Vanillylacetone attenuates cadmium chloride-induced hippocampal damage and memory loss through upregulation of nuclear factor erythroid 2-related factor 2 gene and protein expression  

作　　者：Fahaid H.A.L-Hashem Salah O.Bashir Amal F.Dawood Moutasem S.Aboonq Ismaeel Bin-Jaliah Abdulaiziz M.Al-Garni Mohamed D.Morsy 

机构地区：[1]Department of Physiology,College of Medicine,King Khalid University,Abha,Saudi Arabia [2]Department of Basic Medical Sciences,College of Medicine,Princess Nourah bint Abdulrahman University,P.O.Box 84428,Riyadh 11671,Saudi Arabia [3]Department of Physiology,College of Medicine,Taibah University,Al-Madinah Al-Munawwarah,Saudi Arabia [4]Department of Medicine,College of Medicine,King Khalid University,Abha,Saudi Arabia

出　　处：《Neural Regeneration Research》2024年第12期2750-2759,共10页中国神经再生研究（英文版）

基　　金：funded by the Research Deanship of King Khalid University,No.GRP-215-43 (to FHA);Princess Nourah bint Abdulrohman University Researchers Supporting Project,No.PNURSP2023R110 (to AFD)。

摘　　要：Memory loss and dementia are major public health concerns with a substantial economic burden.Oxidative stress has been shown to play a crucial role in the pathophysiology of hippocampal damage-induced memory impairment.To investigate whether the antioxidant and anti-inflammatory compound vanillyla cetone(zingerone) can protect against hippocampal damage and memory loss induced by cadmium chloride(CdCl_(2)) administration in rats,we explo red the potential involvement of the nuclear factor erythroid 2-related factor 2(Nrf2) signaling pathway,which is known to modulate oxidative stress and inflammation.Sixty healt hy male Wistar rats were divided into five groups:vehicle-treated(control),vanillylacetone,CdCl_(2),vanillylacetone+ CdCl_(2),vanillylacetone+ CdCl_(2)+ brusatol(a selective pharmacological N rf2inhibitor) groups.Vanillylacetone effectively attenuated CdCl_(2)-induced damage in the dental gyrus of the hippocampus and improved the memory function assessed by the Morris Water Maze test.Additionally,vanillylacetone markedly decreased the hippocampal tissue levels of inflammatory biomarkers(interleukin-6,tumor necrosis factor-α,intracellular cell adhesive molecules) and apoptosis biomarkers(Bax and cleaved caspase-3).The control and CdCl_(2)-treated groups treated with va nillylacetone showed reduced generation of reactive oxygen species,decreased malondialdehyde levels,and increased superoxide dismutase and glutathione activities,along with significant elevation of nuclear Nrf2 mRNA and protein expression in hippocampal tissue.All the protective effects of vanillylacetone we re substantially blocked by the co-administration of brusatol(a selective N rf2 inhibitor).Va nillylacetone mitigated hippocampal damage and memory loss induced by CdCl_(2),at least in part, by activating the nuclear transcription factor Nrf2.Additionally,vanillylacetone exerted its potent antioxidant and antiinflammatory actions.

关 键 词：HIPPOCAMPUS NEUROPROTECTIVE Nrf2 gene oxidative stress vanillylacetone 

分 类 号：R749.16[医药卫生—神经病学与精神病学]