Настоящото проучване е проведено за изследване на защитния ефект на богата на водород вода върху чернодробната функция на пациенти с колоректален рак (CRC), лекувани с химиотерапия mFOLFOX6. Проектирано е контролирано, рандомизирано, единично сляпо клинично изпитване. Общо 152 пациенти с CRC бяха наети от Отделението по онкология на болница Taishan (Taian, Китай) между юни 2010 г. и февруари 2016 г., сред които 146 отговаряха на критериите за включване. Впоследствие 144 пациенти са рандомизирани в групите за лечение (n = 80) и плацебо (n = 64). В края на проучването в окончателния анализ бяха включени 76 пациенти в групата за лечение с водород и 60 пациенти в групата на плацебо. Промените в чернодробната функция след химиотерапията, като променени нива на аланин аминотрансфераза (ALT), аспартат трансаминаза (AST), алкална фосфатаза, индиректен билирубин (IBIL) и директен билирубин.
Вредните ефекти на химиотерапията mFOLFOX6 върху чернодробната функция са представени главно от повишени нива на ALT, AST и IBIL. Богатата на водород група вода не показва значителни разлики в чернодробната функция преди и след лечението, докато групата на плацебо показва значително повишени нива на ALT, AST и IBIL . По този начин водата, богата на водород, изглежда облекчава свързаното с mFOLFOX6 увреждане на черния дроб .
1. Christova TY, Gorneva GA, Taxirov SI, Duridanova DB, Setchenska MS. Effect of cisplatin and cobalt chloride on antioxidant enzymes in the livers of Lewis lung carcinoma bearing mice: Protective role of heme oxygenase. Toxicol Lett. 2003;138:235–242. doi: 10.1016/S0378-4274(02)00416-2.
2. Koc A, Duru M, Ciralik H, Akcan R, Sogut S. Protective agent, erdosteine, against cisplatin-induced hepatic oxidant injury in rats. Mol Cell Biochem. 2005;278:79–84. doi: 10.1007/s11010-005-6630-z.
3. Robinson K, Lambiase L, Li J, Monteiro C, Schiff M. Fatal cholestatic liver failure associated with gemcitabine therapy. Dig Dis Sci. 2003;48:1804–1808. doi: 10.1023/A:1025415616592.
4. Bibeau F, Azria D, Chateau MC, Borrelly C, Ychou M, Quenet F, Rouanet P. Vascular hepatic injury following neoadjuvant treatment for a cardial adenocarcinoma. Gastroenterol Clin Biol. 2006;30:611–613. doi: 10.1016/S0399-8320(06)73237-7. (In French)
5. Huang CS, Kawamura T, Toyoda Y, Nakao A. Recent advances in hydrogen research as a therapeutic medical gas. Free Radic Res. 2010;44:971–282. doi: 10.3109/10715762.2010.500328.
6. Cardinal JS, Zhan J, Wang Y, Sugimoto R, Tsung A, McCurry KR, Billiar TR, Nakao A. Oral hydrogen water prevents chronic allograft nephropathy in rats. Kidney Int. 2010;77:101–109. doi: 10.1038/ki.2009.421.
7. Mao YF, Zheng XF, Cai JM, You XM, Deng XM, Zhang JH, Jiang L, Sun XJ. Hydrogen-rich saline reduces lung injury induced by intestinal ischemia/reperfusion in rats. Biochem Biophys Res Commun. 2009;381:602–605. doi: 10.1016/j.bbrc.2009.02.105.
8. National Comprehensive Cancer Network: (NCCN) Clinical Practice Guidelines in Oncology. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Colon Cancer. 2012 2011 Aug 30; Version 1. Accessed.
9. Fong Y, Bentrem DJ. CASH (chemotherapy-associated steatohepatitis) costs. Ann Surg. 2006;243:8–9. doi: 10.1097/01.sla.0000193599.57858.9b.
10. Maor Y, Malnick S. Liver injury induced by anticancer chemotherapy and radiation therapy. Int J Hepatol. 2013;2013:815105. doi: 10.1155/2013/815105.
11. Pawlik TM, Olino K, Gleisner AL, Torbenson M, Schulick R, Choti MA. Preoperative chemotherapy for colorectal liver metastases: Impact on hepatic histology and postoperative outcome. J Gastrointest Surg. 2007;11:860–868. doi: 10.1007/s11605-007-0149-4.
12. Vauthey JN, Pawlik TM, Ribero D, Wu TT, Zorzi D, Hoff PM, Xiong HQ, Eng C, Lauwers GY, Mino-Kenudson M, et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol. 2006;24:2065–2072. doi: 10.1200/JCO.2005.05.3074.
13. Tamandl D, Klinger M, Eipeldauer S, Herberger B, Kaczirek K, Gruenberger B, Gruenberger T. Sinusoidal obstruction syndrome impairs long-term outcome of colorectal liver metastases treated with resection after neoadjuvant chemotherapy. Ann Surg Oncol. 2011;18:421–430. doi: 10.1245/s10434-010-1317-4.
