Mitochondrial functions of THP-1 monocytes following the exposure to selected natural compounds

作者：Schultze Nadin^*; Wanka Heike; Zwicker Paula; Lindequist Ulrike; Haertel Beate

来源：Toxicology, 2017, 377: 57-63.

DOI：10.1016/j.tox.2016.12.006

• THP-1 cells
• Cyclosporine A
• Deoxynivalenol
• Cannabidiol
• Immunotoxicity
• Mitochondrial functions

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 24 h to two different concentrations (IC10 and IC50 determined by MIT) 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. Mitochondria] dysfunction may be one explanation for the cytotoxicity of CBD and CsA also in other in immune cells.

• 出版日期2017-2-15