Serofendic acid protects from iodinated contrast medium and high glucose probably against superoxide production in LLC-PK1 cells.
BACKGROUND
It is well known that patients with chronic kidney disease, including diabetic nephropathy, often develop cardiovascular diseases. In case of radiographic procedures, reduced renal function may be deteriorated by the use of iodinated contrast medium (CM). This is known as CM-induced nephropathy. In this study, we have focused on the mechanisms of this type of injury in diabetic nephropathy and the preventive effects of serofendic acid.


METHODS
We evaluated the cytotoxicity of CM and high glucose on tubular epithelial cells using an LLC-PK1 cell line, and measured cell viability with an alamarBlue assay. We further evaluated superoxide production levels measured by dihydroethidium. We also examined the protective effects of serofendic acid on cytotoxicity with superoxide production of CM and high glucose.


RESULTS
CM reduced cell numbers in a dose-dependent and time-dependent manner in LLC-PK1 cells. Furthermore, cytotoxicity of CM in diluted concentration was additively influenced by high glucose. CM and high glucose increased superoxide production, which was evaluated by the response to dihydroethidium, and was suppressed by serofendic acid. Cytotoxicity of CM, high glucose, and H(2)O(2) was suppressed by serofendic acid, as well as the suppression by N-acetylcysteine on CM toxicity. Interestingly, the recovery by serofendic acid in H(2)O(2)- and high glucose-induced cellular injury was to the basal level, in contrast with the partial recovery from CM-induced injury. Finally, serofendic acid suppressed CM-induced injury and high glucose-induced apoptosis.


CONCLUSIONS
These results suggest that CM and high glucose induce cytotoxicity and oxidative stress in LLC-PK1 cells and that serofendic acid protects the injury probably from superoxide generation.
Kitamura
Osamu
O
Division of Molecular Medicine, University of Shizuoka School of Pharmaceutical Sciences, Shizuoka, Japan.
Uemura
Kazuhide
K
Kitamura
Hisayo
H
Sugimoto
Hachiro
H
Akaike
Akinori
A
Ono
Takahiko
T
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000633:toxicity*; D019610:Cytoprotection; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000633:toxicity; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018374:LLC-PK1 Cells; D018384:Oxidative Stress / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism*; D013552:Swine; D013997:Time Factors; D014283:Triiodobenzoic Acids / Q000633:toxicity*
D000975:Antioxidants; D003287:Contrast Media; D004224:Diterpenes; D014283:Triiodobenzoic Acids; C452642:serofendic acid; D013481:Superoxides; D006861:Hydrogen Peroxide; D005947:Glucose; D000111:Acetylcysteine