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Trichostatin A Shows Transient Protection from Chronic Alcohol-Induced Reactive Oxygen Species (ROS) Production in
Tiyash Parira1, Gloria Figueroa1, Sherly Granado1
1Department of Immunology and Nano-Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.
Journal of Alcoholism and Drug Dependence
|January 1, 2019
Summary
Trichostatin A (TSA) offers transient protection against alcohol-induced ROS in human dendritic cells, but long-term exposure causes toxicity. The antioxidant regulator Nrf2 may mediate TSA's effects, warranting further investigation.
Area of Science:
- Immunology
- Cell Biology
- Toxicology
Background:
- Chronic alcohol exposure induces oxidative stress (ROS) in immune cells.
- Dendritic cells play a crucial role in immune responses.
- Histone deacetylase (HDAC) inhibitors are being explored for therapeutic potential.
Purpose of the Study:
- To investigate if Trichostatin A (TSA) can inhibit or reverse alcohol-induced ROS in human monocyte-derived dendritic cells (MDDCs).
- To examine the impact of alcohol and TSA on ROS production and the antioxidant regulator Nrf2 in MDDCs.
Main Methods:
- MDDCs were chronically treated with varying concentrations of alcohol (0.1% and 0.2%).
- Intracellular, extracellular, and total ROS levels were measured using DCF-DA and imaging flow cytometry.
- Nrf2 expression was analyzed via qRT-PCR and western blot; in silico analysis of relevant genes was performed.
Main Results:
- Alcohol rapidly increased intracellular ROS levels in MDDCs.
- TSA demonstrated a transient protective effect, reducing ROS only up to 15 minutes post-treatment.
- Chronic alcohol exposure upregulated Nrf2 expression in a dose-dependent manner, an effect enhanced by TSA at higher alcohol concentrations.
Conclusions:
- TSA provides a temporary protective effect against alcohol-induced ROS in MDDCs.
- Prolonged co-exposure to alcohol and TSA leads to cellular toxicity.
- Nrf2 may be involved in TSA's mechanism, but further research is needed to elucidate the molecular pathways.
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