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Aberrant TGF‑β/Smad7 signaling has been reported to be an important mechanism underlying the pathogenesis of ulcerative colitis. Therefore, the present study aimed to investigate the effects of a number of potential anti‑colitis agents on intestinal epithelial permeability and the TGF‑β/Smad7 signaling pathway in an experimental model of colitis. A mouse model of colitis was first established before anti‑TNF‑α and 5‑aminosalicyclic acid (5‑ASA) were administered intraperitoneally and orally, respectively. Myeloperoxidase (MPO) activity, histological index (HI) of the colon and the disease activity index (DAI) scores were then detected in each mouse. Transmission electron microscopy (TEM), immunohistochemical and functional tests, including Evans blue (EB) and FITC‑dextran (FD‑4) staining, were used to evaluate intestinal mucosal permeability. The expression of epithelial phenotype markers E‑cadherin, occludin, zona occludens (ZO‑1), TGF‑β and Smad7 were measured. In addition, epithelial myosin light chain kinase (MLCK) expression and activity were measured. Anti‑TNF‑α and 5‑ASA treatments was both found to effectively reduce the DAI score and HI, whilst decreasing colonic MPO activity, plasma levels of FD‑4 and EB permeation of the intestine. Furthermore, anti‑TNF‑α and 5‑ASA treatments decreased MLCK expression and activity, reduced the expression of Smad7 in the small intestine epithelium, but increased the expression of TGF‑β. In mice with colitis, TEM revealed partial epithelial injury in the ileum, where the number of intercellular tight junctions and the expression levels of E‑cadherin, ZO‑1 and occludin were decreased, all of which were alleviated by anti‑TNF‑α and 5‑ASA treatment. In conclusion, anti‑TNF‑α and 5‑ASA both exerted protective effects on intestinal epithelial permeability in an experimental mouse model of colitis. The underlying mechanism may be mediated at least in part by the increase in TGF‑β expression and/or the reduction in Smad7 expression, which can inhibit epithelial MLCK activity and in turn reduce mucosal permeability during the pathogenesis of ulcerative colitis.

Bothrops leucurus is responsible for most cases of snakebite in Northeast Brazil; however, this species is not included in the pool of venoms used in antivenom production in Brazil. The serotherapy has logistical and effectiveness limitations, which stimulates the search for therapeutic alternatives. Chlorogenic acid and rosmarinic acid present several biological activities, but their antiophidic potential has been poorly explored. Thus, the aim of this approach was to evaluate the potential inhibitory effects of these compounds on B. leucurus venom. Initially, the enzymatic inhibition of toxins was evaluated in vitro. Then, anti-hemorrhagic, anti-myotoxic, and anti-edematogenic assays were performed in vivo, as well analysis of several biochemical markers and hemostatic parameters. In addition, the interaction of inhibitors with SVMP and PLA 2 was investigated by docking analysis. Results revealed that compounds inhibited in vitro the enzymatic activities and venom-induced edema, with a decrease in both myeloperoxidase and interleukin quantification. The inhibitors also attenuated the hemorrhagic and myotoxic actions and mitigated changes in serum biochemical and hemostatic markers, as well as decreased lipid peroxidation in liver and kidney tissues. Docking analysis revealed attractive interactions of both inhibitors with the zinc-binding site of SVMP and, in the case of PLA 2 , chlorogenic acid showed a similar inhibition mechanism to that described for rosmarinic acid. The results evidenced the antiophidic potential of both compounds, which showed higher efficiency than antivenom serum. Thus, both inhibitors are promising candidates for future adjuvants to be used to complement antivenom serotherapy., (Copyright © 2022. Published by Elsevier Masson SAS.)

Background: Mastitis is a common disease occurs in breast-feeding mothers, but published data are poor. This study aimed to study the effects of Tanshinones on treating mastitis., Methods: Clinical trials performed in 58 breast-feeding mothers were carried out. B-ultrasound and blood test were used to measure the size of breast mass and the change of blood cell counts. BALB/c mice were injected with LPS and then treated by Tanshinone I or Tanshinone IIA/B. Myeloperoxidase (MPO) activity and the release of inflammatory cytokines were tested by MPO kit, RT-qPCR and ELISA. Mouse mammary epithelial cells (mMECs) were isolated and the effects of Tanshinones were measured by conducting CCK-8 assay, flow cytometry, RT-qPCR and ELISA., Results: Patients treated by Cefprozil combined with Tanshinone got better outcomes than patients treated by Cefprozil alone. In animal trials, Tanshinone I and Tanshinone IIA/B significantly reduced MPO activity, and the levels of TNF-α, IL-1β and IL-6 in serum and mammary gland tissues. In mMECs, Tanshinone I and Tanshinone IIA/B attenuated LPS-induced viability loss and apoptosis. And they effectively inhibited the release of TNF-α, IL-1β and IL-6. Also, Tanshinone I and Tanshinone IIA/B significantly attenuated LPS-evoked NF-κB activation., Conclusion: Tanshinone I and Tanshinone IIA/B have potentials in treating mastitis. The beneficial effects might be through regulating NF-κB activation., (Copyright © 2021. Published by Elsevier Masson SAS.)

This study aimed to examine the possible association between the oxidative stress parameters and clomiphene citrate resistance in polycystic ovary syndrome. The demographic data, hormone profiles and oxidant and antioxidant values of 50 clomiphene citrate-resistant polycystic ovary syndrome patients (Group 1), 32 clomiphene citrate-sensitive polycystic ovary syndrome patients (Group 2) and 87 non-polycystic ovary syndrome patients (Group 3) were compared. The average age, follicle-stimulating hormone, oestradiol, thyroid-stimulating hormone and prolactin values of the three groups were found to be homogeneous. Ferroxidase, catalase and myeloperoxidase levels were determined to be lower in the clomiphene citrate-resistant group compared to clomiphene citrate-sensitive and non-polycystic ovary syndrome groups ( p  < .001). As a result, Polycystic ovary syndrome patients with clomiphene resistance had lower antioxidant (catalase and ferroxidase) levels compared to those who were sensitive to clomiphene and who did not have polycystic ovary syndrome. The myeloperoxidase levels also demonstrated the same trend, which might be due to a compensation mechanism.Impact Statement What is already known on this subject? In the literature, there are many studies evaluating the association between PCOS and oxidative stress. No research related to antioxidants in clomiphene citrate-sensitive and clomiphene citrate-resistant PCOS patients was found in the relevant literature. What do the results of this study add? In this study, the antioxidants catalase and ferroxidase were found to be lower in PCOS women compared to non-PCOS; however, they were the lowest in clomiphene citrate-resistant PCOS women. Interestingly, myeloperoxidase, which is a part of oxidative stress, was also found to be higher in the non-PCOS group. What are the implications of these findings for clinical practice and/or further research? This study contributes to the literature because it is the first to compare the relation between CC and oxidant and antioxidant markers. These markers will be a guide for PCOS management in patients with CC-R.

