PMID- 37834219
OWN - NLM
STAT- MEDLINE
DCOM- 20231101
LR  - 20231101
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 19
DP  - 2023 Sep 30
TI  - Mitoquinone Alleviates Donation after Cardiac Death Kidney Injury during 
      Hypothermic Machine Perfusion in Rat Model.
LID - 10.3390/ijms241914772 [doi]
LID - 14772
AB  - Transplanted organs are subjected to harmful conditions through stopping blood 
      flow, hypothermic storage of the graft, and subsequent reperfusion. In 
      particular, kidneys donated from patients after cardiac arrest (DCD) are 
      classified as more vulnerable to ischemia-reperfusion injury (IRI). Hypothermic 
      machine perfusion is proposed as a solution for better kidney storage before 
      transplantation, and it is a good platform for additional graft treatment. 
      Antioxidants have gained interest in regenerative medicine due to their ability 
      to scavenge reactive oxygen species (ROS), which play a key role in IRI. We 
      evaluated the effect of Mitoquinone (MitoQ), a strong mitochondria-targeted 
      antioxidant, administered directly to the perfusing buffer. Rat kidneys were 
      isolated, randomly classified into one of the following groups, donation after 
      brainstem death (DBD), DCD, and DCD with MitoQ, and perfused for 22 hours with a 
      hypothermic machine perfusion system. Subsequently, we detected levels of kidney 
      injury (KIM-1) and oxidative stress (ROS/RNS, cytochrome C oxidase, and 
      mitochondrial integrity) markers. We compared the activation of the apoptosis 
      pathway (caspase 3 and 9), the concentration of phosphorylated Akt (pAkt), and 
      the pAkt/total Akt ratio. MitoQ reduces KIM-1 concentration, total ROS/RNS, and 
      the level of caspases. We observed a decrease in pAkt and the pAkt/total Akt 
      ratio after drug administration. The length of warm ischemia time negatively 
      impacts the graft condition. However, MitoQ added to the perfusing system as an 
      'on pump' therapy mitigates injury to the kidney before transplantation by 
      inhibiting apoptosis and reducing ROS/RNS levels. We propose MitoQ as a potential 
      drug for DCD graft preconditioning.
FAU - Radajewska, Anna
AU  - Radajewska A
AD  - Division of Clinical Chemistry and Laboratory Hematology, Department of Medical 
      Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, Borowska 
      211A, 50-556 Wroclaw, Poland.
FAU - Szyller, Jakub
AU  - Szyller J
AD  - Division of Clinical Chemistry and Laboratory Hematology, Department of Medical 
      Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, Borowska 
      211A, 50-556 Wroclaw, Poland.
FAU - Krzywonos-Zawadzka, Anna
AU  - Krzywonos-Zawadzka A
AUID- ORCID: 0000-0003-3534-7306
AD  - Division of Clinical Chemistry and Laboratory Hematology, Department of Medical 
      Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, Borowska 
      211A, 50-556 Wroclaw, Poland.
FAU - Olejnik, Agnieszka
AU  - Olejnik A
AUID- ORCID: 0000-0001-5130-7609
AD  - Division of Clinical Chemistry and Laboratory Hematology, Department of Medical 
      Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, Borowska 
      211A, 50-556 Wroclaw, Poland.
FAU - Sawicki, Grzegorz
AU  - Sawicki G
AD  - Division of Clinical Chemistry and Laboratory Hematology, Department of Medical 
      Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, Borowska 
      211A, 50-556 Wroclaw, Poland.
AD  - Department of Anatomy, Physiology and Pharmacology, College of Medicine, 
      University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
FAU - Bil-Lula, Iwona
AU  - Bil-Lula I
AUID- ORCID: 0000-0002-2769-0166
AD  - Division of Clinical Chemistry and Laboratory Hematology, Department of Medical 
      Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, Borowska 
      211A, 50-556 Wroclaw, Poland.
LA  - eng
GR  - 2017/27/B/NZ4/00601/National Science Centre, Poland/
PT  - Journal Article
DEP - 20230930
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 47BYS17IY0 (mitoquinone)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (Antioxidants)
SB  - IM
MH  - Humans
MH  - Rats
MH  - Animals
MH  - Reactive Oxygen Species
MH  - *Organ Preservation
MH  - Proto-Oncogene Proteins c-akt
MH  - Kidney/metabolism
MH  - Perfusion
MH  - *Reperfusion Injury/metabolism
MH  - Antioxidants
MH  - Death
PMC - PMC10572969
OTO - NOTNLM
OT  - MitoQ
OT  - hypothermic machine perfusion
OT  - ischemia-reperfusion injury
OT  - kidney graft
OT  - oxidative stress
COIS- The authors declare no conflict of interest.
EDAT- 2023/10/14 10:44
MHDA- 2023/11/01 12:42
PMCR- 2023/09/30
CRDT- 2023/10/14 01:03
PHST- 2023/08/22 00:00 [received]
PHST- 2023/09/27 00:00 [revised]
PHST- 2023/09/28 00:00 [accepted]
PHST- 2023/11/01 12:42 [medline]
PHST- 2023/10/14 10:44 [pubmed]
PHST- 2023/10/14 01:03 [entrez]
PHST- 2023/09/30 00:00 [pmc-release]
AID - ijms241914772 [pii]
AID - ijms-24-14772 [pii]
AID - 10.3390/ijms241914772 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Sep 30;24(19):14772. doi: 10.3390/ijms241914772.