Decreased Myeloperoxidase Levels Research Articles

Therapeutic effect of Atractylenolide I on Aspergillus fumigatus keratitis by affecting MyD88/ NF-κB pathway and IL-1β, IL-10 expression.

Atractylenolide I (AT-I) is a natural sesquiterpene with anti-inflammatory effects. The purpose of this study was to research the anti-inflammatory effect of AT-I on Aspergillus fumigatus(A. fumigatus) keratitis in mice. Cytotoxicity test and cell scratch test were used to determine the therapeutic concentrations of corneal infections. In vivo and in vitro studies, mouse cornea and human corneal epithelial cells (HCECs) infected with A. fumigatus were treated with AT-I or dimethyl sulfoxide (DMSO). Then, to analyze the effect of AT-I on inflammatory response, namely neutrophil or macrophage recruitment and the expression of cytokines involving MyD88, NF-κB, interleukin 1β (IL-1β) and interleukin 10 (IL-10). To study the effects of the drug, the techniques used include slit-lamp photography, immunofluorescence, myeloperoxidase (MPO) detection, quantitative real-time polymerase chain reaction (QRT-PCR), and western blot. At the same time, in order to explore the combined effect of the drug and natamycin, slit-lamp photographs and clinical scores were used to visually display the disease process. No cytotoxicity was observed under the action of AT-I at a concentration of 800μM. In mouse models, AT-I significantly suppressed inflammatory responses, reduced neutrophil and macrophage recruitment, and decreased myeloperoxidase levels early in infection. Studies have shown that AT-I may reduce the levels of IL-1β and IL-10 by inhibiting the MyD88/ NF-κB pathway. The drug combined with natamycin can increase corneal transparency in infected mice. AT-I may inhibit MyD88 / NF-κB pathway and the secretion of inflammatory factors IL-1 β and IL-10 to achieve the therapeutic effect of fungal keratitis.

Sulforaphane Exerts Beneficial Immunomodulatory Effects on Liver Tissue via a Nrf2 Pathway-Related Mechanism in a Murine Model of Hemorrhagic Shock and Resuscitation.

Our research explores the immunomodulatory effects of sulforaphane (SFN), a well-known nuclear factor erythroid 2-related factor 2 (Nrf2) pathway agonist, on the sterile inflammation of and ischemia-reperfusion injuries to the liver after hemorrhagic shock (HS) followed by resuscitation (R). Male C57/BL6 wild-type and transgenic ARE-luc mice were exposed to mean arterial pressure-controlled HS. Fluid resuscitation was performed after 90 min of HS, and SFN was administrated intraperitoneally after that. The animals were sacrificed at 6 h, 24 h, and 72 h after resuscitation, and their livers were extracted to perform H&E staining and myeloperoxidase (MPO) activity analysis. The Kupffer cells were isolated for cytokines profile measurements and Nrf2 immunofluorescence staining. Further, the ARE-luc mice were used to assess hepatic Nrf2 activity in vivo. We identified that SFN-activated Kupffer cells’ Nrf2 pathway and modulated its cytokines expression, including TNF-α, MCP-1, KC/CXCL1, IL-6, and IL-10. Furthermore, SFN mitigated liver ischemia-reperfusion injury, as evidenced by the downregulation of the Suzuki score and the enhanced hepatic Nrf2 activity. The in vivo SFN treatment decreased neutrophils infiltration, as shown by the decreased MPO levels. Our study shows that SFN can decrease HS/R-induced hepatic ischemia-reperfusion injury and modulate the activity of Kupffer cells via an Nrf2-dependent pathway.

