Gliclazide does not fully prevent 2-deoxy-D-ribose-induced oxidative damage because it does not restore glutathione content in a pancreatic β-cell line.
We compared the effects of gliclazide, an antidiabetic agent with antioxidant properties, and N-acetyl-L-cysteine (NAC), a glutathione precursor, in protecting against 2-deoxy-D-ribose- (dRib-) induced oxidative damage in HIT-T15 cells. Using trypan blue staining and flow cytometry with annexin V/PI staining, gliclazide treatment slightly reversed dRib-induced cell death and apoptosis, and NAC treatment markedly reduced both measures. Likewise, flow cytometry using DHR 123 staining showed that the levels of dRib-induced reactive oxygen species (ROS) were partially suppressed by gliclazide and completely inhibited by NAC. Using electron spin resonance spectrometry, gliclazide and NAC scavenged hydroxyl radicals generated by Fenton reaction to a similar degree in a cell-free system. NAC, but not gliclazide, completely restored the intracellular glutathione depleted by dRib using monochlorobimane fluorescence and glutathione assays. Thus, gliclazide treatment suppressed dRib-induced oxidative damage in HIT-T15 cells less than NAC did because gliclazide did not restore the intracellular glutathione content as effectively as NAC. In addition, the elevation of intracellular glutathione rather than free radical scavenging might be an important mechanism for protecting against dRib-induced oxidative damage in a β-cell line.
Department of Internal Medicine, Jeju National University School of Medicine, 66 Jejudaehakno, Jeju 690-756, Republic of Korea. okdom@medimail.co.kr
Gwanpyo
G
Koh
Min-Kyoung
MK
Kim
Eun-Jin
EJ
Yang
Dae-Ho
DH
Lee
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003855:Deoxyribose / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D005907:Gliclazide / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
D007004:Hypoglycemic Agents; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D003855:Deoxyribose; D005907:Gliclazide; D005978:Glutathione; D000111:Acetylcysteine