title: Inhibition of Poly-(ADP-Ribose) Polymerase Protects the Kidney in a Canine Model of Endotoxic Shock.
abstract: Poly-(ADP-ribose) polymerases (PARPs), a super family of enzymes, play important roles in preserving genomic integrity, regulating transcriptions, protecting telomeres and determining cell fate. PARP overactivation leads to metabolic disorder and cell injury via depletion of energy substance. However, it is still unclear whether PARP overactivation happens during acute kidney injury (AKI) caused by endotoxic shock (ES). Here, we built a canine model of lipopolysaccharide-induced ES to explore the role of PARP during the development AKI. We also used an intravenous injection of 3-aminobenzamide (3-AB) to further explore whether PARP inhibition rescues the kidney from injury. Cell fate and energy metabolism were detected to explore the underlying mechanisms. As a result, Western blot and immunohistochemistry assays showed PARP overactivation in the very early phase of ES. Through PARP inhibition by 3-AB, we observed significant improvement of systemic hemodynamics, renal hemodynamics, renal oxygen metabolism and renal tubular cell apoptosis. These findings indicated that overactivation of PARP plays an important role in septic AKI. Inhibition of PARP overactivation may protect renal function against hemodynamic disorder, renal metabolism disturbance and renal cell apoptosis during endotoxic AKI.
authors.affiliation: Surgical Intensive Care Unit, Dalian Municipal Central Hospital, Dalian City, China.
authors.forename: Si-bo
authors.initials: SB
authors.lastname: Liu
authors.forename: Jinjie
authors.initials: J
authors.lastname: Liu
authors.forename: Da-wei
authors.initials: DW
authors.lastname: Liu
authors.forename: Xiao-ting
authors.initials: XT
authors.lastname: Wang
authors.forename: Rong-li
authors.initials: RL
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000627:therapeutic use; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006439:Hemodynamics; D007668:Kidney / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D010101:Oxygen Consumption; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use*; D012079:Renal Circulation; D012772:Shock, Septic / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide