Efficacy of Mitochondrial Antioxidant Plastoquinonyl-decyl-triphenylphosphonium Bromide (SkQ1) in the Rat Model of Autoimmune Arthritis.
Rheumatoid arthritis is one of the most common autoimmune diseases. Many antioxidants have been tested in arthritis, but their efficacy was, at best, marginal. In this study, a novel mitochondria-targeted antioxidant, plastoquinonyl-decyl-triphenylphosphonium bromide (SkQ1), was tested in vivo to prevent and cure experimental autoimmune arthritis. In conventional Wistar rats, SkQ1 completely prevented the development of clinical signs of arthritis if administered with food before induction. Further, SkQ1 significantly reduced the fraction of animals that developed clinical signs of arthritis and severity of pathological lesions if administration began immediately after induction of arthritis or at the onset of first symptoms (day 14 after induction). In specific pathogen-free Wistar rats, SkQ1 administered via gavage after induction of arthritis did not reduce the fraction of animals with arthritis but decreased the severity of lesions upon pathology examination in a dose-dependent manner. Efficacious doses of SkQ1 were in the range of 0.25-1.25 nmol/kg/day (0.13-0.7 μg/kg/day), which is much lower than doses commonly used for conventional antioxidants. SkQ1 promoted apoptosis of neutrophils in vitro, which may be one of the mechanisms underlying its pharmacological activity. Considering its low toxicity and the wide therapeutic window, SkQ1 may be a valuable additional therapy for rheumatoid arthritis.
Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia; Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
Alexander A
AA
Andreev-Andrievskiy
Institute of Cytology and Genetics, Novosibirsk, Russia.
Nataliya G
NG
Kolosova
Institute of Cytology and Genetics, Novosibirsk, Russia.
Natalia A
NA
Stefanova
Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.
Maxim V
MV
Lovat
Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.
Maxim V
MV
Egorov
Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.
Vasily N
VN
Manskikh
Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia; Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.
Roman A
RA
Zinovkin
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.
Ivan I
II
Galkin
Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.
Anastasia S
AS
Prikhodko
Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.
Maxim V
MV
Skulachev
Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia; Martsinovsky Institute of Medical Parasitology and Tropical Medicine, Sechenov First Moscow State Medical University, Moscow, Russia.
Alexander N
AN
Lukashev
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D002460:Cell Line; D024043:Collagen Type II; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007596:Joints / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017208:Rats, Wistar; D013997:Time Factors
C532038:10-(6'-plastoquinonyl)decyltriphenylphosphonium; D000975:Antioxidants; D018501:Antirheumatic Agents; D024043:Collagen Type II; D010971:Plastoquinone