Full Text:   <1866>

CLC number: Q74; R459.9

On-line Access: 2013-05-04

Received: 2012-12-17

Revision Accepted: 2013-04-01

Crosschecked: 2013-04-08

Cited: 9

Clicked: 3533

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2013 Vol.14 No.5 P.382-391


Protective effect of hydrogen-rich saline on ischemia/reperfusion injury in rat skin flap

Author(s):  Ling Zhao, You-bin Wang, Shi-rui Qin, Xue-mei Ma, Xue-jun Sun, Ming-lian Wang, Ru-gang Zhong

Affiliation(s):  College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China; more

Corresponding email(s):   wy.benz@yahoo.com.cn, xmma@bjut.edu.cn

Key Words:  Hydrogen-rich saline, Ischemia/reperfusion, Skin flaps, Oxidative damage, Inflammation

Ling Zhao, You-bin Wang, Shi-rui Qin, Xue-mei Ma, Xue-jun Sun, Ming-lian Wang, Ru-gang Zhong. Protective effect of hydrogen-rich saline on ischemia/reperfusion injury in rat skin flap[J]. Journal of Zhejiang University Science B, 2013, 14(5): 382-391.

@article{title="Protective effect of hydrogen-rich saline on ischemia/reperfusion injury in rat skin flap",
author="Ling Zhao, You-bin Wang, Shi-rui Qin, Xue-mei Ma, Xue-jun Sun, Ming-lian Wang, Ru-gang Zhong",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Protective effect of hydrogen-rich saline on ischemia/reperfusion injury in rat skin flap
%A Ling Zhao
%A You-bin Wang
%A Shi-rui Qin
%A Xue-mei Ma
%A Xue-jun Sun
%A Ming-lian Wang
%A Ru-gang Zhong
%J Journal of Zhejiang University SCIENCE B
%V 14
%N 5
%P 382-391
%@ 1673-1581
%D 2013
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1200317

T1 - Protective effect of hydrogen-rich saline on ischemia/reperfusion injury in rat skin flap
A1 - Ling Zhao
A1 - You-bin Wang
A1 - Shi-rui Qin
A1 - Xue-mei Ma
A1 - Xue-jun Sun
A1 - Ming-lian Wang
A1 - Ru-gang Zhong
J0 - Journal of Zhejiang University Science B
VL - 14
IS - 5
SP - 382
EP - 391
%@ 1673-1581
Y1 - 2013
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1200317

Objective: Skin damage induced by ischemia/reperfusion (I/R) is a multifactorial process that often occurs in plastic surgery. The mechanisms of I/R injury include hypoxia, inflammation, and oxidative damage. Hydrogen gas has been reported to alleviate cerebral I/R injury by acting as a free radical scavenger. Here, we assessed the protective effect of hydrogen-rich saline (HRS) on skin flap I/R injury. Methods: Abdominal skin flaps of rats were elevated and ischemia was induced for 3 h; subsequently, HRS or physiological saline was administered intraperitoneally 10 min before reperfusion. On postoperative Day 5, flap survival, blood perfusion, the accumulation of reactive oxygen species (ROS), and levels of cytokines were evaluated. Histological examinations were performed to assess inflammatory cell infiltration. Results: Skin flap survival and blood flow perfusion were improved by HRS relative to the controls. The production of malondialdehyde (MDA), an indicator of lipid peroxidation, was markedly reduced. A multiplex cytokine assay revealed that HRS reduced the elevation in the levels of inflammatory cytokines, chemokines and growth factors, with the exception of RANTES (regulated on activation, normal T-cell expressed and secreted) growth factor. HRS treatment also reduced inflammatory cell infiltration induced by I/R injury. Conclusions: Our findings suggest that HRS mitigates I/R injury by decreasing inflammation and, therefore, has the potential for application as a therapy for improving skin flap survival.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Arato, E., Kurthy, M., Sinay, L., Kasza, G., Menyhei, G., Hardi, P., Masoud, S., Ripp, K., Szilagyi, K., Takacs, I., et al., 2010. Effect of vitamin E on reperfusion injuries during reconstructive vascular operations on lower limbs. Clin. Hemorheol. Microcirc., 44(2):125-136.