Protective effects of pre-treatment with exogenous porcine glucagon-like peptide-2 and its microspheres of piglets with lipopolysaccharide-induced intestinal inflammation

Context Glucagon-like peptide-2 (GLP-2) is an intestinotrophic growth hormone that can accelerate intestinal development and recovery from injury. However, the half-life of GLP-2 is short, thus it must be administered frequently. Moreover, its effects during weaning are unclear. Aims We tested the effects of porcine GLP-2 (pGLP-2) and pGLP-2 microspheres on lipopolysaccharide (LPS)-induced intestinal inflammation in weaning piglets. Methods Eighteen female weaning piglets aged 21 days (5.38 ± 0.72 kg initial bodyweight) were randomly assigned to three treatment groups: (1) control, (2) GLP-2, and (3) GLP-2 microsphere (MS) group. Control piglets were injected intraperitoneally with 3 mL of saline solution from Days 1 to 7, GLP-2 piglets were injected intraperitoneally with 100 μg pGLP-2/kg bodyweight from Days 1 to 7, and MS piglets were injected intraperitoneally with 200 mg GLP-2 microspheres on Day 1 and with 3 mL saline solution from Days 2 to 7. On Day 8, all piglets were injected with 100 μg LPS/kg bodyweight. Key results Piglets in the GLP-2 and MS groups showed markedly increased average daily weight gain on Day 7, decreased serum myeloperoxidase, LPS and keratinocyte growth factor levels, and increased serum interleukin-10 levels compared with the control group. In addition, the GLP-2 group showed decreased myeloperoxidase content in the duodenum and ileum, and reduced caspase-3 activity in the duodenum and jejunum, whereas MS piglets showed decreased myeloperoxidase levels and suppressed caspase-3 activity in the duodenum and jejunum. Moreover, administration of pGLP-2 or pGLP-2 microspheres resulted in decreased interleukin-8 and interferon-γ mRNA expression levels in the jejunum, as compared with the control group. Conclusions Our results indicated that pGLP-2 promotes growth, and ameliorates LPS-induced serum and intestinal inflammatory responses in piglets. Furthermore, pGLP-2 microspheres can achieve similar therapeutic effects as pGLP-2 under the premise of fewer injections. Implications pGLP-2 microspheres have considerable potential for the treatment of weaning-induced intestinal inflammation in piglets.

CLEC-1 Acts as a Negative Regulator of Dectin-1 Induced Host Inflammatory Response Signature in Aspergillus fumigatus Keratitis.

PurposeC-type lectin-like receptor-1 (CLEC-1) is a member of the Dectin-1 cluster of pattern recognition receptors (PRRs). It is involved in host immunity, has immunoregulatory function, and supports allograft tolerance. Our study aimed to describe the role of CLEC-1 in response to fungal keratitis, in situ, in vivo, and in vitro.MethodsQuantitative polymerase chain reaction (qRT-PCR) and immunofluorescence were used to detect the expression of CLEC-1 in corneas of patients with Aspergillus fumigatus (A. fumigatus) keratitis. In vitro and in vivo experiments were designed in THP-1 macrophages and C57BL/6 mouse models, respectively. The expression of CLEC-1 in corneas of mice model was determined by qRT-PCR, Western blot, and immunofluorescence. CLEC-1 overexpression in mouse corneas was achieved by intrastromal injection of adeno-associated virus (AAV) vectors. Disease response was evaluated by slit-lamp photography, clinical score, and colony forming unit (CFU). Bioluminescence imaging system image acquisition, myeloperoxidase (MPO) assays, immunofluorescence staining, qRT-PCR, and Western blot were used to investigate the role of CLEC-1. To further define the role of CLEC-1, we used lentivirus vectors to overexpress CLEC-1 or/and Dectin-1 in THP-1 macrophages.ResultsThe expression of CLEC-1 was increased in corneas of patients with A. fumigatus keratitis. In corneas of mice from the A. fumigatus keratitis model, the expression of CLEC-1 was decreased in the acute inflammatory stage and increased during convalescence. Following Natamycin treatment, CLEC-1 was upregulated in A. fumigatus keratitis mice. Compared with normal C57BL/6 mice, overexpression of CLEC-1 converted the characteristic susceptible response to resistance, as demonstrated by slit-lamp photography and clinical score. In vivo studies revealed decreased MPO levels and neutrophils recruitment and higher fungal load after the upregulation of CLEC-1. Compared with control corneas, CLEC-1 overexpression impaired corneal pro-inflammatory cytokine IL-1β production.ConclusionsThese findings demonstrate that CLEC-1 may act as a negative regulator of Dectin-1 induced host inflammatory response via suppressing neutrophils recruitment and production of pro-inflammatory cytokine IL-1β production in response to A. fumigatus keratitis.

