Experimental verification of age-dependent cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced computed tomography.
OBJECTIVE
The aim of this study was to investigate age-dependent cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced computed tomography (DCE-CT).


METHODS
The DCE-CT studies were performed in 23 rats aged 4 weeks (n = 6), 6 weeks (n = 6), 8 weeks (n = 6), and 24 weeks (n = 5) on days 0, 2, 4, and 7. The rats were given intraperitoneally cisplatin 3.6 mg/kg body weight (BW) on day 0. The contrast clearance per unit renal volume (K (1)) was estimated using the Patlak model, and that of the entire kidney (K) was obtained by multiplying K(1) by the renal volume (V).


RESULTS
On day 0, the K(1) value increased up to 8 weeks and dropped thereafter. The V and K values increased with age. The K value per unit BW was maximum at 4 weeks, remained relatively unchanged between 6 and 8 weeks, and dropped thereafter. The BW, K(1), and K values normalized by those on day 0 became lower in old rats than in young ones, and the differences among rats of different ages became greater with days after cisplatin injection, indicating that the cisplatin-induced nephrotoxicity becomes more severe with age.


CONCLUSIONS
This study demonstrated the existence of age-dependent difference in cisplatin-induced nephrotoxicity in rats.
Tachibana
Atsushi
A
Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Nagasawa
Ayumu
A
Kitamura
Akihiro
A
Miyazaki
Shohei
S
Murase
Kenya
K
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003287:Contrast Media; D004195:Disease Models, Animal; D007479:Iopamidol; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D009929:Organ Size; D011856:Radiographic Image Enhancement / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014057:Tomography, X-Ray Computed / Q000379:methods*
D000970:Antineoplastic Agents; D003287:Contrast Media; D007479:Iopamidol; D002945:Cisplatin