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

Fahaid H Al-Hashem; Salah O Bashir; Amal F Dawood; Moutasem S Aboonq; Ismaeel Bin-Jaliah; Abdulaiziz M Al-Garni; Mohamed D Morsy

doi:10.4103/1673-5374.391300

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

Neural Regen Res. 2024 Dec 1;19(12):2750-2759. doi: 10.4103/1673-5374.391300. Epub 2023 Dec 21.

Authors

Fahaid H Al-Hashem¹, Salah O Bashir¹, Amal F Dawood², Moutasem S Aboonq³, Ismaeel Bin-Jaliah¹, Abdulaiziz M Al-Garni⁴, Mohamed D Morsy¹

Affiliations

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.

PMID: 38595292
DOI: 10.4103/1673-5374.391300

Abstract

JOURNAL/nrgr/04.03/01300535-202412000-00030/figure1/v/2024-04-08T165401Z/r/image-tiff 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 vanillylacetone (zingerone) can protect against hippocampal damage and memory loss induced by cadmium chloride (CdCl2) administration in rats, we explored 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 healthy male Wistar rats were divided into five groups: vehicle-treated (control), vanillylacetone, CdCl2, vanillylacetone + CdCl2, vanillylacetone + CdCl2 + brusatol (a selective pharmacological Nrf2 inhibitor) groups. Vanillylacetone effectively attenuated CdCl2-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 CdCl2-treated groups treated with vanillylacetone 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 were substantially blocked by the co-administration of brusatol (a selective Nrf2 inhibitor). Vanillylacetone mitigated hippocampal damage and memory loss induced by CdCl2, at least in part, by activating the nuclear transcription factor Nrf2. Additionally, vanillylacetone exerted its potent antioxidant and anti-inflammatory actions.