Will the new "Skulachev ions" help with a stroke?
The "discharge" of mitochondria protects the brain from the effects of stroke
These are the conclusions of the work published in Biochemistry and Biophysics Acta – Bioenergetics by a group of researchers from Lomonosov Moscow State University led by V.P.Skulachev (Khailova et al., A short-chain alkyl derivative of Rhodamine 19 acts as a mild uncoupler of mitochondria and a neuroprotector).
It is known that many pathological conditions are associated with an increase in the production of free radicals in the "energy stations of cells" of mitochondria, which have a negative effect on various cell structures (oxidative stress). This process directly depends on the size of the mitochondrial membrane potential – the higher it is, the more free radicals the mitochondria produces.
It is possible to reduce the damage associated with oxidative stress due to the pathological activity of mitochondria by organizing the leakage of excess charge through the mitochondrial membrane. This protective mechanism is called the dissociation of oxidative phosphorylation, it is used by cells of various tissues in natural conditions, but it can also be triggered with the help of synthetic compounds. However, the possibility of medical use of such molecules is limited by an extremely small therapeutic window – the difference between therapeutic and toxic doses of the drug. The fact is that a sharp decrease in the membrane potential leads to a violation of the main function of the mitochondria – the synthesis of ATP, the universal "fuel" necessary to maintain the vital activity of the cell and the body as a whole.
The group of Academician Skulachev created a number of substances – cationic disconnectors, the chemical structure of which allows them to selectively accumulate in mitochondria and reduce excess mitochondrial potential. At the same time, the effect of cationic disconnectors is self–regulating - since these are negatively charged molecules, the rate of their penetration into the mitochondria is directly proportional to the mitochondrial potential. However, the mitochondrial potential decreases as the concentration of the cationic uncoupler inside the mitochondria increases.
In the published work, the properties of a new soft disconnector – butyl ether of rhodamine-19 (C4R1) were investigated. It has been shown that this substance effectively accumulates in the mitochondria to a certain concentration without disrupting their vital functions. In experiments on rat models of ischemic stroke, it was shown that the introduction of C4R1 after a reversible violation of cerebral circulation significantly reduces the scale of brain damage in animals and related neurological disorders. Thus, in rats that received intravenous injection of the compound, brain edema decreased approximately 4 times compared to the control group (on average 20% and 5%, respectively), and the area of ischemic brain damage decreased by 25-30%. The performed tests for coordination of movements also showed that the use of C4R1 led to a significant reduction in post-stroke neurological deficit in experimental rodents.
The leading researcher of the Laboratory of Mitochondrial Structure and Function of the Research Institute of the Russian Academy of Medical Sciences agreed to comment on the results of the research for copper news. Belozersky, Doctor of Biological Sciences Egor Plotnikov:
– It should be noted that the prevention of the production of oxygen radicals in mitochondria is, according to scientists, the fundamental principle of the fight against many diseases. Moreover, according to the free radical theory of aging, drugs that suppress oxidative stress in mitochondria may be effective means of preventing aging of the body. Interestingly, the mitochondrial soft disconnectors studied in this work are an integral part of other promising drugs that are being actively developed within the framework of the project "practical application of Skulachev ions". If you chemically "sew" an antioxidant molecule to the molecule of such a disconnector, then you can get an antioxidant directed to the mitochondria. Such a compound will have both the properties of a disconnector that normalizes the mitochondrial potential, and the properties of an antioxidant that "extinguishes" oxygen radicals that have already arisen. Clinical studies on the use of such molecules in the treatment of a number of diseases are currently being actively conducted.
But molecules without the antioxidant part can also be promising drugs. Thus, the C4R1 disconnector effectively protects the brain from ischemic damage, which means that in the future, if clinical trials are successful, it can be used for the treatment of stroke and a number of other neurological diseases.
Portal "Eternal youth" http://vechnayamolodost.ru04.09.2014