Експериментальна та клінічна фізіологія і біохіміяDiabetic neuropathy is one of the major disabling complications of diabetes mellitus (DM), and there remain relevant both problems of the pathogenesis, and treatment and prevention of it, as it is not possible to achieve positive results in the stabilization in the state of the body by only providing adequate glycemic control, as even minor fluctuations in blood glucose levels increase risk of the neuropathy. As a way of correction of the electrophysiological parameters of the neuromuscular complex activity under DM oxymethylethylpyridine succinate was chosen which is a derivative of 3-hydroxypyridine and succinic acid and belongs to the group of heteroaromatic antioxidants with membrane-protective action.
Parameters of bioelectrical activity of neuromuscular complex of rat in experimental DM were investigated, as well as after the administration of oxymethylethylpyridine succinate. DM was modelled using alloxan monohydrate infused intraperitoneally at the dose of 155 mg/kg of body weight of a rat. According to the experimental protocol, animals were divided into two groups: group 1 included animals with experimental DM (control, n=14), group 2 included animals with experimental DM under the oxymethylethylpyridine succinate treatment (n=13). Only the animals with blood glucose level not less than 15 mmol/L, were taken into the experiment. Blood glucose levels in the animals of the first group made 26,63±1,03 mmol/L. Further, the animals of the group 2 were exposed to the treatment with oxymethylethylpyridine succinate at the dose of 25 mg/kg intraperitoneally, once a day. On the 21st day of the experiment prior to administration of the drug the blood glucose level was 25,97±1,04 mmol/L, and after the treatment with the drug, on the 30th day it was 21,03±0,84 mmol/L. The acute experiment was performed under general anesthesia using thiopental at 50 mg/kg.
The investigation of the activity of neuromuscular complex was performed by applying rectangular stimuli of 1 to 2 thresholds onto the sciatic nerve, using bipolar electrodes, and the recording was carried out from the gastrocnemius muscle of a rat. The animals of the group 2 showed decrease in the threshold of excitation of the gastrocnemius muscle by 53,52% (p<0.001), increase in chronaxy by 46,82% (p<0.001), which was probably of a compensatory nature, and the increase in the amplitude of the action potential (AP) of the gastrocnemius muscle twice the control (p<0.01), and increase in its duration by 29,24% (p<0.001) in response to oxymethylethylpyridine succinate within 10 days of experiment. When paired stimuli were applied, this group showed no significant changes (p>0.05) in the restoration of the amplitude of the AP in response to 2nd stimulus after the injection of the drug, when compared to the animals of the group 1.
It was concluded that under the usage of this drug in experimental DM did improve the processes of excitation in the peripheral structures, as evidenced by the lowering of the threshold of excitation and increase in the amplitude of AP of the gastrocnemius muscle by membrane stabilizing and antioxidative activities of this drug. It was suggested that the efficiency of this drug could be increased by increasing the dosage or duration of treatment, which, in turn, could improve conductivity in peripheral structures and would be sufficient for the correction of the duration of refractory periods of the gastrocnemius muscle.
Ключові слова: experimental diabetes mellitus, neuromuscular complex, oxymethylethylpyridine succinate
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