Vitamin B6 Via p-JNK/Nrf-2/NF-κB Signaling Ameliorates Cadmium Chloride-Induced Oxidative Stress Mediated Memory Deficits in Mice Hippocampus

• Published in: Current neuropharmacology Vol. 23; no. 1; pp. 116 - 127
• Main Authors: Nasir, Abdul, Ur Rahman, Mujeeb, Khan, Manzar, Zahid, Muhammad, Shahab, Muhammad, Jiao, Hongjun, Zeb, Amir, Shah, Shahid Ali, Khan, Haroon
• Format: Journal Article
• Language: English
• Published: United Arab Emirates Bentham Science Publishers 2024
• Subjects: Animals; Antioxidants - pharmacology; Cadmium Chloride - toxicity; Disks Large Homolog 4 Protein - metabolism; Hippocampus - drug effects; Hippocampus - metabolism; Male; Memory Disorders - chemically induced; Memory Disorders - drug therapy; Mice; Molecular Docking Simulation; Neuroinflammatory Diseases - drug therapy; Neuroinflammatory Diseases - metabolism; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; Oxidative Stress - drug effects; Signal Transduction - drug effects; Synaptophysin; Vitamin B 6 - pharmacology; Oxidative stress; neurodegenerative disease; neurotoxicity; antiinflammatory; neuroinflammation; Alzheimer's disease
• ISSN: 1570-159X; 1875-6190; 1875-6190
• DOI: 10.2174/1570159X22999240730154422

Background: Cadmium chloride (Cd) is a pervasive environmental heavy metal pollutant linked to mitochondrial dysfunction, memory loss, and genetic disorders, particularly in the context of neurodegenerative diseases like Alzheimer's disease (AD).
Methods: This study investigated the neurotherapeutic potential of vitamin B6 (Vit. B6) in mitigating Cd-induced oxidative stress and neuroinflammation-mediated synaptic and memory dysfunction. Adult albino mice were divided into four groups: Control (saline-treated), Cd-treated, Cd+Vit. B6- treated, and Vit. B6 alone-treated. Cd and Vit. B6 were administered intraperitoneally, and behavioral tests (Morris Water Maze, Y-Maze) were conducted. Subsequently, western blotting, antioxidant assays, blood glucose, and hyperlipidemia assessments were performed.
Results: Cd-treated mice exhibited impaired cognitive function, while Cd+Vit. B6-treated mice showed significant improvement. Cd-induced neurotoxic effects, including oxidative stress and neuroinflammation, were observed, along with disruptions in synaptic proteins (SYP and PSD95) and activation of p-JNK. Vit. B6 administration mitigated these effects, restoring synaptic and memory deficits. Molecular docking and MD simulation studies confirmed Vit. B6's inhibitory effect on IL-1β, NRF2, and p-JNK proteins.
Conclusion: These results highlight Vit. B6 as a safe therapeutic supplement to mitigate neurodegenerative disorders, emphasizing the importance of assessing nutritional interventions for combating environmental neurotoxicity in the interest of public health.