Comparison of ischemic preconditioning and BotulinumA Toxin injection for the prevention of ischemia-reperfusion injury in musculocutaneous flaps

Background/aimThe aim of the study was to evaluate the protective effect of Botulinum A toxin injection against ischemia-reperfusion injury.Materials and methodsThirty-two Sprague-Dawley rats were divided into: control, ischemia-reperfusion, ischemic preconditioning, and botulinum groups. In all groups the musculocutaneous pedicle flap was occluded for 4 h, and then reperfused to induce ischemia-reperfusion injury. Serum and tissue myeloperoxidase (MPO) and nitric oxide (NO) levels were measured at 24 h and at 10 days.ResultsTissue MPO levels did not differ significantly between the ischemic preconditioning and botulinum groups at 24 h but was significantly lower in the botulinum group at 10 days. Tissue NO levels were significantly higher in the ischemic preconditioning group compared to the botulinum group at 24 h and at 10 days. Serum MPO showed no significant difference between these two groups at 24 h but was significantly lower in the ischemic preconditioning group compared to the botulinum group at 10 days. Serum NO levels were not significantly different at 24 h but significantly higher in the botulinum group at 10 days.ConclusionFindings show that botulinum has a protective effect against the ischemia-reperfusion injury via increased NO and decreased MPO levels in tissue. Based on tissue NO levels, ischemic preconditioning was significantly higher than botulinum.

Effect of Saccharomyces cerevisiae UFMG A-905 in a murine model of food allergy.

Food allergy is triggered when there is an abnormal activation of the immune system by food allergens. Currently, there is no curative therapy for this pathological condition. Due to the immunomodulatory properties of probiotics they are potential candidates as therapeutic tools for food allergy. Therefore, the aim of this study was to evaluate the probiotic effect of Saccharomyces cerevisiae UFMG A-905 (905) in an in vivo model of food allergy. Probiotic effect was assessed by clinical, histological, immunological and microbiological parameters analysis. Furthermore, we also evaluated if 905 after inactivation has an effect, as well as if such an effect is dose dependent. Our results showed that oral administration of only viable 905 promotes a significant attenuation of tissue injury and myeloperoxidase (MPO) activity levels. Moreover, the treatment reduced interleukin 17 levels, and administration of the supernatant from the yeast culture also promoted a significant decrease in MPO levels. However, considering the systemic parameters, immunoglobulin (Ig)E and IgG anti-ovalbumin, which are essentials for triggering the allergic process, there was no effect, suggesting that the yeast promotes a local but not a systemic effect in the model evaluated. In addition, we found that only high doses of viable 905 were able to attenuate the signs of inflammation. In conclusion, oral administration of 905 led to a local effect that depends on the viability of the yeast.

Wedelolactone suppresses IL-1β maturation and neutrophil infiltration in Aspergillus fumigatus keratitis

PurposeWedelolactone, a chemical compound extracted from Wedelia calendulacea or Eclipta alba, has been reported to regulate key steps in inflammation. However, the effects of wedelolactone on fungal keratitis are not known. Hence, we aimed to characterize the impact of wedelolactone in Aspergillus fumigatus keratitis. MethodsAspergillus fumigatus was used to establish an in vivo mouse model of fungal keratitis and an in vitro model of THP-1 macrophages. Mice and THP-1 macrophages were pre-treated with wedelolactone. Clinical evaluation, myeloperoxidase (MPO) assay, neutrophil staining, western blot and quantitative polymerase chain reaction (qRT-PCR) were used to assess the effect of wedelolactone on A. fumigatus infection. Therapeutic effect of natamycin treatment with or without wedelolactone was measured via slit lamp microscopy. ResultsWe confirmed that wedelolactone attenuated the infiltration of neutrophils and decreased MPO level at earlier time points in mice with A. fumigatus keratitis. Pre-treatment with wedelolactone decreased pro-inflammatory cytokine interleukin 1 beta (IL-1β) maturation by inhibiting caspase-1 activity. Combined with natamycin, wedelolactone protected corneal transparency in mouse with fungal keratitis. ConclusionPresent findings indicated that wedelolactone reduced host immune responses by attenuating neutrophil recruitment and IL-1β maturation in Aspergillus fumigatus keratitis. Wedelolactone combined with an antifungal medicine could be a potential therapy for reducing lesion severity in fungal keratitis.

