Preview

Bone and soft tissue sarcomas, tumors of the skin

Advanced search

Dynamics of antioxidant defense system indicators in children with osteosarcoma during high-dose chemotherapy with methotrexate

Abstract

One of the factors of Mtx toxicity during high-dose chemotherapy is its prooxidant action. For the compensation of arising oxidative stress such antioxidant drugs as ademetionin are used in clinical. The purpose of the study: investigation of the dynamics of antioxidant defense system indicators in children during high-dose chemotherapy. The object of study: 246 patients who received high-dose Mtx chemotherapy, aged 9–15 years.
Methods. Determination of GGT, GR, SOD and OAOS in blood on key hours from the start of Mtx administration – 4, 24, 42, 48; determination of their biokinetics parameters.
Results. For the first 4 courses the regularities are found: GGT activity and SOD have a maximum increase in the 4th hour, further reduced. SOD activity recovers slightly up to 48th hour. Levels of GR and OAOS are the lowest for the 4th hour, then increased to a level above the reference one.
Conclusion. Oxidative stress caused by the action of Mtx, can be compensated by coadministration of ademetionine, which has a positive effect on all measured indicators. After 4 courses of high-dose Mtx chemotherapy hepatotoxicity increases despite of treatment with ademetionine the degree of hepatotoxicity is growing, which founds the reflection in the dynamics of SOD and GGT.

About the Authors

E. V. Neborak
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russian Federation
Russian Federation

Moscow



A. V. Lebedeva
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russian Federation
Russian Federation

Moscow



E. G. Golovnya
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russian Federation
Russian Federation

Moscow



D. V. Nisichenko
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russian Federation
Russian Federation

Moscow



A. Z. Dzampaev
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russian Federation
Russian Federation

Moscow



V. N. Baykova
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russian Federation
Russian Federation

Moscow



M. D. Aliev
N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russian Federation
Russian Federation

Moscow



References

1. Дзампаев А.З., Нисиченко Д.В., Хестанов Д.Б., Алиев М.Д. Эндопротезирование как приоритетное направление в комбинированном лечении костных сарком у детей. Онкопедиатрия. 2014, № 1, с. 50-53.

2. Jaffe N., Gorlick R. High-Dose Methotrexate in Osteosarcoma: Let the Questions Surcease – Time for Final Acceptance. J. of Clin. Onc. 2008, v. 28, No. 27, p. 4365-4366.

3. Гудман A., Гилман A.Г. Клиническая фармакология. Кн. 3. Пер. с англ. М.: ППП, 2006, c. 10791083.

4. Milone M.C. Therapeutic Drug Monitoring of Selected Anticancer Drugs: Pharmacogenomics Issues. A. Dasgupta. Therapeutic Drug Monitoring. Elsevier Inc. 2012, p. 291-321.

5. Uzar E., Koyuncuoglu H.R. et al. The activities of antioxidant enzymes and the level of malondialdehyde in cerebellum of rats subjected to methotrexate: protective effect of caffeic acid phenethyl ester. Mol. Cell Biochem. 2006, v. 291 (1-2), p. 63-68.

6. Vardi N., Parlakpinar Н., Ates B. Beneficial effects of chlorogenic acid on methotrexate-induced cerebellar Purkinje cell damage in rats. J. Chem. Neuroanat. 2012, v. 43 (1), p. 43-47.

7. Фролов Б.А., Калинина О.В., Кириллова А.В., Штиль А.А. Преодоление гепатотоксичности метотрексата: роль тритерпеноидов. Клиническая онкогематология. 2013, т 6, № 1, с. 1-10.

8. Байкова В.Н., Байков К.Э., Иванов А.В., Кошечкин К.А., Калинкина А.В., Паршина Н.А., Арзамасцев А.П., Дурнов Л.А. Антиоксидантные препараты, их место и роль в детской онкологии. Практикующий врач сегодня. М., 2005, № 1, с. 29-32.

9. Rashid K., Sinha K., Sil P.C. An update on oxidative stress-mediated organ pathophysiology. Food Chem. Toxicol. 2013, v. 62, p. 584-600. DOI: 10.1016/j.fct.2013.09.026. Review.

10. Погодина Е.А., Стрижевская А.М., Шварова А.В., Иванова Н.М., Байкова В.Н. Изменение состояния антиоксидантной защиты при высокодозной химиотерапии метотрексатом у детей с остеосаркомой. Вестник РОНЦ им. Н.Н. Блохина РАМН. 2013, т. 24, № 1, с. 19-23.

11. Денисова Н.А., Плетенева Т.В., Байкова В.Н., Березов Т.Т. Кинетические характеристики биохимических показателей при приеме препарата «Консупрен» после аллогенной трансплантации почки. Бюллетень экспериментальной биологии и медицины. 2004, т. 138, № 10, с. 458-462.

