title: Nephroprotective effects of (-)-α-bisabolol against ischemic-reperfusion acute kidney injury.
abstract: BACKGROUND
  Ischemia/reperfusion (I/R) in kidney is commonly related to acute kidney injury (AKI), essentially through oxidative stress. (-)-α-Bisabolol is a sesquiterpene isolated from the essential oil of a variety of plants, including chamomile, which has important antioxidant activity.
  
  
  METHODS
  This study intends to evaluate the nephroprotective activity of (-)-α-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 60min. and 48h of reperfusion. The animals were treated orally with Bis (100mg/kg) or vehicle for 24h 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.
  
  
  CONCLUSIONS
  (-)-α-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.
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Ceará, Brazil.
authors.forename: Tiago Lima
authors.initials: TL
authors.lastname: Sampaio
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Ceará, Brazil. Electronic address: ramonppessoa@gmail.com.
authors.forename: Ramon Róseo Paula Pessoa Bezerra de
authors.initials: RR
authors.lastname: Menezes
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Ceará, Brazil.
authors.forename: Marcus Felipe Bezerra
authors.initials: MF
authors.lastname: da Costa
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Ceará, Brazil.
authors.forename: Gdayllon Cavalcante
authors.initials: GC
authors.lastname: Meneses
authors.affiliation: Instituto Clodomiro Picado, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Mauren Cristina Villalta
authors.initials: MC
authors.lastname: Arrieta
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Ceará, Brazil.
authors.forename: Adriano José Maia
authors.initials: AJ
authors.lastname: Chaves Filho
authors.affiliation: School of Veterinar y Medicine, State University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Glayciane Bezerra
authors.initials: GB
authors.lastname: de Morais
authors.affiliation: Department of Clinical Medicine, School of Medicine, Federal University of Ceará, Fortaleza, Ceara, Brazil.
authors.forename: Alexandre Braga
authors.initials: AB
authors.lastname: Libório
authors.affiliation: Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Renata Sousa
authors.initials: RS
authors.lastname: Alves
authors.affiliation: School of Veterinar y Medicine, State University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Janaína Serra Azul Monteiro
authors.initials: JS
authors.lastname: Evangelista
authors.affiliation: Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Alice Maria Costa
authors.initials: AM
authors.lastname: Martins
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D020843:Chamomile / Q000737:chemistry; D005452:Fluoresceins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007684:Kidney Tubules / Q000187:drug effects; D008297:Male; D000081222:Monocyclic Sesquiterpenes; D009392:Nephrectomy; D009822:Oils, Volatile / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011507:Proteinuria / Q000188:drug therapy; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015815:Cell Adhesion Molecules; D005452:Fluoresceins; D005978:Glutathione; D000081222:Monocyclic Sesquiterpenes; D009822:Oils, Volatile; D010936:Plant Extracts; D020011:Protective Agents; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D017392:Thiobarbituric Acid Reactive Substances; D014527:Uric Acid; C110936:Havcr1 protein, rat; C029569:diacetyldichlorofluorescein; C004497:bisabolol
keywords: (−)-α-Bisabolol; Acute kidney injury; Ischemia/reperfusion; KIM-1