Review Article
Volume 10 Issue 4 - 2021
The Problem of Hepatotoxicity of Antituberculosis Drugs and Polymorphism of GSTT1 and GSTM1 Glutathione Transferase Enzymes
Lesnevskyi Oleksandr1*, Bazhora Yuriy2, Smetiuk Olena3 and Chesnokova Marina3
1Faculty of Clinical Immunology, Genetics and Medical Biology, Odessa National Medical University, Odessa, Ukraine
2Professor, Faculty of Clinical Immunology, Genetics and Medical Biology, Odessa National Medical University, Odessa, Ukraine
3Assistant Professor, Faculty of Clinical Immunology, Genetics and Medical Biology, Odessa National Medical University, Odessa, Ukraine
*Corresponding Author: Lesnevskyi Oleksandr, Faculty of Clinical Immunology, Genetics and Medical Biology, Odessa National Medical University, Odessa, Ukraine.
Received: March 11, 2021; Published: March 31, 2021




Abstract

Introduction: Tuberculosis is recognized as one of the most pressing problems of modern medicine all over the world. It is not only a medical problem, it is a social problem, which reflects the socio-economic condition of the country, the cultural and educational level and well-being of the population, the degree of healthcare development. Despite the downward trend in tuberculosis in Ukraine in recent years, in 2018 the incidence was 62.3 per 100,000 population. The highest incidence rates of all forms of tuberculosis are observed in the southeastern region, including the Odessa region, which requires improvement of treatment and prevention of the disease. Each tuberculosis patient undergoes long-term multicomponent chemotherapy drug therapy according to WHO-recommended regimens. Some of the most threatening organotoxic side effects are hepatotoxicity and nephrotoxicity caused by anti-TB drugs. Detoxification of anti-tuberculosis drugs occurs in the liver with the participation of a two-phase xenobiotic detoxification system. Phase I is aimed at changing the polarity of the xenobiotic molecule. Phase II enzymes convert intermediate metabolites to water-soluble compounds that are excreted in the body. One of the most important second phase enzymes is glutathione transferase (GST type T and M) conjugation enzymes. Known polymorphism of the GSTT1 and GSTM1 genes, which determines the presence or absence of functional activity of these enzymes. The influence of polymorphism of these genes on the development of hepatotoxicity is poorly understood, and inconsistent results have been obtained.

Aim of the Study: Detection of liver dysfunction in patients with pulmonary tuberculosis on the background of GSTT1 and GSTM1 gene polymorphism.

Materials and Methods: The study involved patients with pulmonary tuberculosis (first diagnosed pulmonary tuberculosis (FDPT) and chronic pulmonary tuberculosis (CPT)) who underwent standard anti-tuberculosis therapy. Analysis of hepatotoxic effects of antituberculosis drugs was carried out using blood biochemical studies. GSTT1 and GSTM1 gene polymorphism was determined by multiplex PCR in the study of DNA from blood samples.

Results and Conclusion: Two months after the start of treatment, no statistically significant differences were found between the AST and ALT levels in the patients with the absence or presence of GSTT1 and GSTM1 gene deletions. In addition, in the group of patients with no GSTM1 gene, there was a significant increase in AST and ALT aminotransferases compared to the group with the presence of the enzyme. In patients with CPT with no GSTT1 enzyme, unlike the group with the presence of the enzyme, showed a significant increase in total (12.0 ± 2.69 vs 9.9 ± 1.44, p = 0.03) and indirect (9, 25 ± 2.08 vs 7.4 ± 1.06, p = 0.02) bilirubin compared with patients with FDPT, indicating a more severe liver lesion than patients with enzyme.

 

Keywords: Xenobiotic Detoxification Genes; Tuberculosis; First Diagnosed Pulmonary Tuberculosis (FDPT); Chronic Pulmonary Tuberculosis (CPT)

References

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Citation: Lesnevskyi Oleksandr., et al. “The Problem of Hepatotoxicity of Antituberculosis Drugs and Polymorphism of GSTT1 and GSTM1 Glutathione Transferase Enzymes”. EC Pulmonology and Respiratory Medicine 10.4 (2021): 44-51.

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