Background/aim: Premature birth is a major problem that results in an increased risk of mortality and morbidity. The management of such infants consists of supraphysiological oxygen therapy, which affects brain development due, in part, to the deterioration caused by reactive oxygen species (ROS). We showed previously that exogenously administered uridine provides neuroprotection in a neonatal rat model of hyperoxic brain injury. Hence, the aim of the present study was to investigate the effects of uridine on ROS in the same setting., Materials and Methods: Hyperoxic brain injury was induced by subjecting a total of 53 six-day-old rat pups to 80% oxygen (the hyperoxia group) for a period of 48 h. The pups in the normoxia group continued breathing room air (21% oxygen). Normoxia + saline or hyperoxia + saline or hyperoxia + uridine 100 mg/kg or hyperoxia + uridine 300 mg/kg or hyperoxia + uridine 500 mg/kg was injected intraperitoneally (i. p.) 15 min prior to the hyperoxia procedure. The pups were decapitated and the brains were homogenized to analyze superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), and malondialdehyde (MDA) enzymes as well as DJ-1 (protein deglycase DJ-1) — an oxidative stress-sensitive protein., Results: Hyperoxia-induced may cause overproduction of oxygen radicals and the oxidant/antioxidant balance may be disturbed in the brain. Brain MPO and MDA levels were significantly increased in saline-receiving pups exposed to hyperoxia. Brain SOD and GSH-Px levels were significantly decreased in saline-receiving pups exposed to hyperoxia. Our results showed that uridine administration prevented the hyperoxia-induced decrease in SOD and GSH-Px while counteracting the hyperoxia-induced increase in MPO and MDA in a dose-dependent manner. Uridine also increased the DJ-1 levels in brains of rat pups subjected to hyperoxia., Conclusion: These data suggest that uridine exhibits antioxidative properties which may mediate the protective effects of uridine in a neonatal rat model of hyperoxic brain injury., Competing Interests: The authors declare no conflicts of interest with regard to the present study., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

The present study was performed to evaluate the anti-ulcerogenic activity of Acacia senegal (Gum Arabic) against ethanol-induced gastric mucosal injury in rats. Thirty-six adult male albino rats were divided into 4 groups: group 1 served as a control; group 2 consisted of rats that received 15% of gum in drinking water for 2 weeks; group 3 comprised ulcerated animals administered 5 mL of ethanol/kg body weight by gavage; and group 4 consisted of rats received 15% of gum in drinking water for 2 weeks before ethanol administration. Superoxide dismutase (SOD) glutathione peroxidase (GPx), malondialdehyde (MDA), prostaglandin E 2 (PGE 2 ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-B1), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein, and albumin were assayed in addition to histological study. The results revealed that ethanol decreased SOD, GPx, and PGE 2 in tissue and serum total protein and albumin, while increased MDA in tissue, serum TNF-α, IL-B1, PGE 2 , ALT, AST, and ALP. Histological findings showed less edema and leucocytes infiltration compared with ulcer group. Furthermore, gum administration elevated PGE 2 , SOD, and GPx and significantly reduced MDA, TNF-α, and IL-B2. In conclusion, Gum Arabic can enhance gastric protection and sustain the integrity of the gastric mucosa. Novelty The selected dose of Gum Arabic has the ability to decrease the pro-inflammatory cytokines in plasma and gastric tissue, thus enhancing gastric protection and maintaining the integrity of the gastric mucosa. Gum Arabic can compensate for the loss of antioxidants.

Vincetoxicum arnottianum (Wight) of family Apocynaceae is a rich source of therapeutic alkaloids, phenolics and flavonoids. Study aims to evaluate the protective potential of methanol extract of Vincetoxicum arnottianum (VAM) on bisphenol A (BPA)-induced testicular toxicity in male Sprague Dawley rat. Quantitative analysis of VAM for total phenolic (TPC), total flavonoid (TFC) and total alkaloid content (TAC) along with HPLC analysis for polyphenolics was carried out. BPA-induced testicular toxicity was determined through analysis of antioxidant enzymes, DNA damages and testicular histopathology along with reproductive hormones in serum of rat. VAM was constituted of TFC (382.50 ± 1.67 μg GAE/mg), TPC (291.17 ± 0.82 μg RE/mg), TAC (16.5 ± 0.5%), ferulic acid (2.2433 μg/mg) and vanillic acid (2.1249 μg/mg). VAM co-administration to BPA-treated rats attenuated the toxic effects of BPA and restored the body and testis weights. Altered level of luteinizing hormone (LH), testosterone and follicle-stimulating hormone (FSH) in serum, and level of antioxidants (GSH, POD, CAT and SOD) and nitric oxide in testis tissues of BPA-induced toxicity were significantly restored by VAM. Histological and comet assay studies also sanctioned the protective potential of VAM in BPA-intoxicated rats. The presence of polyphenols and alkaloids might contribute towards the scavenging and ameliorative potential of VAM in testicular toxicity induced by BPA., (© 2020 Blackwell Verlag GmbH.)

