Protective effect of grape seed polyphenols against high glucose-induced oxidative stress.
We aimed to clarify whether grape seed polyphenols (GSPs) are candidates therapeutic agents against diabetes mellitus, and to determine what degree of GSP oligomerization has the most potent efficacy. We studied the protective effects of various molecular weight GSPs (monomer, oligomer, polymer, and oligonol) on high glucose-induced cytotoxicity. In the present study, a high concentration of glucose (30 mM) induced cytotoxicity and oxidative stress (reactive oxygen species and nitric oxide) in cultured LLC-PK1 cells, but treatment with GSPs, especially oligomer GSPs, had potent protective effects against high glucose-induced oxidative stress. In addition, high glucose induced nuclear translocation of nuclear factor-kappa B, and increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and bax, but GSP treatment inhibited them. These results indicate that GSPs have protective effects against high glucose-induced cytotoxicity, and among them, oligomer GSPs have more potent effects than other GSPs (monomer, polymer, and oligonol) on high glucose-induced renal cell damage.
Fujii
Hajime
H
Institute of Natural Medicine, University of Toyama.
Yokozawa
Takako
T
Kim
Young Ae
YA
Tohda
Chihiro
C
Nonaka
Gen-ichiro
G
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism / Q000517:prevention & control*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D021381:Protein Transport / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D005419:Flavonoids; D016328:NF-kappa B; D010636:Phenols; D059808:Polyphenols; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D005947:Glucose