[2]Aydogan, H., Gurlek, A., Parlakpinar, H., Askar, I., Bay-Karabulut, A., Aydogan, N., Fariz, A., Acet, A., 2007. Beneficial effects of caffeic acid phenethyl ester (CAPE) on the ischaemia-reperfusion injury in rat skin flaps. J. Plast. Reconstr. Aesthet. Surg., 60(5):563-568.

[3]Buchholz, B.M., Kaczorowski, D.J., Sugimoto, R., Yang, R., Wang, Y., Billiar, T.R., McCurry, K.R., Bauera, A.J., Nakao, A., 2008. Hydrogen inhalation ameliorates oxidative stress in transplantation induced intestinal graft injury. Am. J. Transplant., 8(10):2015-2024.

[4]Chen, H., Sun, Y.P., Hu, P.F., Liu, W.W., Xiang, H.G., Li, Y., Yan, R.L., Su, N., Ruan, C.P., Sun, X.J., et al., 2011. The effects of hydrogen-rich saline on the contractile and structural changes of intestine induced by ischemia-reperfusion in rats. J. Surg. Res., 167(2):316-322.

[5]Dacho, A., Lyutenski, S., Aust, G., Dietz, A., 2009. Ischemic preconditioning in a rat adipocutaneous flap model. HNO, 57(8):829-834 (in German).

[6]Fukuda, K., Asoh, S., Ishikawa, M., Yamamoto, Y., Ohsawa, I., Ohta, S., 2007. Inhalation of hydrogen gas suppresses hepatic injury caused by ischemia/reperfusion through reducing oxidative stress. Biochem. Biophys. Res. Commun., 361(3):670-674.

[7]Gurlek, A., Celik, M., Parlakpinar, H., Aydogan, H., Bay-Karabulut, A., 2006. The protective effect of melatonin on ischemia-reperfusion injury in the groin (inferior epigastric) flap model in rats. J. Pineal Res., 40(4):312-317.

[8]Harder, Y., Amon, M., Laschke, M.W., Schramm, R., Rucker, M., Wettstein, R., Bastiaanse, J., Frick, A., Machens, H.G., Küntscher, M., et al., 2008. An old dream revitalised: preconditioning strategies to protect surgical flaps from critical ischemia and ischaemia-reperfusion injury. J. Plast. Reconstr. Aesthet. Surg., 61(5):503-511.

[9]Hayashida, K., Sano, M., Ohsawa, I., Shinmura, K., Tamaki, K., Kimura, K., Endo, J., Katayama, T., Kawamura, A., Kohsaka, S., et al., 2008. Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochem. Biophys. Res. Commun., 373(1):30-35.

[10]Henderson, P.W., Singh, S.P., Weinstein, A.L., Nagineni, V., Rafii, D.C., Kadouch, D., Krijgh, D.D., Spector, J.A., 2010. Therapeutic metabolic inhibition: hydrogen sulfide significantly mitigates skeletal muscle ischemia reperfusion injury in vitro and in vivo. Plast. Reconstr. Surg., 126(6):1890-1898.

[11]Imai, S., Kozai, H., Matsuda, M., Hasegawa, G., Obayashi, H., Togawa, C., Yamamura, T., Watanabe, K., Miyatani, S., Yoshikawa, T., et al., 2008. Intervention with delivery of diabetic meals improves glycemic control in patients with type 2 diabetes mellitus. J. Clin. Biochem. Nutr., 42(1):59-63.

[12]Ito, M., Ibi, T., Sahashi, K., Ichihara, M., Ito, M., Ohno, K., 2011. Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. Med. Gas Res., 1(1):24.

[13]Kajiya, M., Sato, K., Silva, M.J., Ouhara, K., Do, P.M., Shanmugam, K.T., Kawai, T., 2009. Hydrogen from intestinal bacteria is protective for concanavalin A-induced hepatitis. Biochem. Biophys. Res. Commun., 386(2):316-321.

[14]Kang, K.M., Kang, Y.N., Choi, I.B., Gu, Y., Kawamura, T., Toyoda, Y., Nakao, A., 2011. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med. Gas Res., 1(1):11.

