Methylene Blue Protects the Isolated Rat Lungs from Ischemia–Reperfusion Injury by Attenuating Mitochondrial Oxidative Damage
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Impaired mitochondrial function is a key factor attributing to the lung ischemia reperfusion injury (LIRI). Methylene blue (MB) has been reported to attenuate brain and renal ischemia–reperfusion injury. We hypothesized that MB also could have a protective effect against LIRI by preventing mitochondrial oxidative damage.
Isolated rat lungs were assigned to the following four groups (n = 6): a sham group: perfusion for 105 min without ischemia; I/R group: shutoff of perfusion and ventilation for 45 min followed by reperfusion for 60 min; and I/R + MB group and I/R + glutathione (GSH) group: 2 mg/kg MB or 4 μM glutathione were intraperitoneally administered for 2 h, and followed by 45 min of ischemia and 60 min of reperfusion.
MB lessened pulmonary dysfunction and severe histological injury induced by ischemia–reperfusion injury. MB reduced the production of reactive oxygen species and malondialdehyde and enhanced the activity of superoxide dismutase. MB also suppressed the opening of the mitochondrial permeability transition pore and partly preserved mitochondrial membrane potential. Moreover, MB inhibited the release of cytochrome c from the mitochondria into the cytosol and decreased apoptosis. Additionally, MB downregulated the mRNA expression levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-18).
MB protects the isolated rat lungs against ischemia–reperfusion injury by attenuating mitochondrial damage.
KeywordsMethylene blue Isolated lung reperfusion Lung ischemia–reperfusion injury Mitochondrial damage
This work was supported by the following Grants: National Natural Science Foundation of China (81270126); Fundamental Research Funds for the Central Universities (JUSRP51412B); The Science Funds for Health and Family Planning Commission of Sichuan Province (150234); Jiangsu Province Natural Science Foundation (BK20161141); and Graduate Student Research Innovation Project (KYZZ16_0312, KYLX15_1196).
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
This research involved rats. The study was approved by the Animal Care and Use Committee of Jiangnan University.
- 2.Ovechkin AV, Lominadze D, Sedoris KC, Robinson TW, Tyagi SC, Roberts AM (2007) Lung ischemia-reperfusion injury: implications of oxidative stress and platelet-arteriolar wall interactions. Arch Physiol Biochem 113(1):1–12. https://doi.org/10.1080/13813450601118976 CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Silachev DN, Plotnikov EY, Pevzner IB, Zorova LD, Babenko VA, Zorov SD, Popkov VA, Jankauskas SS, Zinchenko VP, Sukhikh GT, Zorov DB (2014) The mitochondrion as a key regulator of ischaemic tolerance and injury. Heart Lung Circ 23(10):897–904. https://doi.org/10.1016/j.hlc.2014.05.022 CrossRefPubMedGoogle Scholar
- 10.Kuliaviene I, Baniene R, Virketyte S, Kincius M, Jansen E, Gulbinas A, Kupcinskas L, Trumbeckaite S, Borutaite V (2016) Methylene blue attenuates mitochondrial dysfunction of rat kidney during experimental acute pancreatitis. J dig dis 17(3):186–192. https://doi.org/10.1111/1751-2980.12328 CrossRefPubMedGoogle Scholar
- 12.Ahmed ME, Tucker D, Dong Y, Lu Y, Zhao N, Wang R, Zhang Q (2016) Methylene blue promotes cortical neurogenesis and ameliorates behavioral deficit after photothrombotic stroke in rats. Neuroscience 336:39–48. https://doi.org/10.1016/j.neuroscience.2016.08.036 CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Collange O, Charles AL, Bouitbir J, Chenard MP, Zoll J, Diemunsch P, Thaveau F, Chakfe N, Piquard F, Geny B (2013) Methylene blue protects liver oxidative capacity after gut ischaemia-reperfusion in the rat. Eur J Vasc Endovasc Surg 45(2):168–175. https://doi.org/10.1016/j.ejvs.2012.11.011 CrossRefPubMedGoogle Scholar
- 21.Galindo MF, Jordan J, Gonzalez-Garcia C, Cena V (2003) Reactive oxygen species induce swelling and cytochrome c release but not transmembrane depolarization in isolated rat brain mitochondria. Br J Pharmacol 139(4):797–804. https://doi.org/10.1038/sj.bjp.0705309 CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Schauer RJ, Gerbes AL, Vonier D, Meissner H, Michl P, Leiderer R, Schildberg FW, Messmer K, Bilzer M (2004) Glutathione protects the rat liver against reperfusion injury after prolonged warm ischemia. Ann Surg 239(2):220–231. https://doi.org/10.1097/01.sla.0000110321.64275.95 CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Brinkkoetter PT, Song H, Losel R, Schnetzke U, Gottmann U, Feng Y, Hanusch C, Beck GC, Schnuelle P, Wehling M, van der Woude FJ, Yard BA (2008) Hypothermic injury: the mitochondrial calcium, ATP and ROS love-hate triangle out of balance. Cell Physiol Biochem 22(1–4):195–204. https://doi.org/10.1159/000149797 CrossRefPubMedGoogle Scholar
- 35.Fenn AM, Skendelas JP, Moussa DN, Muccigrosso MM, Popovich PG, Lifshitz J, Eiferman DS, Godbout JP (2015) Methylene blue attenuates traumatic brain injury-associated neuroinflammation and acute depressive-like behavior in mice. J Neurotrauma 32(2):127–138. https://doi.org/10.1089/neu.2014.3514 CrossRefPubMedPubMedCentralGoogle Scholar