During aesthetic correction, it is very important for a doctor to improve not only the appearance of the patient, relieving him of wrinkles and creases, but also to work on the condition of his skin. Therefore, for rejuvenation, it is necessary to use products that restore the reparative properties of the skin.

Succinate in Hyalual® is just that improving component which is favorably allocated in the market of biorevitalizants.  Why succinate is so useful for the skin, and how exactly it allows you to restore its reparative properties with estet-portal.com shared a dermatologist, cosmetologist, head of the Hyalual training center (Moscow) – Anna Kupriyanova and Doctor of Biological Sciences, Chief Researcher, Laboratory of Bioenergetics and Hypoxia Problems, Research Institute of General Pathology and Pathophysiology, Moscow – Julia Kirova.

The role of succinate in skin repair

The study of the effects of succinate mediated through the specific receptor SUCNR1 began in 2004, when the succinate receptor was identified in kidney cells as a stimulator of renin secretion.

According to modern concepts, succinate is a molecular marker of hypoxic/ischemic conditions.

Sodium succinate (Hyalual®) is produced by mitochondria not only during the direct oxidative development of the Krebs cycle (with a sufficient level of O2 in the cell), but also during the reversal of the Krebs cycle during hypoxia.

Urgent antihypoxic SUCNR1-dependent effects of sodium succinate can be realized locally in the area of ​​ischemic tissue according to the type of autocrine / paracrine signal (vasodilation), as well as at the systemic level (renin secretion by the kidneys, increase in blood pressure).

Previously, studies of SUCNR1 activity were performed on the tissues of the kidneys, heart, retina, liver, and practically did not affect the skin, while the positive effects of the succinate-containing Hyalual® preparation; from Hyalual used in dermatology and cosmetology are well known. They consist of:

  • acceleration of wound healing;
  • skin rejuvenation;
  • eliminate hyperpigmentation;
  • anti-inflammatory and antiallergic action.

A unique discovery in cosmetology: a safe alternative to laser skin rejuvenation

Survey studies on the effect of succinate on the skin In connection with the need to substantiate the legitimacy of the practical use of the succinate-containing preparation Hyalual® in order to restore the reparative properties of the skin; A study was initiated on the basis of the Laboratory of Bioenergetics and Hypoxia Problems of the Research Institute of General Pathology and Pathophysiology (Moscow). The aim of the study was to identify possible SUCNR1-mediated mechanisms for the activity of the succinate-containing Hyalual preparation in the skin.

Main SUCNR1

‑Mechanisms of Succinate-Containing Hyalual Activity in the Skin:

Stimulation of fibroblast proliferation
  • Vascular wall remodeling
  • Physiological stimulation of the production of endogenous growth factors
    •  

Preparations (substances) used: succinate-containing preparation Hyalual® (drug for the redermalization course procedure, injection form; hyaluronic acid concentration 1.1%, 1.8%, 2.2%; succinate content 1.6%), mexidol (injection form, 50 mg / ml), saline solution (injection form), 1.6% sodium succinate solution, pure high molecular weight hyaluronic acid at a concentration of 1%, 1.8%, 2%.

Intradermal administration of Hyalual and comparators was carried out three times with two-week breaks. The results of

Western blot analysis

revealed SUCNR1 in skin samples of the anterior abdominal wall of rats from all experimental groups. Three injections of drugs at two-week intervals according to the standard scheme did not affect the level of the receptor, which did not differ from the baseline (in the skin of intact rats). The fact that there was no decrease in SUCNR1 after Hyalual®; may indicate the choice of an adequate dose, with the abolition of which the risk of developing dependence on the drug and the withdrawal syndrome is minimal.

 

To assess the effect of the drug on the skin,

staining of skin sections with hematoxylin-eosin

was performed. For staining, transverse sections of the dermis (papillary, reticular layers) and hypodermis of the skin of the anterior abdominal wall of control (injections of saline) and experimental (injections of Hyalual) rats were obtained. In the dermis of the control animals, high content of spindle-shaped fibroblasts, macrophages and mast cells was detected. In comparison with the control, in the skin sections of experimental animals, the number of fibroblasts increased, and the morphology of these cells changed (the size and number of processes increased), which indicates their activation. Also, on sections of the skin of experimental rats, signs of vasodilation and an increase in the density of the vascular network were revealed). It should be noted that stimulation of fibroblast proliferation by succinate in combination with HA has been noted in other studies.

Immunohistochemical staining

of skin sections of control and experimental rats using antibodies to SUCNR1 showed that cellular elements of the skin (keratinocytes, fibroblasts, macrophages, mast cells, smooth muscle cells, endotheliocytes) express the receptor to varying degrees, and the highest levels of SUCNR1 were found in mast cells, neutrophils and macrophages. The intensity of SUCNR1 expression did not change after completion of the course of Hyalual administration. The data of

morphological and immunohistochemical studies

indicate the implementation of SUCNR1-dependent mechanisms of activity of the succinate-containing preparation Hyalual. Due to the fact that the receptor is expressed in large quantities in macrophages, mast cells, neutrophils, it can be assumed that not only direct effect of Hyalual on fibroblasts and keratinocytes of the skin (activation, proliferation, migration), but also mediated by immune cells, as more sensitive sensors of succinate levels.

It is known that the activation of keratinocytes and the switch from an inactive status to a migratory, proliferative, pro-inflammatory state occurs under the action of pro-inflammatory cytokines secreted by macrophages and mast cells. They play a critical role in the proliferation and migration of dermal fibroblasts, tissue remodeling, and wound healing. Macrophages produce soluble mediators that regulate the migration, proliferation and synthesis of collagen by fibroblasts.

Activation of skin repair with succinate-containing Hyalual The presence of the succinate receptor (SUCNR1) on the surface of almost all dermal components (fibroblasts, mast cells, macrophages, endotheliocytes) indicates the involvement of the succinate-containing drug in the functional activation of skin cells, proliferation, migration, secretion of growth factors, cytokines, chemokines — those. Hyalual® to the mechanisms of regeneration, renewal and reparation.

The data obtained indicate the great potential of Hyalual®; for solving numerous problems in reparative medicine, cosmetology, plastic surgery and trichology.

Use of the succinate-containing Hyalual® preparation; from

Hyalual can be considered as an effective approach in correcting age-related skin changes associated with the activation of inflammation mechanisms, a decrease in the reparative and proliferative potential of the skin and underlying tissues.

Multi-acid discs for skin regeneration

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