Oxidative Stress-related Inflammation Research Articles

Sufentanil-induced Nrf2 protein ameliorates cerebral ischemia-reperfusion injury through suppressing neural ferroptosis

As an oxidative stress and inflammation-related disease, cerebral ischemia-reperfusion injury (CIRI) is a prevalent pathogenic factor of ischemic stroke (IS) and seriously degrades the life quality of human beings. As an opioid analgesic for anesthesia, Sufentanil (SUF) can activate the Nrf2 protein-induced anti-oxidant effects, which indicate that SUF may be used as alternative drug for CIRI therapy, but little is known regarding to its molecular mechanisms. Thus, this research aimed to examine whether SUF pre-treatment alleviated CIRI through the modulation of Nrf2 protein-mediated antioxidant activity. Our research revealed that middle cerebral artery occlusion/reperfusion (MCAO/R)-treated rats exhibited apparent CIRI-related symptoms and induced damages in rats' brain, which were all notably mitigated in the MCAO/R rats. The subsequent in vitro cellular experiments verified that oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cytotoxicity were apparently reversed by SUF co-treatment in HT22 and BV2 cells, and it was also validated that SUF was capable of suppressing inflammation and ferroptosis in CIRI models by inhibiting oxidative stress-related damages. Mechanistically, the Akt/GSK-3β pathway was excessively activated by SUF to promote Nrf2 protein expressions and enhance Nrf2-meidated anti-oxidant effects, and it was found that SUF-induced protective effects during CIRI progression were all abrogated by co-treating cells with MK2206 (Akt inhibitor), NP-12 (GSK-3β inhibitor), or ML385 (Nrf2 inhibitor). In conclusion, SUF activated the Akt/GSK-3β pathway to initiate Nrf2 protein-mediated antioxidant effects, which further suppressed oxidative stress-related inflammation and ferroptosis to ameliorate CIRI progression, and SUF could potentially be used as novel therapeutic agent for CIRI treatment in clinic.

Structural characterization of Aspalatus linearis polysaccharide and its improving effect on acute alcoholic liver injury.

Polysaccharides from natural sources can regulate the composition of intestinal flora through the "gut-liver axis" pathway, potentially ameliorating alcoholic liver injury. Aspalathus linearis, also known as rooibos, is one such natural product that has shown promise in this regard. This study looked at the structural properties of A. linearis polysaccharide (ALP) and how well it would work to treat acute alcoholic liver impairment. This study looks at the composition of monosaccharides, functional groups, and molecular weight (Mw) of a newly discovered water-soluble polysaccharide, named ALP. The polysaccharide is composed of pyranose rings, amide groups, and sulfate groups linked by β-glycosidic linkage. It has a relative Mw of 4.30×103kDa and is composed of glucose, rhamnose, and some other monosaccharides. The study found that treating mice with the model of acute alcoholic liver disease with ALP could alleviate pathological symptoms, inhibit the release of inflammatory cytokines, and suppress indicators of oxidative stress. Experiments have shown that different doses of ALP can activate the P4502E1/Keap1-Nrf2-HO-1 signaling pathway. The regulation of inflammatory factors and downstream antioxidant enzymes occurs as a result. Based on these data, it is likely that ALP protects the liver via the "gut-liver axis" pathway by reducing oxidative stress-related damage, inflammation, and alcohol-related alterations to the gut microbiome. The results indicate that ALP mitigates injury caused by oxidative stress, inflammatory responses, and changes in the gut microbiota induced by alcohol through the "gut-liver axis" pathway, which provides protection to the liver. This provides preliminary evidence for the development of related drugs. PRACTICAL APPLICATION: Researchers extracted a polysaccharide from fresh leaves of Auricularia auricula. The polysaccharide was purified and determined to have a predominantly homogeneous molecular weight. An acute alcoholic liver damage mouse model was established, and it was concluded that the polysaccharide could ameliorate liver injury in mice through the "gut-liver axis" pathway. This novel polysaccharide can be used as an additive to develop functional foods with beneficial effects, which can positively impact the daily maintenance of consumers.

The Interaction between Zinc and Cadmium from Antioxidant and Anti-Inflammatory Perspectives. Is Zinc a Natural Protector?

