Evaluation of the effect of the combination of glucosamine derivatives with quercetin on the morphofunctional state of the thymus and spleen of rats under the toxic effect of doxorubicin

Abstract

In the rating of the most used antineoplastic drugs, the antibiotic of the anthracycline series doxorubicin occupies a significant place. The introduction of doxorubicin into clinical practice has made it possible to improve the current and delayed results of treatment; however, the non-selective spectrum of its cytostatic action is manifested by a number of drug-dependent side effects, among them cardio- and myelotoxicities are the most characteristic ones. Among the modern and proven approaches to the pharmacocorrection of the organotoxic effect of doxorubicin, it is considered traditional to carry out the supporting therapy using drugs of various pharmacotherapeutic groups, which action is directed to the corresponding affected organ/target system. A significant disadvantage of this approach is the creation of prerequisites for polypharmacy and, consequently, all the negative consequences of its use. Currently, scientific data on the prospects of searching for products of the supporting therapy among biologically active substances of natural origin and their combinations characterized by a universal multicomponent mechanism of the cytocorrective action, pronounced therapeutic effectiveness and a high safety profile continue to appear.Aim. To study the combination of glucosamine derivatives with quercetin as a potential сorrector of the immunotoxic action of doxorubicin in the experiment in rats.Materials and methods. The study in evaluating the corrective effect of the combination of glucosamine derivatives with quercetin under conditions of doxorubicin intoxication was performed on 75 rats. To simulate intoxication, experimental animals (excluding the intact group) were injected intraperitoneally with doxorubicin in the dose of 5 mg/kg of the body weight once a week for four weeks. The combination under research was administered once daily intragastrically for 28 days after the first injection of the cytostatic. The histomorphological studies of the thymus and spleen were performed using standard methods of light microscopy.Results. In the course of the study, it was shown that under the effect of the combination of glucosamine derivatives with quercetin studied a decrease in dystrophic changes in the thymus and spleen of rats was observed, the intensity of regeneration processes increased, indicating the restoration of the functional state of immunocompetent organs. By the severity of the protective effect the combination studied was superior to monocomponent reference samples of glucosamine hydrochloride and quercetin.Conclusions. The combination of glucosamine derivatives with quercetin has a corrective effect on the state of the organs of immunogenesis (thymus and spleen) under conditions of the development of doxorubicin intoxication in rats and is a promising subject for further pharmacological study as a modifier of the immunosuppressive effect of doxorubicin.