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.

MATERIALS AND 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: Yun-peng Wang, Gang Li, Lu-lin Ma, Yi Zheng, Shu-dong Zhang, Hong-xian Zhang, Min Qiu, Xin Ma
• Journal: The Journal of surgical research (J Surg Res) Vol. 186 Issue 1 Pg. 390-7 (Jan 2014) ISSN: 1095-8673 [Electronic] United States
• PMID: 23972620 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Cholinergic Antagonists
• Quinuclidines
• Transcription Factor RelA
• penehyclidine
• Malondialdehyde
• Superoxide Dismutase
• p38 Mitogen-Activated Protein Kinases
• Caspase 3

Topics

• Animals
• Caspase 3 (analysis)
• Cholinergic Antagonists (therapeutic use)
• Kidney (blood supply)
• Male
• Malondialdehyde (analysis)
• Oxidative Stress
• Quinuclidines (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, metabolism)
• Superoxide Dismutase (metabolism)
• Transcription Factor RelA (analysis)
• p38 Mitogen-Activated Protein Kinases (metabolism)