Cadmium is known as a toxicant for animals and human beings. Despite of its toxic properties it is used in many industrial branches. Thus, people are likely to be exposed to cadmium due to professional and environmental reasons. The underlying mechanisms of cadmium toxication are oxidative stress, oxidative stress-related inflammation and interaction with bio-elements. Many studies have reported a protective role of zinc against cadmium toxication in animals and at cellular levels. Thus, this review revealed the protective effect of zinc from antioxidant and anti-inflammatory perspectives. In this study, documents analyzing the interaction between Zn and Cd in metabolism were examined.

Songorine inhibits oxidative stress-related inflammation through PI3K/AKT/NRF2 signaling pathway to alleviate lipopolysaccharide-induced septic acute lung injury

Objective The present study aimed to investigate the protective action and mechanism of songorine on sepsis-induced acute lung injury (ALI). Methods The sepsis-induced ALI mouse and cell models were established by lipopolysaccharide (LPS) induction. Lung injury was assayed by hematoxylin and eosin staining, lung injury score, and lung wet-to-dry (W/D) weight ratio. Apoptosis in lung tissues was evaluated by TUNEL assay, and the expression of apoptosis-related markers (Bcl2, Bax, and caspase-3) was measured by western blotting. Levels of pro-inflammatory factors and oxidative stress markers in the bronchoalveolar lavage fluid (BALF) of mice were measured by ELISA and RT-qPCR. The expression of PI3K/AKT/NRF2 pathway-related proteins was analyzed by western blotting. Results Songorine treatment at 40 mg/kg mitigated sepsis-induced ALI, characterized by improved histopathology, lung injury score, and lung W/D weight ratio (p < 0.05). Moreover, songorine markedly attenuated sepsis-induced apoptosis in lung tissues; this was evidenced by an increase in Bcl2 levels and a decrease in Bax and caspase-3 levels (p < 0.01). Also, songorine reduced levels of proinflammatory cytokines (TNF-α, IL-6, IL-1β and MPO) and oxidative stress regulators (SOD and GSH) in the BALF of LPS-induced sepsis mice and RAW264.7 cells (p < 0.05). In addition, songorine upregulated the PI3K/AKT/NRF2 pathway-related proteins in LPS-induced sepsis mice and RAW264.7 cells (p < 0.05). Furthermore, LY294002 (a PI3K inhibitor) treatment reversed the protective effect of songorine on sepsis-induced ALI. Conclusion Songorine inhibits oxidative stress-related inflammation in sepsis-induced ALI via the activation of the PI3K/AKT/NRF2 signaling pathway.

HPLC-DAD Analysis and Versatile Bioactivities of Turkish Sunflower Honeys Using Chemometric Approaches.

Sunflower honey (SH) is bright yellow, fragrant, pollen-flavoured, slightly herbaceous and has a unique taste. The present research aims to examine the enzyme inhibitory, antioxidant, anti-inflammatory, antimicrobial and anti-quorum sensing activities and phenolic compositions of 30 sunflower honeys (SHs) produced from several regions of Turkey with chemometric study. SAH from Samsun exhibited the best antioxidant activity in β-carotene linoleic acid (IC50 : 7.33±0.17 mg/mL) and CUPRAC (A0.50 : 4.94±0.13 mg/mL) assays, anti-urease activity (60.63±0.87 %) and anti-inflammatory activity against COX-1 (73.94±1.08 %) and COX-2 (44.96±0.85 %). SHs exhibited mild antimicrobial activity against the test microorganisms while they showed high quorum sensing inhibition zones measured in the range of 42-52 mm against the CV026 strain. The phenolic composition was determined by high performance liquid chromatography with diode array detection (HPLC-DAD) system and levulinic, gallic, p-hydroxybenzoic, vanillic and p-coumaric acids were identified in all studied SHs. The classification of SHs was performed the using PCA and HCA. This study revealed that phenolic compounds and biological properties are effective in classification of SHs according to their geographical origin. The results suggest that studied SHs could be valued as potential agents with versatile bioactivities in oxidative stress-related disease, microbial infections, inflammation, melanoma, and peptic ulcer.

