RU2283116C2 - Method for increasing survival rate of isolated skin pedicle flap in animals having reduced antioxidation background - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves administering macrolide preparation of azithromycin. The drug is applied in concentrations 10 and 30 mg/kg once a day during 7 days. Then, skin flap necrosis zone dimensions are measured and lipid peroxidation intensity is determined.

EFFECT: wide range of functional applications.

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Description

The invention relates to medicine, namely to experimental pharmacology and cardiology.

The prototype of this invention is: "Methodological recommendations for the quantitative assessment of the effect of drugs on tissue viability in conditions of reduced blood circulation." Approved by Farm. Committee of the USSR Ministry of Health 05.16.1986. Protocol No. 9 (Authors: Lyubimov B.I., Sholokhov V.M. et al.).

Simulation of the assessment of the area of aseptic necrosis in the conditions of reduced blood circulation and the survival of ischemic tissues in conditions of reduced antioxidant background is a distinctive addition to the prototype used.

Currently, the following antioxidant substances are used to limit the area of aseptic necrosis in conditions of reduced blood circulation, and therefore, to increase the survival of ischemic tissues.

Classification of compounds with antioxidant activity by the mechanism of action.

1. Means inhibiting the development of LP.

1.1. Polyunsaturated fatty acid stabilizers with respect to phospholipase A and phospholipase inhibitors.

1.2. Xanthine oxidase, myeloperoxidase, cyclooxygenase, lipoxykinase and other lipid peroxidase inhibitors.

1.3. Stabilizers of endogenous enzymatic antioxidant systems (SOD, catalase, ceruloplasmin).

2. Means that interact with reactive oxygen species, hydrolysis and other primary products of lipid peroxidation: traps of free radicals (phenolic compounds, flavonoids and sulfur-containing compounds, α-tocopherol and other compounds).

3. Agents inhibiting the catholization of LPO Fe ²⁺ and other metals (ciruloplasmin, histidine-containing dipeptides - carnosine, anserine, EDTA, citrate, cyanides, etc.).

4. Structural antioxidants that affect the stationarity of phospholipid metabolism in membrane structures (steroids and other membrane stabilizers).

5. Proton activators, potentiating the effect of phenolic and some other antioxidants (ascorbate, citrate).

At the same time, treatment with these substances has certain disadvantages. One of the disadvantages is that all of the listed antioxidant substances have a systemic effect on the antioxidant background of the body, which is currently regarded as an unfavorable factor in terms of side effects. Therefore, drugs with a predominantly non-systemic local antioxidant effect are of particular interest, which is most beneficial for organ pathology associated with ischemia.

To eliminate this drawback, the macrolide antibiotic azithromycin is used in concentrations of 10 and 30 mg / kg, which specifically accumulates in activated neutrophils and is transported to the aseptic inflammation zone, where, being excreted unchanged, it reduces the “oxidative burst” induced by neutrophils, thereby reduces the damaging effect of prooxidants on the ischemic area of an isolated skin flap (Strachunsky L.S., Kozlov S.I. Macrolides in modern clinical practice, 1998).

The objective of the invention is to expand the range of antioxidant agents.

The task is achieved due to the fact that in order to increase the survival of an isolated skin flap "on the leg" in animals with a low antioxidant background (NAF), the macrolide preparation azithromycin is used. According to the literature, the drug is most effective in the range from 10 to 30 mg / kg (Strachunsky L.S., Kozlov S.I. Macrolides in modern clinical practice, 1998). We used a small dose of -10 mg / kg and a large dose of 30 mg / kg of azithromycin.

The method was carried out as follows.

The experiments were carried out on white male Wistar rats weighing 230-300 g. The body's low antioxidant background (NAF) was achieved by modeling emotional pain stress by suspending rats from the dorsal fold of the skin for 24 hours (G.V. Kovalev, 1987). On the second day, the skin flap of the anterior abdominal wall was isolated with a size of 1 × 4 cm for 7 days (V.N.Sholokhov, 1984). Azithromycin was administered orally daily at doses of 10 and 30 mg / kg once daily.

The antioxidant effect of the drug was evaluated by comparing the size of the necrosis zone between the experimental groups of animals without treatment and with treatment with azithromycin at doses of 10 and 30 mg / kg. The effect of azithromycin on the indicators of the total activity of lipid peroxidation (lipid peroxidation) in the myocardium was also evaluated by determining the intermediate products of lipid peroxidation: primary - ketodienes, diene conjugates (DC), secondary - MDA, final products - antioxidant activity (AOA) of the plasma (Kamilov F. X., Vinkova G.A., Orlova N.S., 1999; Steel N.D., 1977; Dvinskaya L.M., Nikiforova L.I., 1980;; Bidlack WR., 1973; Vladimirov Yu.A. ., Archakov A.I., 1972).

Example. To determine the objectives of the invention, the following groups were formulated:

- Control (n = 10);

- Azithromycin 10 mg / kg (n = 10);

- Azithromycin 30 mg / kg (n = 10).

EBS was performed in all groups; on the 2nd day, a flap of the skin “on the leg” was isolated. Every day, animals of the 2nd and 3rd groups received intragastric azithromycin once a day. After 7 days, the area of necrosis of the skin flap was measured, and blood was also taken to determine the products of LPO.

The results are presented in table No. 1.

Table number 1. Experimental group % zone of necrosis Content Ketodienov Diene conjugates Malondialdehyde Schiff bases Antioxidant activity of plasma The control 76.07 ± 2.83 0.54 ± 0.01 0.70 ± 0.01 0.62 ± 0.01 0.21 ± 0.01 14.68 ± 0.05 Azithromycin 10 mg / kg 68.89 ± 1.26 * 0.23 ± 0.01 * 0.47 ± 0.01 * 0.67 ± 0.03 0.18 ± 0.02 14.36 ± 2.24 Azithromycin 30 mg / kg 61.25 ± 1.42 * 0.24 ± 0.01 * 0.50 ± 0.01 * 0.62 ± 0.01 0.19 ± 0.01 20.25 ± 5.60 * at p <0.05 in comparison with the control group

As can be seen from the table, azithromycin reduced the area of necrotic tissue, while the content of primary markers of LPO intensity significantly decreased (ketodienes, DC).

Thus, the obtained results indicate the ability of azithromycin to dose-dependently increase the survival of a skin flap under conditions of reduced blood circulation with NAF, realized through the antioxidant effect of the drug.

Claims (1)

A method for increasing the survival of an isolated legged skin flap in animals with a reduced antioxidant background, characterized in that the macrolide preparation azithromycin is used in concentrations of 10 and 30 mg / kg once a day for 7 days.