Chemical safety evaluation is in the midst of a transition from traditional whole-animal toxicity testing to molecular pathway-based in vitro assays and in silico modeling. However, to facilitate the shift in reliance on apical effects for risk assessment to predictive surrogate metrics having characterized linkages to chemical mechanisms of action, targeted in vivo testing is necessary to establish these predictive relationships. In this study, we demonstrate a means to predict thyroid-related metamorphic success in the model amphibian Xenopus laevis using relevant biochemical measurements during early prometamorphosis. The adverse outcome pathway for thyroperoxidase inhibition leading to altered amphibian metamorphosis was used to inform a pathway-based in vivo study design that generated response-response relationships. These causal relationships were used to develop Bayesian probabilistic network models that mathematically determine conditional dependencies between biochemical nodes and support the predictive capability of the biochemical profiles. Plasma thyroxine concentrations were the most predictive of metamorphic success with improved predictivity when thyroid gland sodium-iodide symporter gene expression levels (a compensatory response) were used in conjunction with plasma thyroxine as an additional regressor. Although thyroid-mediated amphibian metamorphosis has been studied for decades, this is the first time a predictive relationship has been characterized between plasma thyroxine and metamorphic success. Linking these types of biochemical surrogate metrics to apical outcomes is vital to facilitate the transition to the new paradigm of chemical safety assessments., (Published by Oxford University Press on behalf of the Society of Toxicology 2020. This work is written by US Government employees and is in the public domain in the US.)

The aim of the present study was to investigate the antioxidant mechanisms of dexmedetomidine against lung injury during intestinal ischemia reperfusion (IIR) in rats. The model of IIR‑induced acute lung injury was established by occluding the superior mesenteric artery (SMA) for 1 h and reperfusing for 2 h using Sprague‑Dawley rats. Pathological examination was used to assess the extent of the lung injury. Oxidative stress was evaluated by measuring malondialdehyde, myeloperoxidase and superoxide dismutase in the lung and plasma. The proinflammatory cytokines tumor necrosis factor‑α and interleukin‑6 were determined via an enzyme‑linked immunosorbent assay. The mRNA and protein expression of nuclear factor‑erythroid 2 related factor 2 (Nrf2) and heme oxygenase 1 (HO‑1) were determined using a reverse transcription‑quantitative polymerase chain reaction and western blotting. Pretreatment with dexmedetomidine significantly inhibited the oxidative stress response and proinflammatory factor release caused by IIR compared with the normal saline group (MDA and SOD in lung and plasma, P<0.05; MPO, IL‑1β and TNF‑α in lung and plasma, P<0.05). Dexmedetomidine improved pulmonary pathological changes in IIR rats compared with the normal saline group. Investigations into the molecular mechanism revealed that dexmedetomidine increased the expression levels of Nrf2 and HO‑1 via activating α2 adrenergic receptors compared with the normal saline group. The antagonism of α2 adrenergic receptors may reverse the protective effect of dexmedetomidine on lung injury during IIR, including decreasing the expression levels of Nrf2 and HO‑1, elevating the oxidative stress response and increasing the proinflammatory factor release. In conclusion, pretreatment with dexmedetomidine demonstrated protective effects against lung injury during IIR via α2 adrenergic receptors. The Nrf2/HO‑1 signaling pathway may serve a function in the protective effect of dexmedetomidine.

Background: Exogenous 6-benzyladenine (6-BA) could improve leaf defense system activity. In order to better understand the regulation mechanism of exogenous 6-benzyladenine (6-BA) on waterlogged summer maize, three treatments including control (CK), waterlogging at the third leaf stage for 6 days (V3-6), and application of 100 mg dm - 3 6-BA after waterlogging for 6 days (V3-6-B), were employed using summer maize hybrid DengHai 605 (DH605) as the experimental material. We used a labeling liquid chromatography-based quantitative proteomics approach with tandem mass tags to determine the changes in leaf protein abundance level at the tasseling stage., Results: Waterlogging significantly hindered plant growth and decreased the activities of SOD, POD and CAT. In addition, the activity of LOX was significantly increased after waterlogging. As a result, the content of MDA and H 2 O 2 was significantly increased which incurred serious damages on cell membrane and cellular metabolism of summer maize. And, the leaf emergence rate, plant height and grain yield were significantly decreased by waterlogging. However, application of 6-BA effectively mitigated these adverse effects induced by waterlogging. Compared with V3-6, SOD, POD and CAT activity of V3-6-B were increased by 6.9, 12.4, and 18.5%, LOX were decreased by 13.6%. As a consequence, the contents of MDA and H 2 O 2 in V3-6-B were decreased by 22.1 and 17.2%, respectively, compared to that of V3-6. In addition, the leaf emergence rate, plant height and grain yield were significantly increased by application of 6-BA. Based on proteomics profiling, the proteins involved in protein metabolism, ROS scavenging and fatty acid metabolism were significantly regulated by 6-BA, which suggested that application of 6-BA exaggerated the defensive response of summer maize at proteomic level., Conclusions: These results demonstrated that 6-BA had contrastive effects on waterlogged summer maize. By regulating key proteins related to ROS scavenging and fatty acid metabolism, 6-BA effectively increased the defense system activity of waterlogged summer maize, then balanced the protein metabolism and improved the plant physiological traits and grain yield.