Osteopontin contributes to effective neutrophil recruitment, IL-1β production and apoptosis in Aspergillus fumigatus keratitis.

Fungal keratitis is a major cause of corneal ulcers, resulting in significant visual impairment and blindness. A phosphorylated glycoprotein secreted by immunocompetent cells, osteopontin (OPN) mediates cluster formation of the host fungal receptors and enhances the phagocytosis and clearance of pathogenic fungi. However, whether OPN production and function occurs in fungal keratitis is unknown. OPN expression in Aspergillus fumigatus keratitis patient corneas was assessed by quantitative polymerase chain reaction (qRT-PCR) and immunofluorescence. Human neutrophils, THP-1 macrophages and corneal epithelial cells (HCECs) stimulated with A.fumigatus were utilized for invitro experiments. Mouse models of A.fumigatus keratitis were developed by intrastromal injection for invivo experiments. Using siRNAs, neutralizing antibodies, recombinant proteins and inhibitors, the production and role of OPN in A.fumigatus infection was assessed by clinical evaluation, qRT-PCR, immunofluorescence, western blotting and bioluminescence image acquisition. We observed increased corneal OPN expression in A.fumigatus keratitis patients and mouse models compared to controls. OPN production in response to A.fumigatus infection was dependent on LOX-1 and Erk1/2. Compared to controls, OPN knockdown impaired proinflammatory cytokine IL-1β production, which was dependent on 4E-BP1. OPN knockdown decreased myeloperoxidase levels, and resulted in decreased neutrophil recruitment, higher fungal load and increased apoptosis in mouse A.fumigatus keratitis. Our results indicate that OPN is a critical component of the antifungal immune response and is essential for effective neutrophil recruitment, inflammatory cytokine production and apoptosis in A.fumigatus keratitis.

The SIRT1 inhibitor EX-527 suppresses mTOR activation and alleviates acute lung injury in mice with endotoxiemia

It is generally regarded that Sirtuin 1 (SIRT1), a longevity factor in mammals, acts as a negative regulator of inflammation. However, recent studies also found that SIRT1 might be a detrimental factor under certain inflammatory circumstance. In this study, the potential pathophysiological roles and the underlying mechanisms of SIRT1 in a mouse model with endotoxemia-associated acute lung injury were investigated. The results indicated that treatment with the selective SIRT1 inhibitor EX-527 suppressed LPS-induced elevation of TNF-α and IL-6 in plasma. Treatment with EX-527 attenuated LPS-induced histological abnormalities in lung tissue, which was accompanied with decreased myeloperoxidase level and suppressed induction of tissue factor and plasminogen activator inhibitor-1. Treatment with EX-527 also suppressed LPS-induced phosphorylation of eukaryotic translation initiation factor-binding protein 1 (4E-BP1). Co-administration of a mammalian target of rapamycin (mTOR) activator 3-benzyl-5-[(2-nitrophenoxy) methyl]-dihydrofuran-2 (3H)-one (3BDO) abolished the inhibitory effects of EX-527 on 4E-BP1 phosphorylation. Meanwhile, the inhibitory effects of EX-527 on IL-6 induction and the beneficial effects of EX-527 on lung injury were partially reversed by 3BDO. This study suggests that selective inhibition of SIRT1 by EX-527 might alleviate endotoxemia-associated acute lung injury partially via suppression of mTOR, which implies that SIRT1 selective inhibitors might have potential value for the pharmacological intervention of inflammatory lung injury.