Alleviative Effect of Lactoferrin Interventions Against the Hepatotoxicity Induced by Titanium Dioxide Nanoparticles.

The current study was designed to investigate the alleviative effect of lactoferrin interventions against the hepatotoxicity induced by titanium dioxide nanoparticles (TiO2-NPs). Thirty male Wistar rats were divided into six groups with 5 rats in each group. The first and second groups were intragastrically administered normal saline and TiO2-NPs (100 mg/kg body weight) as the negative control (NC) and TiO2-NP groups. The third, fourth, and fifth groups were intragastrically administered lactoferrin at concentrations of 100, 200, and 400 mg/kg body weight in addition to TiO2-NPs (100 mg/kg body weight). The sixth group was intragastrically administered Fuzheng Huayu (FZHY) capsules at a concentration of 4.6 g/kg body weight in addition to TiO2-NPs (100 mg/kg body weight) as the positive control group. After treatment for 4 weeks, the concentrations of lactoferrin were optimized based on the liver index and function results. Subsequently, the alleviative effects of lactoferrin interventions against TiO2-NP-induced hepatotoxicity in rat liver tissues, including the effects on histological damage, oxidative stress-related damage, inflammation, fibrosis, DNA damage, apoptosis, and gene expression, were investigated using histopathological, biochemical, and transcriptomic assays. The results showed that 200 mg/kg lactoferrin interventions for 4 weeks not only ameliorated the liver dysfunction and histopathological damage caused by TiO2-NP exposure but also inhibited the oxidative stress-related damage, inflammation, fibrosis, DNA damage, and apoptosis in the liver tissues of TiO2-NP-exposed rats. The transcriptomic results confirmed that the alleviative effect of lactoferrin interventions against the TiO2-NP exposure-induced hepatotoxicity was related to the activation of the PI3K/AKT signaling pathway.

Transcriptomic analysis reveals that the anti-PCOS effects of Zishen Qingre Lishi Huayu recipe may involve pathways and genes related to autophagy, steroidogenesis, oxidative stress, and inflammation in granulosa cells

Zishen Qingre Lishi Huayu recipe (ZQLHR) is a Chinese medicine compound composed of nine herbs for the treatment of polycystic ovary syndrome (PCOS). It is used to nourish kidneys, clear heat, reduce dampness and dissipation blood stasis by promoting diuresis and blood circulation, dredging the meridians and harmonizing menstruation in the treatment of PCOS. Several clinical studies have shown that ZQLHR is effective in the treatment of PCOS, but the underlying mechanism remains unclear. In this study, we researched on the effects and mechanism of action of ZQLHR during treatment of human granulosa cells (hGCs) obtained from PCOS patients in order to provide a scientific basis for the clinical application of ZQLHR in the treatment of PCOS, emphasize the importance of some genes that have been reported to play a role in the pathogenesis or therapeutic mechanisms of PCOS from the perspective of disease treatment, and identify some new genes and signaling pathways that may play an important role in the treatment of PCOS. KGN cells (a granulosa cell-like tumor cell line) were subjected to a cell counting kit-8 assay to explore the appropriate intervention concentration and duration of ZQLHR. Treated with or without ZQLHR (ZQLHR and control groups), the hGCs obtained from PCOS patients were sequenced using RNA sequencing, and the genes thus detected were further analyzed through Kyoto encyclopedia of genes and genomes enrichment analysis, gene set enrichment analysis, and individuation gene analysis. These genes were also compared with PCOS-related genes in other databases. To further verify the authenticity of the differentially expressed genes between the two groups, the expression of eight randomly selected vital genes and three proteins of interest was verified through real time quantitative polymerase chain reaction and Western blot experiment respectively. The best intervention concentration and duration for ZQLHR to promote the proliferation of KGN cells were 0.2% and 48h respectively in this experiment. Multiple signaling pathways and 55 focus differentially expressed genes, both related to autophagy, steroidogenesis, oxidative stress-related longevity, inflammation, and complications of PCOS, may play an important role in the therapeutic mechanism of action of ZQLHR. The expression of eight genes is consistent with the result of RNA sequencing, and the expression of three proteins of interest is the same as expected. The promotion of hGCs proliferation upon treatment with ZQLHR may be a manifestation of ZQLHR in the treatment of PCOS patients. The positive effects of ZQLHR against PCOS may involve pathways and genes related to autophagy, steroidogenesis, oxidative stress-related longevity, and inflammation in hGCs. Some components of ZQLHR applied for the treatment of PCOS may also be effective for the treatment of some complications of PCOS.

