Xifeng WANG, Lianshuang ZHANG, Tongshen LIU, Wei ZHAO

The protective effects of hydrogen on HO-1 expression in the brainafter focal cerebral ischemia reperfusion in rats

Background/aim: The aim of this study was to investigate whether a hydrogen administration can produce neuroprotective effects after brain ischemia reperfusion in rats. Materials and methods: A brain ischemia reperfusion injury was induced by a 2-h left middle cerebral artery occlusion (MCAO) using an intraluminal filament, followed by 46 h of reperfusion. A hydrogen-rich saline (1 mL/kg body weight i.p.) was administered at the beginning of reperfusion. Saline (1 mL/kg)-treated animals were used as the control. Sham-operated animals were also used. Subsequently, 48 h after the MCAO, histological alternations, heme oxygenase-1 (HO-1) expression, and levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the cerebral cortex and the hippocampus were examined. Results: Hydrogen significantly alleviated brain tissue histological damage, promoted HO-1 expression, upregulated levels of SOD, and decreased the levels of MDA in brain tissue after the ischemia reperfusion injury. Conclusion: The results suggest that the neuroprotective effects of hydrogen may be mediated by promoting HO-1 expression and attenuated the oxidative injury.

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1. Mendis S, Davis S, Norrving B. Organizational Update: The World Health Organization Global Status Report on Noncommunicable Diseases 2014; One more landmark step in the combat against stroke and vascular disease. Stroke 2015; 46: e121-e122.
2. Hankey GJ. Potential new risk factors for ischemic stroke: what is their potential?. Stroke 2006; 37: 2181-2188.
3. Brima T, Otáhal J, Mare P. Increased susceptibility to pentetrazol-induced seizures in developing rats after cortical photothrombotic ischemic stroke at P7. Brain Res 2013; 1507:146-153.
4. Zhai X, Chen X, Shigeo Ohta S, Sun X. Review and prospect of the biomedical effects of hydrogen. Med Gas Res 2014; 4: 19.
5. 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.
6. Du Z, Jia H, Liu J, Zhao X, Wang Y, Sun X. Protective effects of hydrogen-rich saline in uncontrolled hemorrhagic shock. Exp Ther Med 2014; 7: 1253-1258.
7. Ford G, Xu Z, Gates A, Jiang J, Ford BD. Expression Analysis Systematic Explorer (EASE) analysis reveals differential gene expression in permanent and transient focal stroke rat models. Brain Res 2006; 1071: 226-236.
8. Doyle KP, Simon RP, Stenzel-Poore MP. Mechanisms of ischemic brain damage. Neuropharmacology 2008; 55: 310- 318.
9. Allen CL, Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int J Stroke 2009; 4: 461-470.
10. Crack PJ, Taylor JM. Reactive oxygen species and the modulation of stroke. Free Radic Biol Med 2005; 38: 1433- 1444.
11. Coyle JT, Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science 1993; 262: 689-695.
12. Ewen A, Matz P, Chan PH. Free radical pathways in CNS injury. J Neurotrauma 2000; 17: 871-890.
13. Cheng CY, Ho TY, Lee EJ, Su SY, Tang NY, Hsieh CL. Ferulic acid reduces cerebral infarct through its antioxidative and anti-inflammatory effects following transient focal cerebral ischemia in rats. Am J Chin Med 2008; 36: 1105-1119.
14. Ma S, Yin H, Chen L, Liu H, Zhao M, Zhang X. Neuroprotective effect of ginkgolide K against acute ischemic stroke on middle cerebral ischemia occlusion in rats. J Nat Med 2012; 66: 25-31.
15. Siow RC, Sato H, Mann GE. Heme oxygenase-carbon monoxide signaling pathway in atherosclerosis: anti-atherogenic actions of bilirubin and carbon monoxide? Cardiovasc Res 1999; 41: 385-394.
16. Lin TN, Cheung WM, Wu JS, Chen JJ, Lin H, Chen JJ, Liou JY, Shyue SK, Wu KK. 15d-prostaglandin J2 protects brain from ischemia-reperfusion injury. Arterioscler Thromb Vasc Biol 2006; 26: 481-487.
17. He M, Pan H, Chang RC, So KF, Brecha NC, Pu M. Activation of the Nrf2/HO-1 antioxidant pathway contributes to the protective effects of Lycium barbarum polysaccharides in the rodent retina after ischemia-reperfusion-induced damage. PLoS One 2014; 9: e84800.
18. Sun MH, Pang JH, Chen SL, Han WH, Ho TC, Chen KJ, Kao LY, Lin KK, Tsao YP. Retinal protection from acute glaucomainduced ischemia-reperfusion injury through pharmacologic induction of heme oxygenase-1. Invest Ophthalmol Vis Sci 2010; 51: 4798-4808.
19. Simonyi A, Wang Q, Miller RL, Yusof M, Shelat PB, Sun AY, Sun GY. Polyphenols in cerebral ischemia: novel targets for neuroprotection. Mol Neurobiol 2005; 31: 135-147.
20. Park JH, Lee DY, Yun P, Yeon SW, Ko JH, Kim YS, Baek NI. Flavonoids from silkworm droppings and their promotional activities on heme oxygenase-1. J Asian Nat Prod Res 2011; 13: 377-382.
21. Chen MC, Ye YY, Ji G, Liu JW. Hesperidin upregulates heme oxygenase-1 to attenuate hydrogen peroxide-induced cell damage in hepatic L02 cells. J Agric Food Chem 2010; 58: 3330-3335.
22. 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.
23. Qian L, Cao F, Cui J, Huang Y, Zhou X, Liu S, Cai J. Radio protective effect of hydrogen in cultured cells and mice. Free Radic Res 2010; 44: 275-282.