title: Penehyclidine hydrochloride ameliorates renal ischemia-reperfusion injury in rats.
abstract: BACKGROUND
  Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney failure by mechanisms that involve oxidative stress, inflammation, and apoptosis. Penehyclidine hydrochloride (PHC), a selective anticholinergic agent, possesses anti-inflammatory, antioxidative stress, and antiapoptotic effects. Therefore, we investigated the ability of PHC to ameliorate renal I/R injury in Sprague-Dawley rats.
  
  
  METHODS
  Rats were randomly assigned to three groups (35 rats per group): sham operated, saline-treated I/R, and PHC-treated I/R. After removing the right kidney, renal I/R injury was induced by clamping the left renal artery for 45 min followed by reperfusion. The rats were administered PHC (0.45 mg/kg, intravenously) or saline 30 min before renal ischemia. The blood and kidneys were harvested at 1, 3, 6, 12, or 24 h after reperfusion. Renal function and histologic changes were assessed. Markers of oxidative stress, inflammation, and apoptosis in the kidneys were also measured.
  
  
  RESULTS
  PHC treatment significantly attenuated renal dysfunction and histologic damage caused by I/R injury. The treatment also decreased malondialdehyde level and attenuated the reduction in superoxide dismutase activity in the kidney. Moreover, the levels of activated p38 mitogen-activated protein kinase, nuclear factor kappa B, and caspase 3 were lower in the PHC-treated animals.
  
  
  CONCLUSIONS
  PHC protected rat kidneys from I/R injury by attenuating oxidative stress, inflammatory response, and apoptosis. Thus, PHC may represent a novel practical strategy for the treatment of renal I/R injury.
authors: Department of Urology, Peking University Third Hospital, Beijing 100191, People's Republic of China.
authors: Yun-peng
authors: YP
authors: Wang
authors: Gang
authors: G
authors: Li
authors: Lu-lin
authors: LL
authors: Ma
authors: Yi
authors: Y
authors: Zheng
authors: Shu-dong
authors: SD
authors: Zhang
authors: Hong-xian
authors: HX
authors: Zhang
authors: Min
authors: M
authors: Qiu
authors: Xin
authors: X
authors: Ma
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000032:analysis; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018384:Oxidative Stress; D011812:Quinuclidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D051996:Transcription Factor RelA / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018680:Cholinergic Antagonists; D011812:Quinuclidines; D051996:Transcription Factor RelA; C486140:penehyclidine; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: Apoptosis; Inflammation; Ischemia–reperfusion injury; Kidney; Oxidative stress; Penehyclidine hydrochloride