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.