Associations between ambient wood smoke and other particulate pollutants and biomarkers of systemic inflammation, coagulation and thrombosis in cardiac patients

BackgroundIncreased particulate air pollution has been associated with both an increased risk of myocardial infarction (MI) and adverse changes in cardiac biomarkers. Up to 30% of ambient wintertime fine particles (PM2.5) in Rochester, NY are from wood burning. Our study examined associations between ambient levels of a marker of wood smoke (Delta-C) and other particulate air pollutants and biomarkers of inflammation, coagulation and thrombosis. MethodsWe measured blood concentrations of C-reactive protein (CRP), D-dimer, fibrinogen, P-selectin, platelet factor 4 (PF-4), von Willebrand factor (vWF), and myeloperoxidase (MPO) of 135 patients undergoing cardiac catheterization during the winters of 2011–2013. We coupled these data with hourly ambient concentrations of Delta-C, black carbon (BC; marker of traffic pollution), and ultrafine (10–100nm; UFP), accumulation mode (100–500nm; AMP), and fine particles (<2.5µm; PM2.5). Using linear regression models, we estimated the change in each biomarker associated with increased pollutant concentrations at intervals between 1 and 96h preceding blood collection. ResultsEach 0.13µg/m3 increase in Delta-C concentration in the prior 12h was associated with a 0.91% increase in fibrinogen levels (95% CI=0.23%, 1.59%), but unexpectedly in the prior 48h, each 0.17µg/m3 increase in Delta-C concentration was associated with a 2.75% decrease in MPO levels (95% CI=−5.13%,−0.37%). We did not see associations between Delta-C concentrations and any other biomarkers. Interquartile range (IQR) increases in PM2.5, BC, UFP, and AMP concentrations were generally associated with increased CRP and fibrinogen, but not PF4, D-dimer, vWF, or P-selectin. ConclusionsIn a population of cardiac patients, we noted adverse changes in fibrinogen associated with increased concentrations of a marker of wood smoke. Increases in PM2.5, BC, AMP, and UFP concentrations in the previous 96h were also associated with adverse changes in markers of systemic inflammation and coagulation, but not with markers of endothelial cell dysfunction or platelet activation.

The impact of arthrocentesis with and without hyaluronic acid injection in the prognosis and synovial fluid myeloperoxidase levels of patients with painful symptomatic internal derangement of temporomandibular joint: a randomised controlled clinical trial.

We aimed to assess the relationship between myeloperoxidase (MPO) and internal derangement (ID) of temporomandibular joint (TMJ) and effects of arthrocentesis procedure, either alone or in combination with hyaluronic acid (HA) injection on the prognosis of ID of TMJ. A prospective randomised controlled trial has been conducted through patients, who underwent arthrocentesis for the treatment of ID of TMJ, were randomly divided into two groups. Group SS (n=10) and Group HA (n=14) patients were assigned 0·9% NaCl solution and sodium hyaluronate intra-articularly, respectively. Synovial fluid samples were assayed for MPO at the time of arthrocentesis and pain visual analogue scale (VAS) and maximum mouth opening (MMO) scores were recorded at pre- and post-operative periods as well as first-week, first-month and third-month intervals. There was a statistically significant decrease in MPO levels between the first to second arthrocenteses only in Group 2 (P=0·001). Both VAS scores and MMO measurements decreased in the course of time following arthrocentesis and donot differ between the patients administered HA or SS. Similarly MPO levels do not change significantly between the two groups at either first or second arthrocenteses. In HA group, MPO levels significantly decreased from first to second sessions. In HA group, MPO levels decreased significantly only in patients with clinical success. Arthrocentesis procedure improves both pain VAS and MMO scores in the course of time, but these parameters do not differ between patients receiving either HA or SS. HA significantly reduces levels of MPO in synovial fluid, but SS does not. HA appears to alleviate inflammation inside the TMJ in patients with TMJ-ID.

Renoprotective effect of diosgenin in streptozotocin induced diabetic rats.

Diabetes mellitus is a multifactorial metabolic disorder associated with genesis of diabetes related vascular diseases. Oxidative stress along with inflammation is the major causative factor leading to diabetic complications. The present study examined the protective effect of diosgenin, a steroidal saponin, in diabetes induced early kidney injury. Diabetes was induced by streptozotocin (45mg/kg) in rats followed by treatment for 28 days with diosgenin (5, 10 and 20mg/kg, oral). Blood glucose levels, lipid profile, serum advanced glycation end-products, biomarkers of kidney damage like urinary protein excretion, kidney hypertrophy index and creatinine in serum and urine were determined. Biochemical analysis of oxidative stress parameters such as superoxide dismutase, catalase, reduced glutathione, lipid peroxidation (LPO) and myeloperoxidase level were evaluated in kidney homogenates. Histopathological evaluation of kidney was also studied. Treatment with diosgenin significantly ameliorated the altered oxidative stress levels in STZ induced diabetic rats resulting in decreased LPO and increased endogenous antioxidant levels in a dose-dependent manner. Blood glucose was significantly decreased at 20mg/kg. The distorted levels of biomarkers suggestive of kidney damage were significantly normalized by diosgenin providing protection to kidneys also confirmed by histopathological studies. Decreased myeloperoxidase levels in diosgenin treatment groups revealed its anti-inflammatory activity. The above study justifies diosgenin as a promising candidate in diabetes associated complication through its antioxidant and anti-inflammatory activity.

