Influence of hydrogen-rich saline on hepatocyte autophagy during laparoscopic liver ischaemia-reperfusion combined resection injury in miniature pigs

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Introduction: The purpose of this study was to investigate the protective effect of hydrogen-rich saline (HRS) against liver ischaemia-reperfusion combined resection injury.

Material and Methods: Eighteen miniature pigs were randomly divided into three groups: a sham operated group (sham group, laparoscopic liver ischaemia-reperfusion combined resection injury group (IRI group), and a hydrogen-rich saline intervention group (IRI + HRS group). Samples of hepatic tissue and serum were collected at the time of reperfusion and then 3 h, 1 d, and 3 d post reperfusion. Liver function, oxidative stress, autophagy-related mRNA genes, and protein expression were evaluated. Changes in cell and tissue ultrastructure were examined by transmission electron microscopy.

Results: Compared with the sham group, the level of autophagy of hepatocytes increased in the IRI and IRI + HRS groups, corresponding to high oxidative stress and severe liver function injury. Liver function, antioxidant content, autophagy levels, and liver injury were improved after intervention with HRS in the IRI + HRS group compared with the IRI group.

Conclusion: Intervention with hydrogen-rich saline could exert a protective effect against liver ischaemia-reperfusion combined resection injury through the reduction of oxidative stress and hepatocyte autophagy.

1. Baehrecke E.H.: Autophagy: dual roles in life and death? Nature Rev Mol Cell Biol 2005, 6, 505–510.

2. Codogno P., Meijer A.J.: Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ 2005, 12, 1509–1518.

3. Cursio R., Colosetti P., Codogno P., Cuervo A M, Shen H.: The role of autophagy in liver diseases: mechanisms and potential therapeutic targets. Biomed Res Int 2015, 2015, 480508.

4. Farre J.C., Subramani S.: Peroxisome turnover by micropexophagy: an autophagy-related process. Trends Cell Biol 2004, 14, 515–523.

5. Filomeni G., De Zio D., Cecconi F.: Oxidative stress and autophagy: the clash between damage and metabolic needs. Cell Death Differ 2015, 22, 377–388.

6. George J.F., Agarwal A.: Hydrogen: another gas with therapeutic potential. Kidney Int 2010, 77, 85–87.

7. Glantzounis G.K., Salacinski H.J., Yang W., Davidson B.R., Seifalian A.M.: The contemporary role of antioxidant therapy in attenuating liver ischemia-reperfusion injury: a review. Liver Transpl 2005, 11, 1031–1047.

8. Gotoh K., Lu Z., Morita M., Shibata M., Koike M., Waguri S., Dono K., Doki Y., Kominami E., Sugioka A., Monden M., Uchiyama Y.: Participation of autophagy in the initiation of graft dysfunction after rat liver transplantation. Autophagy 2009, 5, 351–360.

9. Guo Z., Zhou B., Li W., Sun X., Luo D.: Hydrogen-rich saline protects against ultraviolet B radiation injury in rats. J Biomed Res 2012, 26, 365–371.

10. Gurusamy K.S., Kumar Y., Ramamoorthy R., Sharma D., Davidson B.R.: Vascular occlusion for elective liver resections. Cochrane Database Syst Rev 2009, CD007530.

11. Hong J.Y., Lebofsky M., Farhood A., Jaeschke H.: Oxidant stress-induced liver injury in vivo: role of apoptosis, oncotic necrosis, and c-Jun NH2-terminal kinase activation. Am J Physiol-Gastrointest Liver Physiol 2009, 296, 572–581.

12. Huang T.L., Wang W.C., Tu C., Yang Z.Y., Bramwell D., Sun X.J.: Hydrogen-rich saline attenuates ischemia-reperfusion injury in skeletal muscle. J Surg Res 2015, 194, 471–480.

13. Karatzas T., Neri A.A., Baibaki M.E., Dontas I.A.: Rodent models of hepatic ischemia-reperfusion injury: time and percentage-related pathophysiological mechanisms. J Surg Res 2014, 191, 399–412.

