Rien que le nom est superbe
Mitochondria-targeted antioxidant (MitoQ) ameliorates age-related arterial endothelial dysfunction in mice.
J Physiol. 2014 Apr 22. [Epub ahead of print] Gioscia-Ryan RA
Age-related arterial endothelial dysfunction, a key antecedent to the development of cardiovascular diseases (CVD), is largely due to a reduction in nitric oxide (NO) bioavailability as a consequence of oxidative stress. Mitochondria are a major source and target of vascular oxidative stress when dysregulated. Mitochondrial dysregulation is associated with primary aging, but its role in age-related endothelial dysfunction is unknown. Our aim was to determine the efficacy of a mitochondria-targeted antioxidant, MitoQ, for ameliorating vascular endothelial dysfunction in old mice. Ex vivo carotid artery endothelium-dependent dilation (EDD) to increasing doses of acetylcholine was impaired ~30% in old (~27 mo.) compared to young (~8 mo.) mice due to reduced NO bioavailability (p
<0.05). Acute (ex vivo) and chronic (4 weeks in drinking water) administration of MitoQ completely restored EDD in older mice by improving NO bioavailability. There were no effects of age or MitoQ on endothelium-independent dilation to sodium nitroprusside. The improvements in endothelial function with MitoQ supplementation were associated with normalization of age-related increases in total and mitochondria-derived arterial superoxide production and oxidative stress (nitrotyrosine abundance), as well as increases in markers of vascular mitochondrial health, including antioxidant status. MitoQ also reversed the age-related increase in endothelial susceptibility to acute mitochondrial damage (rotenone-induced impairment in EDD).
Our results suggest that mitochondria-derived oxidative stress is an important mechanism underlying the development of endothelial dysfunction with primary aging. Mitochondria-targeted antioxidants such as MitoQ represent a
promising, novel strategy for preserving vascular endothelial function with advancing age and preventing age-related CVD.
Curr Med Chem. 2011;18(26):4053-64.
Targeting mitochondrial dysfunction and neurodegeneration by means of coenzyme Q10 and its analogues.
Coenzyme Q10 is a small electron carrier of the respiratory chain with antioxidant properties, widely used for the treatment of mitochondrial disorders. Mitochondrial diseases are neuromuscular disorders caused by impairment of the respiratory chain and increased generation of reactive oxygen species. Coenzyme Q10 supplementation is fundamental in patients with primary coenzyme Q10 deficiency. Furthermore, coenzyme Q10 and its analogues, idebenone and mitoquinone (or MitoQ), have been also used in the treatment of other neurogenetic/neurodegenerative disorders. In Friedreich ataxia idebenone may reduce cardiac hypertrophy and, at higher doses, also improve neurological function. These compounds may also play a potential role in other conditions which have been linked to mitochondrial dysfunction, such as Parkinson disease, Huntington disease, amyotrophic lateral sclerosis and Alzheimer disease. This review introduces mitochondrial disorders and Friedreich ataxia as two paradigms of the tight links existing between oxidative stress, respiratory chain dysfunction and neurodegeneration, and focuses on current and emerging therapeutic uses of coenzyme Q10 and idebenone in neurology.
Free Radic Res. 2011 Mar;45(3):351-8.
An investigation of the effects of MitoQ on human peripheral mononuclear cells.
MitoQ is a ubiquinone derivative targeted to mitochondria which is known to have both antioxidant and anti-apoptotic properties within mammalian cells. Previous research has suggested that the age-related increase in oxidative DNA damage in T lymphocytes might contribute to their functional decline with age. This paper describes the impact of mitoQ on unchallenged or oxidatively challenged ex vivo human peripheral blood mononuclear cells from healthy 25-30 or 55-60 year old volunteers. When cells were challenged with hydrogen peroxide (H(2)O(2)), following mitoQ treatment (0.1-1.0 μM), the ratio of reduced to oxidized forms of glutathione increased, the levels of oxidative DNA damage decreased and there was an increase in the mitochondrial membrane potential. Low levels of mitoQ (0.1 or 0.25 μM) had no impact on endogenous DNA damage, whilst higher levels (0.5 and 1.0 μM) of mitoQ significantly reduced endogenous levels of DNA damage. The results of this investigation suggest that mitoQ may have anti-immunosenescent potential.