Background Despite advances in immunomodulatory agents, most current therapies for multiple sclerosis target lymphocytes or lymphocytic function. However, therapy response may be less than optimal due to demyelination and axonal damage caused by myeloid cells. Purpose To determine if myeloperoxidase (MPO) molecular MRI can evaluate whether combination therapy targeting both lymphoid and myeloid inflammation can improve autoimmune neuroinflammation compared with either drug alone, even at suboptimal doses. Materials and Methods Four groups of 94 female mice (8-10 weeks old) were induced with experimental autoimmune encephalomyelitis (EAE) from August 2, 2016, to March 30, 2018, and divided into saline control ( n = 22), 4-aminobenzoic acid hydrazide (ABAH) therapy group ( n = 19), glatiramer acetate (GA) therapy group ( n = 22), and combination therapy group ( n = 31). Mice were administered suboptimal doses of ABAH, an irreversible inhibitor of MPO; GA, a first-line multiple sclerosis drug; both ABAH and GA; or saline (control). Mice were imaged with bis -5-hydroxytryptamide-diethylenetriaminepentaacetate gadolinium (hereafter, MPO-Gd) MRI. One-way analysis of variance, two-way analysis of variance, Kurskal-Wallis, and log-rank tests were used. P < .05 was considered to indicate statistical significance. Results The combination-treated group showed delayed disease onset (day 11.3 vs day 9.8 for ABAH, day 10.4 for GA, day 9.9 for control; P < .05) and reduced disease severity (clinical score during the acute exacerbation period of 1.8 vs 3.8 for ABAH, 3.1 for GA, 3.9 for control; P < .05). The combination-treated group demonstrated fewer MPO-positive lesions (30.2 vs 73.7 for ABAH, 64.8 for GA, 67.2 for control; P < .05), smaller MPO-positive lesion volume (16.7 mm 3 vs 65.2 mm 3 for ABAH, 69.9 mm 3 for GA, 66.0 mm 3 for control; P < .05), and lower intensity of MPO-Gd lesion activation ratio (0.7 vs 1.9 for ABAH, 3.2 for GA, 2.3 for control; P < .05). Reduced disease severity in the combination group was confirmed at histopathologic analysis, where MPO expression (1779 vs 2673 for ABAH, 2898 for GA; P < .05) and demyelination (5.3% vs 9.0% for ABAH, 10.6% for GA; P < .05) were ameliorated. Conclusion Myeloperoxidase molecular MRI can track the treatment response from immunomodulatory drugs even if the drug does not directly target myeloperoxidase, and establishes that combination therapy targeting both myeloid and lymphocytic inflammation is effective for murine autoimmune neuroinflammation, even at suboptimal doses. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Walczak in this issue.

Pogonatherum crinitum is a promising lead (Pb) hyperaccumulator due to its high Pb tolerance and accumulation ability. However, the mechanisms that support Pb accumulation and tolerance in P. crinitum are not yet clearly understood. An indoor hydroponic experiment was conducted by cultivating P. crinitum seedlings exposed to intermittent Pb stress for 60 days, divided into four stages (T1, T2, T3 and T4), with a 15-day duration per stage. The following concentrations of Pb were used: 0, 500, 0, 500 mg·l -1 and 0, 1000, 0, 1000 mg·l -1 ). Antioxidant enzyme activity, Pb concentration and subcellular distribution of Pb were measured at each of the above stages. The results showed that superoxide dismutase (SOD) activity in shoots, and SOD, peroxidase (POD) and malondialdehyde (MDA) activity in shoots and roots significantly increased from T1 (no Pb stress) to T2 (Pb stress) in both 500 mg·l -1 and 1000 mg·l -1 treatments; however, no significant difference was noted between stages T3 (no Pb stress) and T4 (Pb stress). There was no obvious effect of Pb stress on catalase (CAT) activity in shoots and roots among different stages. The Pb concentration in shoots was up to 5090.90 mg·kg -1 and 7573.57 mg·kg -1 , and the bioconcentration factor (BFC) was 10.18 and 7.57 for the 500 mg·l -1 and 1000 mg·l -1 treatments, respectively, which confirmed the Pb hyperaccumulator characteristics of P. crinitum. For plants under Pb stress, most of the Pb was fixed in the cell walls, with a smaller amount in leaves and root vacuoles. Both SOD and POD scavenging of reactive oxygen radicals and fixing and compartmentalisation of Pb in the cell wall might play important roles in detoxification of P. crinitum seedlings in response to Pb stress. There was no phased response of P. crinitum to intermittent Pb stress and the physiological response to Pb stress may be contiguous., (© 2019 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.)

Objectives: Epiisopiloturine (EPI) and epiisopilosine (EPIIS) are side products in the pharmaceutical industry. The present study aimed to investigate the anti-inflammatory potential of the alkaloids EPI and EPIIS in human neutrophils and mechanical hyperalgesia in mice., Methods: Neutrophils (5 × 10 6  cells/ml) incubated with EPI and EPIIS and stimulated by the addition of N-formyl-methionyl-leucyl-phenylalanine or phorbol 12-myristate-13-acetate. The release of myeloperoxidase (MPO), reactive oxygen species (ROS) production, calcium influx, gene expression of NF-κB and pro-inflammatory cytokines production were evaluated. It was also investigated the effect these alkaloids on carrageenan-induced mechanical hyperalgesia model in mice., Key Findings: We demonstrated that both EPI and EPIIS inhibited the degranulation of activated neutrophils. This effect was accompanied by the reduction in ROS, the prevention of the increase in intracellular Ca 2+ and decrease in the density of cytosolic NF-κB, and inhibition of TNF-α and IL-6 production. Evaluating hypernociception in mice, EPI and EPIIS inhibited carrageenan-induced inflammatory hypernociception and reduced MPO levels., Conclusions: The results obtained suggest EPI and EPIIS not only inhibit neutrophils functions in vitro, but also exhibits anti-inflammatory properties in vivo, acting through the modulation of the activation and/or accumulation of neutrophils in the inflammatory focus. Thus, EPI and EPIIS possess promising anti-inflammatory therapeutic potential., (© 2019 Royal Pharmaceutical Society.)

