Mitochondria-Targeted Plastoquinone Derivative SkQ₁ Decreases Ischemia–Reperfusion Injury during Liver Hypothermic Storage for Transplantation

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D. V. Cherkashina^*, I. A. Sosimchik, O. A. Semenchenko, V. V. Volina, and A. Yu. Petrenko^*

Institute for Problems of Cryobiology and Cryomedicine, Ukrainian National Academy of Sciences, Pereyaslavskaya str. 23, 61015 Kharkov, Ukraine; fax: (+38057) 373-3084; E-mail: alexander_petrenko@cryo.org.ua; daria_cherkashina@ukr.net

^* To whom correspondence should be addressed.

Received October 7, 2010; Revision received March 3, 2011

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The ability of the mitochondria-targeted plastoquinone derivative 10-(6′-plastoquinonyl)decyl triphenylphosphonium (SkQ₁) to decrease ischemia–reperfusion injury in isolated liver during hypothermic storage (HS) was studied. Rat liver was stored for 24 h at 4ºC without or in the presence of 1 μM SkQ₁ with following reperfusion for 60 min at 37ºC. The presence in the storage medium of SkQ₁ significantly decreased spontaneous production of reactive oxygen species and intensity of lipid peroxidation in the liver during HS and reperfusion. The GSH level after HS in solution with SkQ₁ was reliably higher, but reperfusion leveled this effect. At all stages of experiment the presence of SkQ₁ did not prevent the decrease of antioxidant enzyme activities such as catalase, GSH peroxidase, GSH reductase, and glucose-6-phosphate dehydrogenase. The addition of SkQ₁ to the storage medium improved energetic function of the liver, as was revealed in increased respiratory control index of mitochondria and ATP level. SkQ₁ exhibited positive effect on the liver secretory function and morphology after HS as revealed in enhanced bile flow rate during reperfusion and partial recovery of organ architectonics and state of liver sinusoids and hepatocytes. The data point to promising application of mitochondria-targeted antioxidants for correction of the ischemia–reperfusion injury of isolated liver during long-term cold storage before transplantation.

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KEY WORDS: mitochondria-targeted antioxidant, SkQ₁, ischemia–reperfusion injury, hypothermic storage of isolated liver, free radical processes, respiratory activity of mitochondria

DOI: 10.1134/S0006297911090069

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