Riverón FG, Fernández GS, Pandolfi BA, Contreras RJ, López IY

Language: Spanish
References: 13
Page: 221-227
PDF size: 238.83 Kb.

ABSTRACT

Background: in advanced stages of non-small cell lung cancer, treatment is fundamentally based on polychemotherapy. Previous studies relate the development of resistance to cisplatin with increased levels of cellular glutathione, while depletion of this tripeptide has been associated with greater sensitivity to this drug.
Objective: to evaluate the effect of polychemotherapy with cisplatin and vinblastine on intracellular glutathione levels and cellular redox status in patients with non-small cell lung cancer in advanced stages.
Methods: a case-control study was carried out that included 38 patients with non-small cell lung cancer in stages IIIb-IV, who completed the treatment scheme with cisplatin and vinblastine, and 25 apparently healthy individuals as a control group from May 2016 to May 2018 at the Benéfico Jurídico Pneumological Hospital in Havana. The intraerythrocyte concentrations of reduced and oxidized glutathione were determined by an HPLC-UV method. The cellular redox state was calculated using the Nerst equation. The results were expressed as means and standard deviation. The non-parametric U-Mann Whitney test was used to compare the arithmetic means of the response variables.
Results: after treatment, a decrease in reduced glutathione concentrations (920 µM vs. 1252 µM; p=0.036) was observed, as well as changes in the cellular redox state (-338.4 mV vs.-53.2 mV; p=0.029) in contrast to controls.
Conclusions: chemotherapy combined with cisplatin induces a decrease in reduced glutathione levels and changes in the cellular redox state. These effects may contribute to increased survival in patients who respond to treatment.

REFERENCES

1. Kennedy L, Sandhu JK, Harper ME, Cuperlovic M. Role of glutathione in cancer: From mechanisms to therapies. Biomolecules. 2020;10(10):1429.

2. Molina M, Rocha CR, Kinker GS, Pelegrini AL, Menck CF. The balance between NRF2/GSH antioxidant mediated patway and DNA repair modulares cisplatin resistance in lung cancer cell. Sci Rep. 2019;9(1):17639.

3. Pandolfi A, Fernández S, Riverón G, Gutiérrez R, Pupo J, de Armas A, et al. Daño al ADN y capacidad de reparación en pacientes con carcinoma de pulmón de células no pequeñas tratados con poliquimioterapia. Rev Haban Cienc Med[Internet]. 2018[citado 23 Oct 2021];17(2):[aprox. 10p.]. Disponible en: https://www.revhabanera.sld.cu/index.php/rhab/article/view/22083.

4. Min HY, Lee HY. Mechanisms of resistance to chemotherapy in non-small cell lung cancer. Arch Pharm Res. 2021;44(2):146-64.

5. Riverón G, Contreras J, Pérez J, Marín LC, Concepción A, Zúñiga Y. Concentraciones intraeritrocitarias de glutatión reducido y oxidado en una muestra de sujetos sanos de La Habana. Acta Bioclin[Internet]. 2021[citado 6 May 2022];11(22):[aprox. 12p.]. Disponible en: https://redib.org/Record/oai_articulo3320327-concentraciones-intraeritrocitarias-de-glutati%C3%B3n-reducido-y-oxidado-en-una-muestra-de-sujetos-sanos-de-la-habana5.

6. Fernández S, Riverón G, López Y, González D, Fariñas L, Lemus G, et al. Caracterización clínica y marcadores de estrés oxidativo en pacientes con cáncer de pulmón tratados con poliquimioterapia. Rev Cub Med[Internet]. 2021[citado 10 Ene 2022];60(3):[aprox. 8p.]. Disponible en: https://revmedicina.sld.cu/index.php/med/article/view/20436.

7. Aldossary SA. Review on pharmacology of cisplatin: clinical use, toxicity and mechanism of resistance of cisplatin. Biomed Pharmacol J. 2019;12(1):41-52.

8. Bansal A, Simon MC. Glutathione metabolism in cancer progression and testamen to resistance. J Cell Biol. 2018;217(7):2291-98.

9. Srivastava AN, Gupta A, Srivastava S, Natu SM, Mittal B, Negi MPS, et al. Cisplatin combination chemotherapy induces oxidative stress in advanced non-small cell lung cancer patient. Asian Pac J Cancer Prev. 2010;11(2):465-71.

10. Groen HJ, Meijer C, De Vries EG, Mulder NH. Red blood cell glutathione levels in lung cancer patients treated by radiation and continuously infused carboplatin. Anticancer Res. 1996;16(2):1033-7.

11. Jones DP. Redox potential of GSH/GSSG couple: assay and biological significance. Methods Enzymol. 2002;348(1):93-112.

12. Lang D, Wang L, He R, Ma J, Bin Y, Chi X, et al. Exogenous glutathione contributes to cisplatin resistance in lung cancer A549 cell. Am J Transl Res. 2018;10(5):1295-1309.

13. Shah K, Khan MF, Badshah A, Jan SV, Farid A, Bibi H, et al. Effect of cisplatin on glutathione redox status in isolated plasma and cytosolic fraction. Afr J Pharm Pharmacol. 2013;7(2):37-45.