HEPATOTOXIC EFFECT OF THE COMBINED USE OF ISONIAZID, RIFAMPICIN, AND PYRAZINAMIDE IN RATS OF DIFFERENT AGE GROUPS
DOI:
https://doi.org/10.11603/mcch.2410-681X.2026.i3.16731Keywords:
Isoniazid; Rifampicin; Pyrazinamide; hepatotoxicity; age groups of ratsAbstract
Introduction. Ukraine takes the second place in Europe in terms of the rate of TB’s spread. Most drugs used to treat tuberculosis are potential hepatotoxic agents. The aim of the study – to investigate the hepatotoxic effect of the combined administration of isoniazid, rifampicin, and pyrazinamide in rats of different age groups by assessing biochemical parameters of liver functional status. Research Methods. The animals of different age groups received isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA) daily by intragastric administration at doses of 30 mg/kg, 75 mg/kg, and 160 mg/kg body weight respectively, during 14 days. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were determined in blood serum and liver homogenate, and the De Ritis ratio was calculated. Results and Discussion. A statistically significant (p < 0,05) increase in blood serum aminotransferase and ALP activities were established in animals of all age groups that received INH, RIF, and PZA. In the immature rats, ALT and AST activities increased by 87 and 130 %, respectively, in the mature rats – by 45 and 73 %, and in the senior rats – by 60 and 148 % respectively in comparison with the control group. In liver tissue, a statistically significant (p < 0,05) decrease in aminotransferase and ALP activities were observed following the combined administration of INH, RIF, and PZA, indicating hepatocyte cytolysis and impaired protein-synthetic function of the liver. The highest De Ritis ratio was established in the senior animals receiving by the combined administration of drug. Its value was 0,9, which was 1,6 times higher than the normal value. Conclusions. The combined administration of anti-tuberculosis drugs resulted in a statistically significant (p < 0,05) increase aminotransferase and ALP activities in blood serum and their decrease in the liver tissue of rats of all age groups. In animals of all age groups, the De Ritis ratio was below 1. The most vulnerable animals to the hepatotoxic combined effects of ING, RIF, and PZA were immature and senior rats.
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