Combined application of alpha-tocopherol and FC-43 perfluorocarbon emulsion suppresses early postburn lipid peroxidation and improves deformability of erythrocytes.

The effect of FC-43 perfluorocarbon emulsion and alpha-tocopherol on lipid peroxidative damage and deformability of erythrocytes was evaluated in rats (full skin thickness burns over 15-20% of total body surface) at third hour after burns. The animals were divided into five groups: (1) non-burnt non-treated (controls); (2) burnt non-treated; (3) burnt but treated with alpha-tocopherol ("Serva", Germany, 20 mg/kg b.m. i.p.) (4) burnt treated with FC-43 emulsion ("Green Cross Corp.," Japan, 5 ml/kg, i.v.); (5) burnt treated with combination of alpha-tocopherol (20 mg/kg) and FC-43 perfluorocarbon emulsion (5 ml/kg). In the burnt non-treated group the concentration of alpha-tocopherol decreased by 38% (p < 0.05), the levels of malonyl dialdehyde (MDA) and fluorescent damaged products raised by 32% (p < 0.001) and by 52% (p < 0.001) of the controls, respectively, whereas the deformability of red blood cells diminished by 34% (p < 0.001). Both the accumulation of MDA and fluorescent lipid peroxidation products and the decrease in deformability of affected cells were suppressed significantly by alpha-tocopherol treatment which also prevented the decrease in erythrocyte alpha-tocopherol content. FC-43 emulsion lowered the level of MDA but did not restrain the reduction in erythrocyte deformability significantly. The combined application of alpha-tocopherol and FC-43 emulsion immediately after thermal skin injury decreases peroxidative membrane damage and improved erythrocyte deformability more significantly than alpha-tocopherol at the third hour after thermal skin injury.

Suppressive effect of FC-43 perfluorocarbon emulsion on enhanced oxidative haemolysis in the early postburn phase.

The effect of FC-43 perfluorocarbon emulsion on resistance of red blood cells to oxidative haemolysis and lipid peroxidation was evaluated in rats (full skin thickness burns over 15-20 per cent of total body surface area). The content of erythrocyte malonyl dialdehyde (MDA), alpha-tocopherol, glutathione (reduced and oxidized forms) and oxidative haemolysis were measured at 24 h after burn injury. Four groups were employed: (1) non-burned non-treated, (2) non-burned but treated with FC-43 perfluorocarbon emulsion (5 ml/kg bodymass i.v.), (3) burned non-treated, (4) burned but treated with FC-43 emulsion (5 ml/kg bodymass i.v.). The non-burned groups showed no significant differences in oxidative haemolysis, MDA levels or alpha-tocopherol and glutathione content. In the burned non-treated group the oxidative haemolysis elevated by 190 per cent (P < 0.001), MDA content increased by 43 per cent (P < 0.05), whereas the concentration of alpha-tocopherol and reduced glutathione (GSH) decreased significantly by 36 per cent and 18 per cent, respectively. The results showed reduction in the postburn MDA content by 30 per cent (P < 0.02) and oxidative haemolysis by 44 per cent (P < 0.001) after treatment with FC-43 emulsion. FC-43 emulsion did not change significantly the levels of alpha-tocopherol and GSH in erythrocytes after thermal injury. It is concluded that FC-43 perfluorocarbon emulsion administration suppresses early postburn lipid peroxidation and increases the resistance of red blood cells to oxidative haemolysis.

Reduced erythrocyte deformability related to activated lipid peroxidation during the early postburn period.

The role of lipid peroxidation in reduced red cell deformability has been examined after thermal injury of rats (full skin thickness over 15-20 per cent of total body surface). An increased concentration of erythrocyte malonyldialdehyde (MDA) and blood thiobarbituric acid (TBA) reactive product levels during the first 3 days after thermal trauma was established. There was a remarkable decrease in red cell superoxide dismutase (SOD) activity after burns and an increase in glucose-6-phosphate dehydrogenase (G-6-PD) on day 3 postburn. The deformability of erythrocytes was diminished significantly during the first 3 days after burns. There was a significant negative correlation between the deformability and the amount of MDA accumulated in erythrocytes (r = -0.92). Both the accumulation of MDA and the reduction of SOD activity in erythrocytes were suppressed by alpha-tocopherol treatment, which also prevented the decrease in erythrocyte deformability. These results suggest that the activation of the peroxidative process is a possible mechanism for the decreased deformability of erythrocytes during the early stage after thermal injury.

[Changes in the osmotic resistance of the erythrocytes in thermal trauma and the role of free-radical oxidation]. / Promeni v osmotichnata rezistentnost na eritrotsitite pri termichna travma i roliata na svobodnoradikalnoto okislenie.

