We studied the correlation between the effect of α-lipoic acid, emoxipin, reamberin, and mexidol on LPO in vitro and the action of these drugs on insulin sensitivity and tolerance to glucose load in vivo. It was found that the preparations producing prooxidant effect in vitro (α-lipoic acid and reamberin) are characterized by pronounced insulin-potentiating activity, but only slightly increase (α-lipoic acid) or even decrease (reamberin) tolerance to glucose load. 3-Hydroxypyridine derivatives (emoxipin and mexidol) producing an antioxidant effect in vitro increase glucose tolerance, but exhibit relatively weak insulin-potentiating activity. These results suggest that differential use of the studied drugs in patients with diabetes mellitus depending on the type of the disease and individual insulin requirement is a promising trend in medical studies.

We studied the dynamics of lipid peroxidation-antioxidant defense system in rat model of alloxan diabetes and compared it with disorders of carbohydrate and lipid metabolism. It was found that rats not treated with insulin developed hyperglycemia, hypertriglyceridemia, hypocholesterolemia, and hypotocoferolemia with simultaneous accumulation of circulating LPO products 96 h after the administration of alloxan. The severity of hyperglycemia and hypertriglyceridemia decreased, hypercholesterolemia developed, hypotocoferolemia returned to normal, and the tendency to LPO inhibition was observed in rats 10 days after alloxan administration against the background of previous one-week treatment with insulin. In 17 days after the induction of alloxan diabetes preceded by two-week insulin therapy, the content of lipoperoxides reduced below the normal values with simultaneous progression of hypercholesterolemia, hypertriglyceridemia and the increase in serum fructosamine.

Threefold administration of 3-hydroxypyridine derivatives emoxipine and mexidol in optimal doses corresponding to the therapeutic dose range for humans produced an anxiolytic effect and stimulated risk behavior in the elevated plus maze test in rats. These effects were most pronounced after injection of 3-hydroxypyridine derivative emoxipine. Combination of 3-hydroxypyridine cation and succinate anion in the mexidol structure led to attenuation of the anxiolytic effect and less pronounced stimulation of the risk behavior. By the anxiolytic effect and induction of risk behavior, emoxipine and mexidol were close to the reference substance amitriptyline. Reamberin, a succinic acid derivative, had no pronounced tranquilizing properties, but risk behavior induction was similar to that produced by mexidol. In contrast to other test agents, the reference substance α-lipoic acid produced anxiogenic effects and suppressed risk behavior. The obtained results suggest that Russian-made 3-hydroxypyridine derivatives emoxipine and mexidol are promising preparations for the treatment of anxiety disorders.

The effects of original Russian preparations, derivatives of 3-hydroxypyridine and succinic acid (emoxipin, reamberin, mexidol), on the cellular composition of the cerebrocortical and diencephalic structures were studied and correlations of shifts in the cellular composition with changes in the severity of hyperglycemia in rats with alloxan diabetes were analyzed. The efficiency of 3-hydroxypyridine and succinic acid derivatives was evaluated in comparison with α-lipoic acid. Seven injections of the optimal doses of all the studied drugs prevented the neuron loss in layers I-III of the primary somatosensory cortex. In addition, emoxipin, reamberin, and α-lipoic acid prevented astrocyte loss in the neocortical surface layers and of neurons in the hypothalamic paraventricular nucleus. Reamberin limited microglial infiltration of the hippocampal field CA1. Injection of α-lipoic acid augmented the increase in astrocyte count in the paraventricular nucleus and potentiated the reduction of tigroid granularity of CA1 field neurons. Emoxipin and mexidol caused an increase in the counts of neurons and oligodendrocytes in CA1 field. By contrast, reamberin and α-lipoic acid reduced the counts of neurons and oligodendrocytes, respectively, in this hippocampal zone. More favorable effects of emoxipin and mexidol vs. reamberin and α-lipoic acid on the cellular composition of the hippocampus of rats with alloxan diabetes were explained by more effective correction of hyperglycemia under the effect of 3-hydroxypyridine derivatives.