Dihydroquercetin ameliorates LPS-induced neuroinflammation and memory deficit

Dihydroquercetin (DHQ) is a pentahydroxyflavanone that has been used as an important suppliment against oxidative stress related inflammation and neuroinflammation. Neuroinflammation, which is the activation of the defense mechanism of the central nervous system, upon exposure to stimuli like amyloid β, Lewy bodies, lipopolysaccharide (LPS) and reactive oxygen species. It is an important pathophysiological mediator of a number of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis and others. The objective of the present study is to evaluate the neuroprotective effect of DHQ, a potent antioxidant molecule, against LPS induced neuroinflammation. On the first day of the experiment (day-1), neuroinflammation was induced through intracerebroventricular injection of LPS (5 ​μg/5 μl) into each lateral ventricle in the rats. DHQ-0.5, 1 and 2 ​μg/kg was injected into the tail vein in respective groups from day-2 to day-10. Behavioral studies showed that DHQ attenuated the LPS-induced loss in long-term memory and working memory as evaluated by elevated plus maze and Y-maze test, respectively.Further, the biochemical estimations revealed that DHQ dose-dependently attenuated the LPS-induced decrease in acetylcholine level and increased in the acetylcholine-esterase activity in the hippocampal region. DHQ also increased the catalase activity and decreased nitric oxide and lipid peroxidation altered by LPS injection. DHQ also attenuated interleukin-6 in the brain, which has elevated upon LPS induction. The decrease in IL-6 is attributed to its antioxidant activity. Hence, DHQ could be a potential therapeutic candidate in the management of neuroinflammation and related neurodegenerative disorders.

Red yeast rice dietary intervention reduces oxidative stress-related inflammation and improves intestinal microbiota.

Inflammation and oxidative stress play key roles in the aging process, while red yeast rice (RYR), a traditional Chinese fermented food, has anti-oxidant and anti-inflammatory effects. To understand the anti-aging function of RYR in vivo, this study established a D-galactose-induced aging mouse model to verify the positive effects of RYR dietary intervention on aging and explore the related underlying mechanism. Eight weeks of RYR dietary intervention was shown to have a significant inhibitory effect on cognitive decline and hippocampal damage. The molecular mechanistic studies showed that the anti-aging effects of RYR were achieved by (i) improving the oxidative stress-related damage (increasing SOD, CAT, and GSH, and reducing MDA), (ii) regulating the NF-κB inflammation pathway induced by oxidative stress (decreasing the pro-inflammatory cytokines IL-6, TNF-α, IFN-γ, iNOs, and IL-1β, increasing the anti-inflammatory cytokine IL-10, and decreasing the expression of the NF-κB protein), (iii) slowing down apoptosis caused by oxidative stress (reducing the expression of P21 and P53), (iv) restoring the abundance of Lactobacillus, Lachnospiraceae and Rikenellaceae downregulated by D-galactose, and (v) reducing the abundance of Akkermansia and Helicobacter enriched by D-galactose. Mass spectrometry revealed orange pigments (rubropunctatin and monascorubrin) as the main antioxidant components in RYR, which might play key roles in aging inhibition. This study provides theoretical support for the wide application of orange pigments as an antioxidant dietary supplement.

Red algae natural products for prevention of lipopolysaccharides (LPS)-induced liver and kidney inflammation and injuries.