12. Ершов Э.Б. Распространение коэффициента детерминации на общий случай линейной регрессии, оцениваемой с помощью различных версий метода наименьших квадратов (рус., англ.). ЦЭМИ РАН Экономика и математические методы. М.: ЦЭМИ РАН. 2002, т. 38, вып. 3, с. 107-120.

13. Jiang Sh., Jiang D., Tao Y. Experimental Cardiology: Review Role of gamma-glutamyltransferase in cardiovascular diseases. Exp. Clin. Cardiol. 2013, v. 18 (1), p. 53-56.

14. Hanigan M.H. Gamma-glutamyl transpeptidase: redox regulation and drug resistance. Adv. Cancer Res. 2014, v. 122, p. 103-41. DOI: 10.1016/B978-0-12-420117-0.00003-7.

15. Holmboe L., Andersen A.M., Mørkrid L., Slørdal L., Hall K.S. High dose methotrexate chemotherapy: pharmacokinetics, folate and toxicity in osteosarcoma patients. Br. J. Clin. Pharmacol. 2012, v. 73 (1), p. 106-114. DOI: 10.1111/j.1365-2125.2011.04054.x.

16. Quentin M. Anstee, Christopher P. Day S-adenosylmethionine (SAMe) therapy in liver disease: A review of current evidence and clinical utility. J. Hepatol. 2012, v. 57 (5), p. 1097-109. DOI: 10.1016/j.jhep.2012.04.041.

17. Sies H., Jones D.P. Oxidative stress. Encyclopedia of stress. Eds. Fink G. San Diego: Elsevier. 2007, v. 3, p. 45-48.

18. Jones C.I., Zhu H., Martin S.F. et al. Regulation of antioxidants and phase 2 enzymes by shear-induced reactive oxygen species in endothelial cells. Ann. Biomed. Eng. 2007, v. 35, No. 5, p. 683-693.

19. Khalil F.A., El-Kirsh A.A., Ali Kamel E., El-Rahmany N.G. Beneficial effort of propolis extract (bee glue) against methotrexate-induced stress in liver and brain of albino rats. Indian Journal of Medical Research and Pharmaceutical Sciences. 2013 (2), p. 111-113.

20. Akkemiki E., Şenturk M., Ozgeris F.B., Taser P., Ciftci M. In vitro effects of some drugs on human erythrocyte glutathione reductase. Turk. J. Med. Sci. 2011, v. 41 (2), p. 235-241.

21. Gonzalez-Correa J.A., De La Cruz J.P., Martin-Aurioles E., Lopez-Egea M.A., Ortiz P., Sanchez de la Cuesta F. Effects of S-adenosyl-L-methionine on hepatic and renal oxidative stress in an experimental model of acute biliary obstruction in rats. Hepatology. 1997, v. 26 (1), p. 121-127.

22. Brown M., Ball J.G., Wright M.S., Van Meter S., Valentovic M.A. Novel protective mechanisms for S-adenosyl-L-methionine against acetaminophen hepatotoxicity: improvement of key antioxidant enzymatic function. Toxicol. Lett. 2012, v. 212 (3), p. 320-328. DOI: 10.1016/j.toxlet.2012.05.018. Epub 2012 Jun 5.

23. Pey A.L., Majtan T., Sanchez-Ruiz J.M., Kraus J.P. Human cystathionine {beta}-synthase (CBS) contains two classes of binding sites for S-adenosylmethionine (SAM): complex regulation of CBS activity and stability by SAM. Biochem. J. 2013, v. 449 (1), p. 109-121.

24. Miao L., Clair D.K. Regulation of Superoxide Dismutase Genes: Implications in Diseases. Free Radic. Biol. Med. 2009, v. 47 (4), p. 344-356.

25. Милякова М.Н., Шабанов В.В. Возможный механизм и патофизиологическая значимость регуляции активноcти супероксиддисмутазы свободными радикалами кислорода. Биомедицинская химия. 2006, т. 52, вып. 2, с. 130-137.

26. Somi M.H., Hajipour B., Abad G.D., Hemmati M.R., Ghabili K., Khodadadi A., Vatankhah A.M. Protective role of lipoic acid on methotrexate induced intestinal damage in rabbit model. Indian J. Gastroenterol. 2011, v. 30 (1), p. 38-40.

27. Стрижевская А.М., Головня Е.Г., Дзампаев А.З., Байкова В.Н. Биохимические критерии токсичности терапии высокими дозами метотрексата у детей с остеосаркомой. Успехи молекулярной онкологии. 2015, № 1, с. 82-89.


Review

For citations:


Neborak E.V., Lebedeva A.V., Golovnya E.G., Nisichenko D.V., Dzampaev A.Z., Baykova V.N., Aliev M.D. Dynamics of antioxidant defense system indicators in children with osteosarcoma during high-dose chemotherapy with methotrexate. Bone and soft tissue sarcomas, tumors of the skin. 2017;(1):3-11. (In Russ.)

Views: 115


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2219-4614 (Print)
ISSN 2782-3687 (Online)