TITLE:
Quantitative Assessment of Protective Effects of Antioxidant Agents against Drug-Induced Nephrotoxicity Using Dynamic Contrast-Enhanced Computed Tomography
AUTHORS:
Kenya Murase, Akihiro Kitamura, Atsushi Tachibana, Yoshinori Kusakabe, Risa Matsuura, Shohei Miyazaki
KEYWORDS:
Dynamic Contrast-Enhanced Computed Tomography, Drug-Induced Nephrotoxicity, Cisplatin, Glomerular Filtration Rate, Creatinine Clearance, Animal Experiments
JOURNAL NAME:
Open Journal of Medical Imaging,
Vol.6 No.3,
August
25,
2016
ABSTRACT: Purpose: The purpose of this study was to
develop a method for quantifying the extent of renal dysfunction due to
drug-induced nephrotoxicity using dynamic contrast-enhanced computed tomography
(DCE-CT) and to investigate the protective effects of various antioxidant
agents against cis-dichlorodiammineplatinum (cisplatin)-induced nephrotoxicity
in rats using this method. Materials and Methods: The DCE-CT studies were
performed in 8-week-old male Sprague-Dawley rats. The CT scanning started 4 s
before a bolus intravenous injection of iodinated contrast agent (CA) (150
mgI/kg) from the tail vein using an automatic injector and lasted 90 s at 1-s
intervals. The contrast clearance per unit renal volume (K1) was estimated from
the DCE-CT data using the Patlak model. The renal volume (V) was calculated by
manually delineating the kidney on the CT image. The contrast clearance of the
entire kid-ney (K) was obtained by . First, to investigate the effect of CA
itself, the DCE-CT studies were performed without injecting cisplatin 2, 4, and
7 days after the first DCE-CT study on day 0. Second, to investigate the effect
of injected dose of cisplatin, the DCE-CT study was performed after the
intraperitoneal (i.p.) injection of cisplatin (1.8 mg/kg) and was repeated every
other day for one week. Finally, to investigate the protective effects of
antioxidant agents [L-arginine (300 mg/kg), N-acetylcysteine (500 or 1000
mg/kg), methimazole (40 mg/kg), captopril (60 mg/kg), and taurine (750 mg/kg)],
the DCE-CT studies were performed on days 0, 2, 4, and 7 after the i.p.
injection of cisplatin (3.6 mg/kg). For comparison, the DCE-CT data were also
acquired without injecting the antioxidant agents (CDDP group). Results: When
cisplatin was not injected, there were no significant changes in the K value as
compared to that on day 0 within the studied period. The K valuesignificantly
(p