Background: The liver and kidney inflammation due to bacterial infection is one of the most common pathological problems leading to tissue damage or disease. In many liver and kidney disorders, which represent serious global health burden with a high economic cost, oxidative stress-related inflammation and apoptosis are important pathogenic components, finally resulting in acute liver and/or kidney failure. Erythropoietin and its analogues are well known to influence the interaction between apoptosis and inflammation in liver and kidney. Objective: The aim of the present study is to investigate and clarify the effect of Galaxaura oblongata (G. oblongata) red algae on lipopolysaccharides (LPS)-induced acute liver and kidney injury of mice with endotoxemia and associated molecular mechanism from inflammation, apoptosis and oxidative stress levels. Results: The current study cleared out that treatment of rats with the G. oblongata extract prior to LPS injection significantly lowered serum cytokines, including NF-κB, MPO and LPO, and improved liver apoptosis through suppressing protein tyrosine kinase signaling pathway, and that may be due to antibacterial activity as well antioxidant capacity of G. oblongata extract. Conclusion: The present study was cleared out the possibility of administration of G. oblongata red algae as a multi products source for biotechnological, medical, nutraceutical and pharmaceutical applications due to highly antioxidant and anti-inflammatory capacities even although more investigations are required for separating, purifying and characterizing these bioactive compounds.

Injectable thermosensitive chitosan-based hydrogel containing ferulic acid for treating peripheral arterial disease.

Peripheral arterial disease (PAD) affects more than 200 million people worldwide. Recent studies suggest that oxidative stress-related inflammation can lead to the initiation and progression of PAD. Ferulic acid (FA) is a natural phenolic compound and has been proven to have antioxidant and angiogenesis effects. In this study, thermosensitive chitosan-gelatin-based hydrogel was used as a delivery vehicle of FA. The effects of hydrogel encapsulating FA (FA-gel) have been demonstrated in vitro and in vivo. The results revealed that the developed hydrogel with porous structure could provide a sustained release of FA. Post-treatment of FA-gel effectively decreased the oxidative stress-induced damage in human umbilical vein endothelial cells via decreasing endogenous reactive oxygen species production, inflammation-related gene expression and apoptosis level. In the mouse hindlimb ischemia model, the results revealed that FA-gel could improve blood flow, muscle regeneration and decreases inflammation in veins. These results suggested that FA-gel may have a therapeutic potential in PAD.

TRPC6-dependent Ca2+ signaling mediates airway inflammation in response to oxidative stress via ERK pathway

Ozone (O3) plays an extremely important role in airway inflammation by generating reactive oxygen species (ROS) including hydrogen peroxide, then promoting redox actions and causing oxidative stress. Evidences indicate that TRPC6 (canonical transient receptor potential channel 6) is a redox-regulated Ca2+ permeable nonselective cation channel, but its role in the setting of oxidative stress-related airway inflammation remains unknown. Here, we found that both TRPC6−/− mice and mice pretreated with SAR7334, a potent TRPC6 inhibitor, were protected from O3-induced airway inflammatory responses. In vitro, both knockdown of TRPC6 expression with shRNA and TRPC6 blockage markedly attenuated the release of cytokines IL-6 and IL-8 induced by O3 or H2O2 in 16HBE cells (human bronchial epithelial cell line). Treatment with O3 or H2O2 enhanced TRPC6 protein expression in vivo and vitro. We also observed that TRPC6-dependent increase of intracellular Ca2+ concentration ([Ca2+]i) was triggered by H2O2, which consisted of the release from intracellular calcium store and the influx of extracellular Ca2+ and could be further strengthened by 6-h O3 exposure in both 16HBE cells and HBEpiCs (primary human bronchial epithelial cells). Moreover, we confirmed that the activation of MAPK signals (ERK1/2, p38, JNK) was required for the inflammatory response induced by O3 or H2O2 while only the phosphorylation of ERK pathway was diminished in the TRPC6-knockdown situation. These results demonstrate that oxidative stress regulates TRPC6-mediated Ca2+ cascade, which leads to the activation of ERK pathway and inflammation and could become a potential target to treat oxidative stress-associated airway inflammatory diseases.

Oleic Acid Protects against Hepatic Ischemia and Reperfusion Injury in Mice by Inhibiting AKT/mTOR Pathways.

