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Neuroprotective Effects of Probucol against Rotenone-Induced Toxicity via Suppression of Reactive Oxygen Species Production in SH-SY5Y Cells.
- Source :
-
Biological & pharmaceutical bulletin [Biol Pharm Bull] 2024; Vol. 47 (6), pp. 1154-1162. - Publication Year :
- 2024
-
Abstract
- Probucol is a hyperlipidemic drug with antioxidant properties. It has been reported to prevent mitochondrial dysfunction, reduce oxidative stress, and suppress neurotoxicity in neurodegenerative disease models, including Parkinson's disease models. However, the molecular mechanisms underlying the neuroprotective effects of probucol have been not examined yet. Thus, in this study, we investigated whether probucol can alleviate the effects of a mitochondrial complex I inhibitor, rotenone, on a human neuroblastoma cell line (SH-SY5Y). We evaluated the cell viability and cytotoxicity and apoptosis rates of SH-SY5Y cells treated with rotenone and probucol or edaravone, a known free-radical scavenger. Subsequently, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels in the cells were evaluated to determine the effects of probucol on mitochondrial function. We found that rotenone caused cytotoxicity, cell apoptosis, and mitochondrial dysfunction, enhanced ROS generation, and impaired MMP. However, probucol could inhibit this rotenone-induced decrease in cell viability, MMP loss, intracellular ROS generation, and apoptosis. These results suggest that probucol exerts neuroprotective effects via MMP stabilization and the inhibition of ROS generation. Additionally, this effect of probucol was equal to or greater than and more persistent than that of edaravone. Thus, we believe probucol may be a promising drug for the treatment of neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases.
- Subjects :
- Humans
Cell Line, Tumor
Mitochondria drug effects
Mitochondria metabolism
Oxidative Stress drug effects
Antioxidants pharmacology
Probucol pharmacology
Rotenone toxicity
Reactive Oxygen Species metabolism
Neuroprotective Agents pharmacology
Cell Survival drug effects
Apoptosis drug effects
Membrane Potential, Mitochondrial drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1347-5215
- Volume :
- 47
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biological & pharmaceutical bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 38880623
- Full Text :
- https://doi.org/10.1248/bpb.b24-00099