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Published on: July 12, 2012
Protective Effects of Probucol on Different Brain Cells Exposed to Manganese
Erica Blenda da Silva1, Tuany Eichwald2, Viviane Glaser3
1Graduada em Medicina, Área de Ciências da Vida e Saúde, Universidade do Oeste de Santa Catarina (UNOESC), Campus de Joaçaba, SC, 89600-000, Joaçaba, Brazil.
Abstract:
Manganese (Mn) is an essential metal for many functions in the body. However, in excess, it can be neurotoxic and cause a Parkinson-like syndrome, known as manganism. Here, we aimed to identify a protective effect of probucol, a lipid-lowering agent with anti-inflammatory and antioxidant properties, against Mn-induced toxicity in human neuroblastoma (SH-SY5Y) and glioblastoma (C6) cell lines. The cells were incubated with increasing concentrations of Mn followed by probucol addition 1, 3, 6, and/or 24 h to assess the metal toxic doses and measure the protective effect of probucol against Mn-induced oxidative damage. Longer exposition to Mn showed decreased SH-SY5Y cellular viability in concentrations higher than 100 µM, and probucol was able to prevent this effect. The C6 cells were more sensitive to the Mn deleterious actions, decreasing the cell viability after 6 h of 500 µM Mn exposure. In addition, probucol prevents the complex I and II of the mitochondrial respiratory chain (MRC) inhibition caused by Mn and decreased the intracellular ROS production. Taken together, our results showed that Mn toxicity affects differently both cell lines and probucol has a protective effect against the oxidative imbalance in the central nervous system.
Insights
Probucol, an antioxidant drug, protects against manganese (Mn) neurotoxicity by preventing oxidative damage and mitochondrial dysfunction in human brain cells. This study highlights probucol
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Manganese (Mn) is essential but toxic in excess, causing Parkinson-like symptoms (manganism).
- Neuroinflammation and oxidative stress are key mechanisms in Mn neurotoxicity.
- Probucol possesses antioxidant and anti-inflammatory properties with potential neuroprotective roles.
Purpose of the Study:
- To investigate the protective effect of probucol against manganese-induced neurotoxicity.
- To assess probucol's impact on oxidative stress and mitochondrial function in neuronal cell lines.
Main Methods:
- Human neuroblastoma (SH-SY5Y) and glioblastoma (C6) cells were exposed to varying Mn concentrations.
- Cells were treated with probucol at different time points post-Mn exposure.
- Cell viability, reactive oxygen species (ROS) production, and mitochondrial respiratory chain (MRC) complex activity were measured.
Main Results:
- Mn exposure decreased SH-SY5Y cell viability above 100 µM, an effect mitigated by probucol.
- C6 cells exhibited higher sensitivity to Mn, with reduced viability after 6h exposure to 500 µM Mn.
- Probucol prevented Mn-induced inhibition of MRC complexes I and II and reduced intracellular ROS.
Conclusions:
- Manganese toxicity differentially impacts neuronal and glioblastoma cell lines.
- Probucol demonstrates significant neuroprotective effects against Mn-induced oxidative stress and mitochondrial dysfunction.
- These findings suggest probucol as a potential therapeutic agent for managing manganese neurotoxicity.