Oxandrolone is a synthetic oral non-aromatizable testosterone derivative. This drug has been used successfully for several decades to safely treat growth delays in various diseases including Turner's syndrome. Currently the use of oxandrolone is under clinical testing in children with burn injury; the available data indicate that the anabolic steroid increases net muscle protein balance, maintains lean body mass, and reduces intensive care unit stay. Although oxandrolone is already in clinical trials in burn patients, preclinical burn-related studies with oxandrolone - especially those that go beyond muscle-related parameters and focus on burn-associated organ dysfunction, inflammatory response and wound healing - remain to be conducted. In the current project, using a well-characterized murine model of third-degree burn, we have tested the effect of oxandrolone on indices of organ injury, clinical chemistry parameters and plasma levels of inflammatory mediators. In oxandrolone-treated mice (1mg/kg/day for up to 21 days) there was a significant amelioration of burn-induced accumulation of myeloperoxidase levels in heart and lung (but not the liver and kidney) and significantly lower degree of malon dialdehyde accumulation in the liver (but not the heart, lung and kidney). Oxandrolone-treated mice showed a significant attenuation of the burn-induced elevation in circulating alkaline aminotransferase and amylase levels, while blood urea nitrogen and creatinine levels remained unaffected, indicative of protective effects of the anabolic hormone against burn-induced hepatic and pancreatic (but not renal) functional impairment. Multiple burn-induced inflammatory mediators (TNF-α, IL-1α, IL-1β, IL-4, IL-6, IL-10, IL-12, IP-10, G-CSF, GM-CSF and interferon-γ) were significantly lower in the plasma of oxandrolone-treated animals after burn injury than in the plasma of controls subjected to burns. Finally, oxandrolone significantly accelerated burn wound healing. We conclude that oxandrolone improves organ function, modulates the systemic inflammatory response and accelerates wound healing in a murine model of burn injury., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Background: Calcitonin gene-related peptide (CGRP) has antioxidant and anti-inflammatory activities on the pathological damage of acute pancreatitis. However, its molecular mechanism on severe acute pancreatitis (SAP) remains unknown., Aims: To evaluate the influence of CGRP-mediated p38MAPK signaling pathway in rats with SAP., Methods: SD rats were randomly divided into Sham group, SAP group, CGRP group (SAP rats injected with CGRP), SB203580 group (rats injected with p38MAPK pathway inhibitor SB203580), and CGRP8-37 group (SAP rats injected with CGRP8-37). Serum amylase and lipase activities were determined. Histopathological observations were evaluated, and the expression of inflammatory cytokines and oxidative stress-related indexes were measured., Results: Compared with Sham group, SAP rats were increased in the activities of serum amylase and lipase, the pathologic assessment of pancreatic tissue, the levels of TNF-α, IL-1β, IL-6, and IL-8, the content of MDA and MPO, and the expressions of CGRP, and p-p38MAPK protein, but they were decreased in SOD activity and GSH content. The above alterations were aggravated in the CGRP8-37 group when compared with SAP group. Besides, in comparison with SAP group, rats in the CGRP and SB203580 groups presented a reduction in the activities of serum amylase and lipase, the levels of inflammatory cytokines, the content of MDA and MPO, and the expressions of p-p38MAPK protein, while showed an elevation in SOD activity and GSH content., Conclusion: Pretreatment with CGRP alleviated oxidative stress and inflammatory response of SAP rats possibly by suppressing the activity of p38MAPK pathway, and thereby postponing the disease progression.

Alpinetin, a type of novel plant flavonoid derived from Alpinia katsumadai Hayata, has been reported to have anti-inflammatory effects. The aim of this investigation was designed to reveal the protective effects of alpinetin on Lipopolysaccharide (LPS)/d-galactosamine (D-Gal)-induced liver injury in mice. Alpinetin (12.5, 25, 50 mg/kg) were given 1 h before LPS and D-Gal treatment. 12 h after LPS and D-Gal treatment, the liver tissues and serum were collected. Our results showed that alpinetin treatment improved liver histology, indicating a marked decrease of inflammatory cell infiltration and restore hepatic lobular architecture. Alpinetin also inhibited liver myeloperoxidase (MPO) activity and malondialdehyde (MDA) level. Furthermore, LPS/D-Gal-induced tumor necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β) production were dose-dependently inhibited by alpinetin. Alpinetin also attenuated LPS/D-Gal-induced expression of phospho-NF-κB p65 and phospho-IκBα. In addition, alpinetin was found to increase the expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). In conclusion, these findings suggested that alpinetin inhibited liver injury through inhibiting NF-κB and activating the Nrf2 signaling pathway., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Ultraviolet B radiation represents 10% of the total UV radiation that reaches the Earth's surface, being the primary responsible for the biological effects related to skin cancer and photoaging. Ilex Paraguariensis A. St. Hil., known as Yerba mate (YM), is a native tree of South America whose polyphenols in its leaves are described to exhibit photochemoprotective effect and are employed in the treatment of cancer. Additionally, the polyphenols are used to prevent lipid peroxidation and reduce the UV-induced damage, which ultimately decreases the oxidative stress. Thus, the present study aimed to characterize a new YM extract, evaluate the extract cytotoxicity and develop a formulation containing YM extract to prevent UVB-induced damage in mice skin. The YM extract showed high levels of polyphenols, flavonoids, and tannins and exhibited excellent antioxidant activity. Its main components were suggested as chlorogenic acid (1.92%) and caffeic acid (0.41%). Besides, YM extract did not exhibit cytotoxicity in fibroblasts and decreased the activity of myeloperoxidase and metalloproteinase-2 after acute UVB exposure. As a result, the formulation containing the YM extract showed a potential photochemoprotective., (Copyright © 2018. Published by Elsevier B.V.)

Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are clinical conditions caused by trauma, lung infection or sepsis. ALI/ARDS is associated with massive recruitment of neutrophils into the lung with release of reactive oxygen species and excessive inflammatory response that damage alveolar tissue. Here we report the successful use of a potent recombinant chemotaxis inhibitory protein (rCHIPS) derived from Staphylococcus aureus in reducing the severity of ALI/ARDS. Treatment with rCHIPS reduces pulmonary inflammation and permeability in mice after intranasal administration of lipopolysaccharide (LPS). rCHIPS treatment significantly reduces lung myeloperoxidase (MPO) activity, pro-inflammatory cytokines, broncho-alveolar lavage (BAL) fluid protein content as well as histopathological changes. In addition, treatment with rCHIPS significantly diminishes neutrophils and leukocytes recruitment into lung tissue after LPS administration and hence protects mice from reactive oxygen species mediated lung injury. Our finding reveals potential therapeutic benefits of using rCHIPS for the treatment of ALI/ARDS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Acute lung injury (ALI) is a serious disease with morbidity and mortality in patients. Engeletin (dihydrokaempferol 3-rhamnoside) is a flavanonol glycoside. It can be found in the skin of white grapes and white wine and is widely distributed in southeast Asia. In our study, we evaluated the protective and therapeutic effects of engeletin on lipopolysaccharide (LPS)-induced ALI in animal model. We determined the level of peroxisome proliferator-activated receptor-γ (PPAR-γ), nuclear factor kappaB (NF-κB), and IκBα by western blotting. The myeloperoxidase (MPO) activity and lung wet/dry (W/D) ratio in lung tissues were also detected. Histopathological changes and the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β were determined by H&E staining and ELISA. The MPO activity and lung W/D ratio induced by LPS were attenuated by engeletin. The numbers of inflammatory cells and the levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were ameliorated by engeletin. Furthermore, the results also showed that engeletin significantly suppressed LPS-induced NF-κB activation. The expression of PPAR-γ was upregulated by treatment of engeletin. In conclusion, we found that engeletin had protective and therapeutic effects against LPS-induced ALI by activating PPAR-γ. Engeletin is a potentially effective agent for the treatment of lung injury.