Reduced erythrocyte osmotic resistance against the background of elevated blood level of TBA-reactive products was recorded in experimental thermic injury (of IIIa-IIIb degree, involving 15-20 per cent of the body surface). Under the influence of alpha-tocopherol, parallel with the restriction of free-radical oxidation (FRO) activity, there was a rise in erythrocyte membrane osmotic resistance. FRO participation in the mechanisms of reduced erythrocyte osmotic resistance in thermic injury is discussed.

[The correlation between the activity of free-radical peroxidation and erythrocyte hemolysis in experimental thermal trauma]. / Korelatsionna zavisimost mezhdu aktivnostta na svobodno-radikalnoto prekisno okislenie i khemolizata na eritrotsitite pri eksperimentalna termichna travma.

Increased concentration of the products of red-cell free-radical oxidation (FRO), i.e. of malondialdehyde (MDA) and of Schiff bases in red cells and of their hemolysis was recorded in the acute period of experimental thermic injury. Alpha-tocopherol applied after thermic injury suppressed FRO and restricted red cell hemolysis. A strong positive correlation was recorded between hemolysis and MDA (r = 0.97) and between hemolysis and Schiff bases (r = 0.88). This high-grade positive correlation between hemolysis and content of secondary and end products of FRO, as well as their decrease after alpha-tocopherol treatment give grounds to admit that activated peroxidation processes in red cells play a definite role for destabilization of their membranes. The role of hemolysis for secondary FRO activation and for implication of the whole organism in the overall pathologic process, the burn disease, is discussed.

Erythrocyte rheology and lipid peroxidation in burns.

Alterations in the erythrocyte rheology and the contents of activated free radical oxidation products (conjugated dienes, products of thiobarbituric acid and Schiff bases) in the acute phase of experimental thermic injury of the skin were studied. Erythrocyte flexibility reduction and erythrocyte aggregation increase correlated with elevated amounts of free radical oxidation products. Alpha-tocopherol avoided the accumulation of free radical oxidation products and improved both antioxidant defence and erythrocyte rheology. Thus we suppose that free radical oxidation products probably participate in the pathogenesis of erythrocyte rheology disturbances after thermic trauma.

Regulation of traumatic skin wound healing by influencing the process in the neighbouring zone of the wound.

After the burn, the authors immediately applied the albuminous hydrolysate Hydropot, a propolis-urea ointment and Trypsin compresses (3,500 E) to the burned area and its vicinity, and repeated this procedure for several days. Samples for histological examination were taken after the animals' decapitation every 2 hrs. and on the 3rd, 5th and 14th post-injury days. The morphological picture showed a difference in rate and quality of regeneration. The authors are of the opinion that the processes occurring in the neighbourhood of the traumatic skin wound can be influenced and that regeneration can be regulated.

Dependence between the free-radical peroxidation, the activity of the superoxide dismutase glucose-6-phosphate dehydrogenase and erythrocytes haemolysis after thermal trauma and alpha-tocopherol treatment.

Experimental thermal trauma of IIIa-IIIb degree was induced on an area of 15-20% in male Wistar rats weighing 200-250 g. The changes in the content of the products of free-radical oxidation (FRO) - conjugated dienes and thiobarbituric acid (TBA) products in the blood, haemodialysis, the activity of superoxide dismutase (SOD) and of G-6-PHD-ase in the erythrocytes during the acute period after thermal trauma (24, 48 and 72 hours) were traced. The experimental data have shown that the percentage of haemolysed erythrocytes increases with the potentiation of FRO after burning. Intraperitoneal administration of alpha-tocopherol in a dose of 20 mg/kg body mass is followed by a reduction of the FRO products and by a rise in the antioxidative protection and resistance of the erythrocytes. The role of FRO in the pathogenesis of the damage of the erythrocytic membrane after thermal trauma and the protective effect of alpha-tocopherol are discussed.

[Experimental and clinical research on the antidote properties of nivalin in acute atropine poisoning]. / Eksperimentalno i klinichno prouchvane vurkhu antidotnite svoistva na nivalina pri ostrite atropinovi intoksikatsii.

The anticholinesterase properties of nivalin, its low toxicity and penetration through the blood-liquor barrier make it an adequate agent for the treatment of acute atropine intoxications. Regardless of all that it is not mentioned in our toxicological literature and is not used in the clinical practice. iNivalin in doses 0.25-0.5 mg/100 g body mass was applied experimentally to guinea pigs previously treated with atropine with determined LD100. The animals that survived reached 31.1%. Later, nivalin was subcutaneously, intramuscularly and intravenous applied, according to a definite schedule--from 0.05 to 0.25 mg/kg body mass, to 20 subjects, aged from 4 to 43 with acute atropine intoxications. A fast and good effect was reported, particularly as regards the manifestations of the CNS, allowing the reduction of the rest of the therapy. No allergic and toxic manifestations were observed. Nivalin is concluded to be an antidote of choice in the treatment of acute intoxications of that type.