Effect of 3d-metal gluconates on leukocyte parameters of endogenous intoxication

Background. The development of endogenous intoxication in the treatment of oncological pathology with cytostatic drugs complicates targeted therapy, so the search for correctors of these conditions is an actual task. Previously, we have shown in vivo the corrective effect of 3d-metal gluconates on the humoral link of immunity with the administration of the widely used cytostatic cyclophosphamide. It is of interest to evaluate the effect of 3d-metal gluconates on changes in leukocyte parameters of endogenous intoxication affected by cyclophosphamide.

Aim. Evaluation of the effect of 3d-metal gluconates (Mn, Fe, Co, Cu, Zn) on the degree of endogenous intoxication in mice against the background of the cytostatic effect of cyclophosphamide.

Material and methods. The experiment was carried out on white laboratory male mice weighing 25–28 g, divided into 9 groups [1 — intact animals, 2 — administration of cyclophosphamide without treatment, 3 — administration of cyclophosphamide and a comparison drug with an immunostimulating effect, 4 — administration of cyclophosphamide and the comparison drug calcium gluconate, groups 5–9 — administration of cyclophosphamide and gluconates of 3d-metals (MnGl, FeGl, CoGl , CuGl and ZnGl, respectively)], 12 individuals each, kept in the vivarium conditions on a standard diet. Endogenous intoxication was induced by a single injection of cyclophosphamide. 3d-metal gluconates (Mn, Fe, Co, Cu, Zn) and comparison drugs (glucosaminylmuramyl dipeptide in the form of Likopid, and calcium gluconate) were used to correct changes in the immune system. The administration of the drugs was started 24 hours after the administration of the cytostatic and then daily orally during 21 days. Blood sampling was performed on the 22nd day. The assessment of the degree of endogenous intoxication was carried out by determining the leukocyte indices: stress activity index, leukocyte intoxication index, nuclear index of the degree of endotoxicosis, and leukocyte shift index. Statistical processing of the results was performed using the Statistica 10.0 program. To calculate the significance of differences between groups, the nonparametric Mann–Whitney test was used. Changes were considered significant at p <0.05.

Results. After the administration of cyclophosphamide in animals, a significant change in the leukocyte formula, which indicates an acute intoxication of the body, was observed: there was a decrease in the content of monocytes (3 times), segmented neutrophils (1.5 times), an increase in stab neutrophils (2 times), lymphocytes (1.1 times). The intake of 3d-metal gluconates led to the correction of leukocyte indices, the degree of which statistically significantly exceeded the degree of correction by the comparison drugs Licopid and Calcium gluconate (p <0.05), and for Zn (II) gluconate it was from 45 to 84%, for Mn (II) gluconate — from 44 to 100%.

Conclusion. Gluconates of 3d-metals reduce the degree of endogenous intoxication caused by cyclophosphamide, increase the reactivity of phagocytes and the regeneration rate of the leukocyte link. In terms of efficiency, 3d-metal gluconates can be arranged in the following order (according to metals): Mn ˃Zn ˃Cu ˃Co ˃Fe.