CP is a copper-containing ferroxidase of blood plasma, which acts as an acute phase reactant during inflammation. The effect of oxidative modification of CP induced by oxidants produced by MPO, such as HOCl, HOBr, and HOSCN, on its spectral, enzymatic, and anti-inflammatory properties was studied. We monitored the chemiluminescence of lucigenin and luminol along with fluorescence of hydroethidine and scopoletin to assay the inhibition by CP of the neutrophilic respiratory burst induced by PMA or fMLP. Superoxide dismutase activity of CP and its capacity to reduce the production of oxidants in respiratory burst of neutrophils remained virtually unchanged upon modifications caused by HOCl, HOBr, and HOSCN. Meanwhile, the absorption of type I copper ions at 610 nm became reduced, along with a drop in the ferroxidase and amino oxidase activities of CP. Likewise, its inhibitory effect on the halogenating activity of MPO was diminished. Sera of either healthy donors or patients with Wilson disease were co-incubated with neutrophils from healthy volunteers. In these experiments, we observed an inverse relationship between the content of CP in sera and the rate of H 2 O 2 production by activated neutrophils. In conclusion, CP is likely to play a role of an anti-inflammatory factor tempering the neutrophil respiratory burst in the bloodstream despite the MPO-mediated oxidative modifications.

Previous studies on the ability of caffeine to enhance endurance and boost performance have focused on theenergy substrates that are utilized by the skeletal muscle and the brain but nothing of such has been reported on cardiactissue. This study was designed to investigate the effect of caffeine on cardiac tissue metabolism in the rabbit. The study wascarried out on adult male New Zealand rabbits divided into 3 groups (n=5). Group I rabbits served as control and were given0.5ml/Kg of normal saline while group II and III rabbits were administered with 2mg/Kg and 6mg/kg of caffeine respectivelyfor 28 days. Blood samples were collected by retro orbital puncture for biochemical analysis. Animals were sacrificed bycervical dislocation and cardiac tissue biopsies were collected for biochemical and immunohistochemical analysis. Cardiactissue glycogen concentration was determined by anthrone reagent method. Cardiac tissue CPT 1 activity and cAMPconcentration were determined by immunohistochemistry and colorimetry techniques respectively, with assay kits obtainedfrom Biovision Inc. The results showed that Caffeine at 2 and 6 mg/kg significantly inhibited MPO activity from 0.72±0.05to 0.164±0.045 and 0.46±0.12 U/L respectively (p<0.05). Caffeine at 2mg/kg had no effect on serum nitric oxide but at6mg/Kg, it significantly increased serum nitric oxide form 28.01±6.53 to 45.25±3.88µM of nitrite (p<0.05). Also, Caffeineat 2 and 6mg/kg increased cardiac tissue glycogen from 15.62±0.73 to 40.69±6.35 and 38.82±6.91mg/100g respectively andcarnitine palmytol transferase 1 activity from 18.3 to 20 and 25.2% respectively. In conclusion, the study showed that caffeineconsumption increased CPT 1 activity suggesting increased utilization of free fatty acids for energy metabolism and sparingof cardiac tissue glycogen by mechanism(s) which probably involved blockade of A1 adenosine receptors and cAMPsignaling pathway.

Most herbicides applied in crop field, stay in the soil for a period, affecting next crop or even the plants using as green manure. Nowadays, the use of herbicides grow to increase productivity, mainly in the grain producing region north of Rio Grande do Sul state. The objective of this study was to evaluate the effects of herbicides fomesafen and sulfentrazone on antioxidant system in Avena sativa1, Vicia sativa2, Raphanus sativus and Lupinus albus. The plants were exposed to varying concentrations of fomesafen3 (0, 0.125, 0.25 and 0.5 kg ha -1) and sulfentrazone (0, 0.3, 0.6 and 1.2 kg ha-1). For this, the activities of, ascorbat peroxidase, catalase and guaiacol enzymes were analyzed, and the levels of MDA were quantificated. Fomesafen and sulfentrazone promoted alterations in balance of plants generating oxidative stress and elicited the response of the antioxidant system of plants, mainly in the high doses of fomesafen, for the species V. sativa and R. sativus. At the same time, the 1,2 kg ha -1 dose of sulfentrazone generated lipid peroxidation for V. sativa, R. sativus and L. albus. Additionally, A. sativa was the species that demonstrated low alterations on antioxidant system with the exposure to herbicide fomesafen and sulfentrazone. Thus, we can we can suggest that the species present a better response in defense of the oxidative stress generated by the herbicides.

The factors that trigger the pathophysiology of Parkinson's disease (PD) are unknown. However, it is suggested that environmental factors, such as exposure to pesticides, play an important role, in addition to genetic predisposition and aging. Early signs of PD can appear in the gastrointestinal (GI) tract and in the olfactory system, preceding the onset of motor impairments by many years. The present study assessed the effects of oral rotenone administration (30 mg/kg) in inducing GI and olfactory dysfunctions associated with PD in mice. Here we show that rotenone transiently increased myeloperoxidase activity within 24 h of administration. Leucocyte infiltration in the colon, associated with histological damage and disrupted GI motility, were observed following treatment with rotenone for 7 days. Moreover, 7 days of treatment with rotenone disrupted olfactory discrimination in mice without affecting social recognition ability. The presence of specific deficits in olfactory function occurred with a concomitant decrease in tyrosine hydroxylase-positive neurons and an increase in serotonin (5-hydroxytryptamine) turnover in the olfactory bulb. These findings suggest that in Swiss mice, exposure to rotenone induces GI and olfactory dysfunction involving immunological and neurotransmitter alterations, similar to early signs of PD. This provides further evidence for the involvement of the gut-brain axis in PD.

