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Mitochondrial functions of THP-1 monocytes following the exposure to selected natural compounds
Nadin Schultze1, Heike Wanka2, Paula Zwicker1
1Institute of Pharmacy, Pharmaceutical Biology, Ernst-Moritz-Arndt University of Greifswald, D17489 Greifswald, Germany.
Abstract:
The immune system is an important target of various xenobiotics, which may lead to severe adverse effects including immunosuppression or inappropriate immunostimulation. Mitochondrial toxicity is one possibility by which xenobiotics exert their toxic effects in cells or organs. In this study, we investigated the impact of three natural compounds, cyclosporine A (CsA), deoxynivalenol (DON) and cannabidiol (CBD) on mitochondrial functions in the THP-1 monocytic cell line. The cells were exposed for 24h to two different concentrations (IC10 and IC50 determined by MTT) of each compound. The cells showed concentration-dependent elevated intracellular reactive oxygen species (iROS) and induction of apoptosis (except DON) in response to the three test compounds. Mitochondrial functions were characterized by using bioenergetics profiling experiments. In THP-1 monocytes, the IC50 of CsA decreased basal and maximal respiration as well as ATP production with an impact on spare capacity indicating a mitochondrial dysfunction. Similar reaction patterns were observed following CBD exposure. The basal respiration level and ATP-production decreased in the THP-1 cells exposed to the IC50 of DON with no major impact on mitochondrial function. In conclusion, impaired mitochondrial function was accompanied by elevated iROS and apoptosis level in a monocytic cell line exposed to CsA and CBD. Mitochondrial dysfunction may be one explanation for the cytotoxicity of CBD and CsA also in other in immune cells.
Insights
Cyclosporine A (CsA) and cannabidiol (CBD) impair mitochondrial function, increasing reactive oxygen species and apoptosis in immune cells. Deoxynivalenol (DON) showed minimal impact on mitochondria. This suggests mitochondrial dysfunction contributes to CsA and CBD toxicity.
Area of Science:
- Immunotoxicology
- Mitochondrial Biology
- Cellular Toxicology
Background:
- Xenobiotics can adversely affect the immune system, potentially causing immunosuppression or overstimulation.
- Mitochondrial toxicity is a key mechanism through which xenobiotics exert cellular and organ damage.
- Understanding xenobiotic effects on immune cell mitochondria is crucial for assessing toxicity.
Purpose of the Study:
- To investigate the impact of cyclosporine A (CsA), deoxynivalenol (DON), and cannabidiol (CBD) on mitochondrial function in THP-1 monocytic cells.
- To determine if mitochondrial dysfunction contributes to the cytotoxicity of these natural compounds.
Main Methods:
- THP-1 monocytic cells were exposed to varying concentrations (IC10 and IC50) of CsA, DON, and CBD for 24 hours.
- Intracellular reactive oxygen species (iROS) and apoptosis levels were measured.
- Mitochondrial function was assessed using bioenergetics profiling, measuring respiration and ATP production.
Main Results:
- CsA and CBD exposure led to concentration-dependent increases in iROS and apoptosis.
- CsA and CBD at IC50 significantly reduced basal and maximal respiration, ATP production, and spare respiratory capacity, indicating mitochondrial dysfunction.
- DON exposure increased iROS but did not induce significant apoptosis or major mitochondrial dysfunction at the tested concentrations.
- Impaired mitochondrial function correlated with elevated iROS and apoptosis in CsA- and CBD-treated cells.
Conclusions:
- Mitochondrial dysfunction is a key mechanism underlying the observed cytotoxicity of CsA and CBD in THP-1 monocytic cells.
- These findings suggest that mitochondrial impairment may be a common pathway for CsA and CBD toxicity in various immune cells.
- DON exhibits a different toxicity profile with less impact on mitochondrial function in this cell model.
