N-3 PUFA Prevent Oxidative Stress in a Rat Model of Beta-Amyloid-Induced Toxicity

Abstract

Polyunsaturated fatty acids (PUFA) are involved in brain disorders associated to amyloid beta (Aβ) toxicity for which oxidative stress, neurochemical dysfunctions, and neuroinflammation are underlying mechanisms. Here, mechanisms through which lifelong exposure to n-3 PUFA-enriched or n-6/n-3 balanced diets could elicit a protective role in a rat model of Aβ-induced toxicity were investigated. To this aim, we quantified hippocampal reactive oxygen species (ROS) amount, 8-hydroxy-2′-deoxyguanosine and interleukin-10 levels, NADPH oxidase (NOX) 1, NOX2, superoxide dismutase 1, and glutathione contents, as well as plasmatic malondialdehyde. Moreover, in the same experimental groups, we assessed tryptophan, serotonin, and its turnover, kynurenine, and noradrenaline amounts. Results showed increased hippocampal ROS and NOX2 levels, serotonin turnover, kynurenine, and noradrenaline contents in Aβ-treated rats. Both n-6/n-3 balanced and n-3 PUFA enriched diets reduced ROS production, NOX1 and malondialdehyde levels, serotonin turnover, and kynurenine amount in Aβ-injected rats, while increasing NOX2, superoxide dismutase 1, and serotonin contents. No differences in plasmatic coenzyme Q10, reduced glutathione (GSH) and tryptophan levels were detected among different experimental groups, whereas GSH + oxidized glutathione (GSSG) levels were increased in sham animals fed with n-3 PUFA enriched diet and in Aβ-treated rats exposed to both n-6/n-3 balanced and n-3 enriched diets. In addition, Aβ-induced decrease of interleukin-10 levels was prevented by n-6/n-3 PUFA balanced diet. N-3 PUFA enriched diet further increased interleukin-10 and 8-hydroxy-2′-deoxyguanosine levels. In conclusion, our data highlight the possible neuroprotective role of n-3 PUFA in perturbation of oxidative equilibrium induced by Aβ-administration.

Precision Medicine in Alzheimer’s Disease: Investigating Comorbid Common Biological Substrates in the Rat Model of Amyloid Beta-Induced Toxicity

“…Furthermore, it has been shown that expression of COX-2 as well as prostaglandin E2, can be enhanced after phosphorylation of MAPKs and NF-κB induced by oxidative stress ( Onodera et al, 2015 ). In our experience, we have found that Aβ-induced toxicity is also occurring through the increased oxidative biomarker production and NF-κB expression ( Morgese et al, 2021a ; Morgese et al, 2021b ), therefore we can speculate that alterations in oxidative and inflammatory status migh represent putative factors that predispose Aβ-treated rats to increased mechanical pain susceptibility.…”

“…Furthermore, MEL was shown to suppressed NF-κB, an ubiquitary located transcriptional effector of inflammatory mediators, whose activation lead to higher prostaglandin and nitric oxide levels contributing to the development of hyperalgesia ( Petho and Reeh, 2012 ). In this regard, we have very recently shown, in mice, that the icv injection of Aβ led to increased expression of this factor ( Morgese et al, 2021b ). In addition, MEL can prevent IL-6 release NF-κB-induced in Aβ-treated brain slices ( Lau et al, 2012 ) and memory loss secondary to NF-κB activation ( Shen et al, 2007 ).…”

“…An electrochemical detector with a thin-layer amperometric cell (Ultimate 3000RS–ECD, Dionex, ThermoScientifics, Milan, Italy) at a working potential of 0.400 V was used. As previously described, KYN ( Morgese et al, 2021b ) and MEL were quantified with the same method by applying a working potential of 0.550 V. The flow rate was maintained at 0.7 ml/min by an isocratic pump (Shimadzu LC-10 AD, Kyoto, Japan). The mobile phase consisted of an aqueous solution of 75 mM NaH 2 PO 4 , 1.7 mM octane sulfonic acid, 0.3 mM EDTA, acetonitrile 10%, buffered at pH 3.0.…”

Dietary Antarctic Krill Oil Enhances the Oral Bioavailability of Nobiletin but Has No Ideal Synergistic Effect on Improving Memory and Cognition Ability in Aβ1–42 Induced Rats

“…MDA is an important production of lipid peroxide, which is often used to reflect the degree of lipid peroxidation process in tissue. [35] Regards to antioxidative system, superoxide dismutase enzyme (SOD), and GSH exert a crucial effect on hampering pathogenesis of AD via scavenging free radicals. [34,6] Our results demonstrated that the combination of AKO and Nob appeared to reduce the oxidative stress level via a mutual promotion manner.…”

The Therapeutic Potential of Celastrol in Central Nervous System Disorders: Highlights from In Vitro and In Vivo Approaches

“…Furthermore, celastrol might result useful also in other type of disorders comorbid with depression such as Alzheimer’s disease or in animal model of Aβ-induced depressive like phenotype [ 61 ]. Indeed, antioxidant treatments were found to positively reduce depressive behavior in this animal model [ 62 , 63 ]. In good agreement, celastrol was found to be able to affect beta-amyloid production in transgenic Alzheimer’s disease models interacting with BACE-1 through a NF-kB dependent mechanism [ 32 ].…”