Background: Peroxisome proliferator-activated receptor-gamma (PPARγ) exerts anti-inflammatory effects and is therefore a potential target in ulcerative colitis (UC). A novel PPARγ agonist (AS002) developed for local action was evaluated ex vivo in biopsies from UC patients and in vivo in mice with low-grade dextran sodium sulfate (DSS)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis., Methods: Colonic biopsies from UC patients (n = 18) and healthy controls (n = 6) were incubated with AS002 or rosiglitazone (positive control) to measure mRNA expression of the PPARγ-responsive gene ADIPOPHILIN and protein levels of UC-related cytokines (enzyme-linked immunosorbent assay). AS002 absorption was determined in the colonic mucosa of UC patients. DSS-colitis mice received PPARγ agonists or vehicle daily by intrarectal administration starting 2 days before induction of colitis (preventive) or from days 3 to 8 (curative). Myeloperoxidase (MPO) and cytokine levels in colonic mucosa were determined. In addition, AS002 effects were studied in TNBS colitis., Results: AS002 displayed an absorption pattern of a lipophilic drug totally metabolized in the mucosa. AS002 and rosiglitazone increased ADIPOPHILIN mRNA expression (3-fold) and decreased TNF-α, IL-1β, and IL-13 levels in human UC biopsies. In DSS, in both preventive and curative treatment and in TNBS colitis, AS002 protected against macroscopic and histological damage and lowered MPO and TNF-α, IL-1β, and IL-13 levels., Conclusions: AS002 triggers anti-inflammatory PPARγ activity in the human colonic mucosa of UC patients and prevents and reverses colitis in mice. Our data suggest that AS002 has potential for topical maintenance treatment of UC, which warrants further studies in vivo in patients.

Objective: The objective of this study was to determine the expression, and effect of targeting CD11b with a monoclonal antibody in ovarian cancer cells., Methods: CD11b expression was determined in epithelial ovarian cancer (EOC) cell lines and tissues by immunofluorescence and flow cytometry. Cytotoxicity of the CD11b antibody and synergism with chemothearapeutic drugs were determined by the MTT Cell Proliferation Assay in human macrophages, normal ovarian epithelial cells, and in both sensitive and chemoresistant EOC cell lines. Cell migration was assessed with a scratch assay and in vivo effects of the CD11b antibody was assessed with a nude mouse ovarian cancer xenograft model. Data was analyzed with either t-tests or one-way ANOVA., Results: CD11b was unexpectedly expressed in several EOC lines and tissues, but not normal tissues. Targeting CD11b with its monoclonal antibody resulted in intriguing cytotoxic effects in sensitive and chemoresistant EOC lines, while surprisingly not affecting normal cells. More importantly, the cytotoxicity of the CD11b antibody when combined with chemotherapeutic drugs (cisplatin or docetaxel) was significantly synergistic, in both sensitive and chemoresistant EOC cells. The anti-tumorigenic effect of the CD11b antibody was confirmed in an ovarian cancer nude mouse xenograft model., Conclusion: Here we identify CD11b as a novel target, which selectively induces cytotoxicity in ovarian cancer cells., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Objectives: Human serum albumin (HA) is a unique multifunctional protein with neuroprotective properties. We aimed to delineate the mechanisms of HA-induced neuroprotection, supresses inflammatory response and lipid peroxidation after spinal cord injury (SCI)., Methods and Study Design: Adult female Wistar rats weighing 210-250 g were used for the study. The rats were randomly and blindly allocated into five groups. The one-way analysis of variance (ANOVA) for parametric data and Shapiro-Wilk test was used for evaluating the normal distribution of the variables. Kruskal-Wallis for nonparametric data was used to compare groups. Electron and light microscopies were used to demonstrate ultrastructural changes in spinal cord., Results: The HA group was significantly different from all the other groups (p < 0.05). Both MPSS and HA treatments decreased the MPO significantly. HA treatment decreased the lipid peroxidation. HA treatment prevented the worsening of clinical results. In the HA treatment group, the ultrastructure was protected significantly. The neuronal bodies and axonal structures were normal except for some limited edematous spaces., Conclusions: HA improves early clinical results, protects spinal cord ultrastructure, and decreases MPO and LPO levels after spinal cord contusion injury (Tab. 3, Fig. 3, Ref. 39).

Alliin is a garlic organosulfur compound that possesses various pharmacological properties. In the present study, the protective effects and molecular mechanism of alliin on Lipopolysaccharides (LPS)-induced acute lung injury (ALI) were analyzed. LPS-induced ALI was induced in BALB/c mice by intranasal instillation of LPS. Alliin was administered intraperitoneally to mice 1 h after LPS treatment. The results showed that alliin markedly inhibited lung myeloperoxidase (MPO) activity and wet/dry (W/D) ratio induced by LPS. Alliin also inhibited TNF-α and IL-1β in the bronchoalveolar lavage fluid (BALF) induced by LPS. Furthermore, LPS-induced lung pathological injury was attenuated by treatment of alliin. LPS-induced NF-κB activation was significantly inhibited by alliin. In addition, the expression of peroxisome proliferator-activated receptor γ (PPARγ) was up-regulated by treatment of alliin. Taken together, these results suggested that alliin protected against LPS-induced ALI by activating PPARγ, which subsequently inhibited LPS-induced NF-κB activation and inflammatory response. Alliin might be used as an anti-inflammatory agent in the treatment of ALI., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Elevated levels of myeloperoxidase have been demonstrated in women with preeclampsia where it may contribute to endothelial dysfunction mediated, in part, by nitric oxide impairment. In this study, we investigated myeloperoxidase in hypertensive disorders of pregnancy and its contribution to the impairment of the vasodilator nitric oxide. We found higher levels of myeloperoxidase in supernatant from human umbilical vein endothelial cells cultures incubated with plasma from preeclampsia group compared with healthy pregnant women. Further, we measured plasma concentration and activity of myeloperoxidase in 219 healthy pregnant women, 130 gestational hypertension (on antihypertensive therapy or not), and 143 preeclampsia patients (on antihypertensive therapy or not). We found that patients with preeclampsia and gestational hypertension without antihypertensive treatment showed higher levels and activity of this enzyme, respectively. Moreover, the inhibition of myeloperoxidase activity in vitro improved nitric oxide bioavailability. Our results indicate a higher cardiovascular risk in pregnant women with hypertensive disorders, and that active myeloperoxidase may play a role in endothelial dysfunction in these conditions by impairment of nitric oxide availability. Besides, the use of antihypertensive drugs seems to decrease enzyme levels suggesting a new protective feature for these drugs., (© 2017 American Heart Association, Inc.)

