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Biochemistry (Moscow). Papers in Press. Published on November 6, 2017 as Manuscript BM17-381.

Mitochondria-Targeted Antioxidant SkQ1 (10-(6´-Plastoquinonyl)decyltriphenylphosphonium Bromide) Inhibits Mast Cell Degranulation in vivo and in vitro

M. A. Chelombitko1*, O. A. Averina2, T. V. Vasilyeva1, O. Yu. Pletiushkina3, E. N. Popova3, A. V. Fedorov1, B. V. Chernyak3, V. S. Shishkina1, and O. P. Ilinskaya1

Lomonosov Moscow State University, Faculty of Biology, 119991 Moscow, Russia; E-mail: atma69@yandex.ru

2Lomonosov Moscow State University, Institute of Mitoengineering, 119992 Moscow, Russia

3Lomonosov Moscow State University, Institute of Physico-Chemical Biology, 119991 Moscow, Russia

*To whom correspondence should be addressed.

Received August 15, 2017; Revision received September 17, 2017 1
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 cell (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.
KEY WORDS: inflammation, mast cell, degranulation, histamine, mitochondria-targeted antioxidant

DOI: 10.1134/S0006297917120082