Protective Effects of Molsidomine Against Cisplatin-Induced Nephrotoxicity

Background. Cisplatin, an effective chemotherapeutic agent, is used for the treatment of several types of cancers. However, cisplatin has some severe side effects such as nephrotoxicity. On the other hand, molsidomine, a NO donor, has anti-oxidative and vasodilator effects.Objectives. The aim of this study was to estimate the protective effects of molsidomine on cisplatin-induced nephrotoxicity.Material and Methods. Thirty-two rats were randomly divided into 4 groups as follows: (1) control; (2) received a single-dose intraperitoneal (i.p.) injection of 5 mg/kg cisplatin; (3) received single i.p. dose of molsidomine (4 mg/kg/day) for 3 consecutive days before cisplatin treatment; (4) received single i.p. dose of molsidomine (4 mg/kg/day) for 3 consecutive days. The specific biochemical markers, including antioxidants, and the histopathological alterations were evaluated.Results. Cisplatin significantly increased malondialdehyde (MDA) and myeloperoxidase (MPO) levels and decreased glutathione peroxidase (GPX) level. Molsidomine significantly decreased MPO level nearly to control level; however, its ameliorating effects on MDA, SOD, CAT and GPX did not reach to significant levels. Cisplatin-induced elevation of blood-urea-nitrogen and serum-creatinine were diminished after molsidomine administration. Cisplatin also induced severe tubular degeneration, nuclear condensation, apoptosis and scattered patchy inflammation in the histological examination. Molsidomine improved all of these histological damages.Conclusion. In this study, the beneficial effect of molsidomine against cisplatin nephrotoxicity has been evaluated for the first time.

Protective Effects of Molsidomine Against Cisplatin-Induced Nephrotoxicity.

Cisplatin, an effective chemotherapeutic agent, is used for the treatment of several types of cancers. However, cisplatin has some severe side effects such as nephrotoxicity. On the other hand, molsidomine, aNO donor, has anti-oxidative and vasodilator effects. The aim of this study was to estimate the protective effects of molsidomine on cisplatin-induced nephrotoxicity. Thirty-two rats were randomly divided into 4 groups as follows: (1) control; (2) received asingle-dose intraperitoneal (i.p.) injection of 5mg/kg cisplatin; (3) received single i.p. dose of molsidomine (4mg/kg/day) for 3 consecutive days before cisplatin treatment; (4) received single i.p. dose of molsidomine (4mg/kg/day) for 3 consecutive days. The specific biochemical markers, including antioxidants, and the histopathological alterations were evaluated. Cisplatin significantly increased malondialdehyde (MDA) and myeloperoxidase (MPO) levels and decreased glutathione peroxidase (GPX) level. Molsidomine significantly decreased MPO level nearly to control level; however, its ameliorating effects on MDA, SOD, CAT and GPX did not reach to significant levels. Cisplatin-induced elevation of blood-urea-nitrogen and serum-creatinine were diminished after molsidomine administration. Cisplatin also induced severe tubular degeneration, nuclear condensation, apoptosis and scattered patchy inflammation in the histological examination. Molsidomine improved all of these histological damages. In this study, the beneficial effect of molsidomine against cisplatin nephrotoxicity has been evaluated for the first time.

