Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response

Abstract

Neuroinflammation and microglial activation, common components of most neurodegenerative diseases, can be imitated in vitro by challenging microglia cells with Lps. We here aimed to evaluate the effects of agmatine pretreatment on Lps-induced oxidative stress in a mouse microglial BV-2 cell line. Our findings show that agmatine suppresses nitrosative and oxidative burst in Lps-stimulated microglia by reducing iNOS and XO activity and decreasing O2− levels, arresting lipid peroxidation, increasing total glutathione content, and preserving GR and CAT activity. In accordance with these results, agmatine suppresses inflammatory NF-kB, and stimulates antioxidant Nrf2 pathway, resulting in decreased TNF, IL-1 beta, and IL-6 release, and reduced iNOS and COX-2 levels. Together with increased ARG1, CD206 and HO-1 levels, our results imply that, in inflammatory conditions, agmatine pushes microglia towards an anti-inflammatory phenotype. Interestingly, we also discovered that agmatine alone increases lipid peroxidation end product levels, induces Nrf2 activation, increases total glutathione content, and GPx activity. Thus, we hypothesize that some of the effects of agmatine, observed in activated microglia, may be mediated by induced oxidative stress and adaptive response, prior to Lps stimulation.

Epigallocatechin Gallate Protects against Hypoxia-Induced Inflammation in Microglia via NF-κB Suppression and Nrf-2/HO-1 Activation

“…Under normal conditions, Nrf-2 is localised in the cytoplasm and the nuclear translocation of Nrf-2 is inhibited by Keap1. However, under oxidative stress conditions, Nrf-2 is detached from Keap1 and translocated into the nucleus to regulate the expression of antioxidant proteins such as HO-1 [ 56 , 57 ]. Chronic inflammation has been reported in HO-1 deficient models [ 58 ].…”

Cholestasis-Associated Pulmonary Inflammation, Oxidative Stress, and Tissue Fibrosis: The Protective Role of the Biogenic Amine Agmatine

“…The accumulation of cytotoxic molecules such as hydrophobic bile acids and supraphysiological levels of bilirubin in the lung tissue is proposed to be involved in the pathogenesis of oxidative stress and lung injury in cholestasis [21]. The effects of the biogenic amine AGM on oxidative stress biomarkers are widely investigated in various experimental models [33,46,[73][74][75][76]. The direct radical scavenging properties of AGM have been mentioned in previous studies [77,78].…”

“…There are also reports of inflammatory cell infiltration in human cases of cholestasis-induced lung injury [21]. On the other hand, previous studies revealed that AGM acts as an excellent anti-inflammatory agent [46,50,[82][83][84][85][86][87]. A big part of the anti-inflammatory properties of AGM seems to be mediated through the inhibitory effects of this amine on the enzyme inducible nitric oxide synthase (iNOS) [84].…”

“…These data reveal that AGM has excellent protective properties against inflammatory response. The antiinflammatory effects of AGM seem to be mediated through inhibiting the secretion of cytokines from inflammatory cells and the suppression of the NFkB signaling as the primary pathway involved in the inflammatory response [45,46]. On the other hand, this neuro-amine could tremendously mitigate oxidative stress and neuronal damage with various pathologies [46][47][48][49].…”

“…The antiinflammatory effects of AGM seem to be mediated through inhibiting the secretion of cytokines from inflammatory cells and the suppression of the NFkB signaling as the primary pathway involved in the inflammatory response [45,46]. On the other hand, this neuro-amine could tremendously mitigate oxidative stress and neuronal damage with various pathologies [46][47][48][49]. These features make AGM an effective molecule against pathological conditions associated with inflammation and oxidative stress.…”