<p>Agomelatine Attenuates Isoflurane-Induced Inflammation and Damage in Brain Endothelial Cells</p>

Abstract

Background and Purpose Neurotoxicity of anesthetics has been widely observed by clinicians. It is reported that inflammation and oxidative stress are involved in the pathological process. In the present study, we aimed to assess the therapeutic effects of agomelatine against isoflurane-induced inflammation and damage to brain endothelial cells. Materials and Methods MTT assay was used to detect cell viability in order to determine the optimized concentration of agomelatine. The bEnd.3 brain endothelial cells were treated with 2% isoflurane in the presence or absence of agomelatine (5, 10 μM) for 24 h. LDH release was evaluated and the ROS levels were checked using DHE staining assay. The expressions of IL-6, IL-8, TNF-α, VEGF, TF, VCAM-1, and ICAM-1 were evaluated using real-time PCR and ELISA. Real-time PCR and Western blot analysis were used to determine the expression level of Egr-1. Results The decreased cell viability promoted LDH release and elevated ROS levels induced by isoflurane were significantly reversed by the introduction of agomelatine in a dose-dependent manner. The expression levels of IL-6, IL-8, TNF-α, VEGF, TF, VCAM-1, and ICAM-1 were elevated by stimulation with isoflurane, which were significantly suppressed by the administration of agomelatine. The up-regulation of transcriptional factor Egr-1 induced by isoflurane was down-regulated by agomelatine. Conclusion Agomelatine might attenuate isoflurane-induced inflammation and damage via down-regulating Egr-1 in brain endothelial cells.

Effects of Long Noncoding RNA H19 on Isoflurane-Induced Cognitive Dysregulation by Promoting Neuroinflammation

“…Anesthetics can also promote the release of inflammatory cytokines. ISO causes the accumulation of several inflammatory regulators, such as TNF-α [26]. Our conclusion also identified this point by that ISO increased the concentration of TNF-α, IL-6, and IL-1β.…”

“…As a new type of inhalation anesthetic, ISO is widely used in clinical surgery because of its high safety and controllability [26]. In recent years, it has been found that ISO is potentially harmful to the brain of developing mammals by producing persistent neurocognitive dysfunction after ISO anesthesia [27].…”

Agomelatine Prevents Amyloid Plaque Deposition, Tau Phosphorylation, and Neuroinflammation in APP/PS1 Mice

“…Then, the anti-inflammatory activity of agomelatine was studied. The previous report revealed that agomelatine intervention could alleviate isoflurane-induced inflammation by decreasing the level of IL-6, IL-8, TNF-α, VCAM-1, and ICAM-1 in brain endothelial cells ( Cheng et al, 2020 ). Hans O. Kalkman also indicated that agomelatine suppressed inflammation and M1-microglial polarization via modulating IGF1 expression ( Kalkman and Feuerbach, 2016 ).…”

“…Our previous study also found that after agomelatine intervention, tau protein hyperphosphorylation and oxidative injury obviously decreased in Aβ 25–35 -treated BV-2 cells ( Yao et al, 2019 ). Besides, some recent studies suggested that agomelatine may exert anti-inflammatory properties in vitro and in vivo ( Cheng et al, 2020 ; Savran et al, 2020 ). Although less evidence has focused on the effect of agomelatine in AD therapy, there are also limitations.…”

Neuroprotective Effect of Dioscin against Parkinson’s Disease via Adjusting Dual-Specificity Phosphatase 6 (DUSP6)-Mediated Oxidative Stress

“…After 12 h, the cells were given the different concentrations of dioscin (0, 72, 145, 290, 580 and 1160 nM) under 6, 12 and 24 htreatment. Cell viabilities were conducted by MTT method as described above and a suitable concentration of dioscin was optimized [ 34 ].…”