Canna~Fangled Abstracts

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

By December 27, 2016 No Comments
Toxicology. 2016 Dec 21. pii: S0300-483X(16)30338-9. doi: 10.1016/j.tox.2016.12.006.
[Epub ahead of print]

Abstract

pm-2-site-207The 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.

KEYWORDS:

3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide; CBD; Cannabidiol; CsA; Cyclosporine A; DON; Deoxynivalenol; ETC; FCCP; IC(10); IC(50); Immunotoxicity; MTT; Mitochondrial functions; OCR; RSC; THP-1 cells; cannabidiol; carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone; cyclosporine A; deoxynivalenol; electron transport chain; inhibitory concentration 10; inhibitory concentration 50; oxygen consumption rate; respiratory spare capacity

PMID: 28013001
DOI: 10.1016/j.tox.2016.12.006
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