Isolated mitochondria infusion mitigates ischemia-reperfusion injury of the liver in rats.
A recent study showed that the injection of mitochondria isolated from a nonischemic region mitigated myocardial injury. We tested the protective effects of infusing isolated mitochondria on the reperfusion injury in the liver of rats. A partial liver ischemia-reperfusion (I/R) model in male Wistar rats was used. At the 45th minute of liver ischemia, the recipient's spleen was infused with vehicle (I/R-vehicle group) or vehicle containing isolated mitochondria (7.7 × 10 ± 1.5 × 10/mL, I/R-mito group). After a 240-min reperfusion, the serum and livers were collected to assess tissue injury. Our results show that the elevation of serum alanine aminotransferase (414.3 ± 67.1 vs. 208.8 ± 30.2 U/L), the necrosis of hepatocytes on hematoxylin-eosin staining, increase in positive counts in TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining (59.5% ± 4.4% vs. 24.6% ± 9.1%), the expression of cytosolic cytochrome c, cleaved caspase 9, and 4-hydroxynonenal were all reduced in the I/R-mito group, compared with the I/R-vehicle group. The membrane potential of the isolated mitochondria measured by JC-1 fluorescence remained high, and the infused mitochondria were distributed in the liver parenchyma at 240 min after reperfusion. These results demonstrate that an intrasplenic infusion of viable mitochondria isolated from the donor before reperfusion significantly reduced I/R injury in the liver.
Department of Anatomy and Cell Biology, Medical College, National Taiwan University, Taipei, Taiwan. iruelai@gmail.com
Han-Chen
HC
Lin
Shin-Yun
SY
Liu
Hong-Shiee
HS
Lai
I-Rue
IR
Lai
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D022781:Hepatocytes / Q000473:pathology; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000637:transplantation*; D009336:Necrosis; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D013154:Spleen
D045304:Cytochromes c; D000410:Alanine Transaminase; C506435:Casp9 protein, rat; D053453:Caspase 9