title: Evaluation of colistin nephrotoxicity administered at different doses in the rat model.
abstract: OBJECTIVE
  This study evaluated the usefulness of plasma Cystatin C (pCysC) along with urinary neutrophil gelatinase-associated lipocalin (NGAL), γ-glutamyltransferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate (AST) and alanine (ALT) aminotransferase to monitor colistin nephrotoxicity.
  
  
  METHODS
  Male rats were given intramuscular (i.m.) injections of colistin in doses of 150,000 (G1), 300,000 (G2) and 450,000 IU/kg/day (G3) or normal saline (Control), every 12 h for 7 days. After the 14th injection, animals were placed in metabolic cages and urine samples were collected in the next 12 h. Thereafter, animals were euthanized, blood samples were collected and kidneys were removed for histological assessment.
  
  
  RESULTS
  Nephrotoxicity was completely dose-dependent according to pathologic findings. The major insults were acute tubular necrosis in the tubules of G3. No significant change in pCr was observed in all treated groups, but pCysC increased in the G3 compared to the control. In urinary markers, uNGAL level showed a dose dependant increase with significant change in the G2 and G3 groups compared to the control. However, there was no significant change in the AST, ALT, LDH or ALP activities but only GGT increased in the G3 compared to the control.
  
  
  CONCLUSIONS
  Based on colistin doses used in our experimental study on rat model, histopathologic assessment remains the most accurate way to diagnose colistin nephrotoxicity. pCysC appears to be more reliable than pCr, and uNGAL seems to be the most sensitive factor of colistin nephrotoxicity.
authors.affiliation: Laboratory of Pharmacology, Faculty of Medicine, University of Sfax, Tunisia. ghlissi_zohra@yahoo.fr
authors.forename: Zohra
authors.initials: Z
authors.lastname: Ghlissi
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hakim
authors.forename: Hela
authors.initials: H
authors.lastname: Mnif
authors.forename: Fatma Makni
authors.initials: FM
authors.lastname: Ayadi
authors.forename: Khaled
authors.initials: K
authors.lastname: Zeghal
authors.forename: Tarak
authors.initials: T
authors.lastname: Rebai
authors.forename: Zouheir
authors.initials: Z
authors.lastname: Sahnoun
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001224:Aspartic Acid / Q000378:metabolism; D003091:Colistin / Q000008:administration & dosage* / Q000009:adverse effects*; D055316:Cystatin C / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007674:Kidney Diseases / Q000139:chemically induced* / Q000175:diagnosis* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism; D008297:Male; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D000900:Anti-Bacterial Agents; D055316:Cystatin C; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D001224:Aspartic Acid; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D003091:Colistin