Hepatic ischemia-reperfusion (I/R) injury is a serious complication in patients who have undergone hepatic surgery such as orthotopic liver transplantation and partial hepatectomy. Recently, a new cytoprotective agent, ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE), was reported to protect against hepatic I/R injury. However, the protective mechanism of UDCA-LPE is not fully understood. Therefore, we conducted this study to explore its underlying mechanism. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the liver lipid metabolism changes in mice during I/R. KEGG enrichment indicated that UDCA-LPE is likely to exert its protective role by regulating fatty acid (FA) metabolism. Further analysis found that UDCA-LPE significantly increased the ratio of oleic acid (OA) to palmitic acid (PA). We found that mice pretreated with OA improved tolerance to hepatic I/R injury. In addition, the phosphorylation level of AKT was markedly upregulated during oxidative stress to promote p65 nuclear translocation, triggering an inflammatory response that exacerbated cell damage and OA treatment significantly inhibited this process. Notably, OA was found to inhibit H2O2-induced oxidative stress, inflammation, and cell death in HepG2 cells. Furthermore, we found that OA supplementation to the medium did not result in a significant increase in intracellular OA, but marked increase in the ratio of OA to PA, which may be an important mechanism for the inflammatory response induced by oxidative stress during I/R. Finally, we demonstrated that OA increased the level of autophagy in HepG2 cells, which may be one of the protective mechanisms against oxidative stress. Collectively, this study revealed that FA metabolism functionally determines the oxidative stress-related inflammation caused by hepatic I/R. We hypothesize that OA treatment may be a promising strategy for preventing and treating I/R-induced liver damage.

Bismuth Oxide Nanoparticles Induced Oxidative Stress-Related Inflammation in SH-SY5Y Cell Line

Bismuth (III) oxide nanoparticles’ (Bi2 O3 -NPs) unique physicochemical properties have attracted attention in biological, industrial, technological and medical fields. Concurrently, increasing numbers of studies revealing their potential toxic effects and possible toxicity mechanisms are ongoing. In this study, we assessed the toxic potentials of Bi2 O3 -NPs in human SH-SY5Y neuroblastoma cell line. After Bi2 O3 -NPs characterization using TEM, the cytotoxic potentials were evaluated by MTT and LDH assays. The induction of reactive oxygen species production was evaluated by H2 DCFDA. In order to evaluate the oxidative damages, the changes in antioxidant catalase and superoxide dismutase and glutathione levels were determined. The cellular death pathway and the role of immune response were studied by measuring the mRNA expression levels of related genes. Our results showed that Bi2 O3 -NPs decreased the cell viability through disruption on mitochondrial activity (IC50:77.57 µg/mL) and membrane integrity (LDH%50:16.97 µg/mL). At 50 µg/mL Bi2 O3 -NPs, the production of reactive oxygen species (ROS) was induced significantly as well as the catalase and superoxide dismutase levels. In immune response, the mRNA expression levels of interleukin (IL)-6 increased more than 1.5-fold in all doses; whereas, TNF-α, NF-ĸB and MAPK8 expressions remained unchanged. Consequently, Bi2 O3 -NPs induced oxidative stress-related inflammation via activation of proinflammatory cytokine, IL-6.&nbsp;

HPLC-DAD-ESI-QTOF-MS/MS profiling of Zygophyllum album roots extract and assessment of its cardioprotective effect against deltamethrin-induced myocardial injuries in rat, by suppression of oxidative stress-related inflammation and apoptosis via NF-κB signaling pathway.

Zygophyllum album is widely used to treat many cardiovascular diseases (CVDs) and as anti-inflammatory plant. This study aimed to investigate the mechanism of the potential protective effects of Zygophyllum album roots extract (ZARE) against myocardial damage and fibrosis induced by a chronic exposure to deltamethrin (DLM) in rats. Bioactive compounds present in ZARE were analyzed by HPLC-DAD-ESI-QTOF-MS/MS. In vivo, DLM (4 mg/kg body weight), ZARE (400 mg/kg body weight) and DLM with ZARE were administered to rats orally for 60 days. Biochemical markers (LDH, ALT, CK, CK-MB and cTn-I) were assessed in the plasma by an auto-analyzer. Pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were evaluated by a sandwich ELISA. NF-κB was quantified at mRNA levels by real time PCR. Heart tissue was used to determine cardiac oxidative stress markers (MDA, PC, SOD, CAT, and GPx). Masson's Trichrome (MT) and Sirius Red (SR) stainings were used for explored fibrosis statues. Phytochemical analysis using HPLC-DAD-ESI-QTOF-MS/MS revealed the presence of twenty six molecules including phenolic compounds and saponins. ZARE significantly improved the heart injury markers (LDH, ALT, CK, CK-MB and cTn-I), lipid peroxidation (MDA), protein oxidation (PC), antioxidant capacity (SOD, CAT, and GPx), and DNA structure, which were altered by DLM exposure. Moreover, ZARE cotreatment reduced the expressions of NF-κB, decreased plasmatic pro-inflammatory cytokines concentration (TNF-α, IL-1β and IL-6), and suppressed the myocardial collagen deposition, as observed by Sirius Red and Masson's Trichrome staining. ZARE ameliorated the severity of DLM-induced myocardial injuries through improving the oxidative status and reducing profibrotic cytokines production. The ZARE actions could be mediated by downregulation of NF-κB mRNA.

