TY - JOUR
T1 - Prevention of Acute Kidney Injury by Tauroursodeoxycholic Acid in Rat and Cell Culture Models
AU - Gupta, Sandeep
AU - Li, Shunan
AU - Abedin, Md Joynal
AU - Noppakun, Kajohnsak
AU - Wang, Lawrence
AU - Kaur, Tarundeep
AU - Najafian, Behzad
AU - Rodrigues, Cecília M.P.
AU - Steer, Clifford J
PY - 2012/11/9
Y1 - 2012/11/9
N2 - Background: Acute kidney injury (AKI) has grave short- and long-term consequences. Often the onset of AKI is predictable, such as following surgery that compromises blood flow to the kidney. Even in such situations, present therapies cannot prevent AKI. As apoptosis is a major form of cell death following AKI, we determined the efficacy and mechanisms of action of tauroursodeoxycholic acid (TUDCA), a molecule with potent anti-apoptotic and pro-survival properties, in prevention of AKI in rat and cell culture models. TUDCA is particularly attractive from a translational standpoint, as it has a proven safety record in animals and humans. Methodology/Principal Findings: We chose an ischemia-reperfusion model in rats to simulate AKI in native kidneys, and a human kidney cell culture model to simulate AKI associated with cryopreservation in transplanted kidneys. TUDCA significantly ameliorated AKI in the test models due to inhibition of the mitochondrial pathway of apoptosis and upregulation of survival pathways. Conclusions: This study sets the stage for testing TUDCA in future clinical trials for prevention of AKI, an area that needs urgent attention due to lack of effective therapies.
AB - Background: Acute kidney injury (AKI) has grave short- and long-term consequences. Often the onset of AKI is predictable, such as following surgery that compromises blood flow to the kidney. Even in such situations, present therapies cannot prevent AKI. As apoptosis is a major form of cell death following AKI, we determined the efficacy and mechanisms of action of tauroursodeoxycholic acid (TUDCA), a molecule with potent anti-apoptotic and pro-survival properties, in prevention of AKI in rat and cell culture models. TUDCA is particularly attractive from a translational standpoint, as it has a proven safety record in animals and humans. Methodology/Principal Findings: We chose an ischemia-reperfusion model in rats to simulate AKI in native kidneys, and a human kidney cell culture model to simulate AKI associated with cryopreservation in transplanted kidneys. TUDCA significantly ameliorated AKI in the test models due to inhibition of the mitochondrial pathway of apoptosis and upregulation of survival pathways. Conclusions: This study sets the stage for testing TUDCA in future clinical trials for prevention of AKI, an area that needs urgent attention due to lack of effective therapies.
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U2 - 10.1371/journal.pone.0048950
DO - 10.1371/journal.pone.0048950
M3 - Article
C2 - 23152827
AN - SCOPUS:84869049949
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 11
M1 - e48950
ER -