Gadolinium Accumulation and Fibrosis in the Liver after Administration of Gadoxetate Disodium in a Rat Model of Active Hepatic Fibrosis

Abstract

To evaluate the effect of gadoxetate disodium on fibrosis in a rat model of active hepatic fibrosis. The local committee for animal research approved this study. Hepatic fibrosis was induced during 12 weeks of intraperitoneal injection of carbon tetrachloride (CCl(4)). Gadoxetate disodium was administered at 10 mmol/kg for 5 consecutive days starting after the final dose of CCl(4) (clinical dose of gadoxetate disodium is 0.25 mmol/kg). Three groups of Sprague-Dawley rats were studied. Group 1 consisted of six rats treated only with gadoxetate disodium, group 2 consisted of nine rats treated only with CCl(4), and group 3 consisted of nine rats treated with both gadoxetate disodium and CCl(4). Seven days after the final injection of gadoxetate disodium, the rats were sacrificed, and histologic findings and gadolinium deposition in the liver were examined. Fibrosis stage and gadolinium deposition were compared by using the Mann-Whitney test and Student t test. Fibrosis grading in groups 2 and 3 did not differ significantly (mean Batts-Ludwig fibrosis stage in group 2 was 2.67 and in group 3 was 2.78, P = .70; mean Ishak fibrosis stage in group 2 was 3.89 and in group 3 was 4.11, P = .71). Gadolinium deposition in the liver was slightly increased in group 3 in comparison to group 1 (3.2 ppm versus 4.0 ppm, P = .01), although this reversed when corrected as a percentage of total injected dose (0.022% versus 0.017%, P = .003). The high-dose administration of gadoxetate disodium in the setting of active hepatic fibrosis was not associated with increased fibrosis, suggesting that gadoxetate disodium does not incite a nephrogenic systemic fibrosis-like fibrotic change in the setting of active hepatic inflammation.