Evaluation of side effects of Na-Ca exchange inhibitor KB-R7943 used as an analgesic drug in diabetic neuropathy in rats
DOI:
https://doi.org/10.33910/2687-1270-2023-4-1-69-78Keywords:
diabetes mellitus, diabetic neuropathy, ECG, KB-R7943, open field, ratAbstract
This article reports the results of the study of side effects of selective sodium-calcium exchange blocker KB-R7943 used as an analgesic drug in rats with streptozotocin-induced type 1 diabetes mellitus. ECG analysis showed no negative effect of KB-R7943 on the cardiovascular system of control rats and rats with type 1 diabetes mellitus. In open field testing, the behavior (motor activity and signs of anxiety) of rats did not change after the administration of KB-R7943. The tissues of the hippocampus and hypothalamus were analyzed for the level of the gene expression of the voltage-gated sodium channel Nav1.7 (SCN9A), the α2δ-1 subunit of voltage-gated T-type calcium channels (CACNA2D1), Bax and Bcl-2 involved in the pathogenesis of diabetic neuropathy. It was shown that in the hippocampus of rats with DM1, the administration of KB-R7943 led to an increase in CACNA2D1 expression and a decrease in SCN9A expression, while in the control group the level of Nav1.7 mRNA increased under the influence of the drug. The expression of both Bax and Bcl-2 in the hippocampus of control animals after the administration of KB-R7943 increased. In the hypothalamus of the diabetic group, KB-R7943 therapy reduced the level of Bcl-2 mRNA, leaving the level of Bax expression unchanged.
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