title: Poly(ADP-ribose) polymerase inhibition suppresses inflammation and promotes recovery from adrenal injury in a rat model of acute necrotizing pancreatitis.
abstract: BACKGROUND
  Poly(ADP-ribose) polymerase (PARP) participates in multi-organ failure in various inflammatory diseases including acute necrotizing pancreatitis (ANP). Since pancreatitis-associated adrenal insufficiency is partly caused by inflammatory damage to the adrenal cortex, we examined whether PARP antagonism could alleviate adrenal insufficiency in a rat model of ANP.
  
  
  METHODS
  ANP was induced by retrograde infusion of sodium taurocholate into the bile-pancreatic duct. At 30 min prior to taurocholate infusion, rats were pretreated with the PARP inhibitor 3-Aminobenzamide (3-AB, 20 mg/kg) or vehicle. Pancreatic pathological injury, adrenal histology, neutrophil infiltration, cell apoptosis, and serum corticosterone level were assessed at various times points. Activities of poly(ADP-ribosyl)ated protein (PAR), nuclear factor-kappaB (NF-kB), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS) in the adrenal were also examined.
  
  
  RESULTS
  PARP overactivation in ANP rats is associated with reduced serum corticosterone level and marked cellular alterations in adrenocortical tissue. Inflammatory stress caused by ANP reduced adrenal corticosterone release. 3-AB reduced the activation of PARP and inflammatory markers, decreased myeloperoxidase activity, attenuated adrenal morphologic lesions and cells apoptosis, simultaneously improved the impaired adrenal function.
  
  
  CONCLUSIONS
  Our data demonstrate the involvement of PARP overactivation in the pathogenesis of adrenal dysfunction after ANP. PARP inhibition may suppress inflammation and promote functional recovery from adrenal injury.
authors.affiliation: Department of Hepatobilliary & Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.|Hubei Key Laboratory for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Hepatobilliary & Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.|Hubei Key Laboratory for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.
authors.forename: Teng
authors.initials: T
authors.lastname: Zuo
authors.affiliation: Department of Hepatobilliary & Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.|Hubei Key Laboratory for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Hepatobilliary & Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.|Hubei Key Laboratory for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Hepatobilliary & Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Ma
authors.affiliation: Department of Hepatobilliary & Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.|Hubei Key Laboratory for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Hepatobilliary & Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Hepatobilliary & Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.
authors.forename: Kailiang
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Hepatobilliary & Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China. sate.llite@163.com.|Hubei Key Laboratory for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China. sate.llite@163.com.
authors.forename: Weixing
authors.initials: W
authors.lastname: Wang
mesh_terms: D000311:Adrenal Glands / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D000309:Adrenal Insufficiency / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration; D010179:Pancreas / Q000201:enzymology / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases
keywords: 3-Aminobenzamide; Acute necrotizing pancreatitis; Adrenal injury; Adrenal insufficiency; Apoptosis; Poly(ADP-ribose) polymerase