Mitochondrial functions of THP-1 monocytes following the exposure to selected natural compounds. (15th February 2017)

• Record Type: Journal Article
• Authors: Schultze, Nadin; Wanka, Heike; Zwicker, Paula; Lindequist, Ulrike; Haertel, Beate
• Is Part Of: Toxicology. Volume 377(2017)
• Page Start: 57
• Page End: 63
• Publication Date: 2017-02-15
• Subjects: CBD cannabidiol -- CsA cyclosporine A -- DON deoxynivalenol -- ETC electron transport chain -- FCCP carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone -- IC10 inhibitory concentration 10 -- IC50 inhibitory concentration 50 -- MTT 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide -- OCR oxygen consumption rate -- RSC respiratory spare capacity; THP-1 cells -- Cyclosporine A -- Deoxynivalenol -- Cannabidiol -- Immunotoxicity -- Mitochondrial functions; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2016.12.006
• Languages: English
• ISSNs: 0300-483X

Abstract

Highlights: CsA and CBD impair mitochondrial functions in THP-1 cells using XF 96 technology. Both compounds increase intracellular ROS and induce apoptosis. DON has no major influence on mitochondrial functions, iROS and apoptosis. Reduced respiratory spare capacity seems to be associated with iROS and apoptosis. Respiratory spare capacity might be a good indicator for cell viability. 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 24 h 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.