The protective role of telmisartan against nephrotoxicity induced by X-ray contrast media in rat model.
BACKGROUND
Contrast-induced nephropathy is a serious complication of diagnostic and interventional procedures.


OBJECTIVE
To evaluate the nephrotoxicity of high- and low-osmolar contrast media (HOCM, LOCM) on kidneys in Sprague-Dawley rats. Telmisartan was administered to confirm its protective role against nephrotoxicity induced by contrast media.


METHODS
Sixty male rats were randomly divided into six groups (n=10/group). Glycerin was given to all rats except controls to induce renal injury. HOCM (diatrizoate) or LOCM (iohexol) (10 ml/kg b.w., 300 mg I/ml) was given through a caudal vein. Serum creatinine level was measured by an automatical biochemical analyzer. Caspase-3 activity and Angiotensin II (Ang II) level of renal tissue were detected by fluorometric method and radioimmunoassay, respectively. The renal injury was also assessed by hematoxylin and eosin and TdT-mediated deoxyuridine nick end-labeling staining.


RESULTS
In diatrizoate-injected rats, serum creatinine level was increased (P<0.001). There was no significant difference between iohexol animals and glycerol controls in the level of serum creatinine. The renal caspase-3 activity and Ang II levels in HOCM and LOCM groups were higher than those in glycerol control group (P<0.001). The percentage of apoptotic tubular cells and pathological scores were lower in the iohexol animals than that in the diatrizoate animals (P<0.001). In the groups pretreated with telmisartan, no increase in the levels of serum creatinine, renal Ang II, and caspase-3 activity was observed (P>0.05). The renal injuries induced by contrast media were alleviated.


CONCLUSIONS
Both HOCM (diatrizoate) and LOCM (iohexol) could cause renal tubular cell apoptosis in the kidneys damaged by glycerin. LOCM was less toxic to rat kidneys than HOCM. Caspase-3 and Ang II might play a role in renal tubular cell apoptosis induced by contrast media. Telmisartan protected the renal tissue from nephrotoxicity induced by contrast media.
Duan
Shao Bin
SB
Institute of Nephrology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China. DuanSB528@hotmail.com
Wang
Yu Hui
YH
Liu
Fu You
FY
Xu
Xiang Qing
XQ
Wang
Pian
P
Zou
Qin
Q
Peng
You Ming
YM
D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D003287:Contrast Media / Q000009:adverse effects* / Q000737:chemistry; D003404:Creatinine / Q000097:blood; D003973:Diatrizoate / Q000009:adverse effects* / Q000737:chemistry; D020287:In Situ Nick-End Labeling; D007472:Iohexol / Q000009:adverse effects* / Q000737:chemistry; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D009994:Osmolar Concentration; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077333:Telmisartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D003287:Contrast Media; D000804:Angiotensin II; D003973:Diatrizoate; D007472:Iohexol; D003404:Creatinine; D053148:Caspase 3; D000077333:Telmisartan