Aripiprazole prevents renal ischemia/reperfusion injury in rats, probably through nitric oxide involvement.

Abstract

Renal ischemia/reperfusion (I/R) injury is strongly related to morbidity and mortality. Oxidative stress, inflammation, and apoptosis play key roles in renal dysfunction following renal I/R. Aripiprazole is an atypical antipsychotic which used for the treatment of schizophrenia and bipolar disorder. Recent studies have reported aripiprazole as displaying certain anti-inflammatory effects. Regarding the underlying mechanisms of renal ischemia-reperfusion, therefore, nephroprotective effects might be predicted to be seen with aripiprazole. I/R injury was induced by bilateral clamping of the renal pedicles (45min) followed by reperfusion (24h). The mechanism of aripiprazole-mediated nephroprotection was explored by a combined use of aripiprazole and L-NAME (non-selective nitric oxide synthase inhibitor). Animals were given aripiprazole (2.5, 5, 10 and 20mg/kg) intraperitoneally, 30min before ischemia. L-NAME was administered before the aripiprazole injection. Serum creatinine and blood urea nitrogen were assessed after 24h of reperfusion. Serum levels of malondialdehyde (MDA), TNF-α and IL-1β were measured for rats treated with aripiprazole. The extent of necrosis was measured by the stereology method. Ischemia/reperfusion caused significant renal dysfunction and marked renal injury. Aripiprazole reduced creatinine and blood urea nitrogen. Serum levels of MDA, IL-1β and TNF-α were significantly lower in the aripiprazole group. Aripiprazole treatment also decreased the volume of kidney necrosis. The administration of L-NAME reversed the renoprotective effect of aripiprazole on BUN and creatinine, but enhanced the anti-necrotic effect of aripiprazole. The results show that a single dose of aripiprazole significantly improved renal function following ischemia/reperfusion injury - probably through the involvement of nitric oxide.

• Authors: Hanieh Gholampour, Leila Moezi, Hamed Shafaroodi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 813 Pg. 17-23 (Oct 15 2017) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 28734929 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Interleukin-1beta
• Tumor Necrosis Factor-alpha
• Nitric Oxide
• Aripiprazole
• Creatinine
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Aripiprazole (pharmacology)
• Blood Urea Nitrogen
• Creatinine (blood)
• Cytoprotection (drug effects)
• Interleukin-1beta (blood)
• Kidney (drug effects, metabolism, pathology, physiopathology)
• Male
• NG-Nitroarginine Methyl Ester (pharmacology)
• Necrosis
• Nitric Oxide (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (metabolism, pathology, physiopathology, prevention & control)
• Tumor Necrosis Factor-alpha (blood)