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)‑κB p65 into the cytosol. Thus, aminoguanidine prevented β‑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.

Effects of Aminoguanidine on Apoptosis in the Hippocampus and Memory Disorder in a Rat Model of Alzheimer’s Disease

“…Amg is a free radical scavenger that could inhibit AGEs and protect against oxidative injury in the brain (11,17,19). Zhang et al demonstrated that the neuroprotective effects of Amg can be attributed to the capability to reduce Aβ level and anti-AGEs activity (22).…”

“…Nitric oxide and ROS cause neuroinflammation and can lead to neurodegenerative diseases (13-16). Inducible nitric oxide synthase (iNOS) overexpression and increased NO levels are in-volved in AD pathophysiology (17)(18)(19)(20). It is suggested that the inhibition of iNOS may effectively improve AD (13, 17).…”

“…It is suggested that the inhibition of iNOS may effectively improve AD (13, 17). Amino guanidine (Amg) has several biological activities such as oxidative stress inhibition, inflammation suppression, iNOS inhibition, and neurodegeneration reduction (9,(17)(18)(19). Nitric oxide overproduction can be partly responsible for some neurodegenerative damages in AD (9, 13).…”

“…iNOS inhibitors improve spatial memory through their modulatory role (16-19). Chen et al demonstrated that Amg by reducing the expression levels of ROS, NO, iNOS, and cyclooxygenase-2 (COX-2) prevented Aβ-induced AD (19). Amg can reverse the dysfunction of the cholinergic system and improve spatial memory by its modulatory role (21).…”

Aminoguanidine ameliorates ovariectomy-induced neuronal deficits in rats by inhibiting AGE-mediated Aβ production

“…AG is considered to have diverse pharmacological activities, such as the ability to repair tissue damage, prevent brain injury and stroke, and improve spinal cord motor function (Pearse et al, 2003;Di et al, 2008). It also inhibits Aβ-induced nuclear factor (NF)-κB p65 from translocating into the cytosol and prevents Aβ-induced neurological disorders through reducing the expression of iNOS and Cyclooxygenase-2 (COX-2) and inactivating NF-κB (Chen et al, 2017). To summarize, due to the anti-inflammatory and neuromodulatory advantages of AG, we considered it worthwhile to investigate the effects of AG on oestrogen deficiency-induced learning and cognitive impairment and Aβ production mediated by AGEs, which have not yet been reported.…”