Glutathione-dependent enzyme activities of peripheral blood mononuclear cells decrease during the winter season compared with the summer in normal-weight and severely obese adolescents

Oxidative stress-related inflammation is known to play a vital role in obesity-associated cardiovascular disease, contributing to the early stages of the pathology as well as during its development. Therefore, it is of great interest to understand how obesity-induced stress modulates antioxidant enzyme activity during puberty. To this end, 27 severely obese adolescents (body mass index > 30, z-score > 3.7) were recruited from a paediatric weight management centre. Eighteen were recruited during the summer and nine in the winter. All underwent a 4-month weight loss programme consisting in diet and physical activity. Twenty normal-weight age-matched adolescents were recruited from the same geographical area to serve as controls. Blood samples were extracted, and antioxidant enzyme activities were determined in peripheral blood mononuclear cells (PBMCs) and erythrocytes. The enzymes studied included catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. Severely obese adolescents presented lower PBMC-glutathione reductase activity than their corresponding normal-weight counterparts. In addition, glutathione-dependent activities tended to be lower in both groups during the winter compared with summer. These changes coincided with differences in circulating vitamin D levels. Results may suggest that season-dependent factors such as vitamin D could affect glutathione-dependent activities in severely obese as well as in normal-weight adolescents.

Pseudomonas aeruginosa induces cellular senescence in lung tissue at the early stage of two-hit septic mice.

We presume that severe secondary Pseudomonas aeruginosa (PA) infection can lead to cellular senescence in lung tissue and thus contribute to high mortality. We established a two-hit mouse model using cecal ligation and puncture (CLP) followed by sublethal PA lung infection. In lung tissue, increased infiltration of inflammatory cells, elevated lung injury and augmented cellular senescence was shown in mice with CLP followed by sublethal PA infection, and these observations reached a higher rank when higher (H) loads PA (PAO1) were administered to CLP mice (CLP+PAO1-H). Accordingly, oxidative stress-related element gp91phox and inflammation regulator NF-κB were greatly activated in CLP+PAO1-H mice compared to others. There was no obvious inflammation or cellular senescence in sham control, PAO1-infected mice. Consequently, CLP+PAO1-H mice had the highest expression levels of inflammatory cytokines IL-6, TNFα and iNOS among those groups. There was lower bacterial clearance ability in CLP+PAO1-H mice than in other mice. CLP+PAO1-H only had approximately 10% survival after 7 days of investigation and was much lower than others. In conclusion, higher mortality due to increased lung inflammation and cellular senescence are observed in mice with increased loads of PA infection secondary to CLP.

Gut-derived lipopolysaccharides increase post-prandial oxidative stress via Nox2 activation in patients with impaired fasting glucose tolerance: effect of extra-virgin olive oil.

