Ascorbigen — Rifabutin Toxicity Modifier

Abstract

Relevance. Indications for rifabutin use are constantly expanding. It is used in the treatment of extremely complex nosological forms of infectious diseases. However, side effects of the medication, such as gastrointestinal toxicity and myelosuppression, in many cases do not allow the completion of treatment and weaken the patient-s adherence to therapy. This determines the need to find means to reduce the toxic properties of rifabutin.Objective. The aim of the study was to investigate the possibility of correction of gastrointestinal and hematological toxicity of rifabutin with ascorbigen.Material and Methods. The study was performed in male Wistar rats. The drugs were administered per os at therapeutic doses (50 mg/kg daily for 15 days). Ascorbigen was administered 30 minutes before rifabutin. Body weight dynamics, hematological parameters, blood biochemical parameters, electrocardiography, and urinalysis were performed for all animals during the study. Five animals in each group were euthanized on the 1st and 30th days after the end of the treatment course. The internal organs were subjected to histological evaluation.Results. It has been shown that combined treatment with rifabutin and ascorbigen leads to a weakening of the damaging effect of the antibiotic on the mucous membrane of the gastrointestinal tract and accelerates the processes of restoration of its structure. Clinically, this is expressed in the normalization of body weight gain of animals. The combined use of rifabutin with ascorbigen reduces the depth of cytopenia. The number of leukocytes in the peripheral blood of the rats was restored faster. There were no signs of atrophy of spleen-s lymphoid tissue. The administration of ascorbigen before rifabutin has a protective effect on the tissues of the kidneys and testes.Conclusion. Oral administration of ascorbigen 30 minutes before rifabutin significantly reduces the gastrointestinal toxicity and hematotoxicity of rifabutin and prevents the development of spermatogenesis disorders. This allows us to recommend it for combined use in order to improve tolerance to anti-TB treatment.