MitoQ alleviates hippocampal damage after cerebral ischemia: The potential role of SIRT6 in regulating mitochondrial dysfunction and neuroinflammation.

Autor: Ibrahim AA; Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo, Egypt., Abdel Mageed SS; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt. Electronic address: Sherif.abdelmeguid@buc.edu.eg., Safar MM; Department of Pharmacology and Biochemistry, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: marwa.safar@bue.edu.eg., El-Yamany MF; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: mohammed.elyamany@pharma.cu.edu.eg., Oraby MA; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Badr University in Cairo, 11829 Cairo, Egypt. Electronic address: Mamdouh.ahmed@buc.edu.eg.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2023 Sep 01; Vol. 328, pp. 121895. Date of Electronic Publication: 2023 Jun 27.
DOI: 10.1016/j.lfs.2023.121895
Abstrakt: Aims: Mitochondrial perturbations are the major culprit of the inflammatory response during the initial phase of cerebral ischemia. The present study explored the neuroprotective effect of the mitochondrial-targeted antioxidant, Mitoquinol (MitoQ), against hippocampal neuronal loss in an experimental model of brain ischemia/reperfusion (I/R) injury.
Main Methods: Rats were subjected to common carotid artery occlusion for 45 min, followed by reperfusion for 24 h. MitoQ (2 mg/kg; i.p daily) was administered for 7 successive days prior to the induction of brain ischemia.
Key Findings: I/R rats exhibited hippocampal damage evidenced by aggravated mitochondrial oxidative stress, thereby enhancing mtROS and oxidized mtDNA, together with inhibiting mtGSH. Mitochondrial biogenesis and function were also affected, as reflected by the reduction of PGC-1α, TFAM, and NRF-1 levels, as well as loss of mitochondrial membrane potential (△Ψm (. These changes were associated with neuroinflammation, apoptosis, impairment of cognitive function as well as hippocampal neurodegenerative changes in histopathological examination. Notably, SIRT6 was suppressed. Pretreatment with MitoQ markedly potentiated SIRT6, modulated mitochondrial oxidative status and restored mitochondrial biogenesis and function. In addition, MitoQ alleviated the inflammatory mediators, TNF-α, IL-18, and IL-1β and dampened GFAB immunoexpression along with downregulation of cleaved caspase-3 expression. Reversal of hippocampal function by MitoQ was accompanied by improved cognitive function and hippocampal morphological aberrations.
Significance: This study suggests that MitoQ preserved rats' hippocampi from I/R insults via maintenance of mitochondrial redox status, biogenesis, and activity along with mitigation of neuroinflammation and apoptosis, thereby regulating SIRT6.
Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: