Effects of acetylcysteine and probucol on contrast medium-induced depression of intrinsic renal glutathione peroxidase activity in diabetic rats.
BACKGROUND
Antioxidants such as N-acetylcysteine and probucol have been used to protect patients from contrast media-induced nephrotoxicity. The mechanisms underlying these protective effects are not well understood. We hypothesized that acetylcysteine and probucol alter the activity of endogenous antioxidant enzyme activity.


METHODS
Four weeks after induction of diabetes with streptozotocin, diabetic and nondiabetic rats were divided into three groups. Group 1 rats did not receive any antioxidant agents. Group 2 rats were treated with acetylcysteine and group 3 rats with probucol for 1 week before injection of the contrast medium diatrizoate (DTZ).


RESULTS
We found that diabetic rats had higher renal glutathione peroxidase (GPx) activity than normal rats. DTZ suppressed renal GPx activity significantly in both group 1 diabetic and normal rats. Interestingly, renal GPx activity in both diabetic and normal rats pretreated with acetylcysteine or probucol was not inhibited by DTZ. Renal superoxide dismutase (SOD) increased significantly in normal rats after DTZ injection, but not in diabetic rats. Finally, acetylcysteine or probucol did not significantly influence renal SOD.


CONCLUSIONS
These findings suggest that the renal protective effects of acetylcysteine and probucol against contrast-induced oxidative stress and nephrotoxicity may be mediated by altering endogenous GPx activity.
Yen
Hsueh-Wei
HW
Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University, Chung-Ho Memorial Hospital, Kaohsiung, Taiwan.
Lee
Hsiang-Chun
HC
Lai
Wen-Te
WT
Sheu
Sheng-Hsiung
SH
D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D003287:Contrast Media / Q000009:adverse effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology; D003974:Diatrizoate Meglumine / Q000009:adverse effects*; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D005979:Glutathione Peroxidase / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009994:Osmolar Concentration; D011341:Probucol / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase
D000975:Antioxidants; D003287:Contrast Media; D016166:Free Radical Scavengers; D003974:Diatrizoate Meglumine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D011341:Probucol; D000111:Acetylcysteine