Dynamics of metalloproteinase activity as an indicator of regenerative properties of a new derivative of N-acetyl-6-aminohexanic acid in treatment of burns


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Abstract

Background. The basis of the clinical effect of any reparant is determined by the biochemical mechanisms underlying its stimulating effect. Matrix metalloproteinases and tissue inhibitors of metalloproteinases play a central role in the metabolism of connective tissue proteins, in the processes of normal development and remodeling of the cellular matrix, embryogenesis, tissue repair, and neoangi-ogenesis. Thus the study of the pro-regenerative properties of the new derivative of N-acetyl-6-aminohexanoic acid, carried out in parallel with the determination of the activity of matrix metalloproteinases and their tissue inhibitors, is an actual task for the pathogenetic substantiation of the use of this substance for the treatment of thermal skin burns. Aim. To study in an experiment on rats the effectiveness of application the new derivative of N-acetyl-6-aminohexanoic acid in the healing of skin burn wounds, to evaluate the dynamics of the activity of matrix metalloproteinases and their tissue inhibitors in the blood and regenerating tissues at the stages of the wound process. Material and methods. Evaluation of the reparative properties of the new derivative of N-acetyl-6-aminohexanoic acid, applying topically in the form of 2% polyethylene glycol-based ointment, was carried out on white rats in which a thermal skin burn was simulated. Polyethylene glycol was used as a reference drug. The burn regeneration was monitored by a planimetric method according to reduction the area of the wound defect. The levels of type 9 metalloproteinase and type 1 tissue inhibitor of metalloproteinases were determined in blood serum samples and homogenates of regenerating animal tissues by enzyme immunoassay. Results. Planimetric monitoring showed a rapid reduction of the defects areas in animals and their complete scarring 2 days earlier than at usage polyethylene glycol. The dynamics of the concentrations of type 9 metalloproteinase and type 1 tissue inhibitor of metalloproteinases was expressed in a significant decrease in their ratio, hence weakening of proteolysis processes while continuing the processes of remodeling of regenerating tissues. Conclusions. The pro-regenerative properties of the investigated substance were manifested in a significant acceleration of the healing of experimental thermal burns of the skin and the normalization of proteolytic activity and free radical processes in the body.

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About the authors

E. V Andrianova

Tver State Medical University of the Ministry of Health of Russia

Assistant

E. N Egorova

Tver State Medical University of the Ministry of Health of Russia

Dr.Sc. (Med.), Associate Professor

M. B Petrova

Tver State Medical University of the Ministry of Health of Russia

Dr.Sc. (Biol.), Professor

M. A Petrovskaya

Tver State Medical University of the Ministry of Health of Russia

Assistant

S. Ya Skachilova

Russian Scientific Center for the Study of the Safety of Biologically Active Substances

Dr.Sc. (Biol.), Professor

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