ANTIHYPOXIC ACTIVITY OF 2,6-DIMETHYLPYRIDINE-N-OXIDE.

OBJECTIVE: The aim: To study the antihypoxic activity of 2,6-dimethylpyridine-N-oxide in mice using the various experimental models of acute hypoxia under orally or intraperitoneally administration. PATIENTS AND METHODS: Materials and methods: The studies were performed on male CD-1 (SPF) mice. The antihypoxic activity of 2,6-dimethylpyridine-N-oxide was studied in three experimental models of acute hypoxia - hypercapnic hypoxia or hypoxia in a closed space, hemic hypoxia and histotoxic hypoxia at orally administration at doses 0.07; 7.1 and 71 mg/kg (respectively 1/20000, 1/200 and 1/20 of LD50) and at intraperitoneally administration at doses 7.1 and 71 mg/kg in comparison with reference drug Armadin. RESULTS: Results: It is established, that 2,6-dimethylpyridine-N-oxide shows a antihypoxic activity in the all experimental models of acute hypoxia (hypoxia in a closed space, hemic hypoxia and histotoxic hypoxia). Its antihypoxic activity in acute hemic hypoxia and in acute hypoxia in a closed space was significantly higher than of reference drug Armadin, but during acute histotoxic hypoxia did not differ from Armadin. Also at intraperitoneal administration of 2,6-dimethylpyridine-N-oxide demonstrates less pronounced antihypoxic activity than at oral administration in all experimental models of acute hypoxia, but the coefficient efficiency is higher than in the reference drug Armadin. CONCLUSION: Conclusions: 2,6-dimethylpyridine-N-oxide may be recommended for further detailed experimental studies as a perspective antihypoxant.

Investigation of in vivo toxicity of hydroxylamine sulfate and the efficiency of intoxication treatment by α-tocopherol acetate and methylene blue.

OBJECTIVES: Investigation of hydroxylamine sulfate toxicity mechanism in vivo and estimation of α-tocopherol acetate and methylene blue efficiency in poisoning treatments. METHODS: In vivo experiments were conducted on 102 Wistar Han rats. The experiments investigated the hematotoxic and oxidative stress effects of hydroxylamine sulfate in acute and subacute toxicity treatment of animals. Electron Spin Resonance was used for quantitative determination of blood and liver tissue parameters alterations after intoxication. The osmotic fragility of erythrocytes, lipid peroxidation intensity and level of SH-groups in liver of rats were determined by established biochemical assays. RESULTS: Hydroxylamine sulfate cause an acute hematotoxicity and oxidative stress in vivo as demonstrated by the appearance of free oxidized iron in blood, reduced glutathione content and increased lipid peroxidation in liver. The experimental studies showed the formation of Hb-NO, MetHb in erythrocytes and as well of stable complex of reduced iron (Fe(2+)) with hydroxylamine sulfate. Methylene blue treatment does not reduce the Hb-NO or MetHb levels in intoxicated animals while administration of α-tocopherol acetate reduces substantially lipid peroxidation. CONCLUSIONS: Oxidative stress is a key mechanism of acute hematotoxicity caused by hydroxylamine sulfate. Methylene blue is not suitable antidote in case of hydroxylamine intoxication.