Mitochondria-targeted antioxidant SkQ1 (10-(6′-plastoquinonyl)decyltriphenylphosphonium bromide) inhibits mast cell degranulation in vivo and in vitro

Abstract

The therapeutic effect of mitochondria-targeted antioxidant 10-(6´-plastoquinonyl)decyltriphenylphosphonium bromide (SkQ1) in experimental models of acute inflammation and wound repair has been shown earlier. It was suggested that the antiinflammatory activity of SkQ1 is related to its ability to suppress inflammatory activation of the vascular endothelium and neutrophil migration into tissues. Here, we demonstrated that SkQ1 inhibits activation of mast cells (MCs) followed by their degranulation and histamine release in vivo and in vitro. Intraperitoneal injections of SkQ1 in the mouse air-pouch model reduced the number of leukocytes in the air-pouch cavity and significantly decreased the histamine content in it, as well as suppressing MC degranulation in the air-pouch tissue. The direct effect of SkQ1 on MCs was studied in vitro in the rat basophilic leukemia RBL-2H3 cell line. SkQ1 inhibited induced degranulation of RBL-2H3 cells. These results suggest that mitochondrial reactive oxygen species are involved in the activation of MCs. It is known that MCs play a crucial role in regulation of vascular permeability by secreting histamine. Suppression of MC degranulation by SkQ1 might be a significant factor in the antiinflammatory activity of this mitochondria-targeted antioxidant.

The Role Played by Mitochondria in FcεRI-Dependent Mast Cell Activation

“…We have already discussed the role played by ROS in mast cell activation (25) and the present review focuses on the possible role of the mitochondrial ROS in mast cell activation.…”

“…Mitochondria play an important role in regulating the cytosolic Ca 2+ level which is critical for mast cell activation as they are able to accumulate Ca 2+ ( 20 – 23 ). Mitochondrial ROS are also involved in activating mast cell ( 24 , 25 ). Special attention should be given to the transcription factors STAT3 and MITF which play an important role in the development and function of mast cells.…”

Effect of Antioxidants on the Production of MCP-1 Chemokine by EA.hy926 Cells in Response to IL-6

“…In the first two cases, the action of SkQ1 was largely associated with the prevention of NF-kB activation, while the suppression of apoptosis and caspase-dependent destruction of intercellular contacts and endothelial permeability was associated with the prevention of the release of cytochrome c from mitochondria. In addition, SkQ1 inhibited mast cell degranulation in vivo and in vitro, which could also contribute to a decrease in endothelial activation during acute inflammation [42,43]. We have now supplemented this picture with the data that SkQ1 suppresses not only NF-kB-dependent expression and secretion of IL-6 but also IL-6-induced activation of JAK/STAT3 and, as a consequence, expression of MCP-1, which may contribute to the overall therapeutic effect of SkQ1.…”

Plastoquinone-Derivative SkQ1 Improved the Biliary Intraepithelial Neoplasia during Liver Fluke Infection

“…Inactivation of reactive oxygen species under the influence of SkQ1 can occur in several ways: due to the oxidation of the plastoquinone and due to a decrease in the mitochondrial membrane potential, the so-called uncoupling of respiration and ATP synthesis [25]. Thus, SkQ1 is able to inhibit ROS, maintain the redox balance in mitochondria and, due to this, reduce the degree of inflammation [34,35]. In addition, SkQ1 has been shown to have beneficial effects in various pathologies [14,36].…”