title: Prevention of acute kidney injury by tauroursodeoxycholic acid in rat and cell culture models.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America. gupta024@gmail.com
authors.forename: Sandeep
authors.initials: S
authors.lastname: Gupta
authors.forename: Shunan
authors.initials: S
authors.lastname: Li
authors.forename: Md Joynal
authors.initials: MJ
authors.lastname: Abedin
authors.forename: Kajohnsak
authors.initials: K
authors.lastname: Noppakun
authors.forename: Lawrence
authors.initials: L
authors.lastname: Wang
authors.forename: Tarundeep
authors.initials: T
authors.lastname: Kaur
authors.forename: Behzad
authors.initials: B
authors.lastname: Najafian
authors.forename: Cecília M P
authors.initials: CM
authors.lastname: Rodrigues
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Steer
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects; D008297:Male; D020011:Protective Agents / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D020011:Protective Agents; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D020169:Caspases