[15]Karaaslan, O., Ulusoy, M.G., Kankaya, Y., Tiftikcioglu, Y.O., Kocer, U., Kankaya, D., Karaaslan, G.M., Tuncer, S., Berktas, M., 2010. Protective effect of grape seed extract against ischaemia/reperfusion injury in a rat epigastricflap model. J. Plast. Reconstr. Aesthet. Surg., 63(4):705-710.

[16]Küntscher, M.V., Schirmbeck, E.U., Menke, H., Klar, E., Gebhard, M.M., Germann, G., 2002a. Ischemic preconditioning by brief extremity ischemia before flap ischemia in a rat model. Plast. Reconstr. Surg., 109(7):2398-2404.

[17]Küntscher, M.V., Juran, S., Menke, H., Gebhard, M.M., Erdmann, D., Germann, G., 2002b. The role of pre-ischaemic application of the nitric oxide donor spermine/nitric oxide complex in enhancing flap survival in a rat model. Br. J. Plast. Surg., 55(5):430-433.

[18]Manson, P.N., Anthenelli, R.M., Im, M.J., Bulkley, G.B., Hoopes, J.E., 1983. The role of oxygen-free radicals in ischemic tissue injury in island skin flaps. Ann. Surg., 198(1):87-90.

[19]Moon, J.G., Lim, H.C., Gye, M.R., Oh, J.S., Park, J.W., 2008. Postconditioning attenuates ischemia-reperfusion injury in rat skin flap. Microsurgery, 28(7):531-537.

[20]Nagata, K., Nakashima-Kamimura, N., Mikami, T., Ohsawa, I., Ohta, S., 2009. Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology, 34(2):501-508.

[21]Nakao, A., Sugimoto, R., Billiar, T.R., McCurry, K.R., 2009. Therapeutic antioxidant medical gas. J. Clin. Biochem. Nutr., 44(1):1-13.

[22]Nakayama, M., Nakano, H., Hamada, H., Itami, N., Nakazawa, R., Ito, S., 2010. A novel bioactive haemodialysis system using dissolved dihydrogen (H2) produced by water electrolysis: a clinical trial. Nephrol. Dial. Transplant., 25(9):3026-3033.

[23]Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., Katsura, K., Katayama, Y., Asoh, S., Ohta, S., 2007. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med., 13(6):688-694.

[24]Ono, H., Nishijima, Y., Adachi, N., Sakamoto, M., Kudo, Y., Nakazawa, J., Kaneko, K., Nakao, A., 2012. Hydrogen (H2) treatment for acute erythymatous skin diseases. A report of 4 patients with safety data and a non-controlled feasibility study with H2 concentration measurement on two volunteers. Med. Gas Res., 2(1):14.

[25]Siemionow, M., Arslan, E., 2004. Ischemia/reperfusion injury: a review in relation to free tissue transfers. Microsurgery, 24(6):468-475.

[26]Sun, H., Chen, L., Zhou, W., Hu, L., Li, L., Tu, Q., Chang, Y., Liu, Q., Sun, X., Wu, M., et al., 2011. The protective role of hydrogen-rich saline in experimental liver injury in mice. J. Hepatol., 54(3):471-480.

[27]van den Heuvel, M.G., Buurman, W.A., Bast, A., van der Hulst, R.R., 2009. Review: ischaemia-reperfusion injury in flap surgery. J. Plast. Reconstr. Aesthet. Surg., 62(6):721-726.

[28]Xie, K., Yu, Y., Zhang, Z., Liu, W., Pei, Y., Xiong, L., Hou, L., Wang, G., 2010. Hydrogen gas improves survival rate and organ damage in zymosan-induced generalized inflammation model. Shock, 34(5):495-501.

[29]Yan, H., Zhang, F., Kochevar, A.J., Akdemir, O., Gao, W., Angel, M., 2010. The effect of postconditioning on the muscle flap survival after ischemia-reperfusion injury in rats. J. Invest. Surg., 23(5):249-256.

[30]Zheng, X., Mao, Y., Cai, Y., Li, Y., Liu, W., Sun, P., Zhang, J.H., Sun, X., Yuan, H., 2009. Hydrogen-rich saline protects against intestinal ischemia/reperfusion injury in rats. Free Radic. Res., 43(5):478-484.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - Journal of Zhejiang University-SCIENCE