Cannabidiol induced apoptosis in human monocytes through mitochondrial permeability transition pore-mediated ROS production.

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Cannabidiol induced apoptosis in human monocytes through mitochondrial permeability transition pore-mediated ROS production.

Free Radic Biol Med. 2018 Jun 22;:

Authors: Wu HY, Huang CH, Lin YH, Wang CC, Jan TR

Abstract
Cannabidiol (CBD) has been reported to induce apoptosis in immune cells through oxidative stress-related mechanisms. The objective of the present study was to investigate the cellular mechanisms for CBD-induced apoptosis and oxidative stress in human monocytes. Exposure of freshly isolated human monocytes to CBD induced apoptosis in a time- and concentration-dependent manner. Time-course analyses revealed the induction of intracellular reactive oxygen species (ROS) at 1-2h post CBD (16 μM) exposure. By comparison, the CBD treatment rapidly elicited the depolarization of mitochondrial membrane potential (MMP) within 5min, and the oxidation of cardiolipin, a major lipid component of the mitochondrial inner membrane, within 15min. Moreover, CBD induced the release of cytochrome c (Cyt c) from mitochondria. Mechanistic studies revealed that CBD-induced ROS production and apoptosis were not associated with the alteration of mitochondrial superoxide dismutase activity, the electron leakage through mitochondrial respiratory chain, and Fe2+- and Ca2+-mediated mechanisms. In contrast, CBD-induced apoptosis and MMP depolarization were markedly attenuated by the mitochondrial permeability transition pore (MPTP) inhibitor cyclosporin A (CsA), but not the calcineurin inhibitor FK506. Furthermore, CsA prevented cardiolipin oxidation and the MPTP opening induced by CBD. The present study suggests that CBD acts on the mitochondria to elicit ROS generation and apoptosis through MPTP opening and provides critical insights into the cellular mechanisms for CBD-induced oxidative stress in apoptotic monocytes.

PMID: 29940353 [PubMed – as supplied by publisher]


Source: Estudios sobre Cannabidiol (CBD)

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