Nephroprotective effects of (-)-alpha-bisabolol against ischemic-reperfusion acute kidney injury

作者：Sampaio Tiago Lima; Pessoa Bezerra de Menezes Ramon Roseo Paula; Bezerra da Costa Marcus Felipe; Meneses Gdayllon Cavalcante; Villalta Arrieta Mauren Cristina; Chaves Filho Adriano Jose Maia; de Morais Glayciane Bezerra; Liborio Alexandre Braga; Alves Renata Sousa; Azul Monteiro Evangelista Janaina Serra; Costa Martins Alice Maria

来源：Phytomedicine, 2016, 23(14): 1843-1852.

DOI：10.1016/j.phymed.2016.11.008

• Ischemia/reperfusion
• Acute kidney injury
• (-)-alpha-Bisabolol
• KIM-1

Background: Ischemia/reperfusion (I/R) in kidney is commonly related to acute kidney injury (AKI), essentially through oxidative stress. (-)-alpha-Bisabolol is a sesquiterpene isolated from the essential oil of a variety of plants, including chamomile, which has important antioxidant activity.
Study design: This study intends to evaluate the nephroprotective activity of (-)-alpha-bisabolol (Bis) in both in vivo and in vitro models of kidney I/R.
Methods: Male Wistar rats were submitted to right nephrectomy, followed by ischemia by clamping of the renal artery in the left kidney for 60 min. and 48 h of reperfusion. The animals were treated orally with Bis (100 mg/kg) or vehicle for 24 h after reperfusion, and placed in metabolic cages, to evaluate water consumption, diuresis, urinary osmolality, classic biochemical markers and urinary KIM-1 (kidney injury molecule-1). Additionally, the left kidney was collected for histological evaluation and determination of glutathione (GSH) and Thiobarbituric Acid Reactive Substances (TBARS) levels. Tubular epithelial cells LLC-MK2 were used to assess Bis effect on in vitro I/R, by MTT assay. It was performed the cellular respiration tests by flow cytometry: evaluation of the production of cytoplasmic reactive oxygen species by DCFH-DA assay and mitochondrial transmembrane potential analysis with the dye rhodamine 123.
Results: I/R caused alterations in diuresis, water intake, urinary osmolality, plasmatic creatinine, urea and uric acid, creatinine clearance, proteinuria and microalbuminuria. Treatment with Bis ameliorated all of these parameters. Also, KIM-1 level enhanced by I/R was also diminished in groups treated with Bis. The histological examination showed that Bis attenuated the morphological changes caused by I/R, markedly vascular congestion and intratubular deposits of proteinaceous material. Additionally, Bis was able to reduce the changes observed in TBARS and GSH levels in kidney tissue. In in vitro assay, Bis was capable to partially protect the cell lineage against cell damage induced by I/R.
Conclusion: (-)-alpha-Bisabolol has a nephroprotective effect in kidney I/R, with antioxidant effect. Moreover, this result seems to be associated to a direct protective effect on tubular epithelia.

• 出版日期2016-12-15