Comparison of the Effects of Mitochondria-Targeted Antioxidant 10-(6'-Plastoquinonyl)Decyltriphenylphosphonium Bromide (SkQ1) and a Fragment of its Molecule Dodecyltriphenylphosphonium on Carrageenan-Induced Acute Inflammation in Mouse Model of Subcuteneous Air Pouch.

The effect of mitochondria-targeted antioxidant 10-(6'-plastoquinonyl) decyltriphenylphosphonium bromide (SkQ1) and its fragment dodecyltriphenylphosphonium (C12TPP), weak uncouplers of respiration and oxidative phosphorylation, was studied using a mouse model of carrageenan-induced acute inflammation in the subcutaneous air pouch. In our model, SkQ1 demonstrated a strong anti-inflammatory effect that manifested in a decrease in the absolute number of inflammatory cells, mainly neutrophils, and their relative number in parallel with an increase in macrophages and mast cell content in the inflammatory exudate. The concentration of proinflammatory cytokine IL-6 in the exudate also tended to decrease. C12TPP produced no significant effect on the inflammation process.

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

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.

Spontaneous and Experimentally Induced Pathologies in the Naked Mole Rat (Heterocephalus glaber).

The naked mole rat (Heterocephalus glaber, Rüppell, 1842) is a unique eusocial rodent with unusually long lifespan. Therefore, the study of spontaneous and experimentally induced pathologies in these animals is one of the most important tasks of gerontology. Various infections, noninfectious pathologies (including age-dependent changes), and tumors have been described in the naked mole rat. The most frequent pathologies are traumas (bite wounds), purulent and septic complications of traumatic injuries, renal tubular calcinosis, chronic progressive nephropathy, hepatic hemosiderosis, testicular interstitial cell hyperplasia, calcinosis cutis, cardiomyopathy, and dysbiosis-related infectious lesions of the digestive system. However, the summarized data on pathology (including tumor incidence) and on the causes of mortality are insufficient. There are only few publications about the results of experiments where pathologies were induced in the naked mole rat. All these problems could be subjects for promising future studies without which adequate studies on mechanisms providing the long lifespan of the naked mole rat are impossible, as well as the elucidation of causes of tumor resistance of this species.