title: Mitochondrial functions of THP-1 monocytes following the exposure to selected natural compounds.
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 (IC10and IC50determined 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 IC50of 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 IC50of 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.
authors.affiliation: Institute of Pharmacy, Pharmaceutical Biology, Ernst-Moritz-Arndt University of Greifswald, D17489 Greifswald, Germany. Electronic address: nadin.schultze@uni-greifswald.de.
authors.forename: Nadin
authors.initials: N
authors.lastname: Schultze
authors.affiliation: Institute of Physiology, University Medicine of Greifswald, D17495 Karlsburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Wanka
authors.affiliation: Institute of Pharmacy, Pharmaceutical Biology, Ernst-Moritz-Arndt University of Greifswald, D17489 Greifswald, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Zwicker
authors.affiliation: Institute of Pharmacy, Pharmaceutical Biology, Ernst-Moritz-Arndt University of Greifswald, D17489 Greifswald, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lindequist
authors.affiliation: Institute of Pharmacy, Pharmaceutical Biology, Ernst-Moritz-Arndt University of Greifswald, D17489 Greifswald, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Haertel
mesh_terms: D001688:Biological Products / Q000633:toxicity*; D002185:Cannabidiol / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016572:Cyclosporine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014255:Trichothecenes / Q000633:toxicity*
chemical_list: D001688:Biological Products; D017382:Reactive Oxygen Species; D014255:Trichothecenes; D002185:Cannabidiol; D016572:Cyclosporine; C007262:deoxynivalenol
keywords: Cannabidiol; Cyclosporine A; Deoxynivalenol; Immunotoxicity; Mitochondrial functions; THP-1 cells