The effects of topical melatonin on oxidative stress, apoptosis signals,and p53 protein expression during cutaneous wound healing

Elimination of reactive oxygen species (ROS) can be an important strategy to improve healing of wounds. ROS have an effect on proliferation and cell survival signaling, which results in alteration of apoptotic pathways in cells. Melatonin has antioxidant properties on skin wounds. In our study, we investigated the effects of topical melatonin (3%, w/w) on apoptosis and p53 protein expression together with parameters of oxidative stress in a cutaneous excision wound model. Bcl-2 protein levels in wound tissue at the end of days 3, 7, and 14 were significantly increased, while caspase-3 activity and p53 protein expression in wound tissue at the end of days 3, 7, and 14 were also reduced with melatonin treatment during wound healing. On days 3 and 7 after the wound, malondialdehyde level was reduced and glutathione was increased with melatonin treatment. Melatonin decreased myeloperoxidase levels and increased hydroxyproline levels in wound tissue at the end of day 7. However, melatonin had no significant effect on percentage of wound closure. Considering our results, topical melatonin displays antioxidant, antiapoptotic, and p53-inhibitory effects, but these effects are not sufficient for the acceleration of wound closure.

Antioxidant status and glutathione redox potential of erythrocytes in patients with acute coronary syndrome

Indicators of oxidative stress (OS), systemic inflammation, metabolism and redox status of glutathione (GSH) were investigated and compared in patients with ST-segment elevation myocardial infarction on electrocardiograms (STEMI), and patients with unstable angina (UA). The elevated and decreased myeloperoxidase level, superoxide dismutase activity, and moderate increased plasma levels of interleukin-6, while maintaining the antioxidant potential, were found in Group 1. Disorders in pro-/antioxidant balance and systemic inflammatory response were manifested in UA. Increased GSH concentration (and total GSH) in erythrocytes has been established for STEMI patients and the decreased GSH for UA patients. Thus, a significant shift of erythrocytes redox to oxidization and increase (unlike STEMI patients) of glutathione peroxidase activity were recorded. Mechanisms of the pro- and antioxidant functions of red blood cells in acute coronary syndrome are considered. The role of red blood cell glutathione to provide more oxidized intravascular environment for S-glutathionylation and optimization of redox signaling in target cells is pronounced.

Dietary grape seed extract ameliorates symptoms of inflammatory bowel disease in IL10‐deficient mice

Grape seed extract (GSE) is a by-product of the wine industry, with abundant polyphenolic compounds known for their anti-inflammatory and anti-oxidative effects. Using IL10-deficient mice (IL10KO), here we showed that GSE (1% of dry feed weight) ameliorated inflammatory bowel disease indices, increased colonic goblet cell numbers and decreased myeloperoxidase levels in the large intestine. Concomitantly, GSE supplementation attenuated inflammation, decreased the expression of pore forming tight junction protein claudin2, and increased levels of Lactobacilli and Bacteroides in the gut microbiota of IL10KO mice. In summary, our study shows that GSE has protective roles on inflammatory bowel disease through altering gut inflammation, tight junction protein expression, and gut microbiota composition.

6b,11b-Dihydroxy-6b,11b-dihydro-7H-indeno[1,2-b]naphtho[2,1-d]furan-7-one (DHFO), a small molecule targeting NF-κB, demonstrates therapeutic potential in immunopathogenic chronic inflammatory conditions

6b,11b-Dihydroxy-6b,11b-dihydro-7H-indeno[1,2-b]naphtho[2,1-d]furan-7-one (DHFO), an easily synthesisable, orally bioavailable and relatively non-toxic small molecule synthesised in our lab, was previously reported to possess anti-oxidant, 5-lipoxygenase inhibitory, anti-inflammatory and peripheral analgesic activities. The present work deals with exploration of DHFO's efficacy in immunopathogenic chronic inflammatory conditions — arthritis and allergy. In carrageenan-induced inflammatory air pouch, which resembles the arthritic synovium, DHFO effectively reduced inflammatory redness and swelling and neutrophil infiltration. In complete Freund's adjuvant-induced arthritis, DHFO significantly decreased paw oedema and nitrite levels with efficacy comparable to diclofenac. DHFO inhibited neutrophil activation (observed as decreased myeloperoxidase levels), in both the in vivo models of inflammation. Interestingly, DHFO did not ulcerate the gastrointestinal tract, while diclofenac was observed to be extremely ulcerogenic. In antigen-induced active and passive anaphylaxis (allergy) models, DHFO dose-dependently prevented mesenteric mast cell (MC) degranulation with efficacy comparable to ketotifen. DHFO also inhibited compound 48/80 (C48/80)-induced paw oedema and peritoneal MC degranulation. DHFO stabilised p815 murine MCs stimulated by C48/80 and calcium ionophore—A23187, indicating an action downstream of calcium mobilisation. DHFO's anti-allergic mechanism could be two-pronged involving (1) inhibition of IgE production and/or (2) MC stabilisation. DHFO inhibited lipopolysaccharide (LPS)-induced pro-inflammatory mediator release (ROS, NO, IL-6 levels) and COX2 expression in RAW264.7 murine macrophages. Protein expression studies confirmed DHFO's ability to reduce nuclear levels of NF-κB in LPS-stimulated macrophages. Thus, DHFO is a promising non-ulcerogenic synthetic small molecule lead for immunopathogenic chronic inflammatory conditions.

