Diazoxide attenuates hypothermic preservation-induced renal injury via down-regulation of CHOP and caspase-12.
BACKGROUND
Successful clinical organ preservations are a prerequisite for organ transplantation. Diazoxide (DE), which shows a concentration-dependent selectivity for mitoK(+-)-ATP over plasma membrane K(+-)-ATP, displays protective effects during organ preservation. The current study investigated possible protective effects of DE on rat kidneys injured by hypothermic preservation.


METHODS
Forty-eight Sprague-Dawley rats were randomly divided into six groups (n = 8): Celsior groups with kidneys preserved in Celsior solution for 0, 24 and 48 h and DE groups with kidneys preserved in DE (30 μM) plus Celsior solution for 0, 24 and 48 h. Superoxide dismutase (SOD) activity and the quantity of malonaldehyde (MDA) in the kidneys from each group were measured, and the levels of C/EBP homologous protein (CHOP) and caspase-12 were determined by immunohistochemistry staining and real-time reverse transcription quantitative polymerase chain reaction analysis.


RESULTS
SOD activity was significantly higher and the quantity of MDA was significantly lower in the DE groups compared with the Celsior groups at both 24 and 48 h (P < 0.05). The expressions of CHOP and caspase-12 were also lower in DE groups at 24 and 48 h (P < 0.05).


CONCLUSIONS
The present results demonstrate that DE exerts protective effects by attenuating oxidative stress injury through up-regulation of SOD activity and down-regulation of MDA quantity and by decreasing the cell apoptosis in kidneys by reducing the levels of CHOP and caspase-12 during hypothermic preservation.
Xu
Linhao
L
Department of Anatomy and Cell Biology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
Han
Fei
F
Mandal
Arundhuti
A
Rao
Govardhana Narasimha
GN
Zhang
Xiaoming
X
D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053454:Caspase 12 / Q000378:metabolism*; D003451:Cryoprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003981:Diazoxide / Q000494:pharmacology / Q000627:therapeutic use*; D004187:Disaccharides / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004573:Electrolytes / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005971:Glutamates / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006639:Histidine / Q000494:pharmacology; D007035:Hypothermia / Q000150:complications*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology; D023421:Models, Animal; D019188:Organ Preservation Solutions / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism*
C088453:Celsior; D003451:Cryoprotective Agents; C497251:Ddit3 protein, rat; D004187:Disaccharides; D004573:Electrolytes; D005971:Glutamates; D019188:Organ Preservation Solutions; D051742:Transcription Factor CHOP; D008353:Mannitol; D006639:Histidine; D008315:Malondialdehyde; D013482:Superoxide Dismutase; C506443:Casp12 protein, rat; D053454:Caspase 12; D005978:Glutathione; D003981:Diazoxide