Post-prandial phase is characterized by enhanced oxidative stress but the underlying mechanism is unclear. We investigated if gut-derived lipopolysaccharide (LPS) is implicated in this phenomenon and the effect of extra virgin olive oil (EVOO) in patients with impaired fasting glucose (IFG). This is a randomized cross-over interventional study including 30 IFG patients, to receive a lunch with or without 10g of EVOO. Serum LPS, Apo-B48, markers of oxidative stress such as oxidized LDL (oxLDL) and soluble Nox2-derived peptide (sNox2-dp), a marker of nicotinamide-adenine-dinucleotide-phosphate oxidase isoform Nox2 activation, and plasma polyphenols were determined before, 60 and 120min after lunch. In patients not given EVOO oxidative stress as assessed by sNox2-dp and oxLDL significantly increased at 60 and 120min concomitantly with an increase of LPS and Apo-B48. In these patients, changes of LPS were correlated with Apo-B48 (Rs = 0.542, p = 0.002) and oxLDL (Rs = 0.463, p = 0.010). At 120min, LPS (β - 15.73, p < 0.001), Apo-B48 (β - 0.14, p = 0.004), sNox2-dp (β - 5.47, p = 0.030), and oxLDL (β - 42.80, p < 0.001) significantly differed between the two treatment groups. An inverse correlation was detected between polyphenols and oxLDL (R - 0.474, p < 0.005). In vitro study showed that LPS, at the same concentrations found in the human circulation, up-regulated Nox2-derived oxidative stress via interaction with Toll-like receptor 4. Post-prandial phase is characterized by an oxidative stress-related inflammation potentially triggered by LPS, a phenomenon mitigated by EVOO administration.

Nemli ve Yağmurlu Havanın Subklinik İnflamasyon ve Oksidatif Stress Markırları Üzerine Etikileri

Although it is known that the symptoms of rheumatoid arthritis patients increase in cold, humid and rainy days but its mechanism is unclear. It was aimed to investigate the effects on some inflammatory and oxidative stress markers in different weather conditions in rats. Some inflammatory, oxidant and antioxidant markers were measured in sera of healthy rats in sunny, cloudy and rainy days. The levels of reduced glutathione (GSH) and glutathione reductase (GR) were found to be lower in both cloudy and rainy days with respect to sunny days (p = 0.001 and 0.004 respectively). Similarly, α -glutathione-S-transferase levels were found to be lower on rainy days than on sunny days (p = 0.017). Malondialdehyde (MDA) was found to be higher (p = 0.044) in rainy days compared to sunny days. Nitric oxide (NO) and interleukin-1β (IL-1β) were found to be higher in cloudy and rainy days compared to sunny days (p = 0.003 and 0.025, respectively). The findings indicate that oxidative stress-related inflammation is triggered in rainy and cloudy days.

Attenuation of sepsis-induced rat liver injury by epigallocatechin gallate via suppression of oxidative stress-related inflammation

Purpose: To evaluate the effect of epigallocatechin gallate (EGCG) on sepsis-induced liver injury in a rat model of sepsis established by cercal ligation and puncture (CLP). Methods: Male Wistar rats were randomly divided into 6 groups (n = 12): normal control, sepsis, dexamethasone (5 mg/kg), low-dose EGCG (12.5 mg/kg), medium-dose EGCG (25 mg/kg), and highdose EGCG (50 mg/kg) groups. Dexamethasone and EGCG were given once daily. Survival rates following CLP were recorded. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to evaluate liver function. Tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 were determined by ELISA. Superoxide dismutase (SOD) and levels of glutathione (GSH) and malondialdehyde (MDA) were assayed to evaluate oxidative stress. Protein and mRNA expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor (Nrf2) were measured by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Results: Survival rates were significantly (p &lt; 0.05) increased by EGCG (83.3 %) when compared to the untreated sepsis group (33.3 %) or dexamethasone-treated sepsis group (41.7 %). The increase in survival rates was associated with significant decreases in AST, ALT, MDA, and TNF-α, and significant elevations in SOD, GSH, and IL-10. QRT-PCR and Western blotting data indicate that there was increase in hepatic expression of Nrf-2 and HO-1 of EGCG-treated sepsis rats, relative to the untreated sepsis group. Conclusion: These results suggest that EGCG treatment reduces sepsis-induced liver injury and improves the survival rate of rats with polymicrobial sepsis by reducing oxidative stress via regulation of Nrf2/HO-1 signaling. These findings highlight the promising potential of EGCG for the treatment of sepsis. Keywords: Epigallocatechin gallate, Cecal ligation and puncture (CLP), Sepsis, Liver injury, Oxidative stress, Inflammation