Ibuprofen targets neuronal pentraxins expresion and improves cognitive function in mouse model of AlCl3-induced neurotoxicity

Abstract

Abstract. Aluminum is known to exert neurotoxic effects associated with various neurodegenerative disorders, including Alzheimer's disease (AD). Ibuprofen is a well-known non-steroidal anti-inflammatory drug, which has demonstrated potential efficacy in the treatment of numerous inflammatory and neurodegenerative disorders, including AD. The present study aimed to investigate the protective effects of ibuprofen on cognitive function, and the expression levels of neuronal pentraxins (NPs) and interleukin (IL)-1β in an aluminum chloride (AlCl 3 )-induced mouse model of neurotoxicity. The effects of ibuprofen (100 mg/kg/day for 12 days) on learning and memory were evaluated in the AlCl 3 -induced neurotoxic mice using a Morris water maze and open field tests. In addition, ibuprofen was assessed for its effects on the expression levels of NPs and IL-1β in the hippocampus, cortex and amygdala of the brain. Treatment of the AlCl 3 -treated mice with ibuprofen decreased anxiety levels (6.90±0.34 min) compared with the AlCl 3 -treated group (1.80±0.29 min), as indicated by the time spent in the central area in an open field test. Furthermore, the expression levels of NP1 (1.32±0.47) and IL-1β (0.99±0.21) were significantly decreased in the hippocampus of mice following ibuprofen treatment, as compared with the AlCl 3 -treated mice (8.62±1.54 and 7.47±0.53, respectively). In the present study, ibuprofen was able to target novel structures in order to attenuate the inflammation associated with an AlCl 3 -induced mouse model of neurotoxicity; thus suggesting that ibuprofen may be considered a potential therapeutic option for the treatment of neurodegenerative diseases, including AD.

Ibuprofen alters epoxide hydrolase activity and epoxy-oxylipin metabolites associated with different metabolic pathways in murine livers

“…This study analyzed the effects of ibuprofen treatment on oxylipin metabolites. The ibuprofen dose used in this animal study was similar to concentrations used in previous studies 2 , 59 , 60 . The dose of 100 mg/kg/day of ibuprofen used in this study would correspond to a moderate daily dose of ibuprofen in humans.…”

Gender-specific changes in energy metabolism and protein degradation as major pathways affected in livers of mice treated with ibuprofen

“…The average water consumption by mice was measured to ensure that mice got the appropriate levels of ibuprofen. The ibuprofen dose used in this study was similar to the concentrations used in previous studies 1,14,15 . This dosage was chosen as it approximates to a human taking 486 mg/day which is between two to three dosages of 200 mg/day.…”

Molecular mechanisms of aluminum neurotoxicity: Update on adverse effects and therapeutic strategies

“…It is also notable that the use of synthetic prostaglandin E1 (PGE1) analogue, misoprostol, ameliorated Al-induced memory and learning dysfunction through modulation of PGES-PGE2-EP signaling pathway and decreasing PGE2, mPGES-1, EP2, and EP4 expression (Guo et al, 2016). AlCl 3 -exposed mice treated with COX inhibitor ibuprofen also demonstrated that Al toxicity is associated with hippocampal overexpression of neuronal pentraxin 1 (NP1) (Jamil et al, 2016) that is considered one of the key factors of Aβ-induced neurite loss and synaptic dysfunction (Abad et al, 2006).…”