[Nephrotoxicity of high- and low-osmolar contrast media: Protective role of fosinopril or telmisartan in a rat model].
OBJECTIVE
To compare the nephrotoxicity of high- and low-osmolar contrast media (HOCM and LOCM), and to determine the protective role of fosinopril or telmisartan and its possible mechanism.


METHODS
Forty eight healthy SD rats were randomly divided into 6 groups: a normal control group, a glycerol control group, a low-osmolar contrast media (LOCM) group, a high-osmolar contrast media (HOCM) group, a fosinopril group, and a telmisartan group. Glycerine for inducing kidney damage was given to all rats except the normal control group. Twenty-four hours after the injection of glycerine, the mixed fosinopril suspension (10mg/kg) or telmisartan (5mg/kg) was poured into the stomach in the preventive group. Serum creatinine (SCr) and plasma angiotensin II (AngII) levels were detected by an automatical biochemical analyzer and radioimmunoassay; caspase-3 activity and claudin-1 expression of the renal tissue were detected by fluorometric method and immunohistochemical method. The renal injury was assessed by hematoxylin and eosin (HE) staining and terminal deoxynucleotide mediated nick and labeling (TUNEL) staining, respectively.


RESULTS
In diatrizoate-injected rats, SCr and AngII levels were increased (P<0.05). Expression of claudin-1 protein and caspase-3 activity in the renal tissue was upregulated. The histologic changes and percentage of apoptotic cells were milder in the LOCM rats than those in the HOCM rats. In the group pretreated with fosinopril or telmisartan, no increase in the levels of SCr and AngII was discovered. The expression of claudin-1 protein and caspase-3 activity was significantly lower than that in the HOCM group. The renal injuries induced by diatrizoate were alleviated.


CONCLUSIONS
Both HOCM and LOCM could cause cellular apoptosis in the kidney.LOCM was less toxic to rat kidney than HOCM. Nephrotoxicity induced by HOCM might be related to caspase-3, claudin-1 and AngII. Fosinopril or telmisartan may protect the renal tissue from nephrotoxicity induced by diatrizoate.
Duan
Shao-bin
SB
Department of Nephrology, Second Xiangya Hospital of Central South University, Changsha 410011, China.
Zou
Qin
Q
Li
Ying-juan
YJ
Peng
You-ming
YM
Liu
Fu-you
FY
Wang
Yu-hui
YH
Xu
Xiang-qing
XQ
Jiang
Wen-ling
WL
Liu
Ying-hong
YH
Li
Jun
J
D000804:Angiotensin II / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D062445:Claudin-1 / Q000378:metabolism; D003287:Contrast Media / Q000008:administration & dosage / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D005260:Female; D017328:Fosinopril / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077333:Telmisartan
D001562:Benzimidazoles; D001565:Benzoates; D062445:Claudin-1; C568114:Cldn1 protein, rat; D003287:Contrast Media; D020011:Protective Agents; D000804:Angiotensin II; D003404:Creatinine; C505410:Casp3 protein, rat; D053148:Caspase 3; D017328:Fosinopril; D000077333:Telmisartan