Inhibition of H2O2-induced neuroblastoma cell cytotoxicity by a triazine derivative, AA3E2.
Alzheimer's disease is the major cause of senile dementia with the hallmark of beta-amyloid deposition in neurons. Although the main cause(s) of this deposition is not fully understood, however, the wealth of the present literature data supports the pivotal role of reactive oxygen and nitrogen species in both the initiation and progression of beta-amyloid aggregation and deposition. In the present study, we were interested to evaluate the free-radical protecting effect of AA3E2, a triazine derivative with a beta-amyloid-breaking activity, among SK-N-MC neuroblastoma cells exposed to hydrogen peroxide (H(2)O(2)) as an exogenous source of free radicals. Exposure of the cells to different doses of AA3E2 (1-16 microM) for 3h followed by subsequent exposure to a single dose of H(2)O(2) (mainly 150 microM) attenuated the extent of superoxide dismutase (SOD) and catalase (CAT) inhibition by H(2)O(2), in a dose dependent manner. Furthermore, significant reduction was observed in the extent of cellular lactate dehydrogenase release, intracellular ROS and the extent of apoptosis among the cells pre-treated with AA3E2. Based on these data, an antioxidant mode of action is proposed for AA3E2 besides its previously beta-amyloid-breaking activity.
Shaykhalishahi
Hamed
H
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Yazdanparast
Razieh
R
Ha
Hyung-Ho
HH
Chang
Young-Tae
YT
D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D061945:Caspase Inhibitors; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D009447:Neuroblastoma / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014227:Triazines / Q000378:metabolism / Q000494:pharmacology*
D000975:Antioxidants; D061945:Caspase Inhibitors; C545493:N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-N-butyl-6-decyl-1,3,5-triazine-2,4-diamine; D017382:Reactive Oxygen Species; D014227:Triazines; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase