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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.

SUBMITTER: Milosevic K

PROVIDER: S-EPMC8998340 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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

Milosevic Katarina K Stevanovic Ivana I Bozic Iva D ID Milosevic Ana A Janjic Marija M MM Laketa Danijela D Bjelobaba Ivana I Lavrnja Irena I Savic Danijela D

International journal of molecular sciences 20220324 7

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 O<sub>2</sub><sup>-</sup> levels, arresting lipid p ...[more]

PMID: 35408922

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Project description:BackgroundDiabetic nephropathy (DN) is among the most common microvascular complications of diabetes resulting in end-stage renal disease and therefore search for candidates which can ameliorate the kidney function is needed simultaneously with standard diabetic pharmacotherapy. The current study was aimed to investigate the effect of long term sacubitril/valsartan therapy (LCZ696) in diabetic rats to assess its ameliorative impact against various pathological parameters such as oxidative stress, inflammation and glomerulosclerosis associated with chronic DN.MethodsA single dose (60 mg/kg/day) of STZ was used to induce type 1 diabetes in adult male wistar rats. 2 weeks after diabetes induction, these rats were treated orally with valsartan (31 mg/kg) or LCZ696 (68 mg/kg) for 6 weeks. At end of the treatment period, serum and kidney samples were collected and analyzed. The serum levels of glucose, insulin, urea, creatinine, TNF-α, IL-1β, IL-6 and IL-10 levels were estimated. In renal tissue homogenate, the levels of inflammatory markers such as TNF-α, IL-1β, IL-6, NF-kB along with oxidative stress biomarkers including thiobarbituric acid-reacting substances (TBARs), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) were assessed. Histological changes were observed in kidney.ResultsTime course therapy withLCZ696 and valsartan in diabetic rats resulted in significant reduction of serum glucose, urea and creatinine levels (P < 0.05). Additionally, serum of treated diabetic rats showed a diminution in inflammatory (TNF-α, IL-1β, IL-6) and increment in anti-inflammatory (IL-10) cytokines levels (P < 0.05). Tissue homogenate of the kidney extracted from LCZ696 and valsartan treated diabetic rats revealed a substantial reduction in the levels of inflammatory markers such as TNF-α, IL-1β, IL-6, NF-kB and sufficient restoration of anti-oxidant enzyme levels (P < 0.05). Finally, in the histological sections of the kidney, prevention of renal injury was observed with limited necrosis and inflammatory cells infiltration.ConclusionPresent data suggest that LCZ696 has sufficient therapeutic potential to restrict DN progression through inhibiting inflammation, oxidative stress and glomerulosclerosis.

Dataset Information

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

Publications

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

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