3,4-Dihydroxyphenylethanol alleviates early brain injury by modulating oxidative stress and Akt and nuclear factor-κB pathways in a rat model of subarachnoid hemorrhage

Abstract

Abstract. 3,4-Dihydroxyphenylethanol (DOPET) is a naturally occurring polyphenolic compound, present in olive oil and in the wastewater generated during olive oil processing. DOPET has various biological and pharmacological activities, including anticancer, antibacterial and anti-inflammatory effects. This study was designed to determine whether DOPET alleviates early brain injury (EBI) associated with subarachnoid hemorrhage (SAH) through suppression of oxidative stress and Akt and nuclear factor (NF)-κB pathways. Rats were randomly divided into the following groups: Sham group, SAH group, SAH + vehicle group and SAH + DOPET group. Mortality, blood-brain barrier (BBB) permeability and brain water content were assessed. Oxidative stress, Akt, NF-κB p65 and caspase-3 assays were also performed. DOPET induced a reduction in brain water content, and decreased the BBB permeability of SAH model rats. Furthermore, DOPET effectively controlled oxidative stress, NF-κB p65 and caspase-3 levels, in addition to significantly increasing Akt levels in the cortex following SAH. These results provide evidence that DOPET attenuates apoptosis in a rat SAH model through modulating oxidative stress and Akt and NF-κB signaling pathways.

Modulation of LPS-induced nitric oxide production in intestinal cells by hydroxytyrosol and tyrosol metabolites: Insight into the mechanism of action

“…Indeed, Caco-2 cells treated with LPS showed a significant increase in Akt phosphorylation, in accordance to Xiong et al (2015). However, pretreatment with the tested phenolic compounds did not exert in our experimental conditions any effect on Akt phosphorylation, contrary to what demonstrated in hepatocellular carcinoma (Zhao et al, 2014), and neuronal cells (Fu and Hu, 2016) treated with HT. Beyond the Akt-induced IKK activation, LPS is known to induce IĸB phosphorylation also through the activation of kinases such as MAPK p38, JNK, and ERK1/2, all of which are involved in activating key transcription factors, including NF-ĸB (Murakami et al, 2009).…”

Fluoxetine is Neuroprotective in Early Brain Injury via its Anti-inflammatory and Anti-apoptotic Effects in a Rat Experimental Subarachnoid Hemorrhage Model

“…evidence for oxidative stress in SAH rat models, including high levels of oxidative nucleic acid damage, protein oxidation, and lipid peroxidation [22][23][24][25]. Fluoxetine is known to inhibit microglia-derived oxidative stress damage in a Parkinson's disease model [26].…”

Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice

“…These redox-mediated protective effects of HT are complemented by reductions in SREBP-1c expression, mitochondrial abnormalities, and apoptosis [ 19 ], besides diminution of ER stress induced by tunicamycin in human liver cells [ 62 ], with suppression of cell growth in human hepatocellular carcinoma cells via inactivation of AKT and nuclear factor-κB (NF-κB) pathways [ 63 ]. The protective effects of HT are not restricted to the liver as this polyphenol relieves brain damage produced by subarachnoid hemorrhage in rats by preventing oxidative stress and reducing the activity of NF-κB [ 64 ], effects that are also evident in the prevention of neuronal damage induced by dopamine and 6-hydroxydopamine through an enhanced expression of phase II-detoxification enzymes such as NADPH quinone oxidoreductase 1 [ 65 ].…”