan, and John H Zhang
January 2019, Frontiers in pharmacology,
Jing Yu, and Wen-Na Wang, and Nathanael Matei, and Xue Li, and Jin-Wei Pang, and Jun Mo, and Sheng-Pan Chen, and Ji-Ping Tang, and Min Yan, and John H Zhang
September 2018, Experimental neurology,
Jing Yu, and Wen-Na Wang, and Nathanael Matei, and Xue Li, and Jin-Wei Pang, and Jun Mo, and Sheng-Pan Chen, and Ji-Ping Tang, and Min Yan, and John H Zhang
October 2020, Inflammation,
Jing Yu, and Wen-Na Wang, and Nathanael Matei, and Xue Li, and Jin-Wei Pang, and Jun Mo, and Sheng-Pan Chen, and Ji-Ping Tang, and Min Yan, and John H Zhang
November 2017, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association,
Jing Yu, and Wen-Na Wang, and Nathanael Matei, and Xue Li, and Jin-Wei Pang, and Jun Mo, and Sheng-Pan Chen, and Ji-Ping Tang, and Min Yan, and John H Zhang
January 2024, FASEB journal : official publication of the Federation of American Societies for Experimental Biology,
Jing Yu, and Wen-Na Wang, and Nathanael Matei, and Xue Li, and Jin-Wei Pang, and Jun Mo, and Sheng-Pan Chen, and Ji-Ping Tang, and Min Yan, and John H Zhang
February 2018, Neurobiology of disease,
Jing Yu, and Wen-Na Wang, and Nathanael Matei, and Xue Li, and Jin-Wei Pang, and Jun Mo, and Sheng-Pan Chen, and Ji-Ping Tang, and Min Yan, and John H Zhang
August 2018, The Journal of surgical research,
Jing Yu, and Wen-Na Wang, and Nathanael Matei, and Xue Li, and Jin-Wei Pang, and Jun Mo, and Sheng-Pan Chen, and Ji-Ping Tang, and Min Yan, and John H Zhang
April 2015, Toxicology letters,
Copied contents to your clipboard!