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DERMATOPROTECTIVE ACTIVITY OF A COMBINATION OF ENOXIFOL WITH REXOD IN A REDUCED FORM THE BLOOD CIRCULATION IN THE SKIN IN DIABETES MELLITUS AND HYPERCHOLESTERINEMIA

Experiments in rats showed that the 9-diethylaminoethyl-2-(3,4-dioxyphenyl)-imidazo-[1,2-a]-benzimidazole dihydrobromide with the provisional name of enoxifol (0.94 – 15 mg/kg), rexod (recombinant human superoxide dismutase; 0.002 mg/kg) and especially their combination in intravenous administration in a reduced blood circulation in the skin against the background of the normoglycemia and hyperglycemia induced by experimental (alloxanic) diabetes mellitus complicated by exogenous hypercholesterinemia have a pronounced dose-dependent dermatoprotective effect, which may be due to the activation of energy processes and increase the reserve capacity of the antioxidant support network and normalization of carbohydrate and lipid metabolism. A combination of enoxifol with alprostadil in normoglycemia increases significantly dermatoprotective activity of alprostadil and exceeds the activity of the combination of enoxifol with rexod. Under the conditions of normoxia and hypoxia, induced by sodium cyanide, and uncouple of oxidative phosphorylation, induced by 2,4-dinitrophenol, a combination of enoxifol with rexod, increases the viability of cultured osteoblasts and fibroblasts. Enoxifol (7.5 mg/kg, intravenously) has anti-inflammatory effect in edema induced by carrageenan, histamine, serotonin and Freund's complete adjuvant. Enoxifol (7.5 mg/kg, intravenously), rexod (0.02 mg/kg, intravenously) and especially its combination have a pronounced antiulcer action on steroid ulcers of a stomach, enoxifol activity compare poorly of the sea buckthorn oil (10 ml/kg intraperitoneally); the combination of enoximone with rexod much is much superior as enoxifol, rexod and sea buckthorn oil taken from separately.

Figures

Table 1. The histoprotective effect of enoxifol in experiments on the rat tails (М ± m, n = 9).

Figure 1. The influence of intravenous administration of enoxifol, rexod and their combination on the survival of the tail tissues in the reduced blood circulation on the 3rd and 7th day of the study.

Figure 2. The influence of intravenous administration (single and sevenfold) of enoxifol, rexod and their combination on the survival of the ischemic skin fold of the back on the 3rd and 7th day of the study.

Figure 3. The influence of the single intravenous administration of enoxifol (E), rexod (R), combination enoxifol + rexod (E+R), alprostadil (A) and combination enoxifol + alprostadil (E+A) on the survival of the skin flap of the anterior abdominal wall in reduced circulation (arterial insufficiency and venous stasis) on the 3rd, 7th and 10th days of the study.

Keys: here and in figures 4 and 5: * - 7th and 10th days statistically significantly in comparison with 3rd day, ° - 10th day statistically significantly in comparison with 7th day.

Figure 4. The influence of the sevenfold intravenous administration of enoxifol (E), rexod (R), combination enoxifol + rexod (E+R), alprostadil (A) and combination enoxifol + alprostadil (E+A) on the survival of the skin flap of the anterior abdominal wall in reduced circulation (arterial insufficiency and venous stasis) on the 3rd, 7th and 10th days of the study.

Figure 5. The influence of the repeated intravenous administration of combination enoxifol + rexod on the survival of the skin flap of the anterior abdominal wall in case of partial arteriovenous failure against the background of normoglycemia and exogenous hypercholesterinemia on the 3rd, 7th and 10th days of the study.

Figure 6. The influence of the combination enoxifol + rexod (E + R, 7.5 + 0.02 m/kg) (intravenous administration for 14 days) on the level of the glucose, total cholesterol, triglycerides, high density lipoproteins (HDL) and β-lipoproteid aginst the background of normoglycemia, EDM and exogenous hypercholesterinemia.

Figure 7. The influence of enoxifol (E), indomethacin (In) and piroxicam (Pir) on the acute edematisation, induced by carrageenan, CFA, serotonin and histamine.

Figure 8. Antiulcer activity of enoxifol (E), rexod (R), sea buckthorn oil (SBO) ad combination enoxifol + rexod (E + R) in steroid-ethanol damage of a gastric mucosa.

Table 2. Antinecrotic effect of enoxifol (7.5 mg/kg) in ischemic skin (M ± m, n = 8)

Table 3. Antinecrotic effect of rexod (0.02 mg/kg) in ischemic skin (M ± m, n = 7)

Table 4. Antinecrotic effect of enoxifol (7.5 mg/kg) + rexod (0.02 mg/kg) in ischemic skin (M ± m, n = 8).

Table 5. The influence of rexod (0.02 mg/kg) on the antioxidant defense in the ischemic skin (M ± m, n=7).

Table 6. The influence of rexod (0.02 mg/kg) on the system of energy supply in the ischemic skin (M ± m, n=7).

Table 7. The influence of the combination enoxifol (7.5 mg/kg) + rexod (0.01 mg/kg) on the indices of the energy supply systems, the antioxidant defense and lysosomal activity in the ischemic skin (M ± m, n=8).

DOI: 10.18413/2500-235X-2017-3-1-32-48
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