Attenuation of Vanadium-Induced Neurotoxicity in Rat Hippocampal Slices (In Vitro) and Mice (In Vivo) by ZA-II-05, a Novel NMDA-Receptor Antagonist.
Amany Digal LadaguFunmilayo Eniola OlopadePaul L ChazotAdemola Adetokunbo OyagbemiSamuel OhiomokhareOluwabusayo Racheal FolarinTaidinda Tashara GilbertMadison FullerToan LuongAdeboye AdejareJames O OlopadePublished in: International journal of molecular sciences (2023)
Exposure to heavy metals, such as vanadium, poses an ongoing environmental and health threat, heightening the risk of neurodegenerative disorders. While several compounds have shown promise in mitigating vanadium toxicity, their efficacy is limited. Effective strategies involve targeting specific subunits of the NMDA receptor, a glutamate receptor linked to neurodegenerative conditions. The potential neuroprotective effects of ZA-II-05, an NMDA receptor antagonist, against vanadium-induced neurotoxicity were explored in this study. Organotypic rat hippocampal slices, and live mice, were used as models to comprehensively evaluate the compound's impact. Targeted in vivo fluorescence analyses of the hippocampal slices using propidium iodide as a marker for cell death was utilized. The in vivo study involved five dams, each with eight pups, which were randomly assigned to five experimental groups ( n = 8 pups). After administering treatments intraperitoneally over six months, various brain regions were assessed for neuropathologies using different immunohistochemical markers. High fluorescence intensity was observed in the hippocampal slices treated with vanadium, signifying cell death. Vanadium-exposed mice exhibited demyelination, microgliosis, and neuronal cell loss. Significantly, treatment with ZA-II-05 resulted in reduced cellular death in the rat hippocampal slices and preserved cellular integrity and morphological architecture in different anatomical regions, suggesting its potential in countering vanadium-induced neurotoxicity.
Keyphrases
- cerebral ischemia
- cell death
- diabetic rats
- oxidative stress
- high glucose
- subarachnoid hemorrhage
- heavy metals
- drug induced
- public health
- cancer therapy
- healthcare
- temporal lobe epilepsy
- stem cells
- risk assessment
- single molecule
- single cell
- blood brain barrier
- type diabetes
- drug delivery
- wild type
- mental health
- resting state
- metabolic syndrome
- multiple sclerosis
- functional connectivity
- mesenchymal stem cells
- cell therapy
- health information
- machine learning
- bone marrow
- insulin resistance
- artificial intelligence
- drinking water