Effects of intraperitoneal hydrogen injection on nitric oxide synthase mRNA and malondialdehyde following limb ischemia-reperfusion in rabbits

Year 2015, Volume: 49 Issue: 5, 558 - , 24.09.2015

Dai-jun Wang Hua Tian Bao-xiang Zhuang Hong-juan Wu

Abstract

Objective: To investigate the effects of intraperitoneal hydrogen (H2) injection on the mRNA expression levels of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) as well as the serum malondialdehyde (MDA) level in a rabbit model of limb ischemia-reperfusion (I/R)-induced skeletal muscle injury.
Methods: To establish the hind limb I/R animal model, 30 rabbits were randomly assigned to one of three groups: Sham, I/R and IRH. An intraperitoneal injection of H2 was given to the IRH group, while an equivalent amount of air was given to the Sham and I/R groups. At 3, 6, 12 and 24 h post reperfusion, the serum MDA level, as well as the skeletal muscle iNOS and eNOS mRNA expression levels, were determined
Results: Both iNOS mRNA expression and serum MDA levels were higher in the I/R group than the Sham group (P < 0.01) and lower in the IRH group than the I/R group (P < 0.01 or P < 0.05) at various time points after reperfusion. The eNOS mRNA expression level exhibited no significant difference between the I/R and Sham groups following reperfusion but was significantly higher in the IRH group than in the Sham group (P < 0.01 or P < 0.05).
Conclusions: During the I/R process, the expression of iNOS mRNA was up-regulated along with an increase in MDA. Intraperitoneal injection of H2 could down-regulate iNOS mRNA expression and up-regulate eNOS mRNA expression in the I/R process, suggesting a protective effect of H2 in I/R-induced skeletal muscle injury.

 

Keywords

Hydrogen;ischemia-reperfusion;inducible nitric oxide synthase mRNA;endothelial nitric oxide synthase mRNA;malondialdehyde

References

• Baue AE. The horror autotoxicus and multiple-organ fail- ure. Arch Surg 1992;127:1451–62.
• Nanobashvili J, Neumayer C, Fuegl A, Sporn E, Prager M, Polterauer P, et al. Ischaemia/reperfusion injury of skeletal muscle: Mechanisms, morphology, treatment strategies, and clinical applications. European Surgery 2002;34:83–9.
• Guillot M, Charles AL, Chamaraux-Tran TN, Bouitbir J, Meyer A, Zoll J, et al. Oxidative stress precedes skeletal muscle mitochondrial dysfunction during experimental aortic cross-clamping but is not associated with early lung, heart, brain, liver, or kidney mitochondrial impairment. J Vasc Surg 2014;60:1043–51.e5.
• Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987;327:524–6.
• Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiol- ogy, pathophysiology, and pharmacology. Pharmacol Rev 1991;43:109–42.
• Rochette L, Lorin J, Zeller M, Guilland JC, Lorgis L, Cot- tin Y, et al. Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: possible therapeutic tar- gets? Pharmacol Ther 2013;140:239–57.
• Korkmaz A, Kolankaya D. Inhibiting inducible nitric oxide synthase with rutin reduces renal ischemia/reperfusion in- jury. Can J Surg 2013;56:6–14.
• Huang G, Zhou J, Zhan W, Xiong Y, Hu C, Li X, et al. The neuroprotective effects of intraperitoneal injection of hydrogen in rabbits with cardiac arrest. Resuscitation 2013;84:690–5.
• George JF, Agarwal A. Hydrogen: another gas with thera- peutic potential. Kidney Int 2010;77:85–7.
• Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishi- maki K, Yamagata K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radi- cals. Nat Med 2007;13:688–94.
• Dixon BJ, Tang J, Zhang JH. The evolution of molecular hydrogen: a noteworthy potential therapy with clinical sig- nificance. Med Gas Res 2013;3:10.
• Ohsawa I, Nishimaki K, Yamagata K, Ishikawa M, Ohta S. Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochem Biophys Res Commun 2008;377:1195–8.
• Hayashida K, Sano M, Ohsawa I, Shinmura K, Tamaki K, Kimura K, et al. Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun 2008;373:30–5.
• Shingu C, Koga H, Hagiwara S, Matsumoto S, Goto K, Yokoi I, et al. Hydrogen-rich saline solution attenuates renal ischemia-reperfusion injury. J Anesth 2010;24:569– 74.
• Fang Y, Fu XJ, Gu C, Xu P, Wang Y, Yu WR, et al. Hy- drogen-rich saline protects against acute lung injury in- duced by extensive burn in rat model. J Burn Care Res 2011;32:e82–91.
• Fujita K, Seike T, Yutsudo N, Ohno M, Yamada H, Yama- guchi H, et al. Hydrogen in drinking water reduces dopa- minergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine mouse model of Parkinson’s disease. PLoS One 2009;4:e7247.
• Nanobashvili J, Neumayer C, Fügl A, Punz A, Blumer R, Prager M, et al. Ischemia/reperfusion injury of skeletal muscle: plasma taurine as a measure of tissue damage. Sur- gery 2003;133:91–100.
• Wang DJ, Tian H. Effect of Mailuoning injection on 8-iso- prostaglandin F2 alpha and superoxide dismutase in rab- bits with extremity ischemia-reperfusion injury. J Surg Res 2014;192:464–70.
• Wan LL, Xia J, Ye D, Liu J, Chen J, Wang G. Effects of quercetin on gene and protein expression of NOX and NOS after myocardial ischemia and reperfusion in rabbit. Cardiovasc Ther 2009;27:28–33.
• Küçük A, Yucel M, Erkasap N, Tosun M, Koken T, Oz- kurt M, et al. The effects of PDE5 inhibitory drugs on renal ischemia/reperfusion injury in rats. Mol Biol Rep 2012;39:9775–82.