A modified model of gentamicin induced renal failure in rats: toxicological effects of the iodinated X-ray contrast media ioversol and potential usefulness for toxicological evaluation of iodinated X-ray contrast media.
Contrast-induced nephropathy (CIN) remains a serious complication in patients exposed to iodinated X-ray contrast media (ICM). Animal models of CIN are useful to further understand the mechanisms involved, identify novel biomarkers and evaluate potential differences between ICM. The current investigation was undertaken to modify the rat-gentamicin model for potential usefulness for toxicological evaluation of ICM. A dose-range finding study (50, 60 and 70 mg/kg body weight (bw)) of gentamicin was conducted over 4 consecutive days. Based on the kidney histopathology findings, a gentamicin dose of 70 mg/kg bw was chosen to investigate whether ICM would cause further renal damage. Following gentamicin treatment, this group was given a single administration of ioversol (6 gI/kg bw). Blood and urine samples were taken from all animals 3 days before the start of the study and at the end of treatment. Serum and urinary creatinine, urinary N-acetyl-β-D-glucosaminidase (NAG), γ-glutamyl transferase (GGT), total protein, and urine cytology were evaluated as biomarkers of renal damage. Histopathological examination of kidneys was performed. Histopathological examination of the kidneys revealed vacuolation, dilatation, and necrosis of the proximal tubules in the gentamicin-ioversol treatment group. These changes were not seen in the gentamicin-only treatment groups. Data on GGT and urinary epithelial cells show clear differences between rats treated with gentamicin alone versus gentamicin plus ioversol. These findings show that the modified rat-gentamicin model was able to demonstrate the nephrotoxic effect of ioversol.
GE Healthcare AS, Research Biology, Nycoveien 2, P.O. Box 4220, Nydalen, NO-0401 Oslo, Norway. hanne.jensen@nofima.no
Hanne
H
Jensen
Richard W
RW
Doughty
Derek
D
Grant
Oddvar
O
Myhre
D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000652:urine; D000818:Animals; D003287:Contrast Media / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005839:Gentamicins / Q000633:toxicity*; D007677:Kidney Function Tests; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014283:Triiodobenzoic Acids / Q000633:toxicity*
D003287:Contrast Media; D005839:Gentamicins; D014283:Triiodobenzoic Acids; C054871:ioversol