14. Kirkin V., Mc Ewan D.G..: A role for ubiquitin in selective autophagy. Mol Cell 2009, 34, 259–269.

15. Lee J., Giordano S., Zhang J.H.: Autophagy, mitochondria, and oxidative stress: cross-talk and redox signalling. Biochem J 2012, 441, 523–540.

16. Liu S., Zhang J., Yu B., Huang L., Dai B., Liu J., Tang J.: The role of autophagy in lung ischemia/reperfusion injury after lung transplantation in rats. Am J Transpl Res 2016, 8, 3593–3602.

17. Mayhew P.D.: Recent advances in soft tissue minimally invasive surgery. J Small Anim Pract 2014, 55, 75–83.

18. Milovancev M., Townsend K.L.: Current concepts in minimally invasive surgery of the abdomen. Vet Clin North Am Small Anim Pract 2015, 45, 507–522.

19. Ohsawa I., Ishikawa M., Takahashi K., Watanabe M., Ohta S.: Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Med 2007, 13, 688–694.

20. Pankiv S., Clausen T.H., Lamark T., Brech A.: p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 2007, 282, 24131–24145.

21. Peralta C., Jimenez-Castro M.B., Gracia-Sancho J.: Hepatic ischemia and reperfusion injury: effects on the liver sinusoidal milieu. J Hepatol 2013, 59, 1094–1106.

22. Portal-Nunez S., Esbrit P., Alcaraz M.J., Largo R.: Oxidative stress, autophagy, epigenetic changes, and regulation by miRNAs as potential therapeutic targets in osteoarthritis. Biochem Pharmacol 2016, 108, 1–10.

23. Rahal A., Kumar A., Singh V., Yadav B., Tiwari R., Chakraborty S., Dhama K.: Oxidative stress, prooxidants, and antioxidants: the interplay. Biomed Res Int 2014, 2, 74–79.

24. Rautou P.E., Mansouri A., Lebrec D., Durand F., Valla D., Moreau R.: Autophagy in liver diseases. J Hepatol 2010, 53, 1123–1134.

25. Rossi R., Dalle-Donne I., Milzani A., Giustarini D.: Oxidized forms of glutathione in peripheral blood as biomarkers of oxidative stress. Clin Chem 2006, 52, 1406–1414.

26. Ryter S.W., Cloonan S.M., Choi A.M.K.: Autophagy: a critical regulator of cellular metabolism and homeostasis. Mol Cells 2013, 36, 7–16.

27. Scherz-Shouval R., Shvets E., Fass E., Shorer H., Gil L., Elazar Z.: Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. Embo J 2007, 26, 1749–1760.

28. Stewart R.K., Dangi A., Gandhi C.R.: A novel mouse model of depletion of stellate cells clarifies their role in ischemia/reperfusion- and endotoxin-induced acute liver injury. J Hepatol 2014, 60, 298–305.

29. Tassa A., Roux M.P., Attaix D., Bechet D.M.: Class III phosphoinositide 3-kinase-Beclin1 complex mediates the amino acid-dependent regulation of autophagy in C2C12 myotubes. Biochem J 2003, 376, 577–586.

30. Vlahakos D., Arkadopoulos N., Smyrniotis V.: Deferoxamine attenuates lipid peroxidation, blocks interleukin-6 production, ameliorates sepsis inflammatory response syndrome, and confers renoprotection after acute hepatic ischemia in pigs. Artif Organs 2012, 36, 400–408.

31. Xie Z.L., He C.Y., Zou M.H.: AMP-activated protein kinase modulates cardiac autophagy in diabetic cardiomyopathy. Autophagy 2011, 7, 1254–1255.

Journal of Veterinary Research

formerly Bulletin of the Veterinary Institute in Pulawy

Journal Information

IMPACT FACTOR J Vet Res 2017: 0.811

CiteScore 2017: 0.68

SCImago Journal Rank (SJR) 2017: 0.29
Source Normalized Impact per Paper (SNIP) 2017: 0.484


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