Drug-induced hematological changes in rats after anti-tuberculosis therapy

A model of induced polypharmacy in studies of drug-induced changes in blood parameters can be represented by the combined treatment of tuberculosis patients in accordance with current clinical guidelines. Against the background of anti-tuberculosis therapy (ATT), patients experience negative changes in hematological parameters, indicating undesirable effects of anti-tuberculosis drugs (ATD). It is quite difficult to distinguish between the myelosuppressive effect of the specific inflammatory process (tuberculosis) and that of chemotherapy alone. The hematotoxic effect of individual ATDs is known, but how the interaction of a combination of drugs can affect the severity of drug-induced adverse events has not been sufficiently studied. The aim of the study was to analyze the drug-induced effects of standard two-month combined anti-tuberculosis therapy on the hematological parameters of rats, excluding the factors of a specific disease, and to determine early laboratory criteria for detecting changes.

Material and methods. The study material was rat blood serum, in which the following parameters were assessed: iron level, hemoglobin concentration, red blood cell, white blood cell, platelet count and erythrocyte indices (mean corpuscular volume and mean corpuscular hemoglobin) after two months of combined ATT. Experimental group I (EGI) received first-line ATDs for drug-sensitive tuberculosis, while experimental group II (EGII) received second-line (reserve) ATDs for multidrug-resistant tuberculosis. The results were compared with a control group (CG).

Results and discussion. During the experiment, no statistically significant hematological changes were found in the blood of rats in EGI after standard two-month ATT. In contrast, in EGII, after 60 days of second-line ATD combination therapy, a significant decrease in hemoglobin level (by 38.2 %, р < 0.001), mean corpuscular volume (by 32.1 %, р < 0.001), and mean corpuscular hemoglobin (by 25.2 %, p < 0.001) was observed. These findings may serve as early diagnostic criteria for the development of adverse hematotoxic effects of ATDs and require further study to determine the optimal drug administration regimen.

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