Ethylene-Vinyl Alcohol Copolymer Dialyzer Membrane Reduces Protein Oxidation in Hemodialysis Patients

Background: Oxidative stress has been implicated in the cardiovascular complications that affect hemodialysis (HD) patients. Ethylene-vinyl alcohol copolymer (EVAL) dialyzer membrane induces less production of reactive oxygen species as compared to conventional dialyzers. We evaluated the impact of EVAL membrane on plasma protein oxidation in HD patients. Methods: HD patients treated with cellulose triacetate (CTA) dialyzers were selected. In the first study performed in a 2-month crossover design alternating between CTA and EVAL, nonmercaptalbumin and advanced oxidation protein products levels were measured in the predialysis blood from 10 subjects. In the second study, predialysis plasma myeloperoxidase levels were measured before and after a 2-week EVAL treatment on 12 patients. Results: Plasma advanced oxidation protein products levels were reduced after a 2-month EVAL treatment and increased again after CTA treatment, although the nonmercaptalbumin proportions were not affected significantly by the change in dialyzer membranes. The following study, a 2-week EVAL treatment, showed the decrease in myeloperoxidase levels immediately before HD. Conclusion: The frequent use of EVAL dialyzers has been shown to reduce protein oxidation, possibly through the suppression of circulating phagocytes. This novel biocompatible dialyzer is expected to protect cardiovascular mortality in HD patients.

Effect of hydroxyethyl starch 130/0.4 on ischaemia/reperfusion in rabbit skeletal muscle

Tourniquet use is a common tool in surgical procedures of the limbs. Hydroxyethyl starch (HES) 130/0.4 not only has a role in replacement of the liquid deficits due to trauma, bleeding or shock, but it is also effective in enhancing tissue oxygen tension and regulation of microcirculation. The aim of this study was to investigate how 6% HES 130/0.4 affects ischaemia and reperfusion in skeletal muscle. An ischaemia/reperfusion model (3 and 2 h, respectively) was applied in 14 rabbits. Group S (n = 7) was infused with 0.9% NaCl (0.2 ml kg(-1) min(-1)) and group HES was infused with 6% HES 130/0.4 (0.2 ml kg(-1) min(-1)). The total liquid was divided into equal one-thirds and given in the preischaemia, ischaemia and reperfusion phases. Ketamine HCl (30 mg kg(-1)) was used for anaesthesia, and blood pressure, pulse and blood gases were monitored. Muscle biopsies were taken in the preischaemic (A), ischaemic (B) and reperfusion (C) phases. In these samples, nitrite, nitrate, reduced glutathione (GSH) and myeloperoxidase (MPO) were measured to assess oxidative stress elements, and malondialdehyde (MDA) was measured to assess lipid peroxidation. Repeated variance analysis, Mann-Whitney U test and Student's t test were used for statistical analysis of these parameters. In group S, the MPO levels were significantly increased in the reperfusion phase compared with baseline, whereas there was a decrease in MPO levels in the reperfusion period in the HES group. This difference between groups was statistically significant (P = 0.011). The results of this study showed that 6% HES 130/0.4 solution is more effective in the prevention of ischaemia/reperfusion injury than saline when given in the same volume.