Mitochondria-targeted plastoquinone derivative SkQ(1) decreases ischemia-reperfusion injury during liver hypothermic storage for transplantation.

The ability of the mitochondria-targeted plastoquinone derivative 10-(6'-plastoquinonyl)decyl triphenylphosphonium (SkQ(1)) to decrease ischemia-reperfusion injury in isolated liver during hypothermic storage (HS) was studied. Rat liver was stored for 24 h at 4°C without or in the presence of 1 µM SkQ(1) with following reperfusion for 60 min at 37°C. The presence in the storage medium of SkQ(1) 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 SkQ(1) was reliably higher, but reperfusion leveled this effect. At all stages of experiment the presence of SkQ(1) did not prevent the decrease of antioxidant enzyme activities such as catalase, GSH peroxidase, GSH reductase, and glucose-6-phosphate dehydrogenase. The addition of SkQ(1) to the storage medium improved energetic function of the liver, as was revealed in increased respiratory control index of mitochondria and ATP level. SkQ(1) 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.

Mitochondrial function after liver preservation in high or low ionic-strength solutions: a comparison between UW-based and sucrose-based solution.

In this study we evaluated mitochondrial function after liver cold storage and normothermic reperfusion. The preservation solutions were: modified University of Wisconsin (mod UW) and sucrose-based solution (SBS). After cold preservation liver was re-perfused for 1 hour in vitro with Krebs-Ringer buffer at 37 degree C. Samples of tissue were taken for ATP determination. Mitochondrial respiratory parameters, succinate oxidase complex activity, mitochondrial H+- ATPase and intramitochondrial potassium concentration were assayed. It was shown, that brief (1 hour) cold storage and subsequent normothermic reperfusion revealed no difference in liver ATP content between mod UW and SBS groups but resulted in a gradual decrease of 50 percent after 24-hour storage and reperfusion. Mitochondrial potassium ion concentration increased by 40 percent after 1-hour cold storage in the mod UW as compared to control (P value less than 0.05) and SBS. After brief cold storage ADP and uncoupler-stimulated respiration increased by 120 percent in SBS group, unlike mod UW, when succinate was used as substrate, and was more pronounced after 24 hour. Succinate oxidase complex activity did not change over either cold storage or warm reperfusion. Mitochondrial H+-ATPase activities in SBS and mod UW did not differ and both were inhibited after 24-hour cold storage. Our data demonstrate that low ionic strength preservation solution can substantially modulate mitochondrial energy turnover due to substrate oxidation increase. Many of the changes in mitochondrial function follow brief exposure to low temperatures.

[Influence of mitochondrial antioxidant 10-(6-plastoquinonyl)decyltriphenylphosphonium on peroxidation process intensity and respiratory activity of rat isolated liver after hypothermic storage].

The influence of mitochondria-targeted antioxidant 10-(6-plastoquinonyl)decyltriphenylphosphonium (SkQ,) different concentrations on respiratory parameters and lipid peroxidation process intensity in the rat liver after hypothermic storage was investigated. It was shown that cold storage of isolated liver during 18 h results in accumulation of TBA-active products, increase of intensity of Fe(2+)-ascorbate induced lipid peroxidation and depression of mitochondria functional activity. SkQ1 inhibits activation of free radical processes in a dose-dependent manner and it has a positive influence on energetic coupling in mitochondria.

[Effect of 2,4-dinitrophenol on the rat liver respiratory activity and ATP content after hypothermic storage and following reperfusion].

The influence of oxidative phosphorylation uncoupler 2,4-dinitrophenol (DNP) presence in preserving solution on the rat liver respiratory activity and ATP content after 18 h of hypothermic storage (HS) and following normothermic reperfusion (NR) was investigated. DNP presence on the HS stage led to decrease of ATP level as compared with the control. After DNP removal during NR the gradual recovery of oxidative phosphorylation coupling occurred. This fact resulted in improvement of mitochondrial functional state (V4 respiration rate decrease, respiratory control and ATP level increase).

[The cryopreservation of isolated liver cells]. / Kriokonservirovanie izolirovannykh kletok pecheni.

Recent literature data on cryopreservation of isolated hepatocytes are summarized. The hepatocytes are considered to constitute a promising system for investigation of liver metabolic peculiarities as well as for elucidating mechanisms of low temperature effects on biological systems.