Evaluation of glutathione system indicators in the body of patients with lung cancer

Glutathione is very important in cells protecting, however, its high concentration in tumor cells can increase their survival by raising resistance to chemotherapeutic drugs and free radical oxidation. The effectiveness of chemotherapy treatment often depends on the individual genetic characteristics of the patient, his sensitivity to pharmaceutical drugs. According to scarce existing research it is indicated that tolerability of chemotherapy among Asians is lower compared to Caucasians. In this regard, we decided to evaluate the influence of ethnicity on the indicators of the glutathione system in patients with lung cancer and persons not suffering from oncopathology.

We examined 50 people with lung cancer, admitted to the Yakut Republican Oncology Center. The control group was selected based on age, gender and ethnicity and included 50 people. The main criterion for selection in the control group was the absence of cancer. The concentration of reduced glutathione, TBA-active products, activity of glutathione reductase, glutathione-S-transferase, glutathione peroxidase were determined by the spectrophotometric method.

The results of our study showed that the concentration of reduced glutathione (Yakuts by 70.7, Russians by 52.4%), the activity of glutathione peroxidase (Yakuts by 34.4, Russians by 18.6%) in the body of patients had been decreasing. The activity of glutathione reductase in the body of patients with lung cancer decreased in Yakuts by 10.5%, while in Russians it increased by 13.0%.

The results of our research testify to the depletion of the glutathione system in the group of cancer patients of the Yakut ethnicity, which is probably the reason for the severe tolerance of chemotherapy.

1. Alwaleedi S. A. Alterations in antioxidant defense system in hepatic and renal tissues of rats following aspartame intake / S. A. Alwaleedi // Journal of Applied Biology and Biotechnology. – 2016. – №4(2). – P.46–52. DOI: 10.7324/JABB.2016.40207

2. Analysis of GSH and GSSG after derivatization with N-ethylmaleimide / D. Giustarini, I. Dalle-Donne, A. Milzani [et al.] // Nature Protocols. – 2013. – №8 (9). – P.1660-1669. DOI: 10.1038/nprot.2013.095.

3. Bansal A. Glutathione metabolism in cancer progression and treatment resistance / A. Bansal, M. C. Simon // Journal of cell biology. – 2018. – №217 (7). – P.2291–2298. DOI: 10.1083/jcb.201804161

4. Bilinsky. L. M. The role of skeletal muscle in liver glutathione metabolism during acetaminophen overdose / L. M. Bilinsky, M. C. Reed, H. F. Nijhout // Journal of Theoretical Biology. – 2015. – №376. – P.118–133. DOI: 10.1016/j.jtbi.2015.04.006.

5. Corso C. R. Glutathione system in animal model of solid tumors: from regulation to therapeutic target / C. R. Corso, A. Acco // Critical Reviews in Oncology / Hematology. – 2018. – №128. – P.43–57. DOI: https://doi.org/10.1016/j.critrevonc.2018.05.014

6. Emerging regulatory paradigms in glutathione metabolism / Y. Liu, A. S. Hyde, M. A. Simpson [et.al] // Advances in Cancer Research. – 2014. – №112. – P.69–101. DOI: 10.1016/B978-0-12-420117-0.00002-5

7. Ethnic Difference in Hematological Toxicity in Patients with Non-small Cell Lung Cancer Treated with Chemotherapy A Pooled Analysis on Asian versus Non-Asian in Phase II and III Clinical Trials / Y. Hasegawa, T. Kawaguchi, A. Kubo [et.al] // Journal of Thoracic Oncology. – 2011. - №11 (6). P. 1881-1888. ISSN: 1556-0864/11/0611-1881

8. Glutathione fine-tunes the innate immune response toward antiviral pathways in a macrophage cell line independently of its antioxidant properties / M. Diotallevi, P. Checconi, A. T. Palamara [et al.] // Frontiers in Immunology. – 2017. – №8. – P.1239. DOI: 10.3389/fimmu.2017.01239

9. Hollman A. L. The Association between gene-environment interactions and diseases involving the human GST superfamily with SNP variants / A. L. Hollman, P. B. Tchounwou, H. C. Huang // International Journal of Environmental Research and Public Health. – 2016. – №13 (4). – P.1–14. DOI: 10.3390/ijerph13040379

10. Increase in blood glutathione and erythrocyte proteins related to glutathione generation, reduction and utilization in african-american old women with diabetes / G. Shan, F. Yang, L. C. Zhou [et al.] // Journal of Science, Technology and Environment Informatics. – 2015. – №5 (1). – P.1-15. PMID: 26770888

11. Kurutas E. B. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state / E. B. Kurutas // Nutrition Journal. – 2016. – №15. – P.1–22. DOI: 10.1186/s12937-016-0186-5

12. L-Cysteine protects intestinal integrity, attenuates intestinal inflammation and oxidant stress, and modulates NF-iB and Nrf2 pathways in weaned piglets after LPS challenge / Z. Song, G. Tong, K. Xiao [et.al] // Innate Immunity. – 2016. – №22 (3). – P.152–161. DOI: 10.1177/1753425916632303

13. Lu S. C. Glutathione synthesis / S. C. Lu // Biochimica et Biophysica Acta. – 2013. – №1830 (5). – P.3143–3153. DOI: 10.1016/j.bbagen.2012.09.008.

14. Ramsay E. E. Glutathione Sconjugates as prodrugs to target drugresistant tumors / E. E. Ramsay, P. J. Dilda // Frontiers in Pharmacology. – 2014. – №5. – P.1-16. DOI: 10.3389/fphar.2014.00181

15. Real-Time monitoring of glutathione in living cells reveals that high glutathione levels are required to maintain stem cell function / E. M. Jeong, J. H. Yoon, J. Lim [et.al] // Stem Cell Reports. 2018. – №10 (2). – P.600–614. DOI: 10.1016/j.stemcr.2017.12.007

16. Significance of polymorphisms and expression of enzyme-encoding genes related to glutathione in hematopoietic cancers and solid tumors / S. Zmorzynski, G. Uwiderska-Kobacz, D. Koczkodaj [et.al] // BioMed Research International. – 2015. – P.1-6. DOI: http://dx.doi.org/10.1155/2015/853573

17. The concentration of thiobarbituric acid reactive substances (TBARS) and paraoxonase activity in blood of patients with osteoarthrosis after endoprosthesis implantation / D. M. OlszewskaSłonina, D. Mątewski, R. Czajkowski [et. al] // Medical Science Monitor. – 2011. – №17(9). – P.498–504. DOI: 10.12659/MSM.881936.