Aminoguanidine exhibits an inhibitory effect on β-amyloid-induced damage in F98 glioma cells

Abstract

The present study investigated the role of aminoguanidine in the prevention of harmful effects in astroglioma F98 cells induced by β-amyloid treatment. MTT assay was used to analyze cell viability. Expression of inducible nitric oxide synthase (iNOS) was analyzed using western blot analysis. Treatment of the F98 cells with a 15 μM concentration of β-amyloid for 12 h reduced cell viability to 18% compared with the control cells. However, pretreatment with a 30 μM concentration of aminoguanidine for 12 h completely prevented the β-amyloid-induced reduction in cell viability. The production of ROS and the expression of iNOS were significantly (P<0.005) higher in the β-amyloid-treated F98 cells. Aminoguanidine pre-treatment inhibited the β-amyloid-induced increase in the expression of ROS, with increased mRNA and proteins levels of iNOS12 h following treatment at a 30 μM concentration. The β-amyloid treatment also resulted in a marked increase in the expression of cyclooxygenase-2 (COX-2) in F98 cells. By contrast, pre-treatment with aminoguanidine for 12 h led to reduction in the mRNA and protein expression levels of COX-2. Pre-treatment of the F98 cells with aminoguanidine at a 30 μM concentration for 12 h prior to incubation with β-amyloid significantly (P<0.002) reduced the expression of prostaglandin E2 (PGE2). Aminoguanidine pre-treatment also caused the inhibition of β-amyloid-induced translocation of nuclear factor (NF)-β B p65 into the cytosol. Thus, aminoguanidine prevented-amyloid-induced Alzheimer's disease through reductions in the expression levels of NO, iNOS, PGE2 and COX-2, and the inactivation of NF-κB. Therefore, aminoguanidine offers potential for use in the treatment of neurological disorders, including Alzheimer's disease.