title: Evaluation of KIM-1 and NGAL as Early Indicators for Assessment of Gentamycin-Induced Nephrotoxicity In Vivo and In Vitro.
abstract: OBJECTIVE
  The aminolycoside Gentamicin is a widely used antibiotic, applied in equine medicine. Despite its clinical use, concerns remain regarding the potential toxic side-effects, such as nephrotoxicity. Early detection of renal damage is critical in preclinical drug development. This study was aimed to determine whether kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) may be early indicators in the assessment of Gentamycin-induced nephrotoxicity.
  
  
  METHODS
  In our study, a model of Gentamicin-induced nephrotoxicity in male Sprague Dawley rats treated for up to 7 days at 50 or 100mg/kg/day was used to monitor the expressions of novel biomarkers of renal toxicity during the progression of acute kidney injury (AKI). Additionally, biomarkers were assessed in human kidney proximal epithelial cells (HK-2) treated with Gentamicin for 2, 6, 12, 24, 36 or 48h in vitro.
  
  
  RESULTS
  Repeated administration of Gentamicin to rats for 1, 3, or 7 days resulted in a dose- and time-dependent increase in the expression of KIM-1 and NGAL. The expressions of the two biomarkers changed prior to renal tubule damage and increases in serum creatinine (SCr) and blood urea nitrogen (BUN) levels, suggesting their usefulness for predicting Gentamicin-induced acute kidney injury (AKI) in vivo.
  
  
  CONCLUSIONS
  In contrast, no significant increase in the expression of the biomarker genes and proteins were evident in HK-2 cells after treated by Gentamycin for up to 48h, suggesting that they may not be suitable endpoints for sensitive detection of nephrotoxic effects in vitro.
authors.affiliation: Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
authors.forename: Qi-Hui
authors.initials: QH
authors.lastname: Luo
authors.forename: Meng-Lu
authors.initials: ML
authors.lastname: Chen
authors.forename: Zheng-Li
authors.initials: ZL
authors.lastname: Chen
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.forename: An-Chun
authors.initials: AC
authors.lastname: Cheng
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.forename: Yi
authors.initials: Y
authors.lastname: Geng
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000139:chemically induced / Q000175:diagnosis; D000209:Acute-Phase Proteins; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015815:Cell Adhesion Molecules / Q000097:blood*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D005839:Gentamicins / Q000633:toxicity; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D005839:Gentamicins; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; C110936:Havcr1 protein, rat; C097278:Lcn2 protein, rat