14. Laurent A, Nicco C, Van Nhieu Tran J, Borderie D, Chéreau C, Conti F, Jaffray P, Soubrane O, Calmus Y, Weill B, Batteux F. Pivotal role of superoxide anion and beneficial effect of antioxidant molecules in murine steatohepatitis. Hepatology. 2004;39:1277–1285. doi: 10.1002/hep.20177.
15. Pessayre D, Berson A, Fromenty B, Mansouri A. Mitochondria in steatohepatitis. Semin Liver Dis. 2001;21:57–69. doi: 10.1055/s-2001-12929.
16. Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, Dousset B, Morel P, Soubrane O, Chaussade S, et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 2004;15:460–466. doi: 10.1093/annonc/mdh095.
17. Nakano H, Oussoultzoglou E, Rosso E, Casnedi S, Chenard-Neu MP, Dufour P, Bachellier P, Jaeck D. Sinusoidal injury increases morbidity after major hepatectomy in patients with colorectal liver metastases receiving preoperative chemotherapy. Ann Surg. 2008;247:118–124. doi: 10.1097/SLA.0b013e31815774de.
18. Dyson JK, McPherson S, Anstee QM. Non-alcoholic fatty liver disease: Non-invasive investigation and risk stratification. J Clin Pathol. 2013;66:1033–1045. doi: 10.1136/jclinpath-2013-201620.
19. Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007;13:688–694. doi: 10.1038/nm1577.
20. Hayashida K, Sano M, Ohsawa I, Shinmura K, Tamaki K, Kimura K, Endo J, Katayama T, Kawamura A, Kohsaka S, et al. Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun. 2008;373:30–35. doi: 10.1016/j.bbrc.2008.05.165.
21. Buchholz BM, Kaczorowski DJ, Sugimoto R, Yang R, Wang Y, Billiar TR, McCurry KR, Bauer AJ, Nakao A. Hydrogen inhalation ameliorates oxidative stress in transplantation induced intestinal graft injury. Am J Transplant. 2008;8:2015–2024. doi: 10.1111/j.1600-6143.2008.02359.x.
22. Sun Q, Kang Z, Cai J, Liu W, Liu Y, Zhang JH, Denoble PJ, Tao H, Sun X. Hydrogen-rich saline protects myocardium against ischemia/reperfusion injury in rats. Exp Biol Med (Maywood) 2009;234:1212–1219. doi: 10.3181/0812-RM-349.
23. Fukuda K, Asoh S, Ishikawa M, Yamamoto Y, Ohsawa I, Ohta SP. Inhalation of hydrogen gas suppresses hepatic injury caused by ischemia/reperfusion through reducing oxidative stress. Biochem Biophys Res Commun. 2007;361:670–674. doi: 10.1016/j.bbrc.2007.07.088.
24. Cai J, Kang Z, Liu WW, Luo X, Qiang S, Zhang JH, Ohta S, Sun X, Xu W, Tao H, Li R. Hydrogen therapy reduces apoptosis in neonatal hypoxia-ischemia rat model. Neurosci Lett. 2008;441:167–172. doi: 10.1016/j.neulet.2008.05.077.
25. Fu Y, Ito M, Fujita Y, Ito M, Ichihara M, Masuda A, Suzuki Y, Maesawa S, Kajita Y, Hirayama M, et al. Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson’s disease. Neurosci Lett. 2009;453:81–85. doi: 10.1016/j.neulet.2009.02.016.
26. Nakashima-Kamimura N, Mori T, Ohsawa I, Asoh S, Ohta S. Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother Pharmacol. 2009;64:753–761. doi: 10.1007/s00280-008-0924-2.
27. Liu Y, Yang L, Tao K, Vizcaychipi MP, Lloyd DM, Sun X, Irwin MG, Ma D, Yu W. Protective effects of hydrogen enriched saline on liver ischemia reperfusion injury by reducing oxidative stress and HMGB1 release. BMC Gastroenterol. 2014;14:12. doi: 10.1186/1471-230X-14-12. [PMC free article]
28. Liu Q, Shen WF, Sun HY, Fan DF, Nakao A, Cai JM, Yan G, Zhou WP, Shen RX, Yang JM, Sun XJ. Hydrogen-rich saline protects against liver injury in rats with obstructive jaundice. Liver Int. 2010;30:958–968. doi: 10.1111/j.1478-3231.2010.02254.x.
29. Xu XF, Zhang J. Saturated hydrogen saline attenuates endotoxin-induced acute liver dysfunction in rats. Physiol Res. 2013;62:395–403.
30. Levitt MD, Bond JH., Jr Volume, composition, and source of intestinal gas. Gastroenterology. 1970;59:921–929.