Background: Methane is part of the gaseous environment of the intestinal lumen. The purpose of this study was to elucidate the bioactivity of exogenous methane on the intestinal barrier function in an antigen-independent model of acute inflammation., Methods: Anesthetized rats underwent sham operation or 45-min occlusion of the superior mesenteric artery. A normoxic methane (2.2%)-air mixture was inhaled for 15 min at the end of ischemia and at the beginning of a 60-min or 180-min reperfusion. The integrity of the epithelial barrier of the ileum was assessed by determining the lumen-to-blood clearance of fluorescent dextran, while microvascular permeability changes were detected by the Evans blue technique. Tissue levels of superoxide, nitrotyrosine, myeloperoxidase, and endothelin-1 were measured, the superficial mucosal damage was visualized and quantified, and the serosal microcirculation and mesenteric flow was recorded. Erythrocyte deformability and aggregation were tested in vitro., Results: Reperfusion significantly increased epithelial permeability, worsened macro- and microcirculation, increased the production of proinflammatory mediators, and resulted in a rapid loss of the epithelium. Exogenous normoxic methane inhalation maintained the superficial mucosal structure, decreased epithelial permeability, and improved local microcirculation, with a decrease in reactive oxygen and nitrogen species generation. Both the deformability and aggregation of erythrocytes improved with incubation of methane., Conclusion: Normoxic methane decreases the signs of oxidative and nitrosative stress, improves tissue microcirculation, and thus appears to modulate the ischemia-reperfusion-induced epithelial permeability changes. These findings suggest that the administration of exogenous methane may be a useful strategy for maintaining the integrity of the mucosa sustaining an oxido-reductive attack., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia miltiorrhiza and exhibit numerous health promoting properties. The objective of the current study was to examine whether SAB exerts a renoprotective effect by attenuating oxidative stress and inflammatory response through activating phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/Akt) signaling pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats (250-300 g) were obtained and split into four groups with ten rats in each group. The right kidney of all rats was removed (nephrectomy). The rats of the Control group received only saline (occlusion) and served as a sham control group, whereas rats subjected to ischemic reperfusion (IR) insult by clamping the left renal artery served as a postitive control group. The other 2 groups of rats were pretreated with SAB (20 and 40 mg·kg-1·day-1) for 7 days prior IR induction and served as treatment groups (SAB 20+IR; SAB 40+IR). Renal markers creatinine (Cr) and blood urea nitrogen (BUN) were significantly lower in the groups that received SAB. Pretreatment with SAB appears to attenuate oxidative stress by suppressing the production of lipid peroxidation products like malondialdehyde as well as elevating antioxidant activity. The concentration of inflammatory markers and neutrophil infiltration (myeloperoxidase) were significantly decreased. Meanwhile, PI3K protein expression and pAkt/Akt ratio were significantly upregulated upon supplementation with SAB, indicating its renoprotective activity. Taken together, these results indicate that SAB can therapeutically alleviate oxidative stress and inflammatory process via modulating PI3K/Akt signaling pathway and probably ameliorate renal function and thus act as a renoprotective agent.

Valsa canker caused by Valsa mali is commonly present in eastern Asia and cause large economic losses. Because of limited agricultural measures and chemical residues of commonly used fungicides there is an urgent need of alternative plant protecting agents. On this background the activity of cuminic acid, a plant extract from the seed of Cuminum cyminum L, was assessed. The median effective concentration (EC 50 ) values for inhibition of mycelial growth of seven V. mali strains ranged from 3.046 to 8.342 μg/mL, with an average EC 50 value of 4.956 ± 0.281 μg/mL. The antifungal activity was the direct activity of cuminic acid instead of the influence on the pH of media by cuminic acid. After treated with cuminic acid, mycelia dissolved with decreased branches and swelling; cell membrane permeability increased while pectinases activity decreased significantly. Moreover, peroxidase (POD) activity of the apple leaves increased after treated with cuminic acid. Importantly, on detached branches of apple tree, cuminic acid exhibited both protective and curative activity. These results indicated that cuminic acid not only showed the antifungal activity, but also could improve the defense capacity of the plants. Taken together, cuminic acid showed the potential as a natural alternative to commercial fungicides or a lead compound to develop new fungicides for the control of Valsa canker., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Acute kidney injury (AKI) is a serious clinical problem with high rate of mortality and morbidity. Currently used prophylactic and therapeutic strategies to address AKI are limited and warrant further studies. In the present study an attempt was made to investigate the effect of quinacrine, a phospholipase A2 inhibitor against glycerol induced AKI in rats., Methods: Adult female Wistar rats were divided in to five groups. After 24 h of water deprivation rats in groups 3, 4 and 5 received an intraperitoneal injection of quinacrine (3 mg/kg, 10 mg/kg and 30 mg/kg of body weight respectively). Thirty minutes after the first injection of quinacrine animals in groups 3, 4 and 5 received an intramuscular injection of 25% glycerol (10 ml/kg of body weight). The animals in group 2 received 25% glycerol (10 ml/kg of body weight) only whereas rats in group 1 served as control . The quinacrine administration was continued once daily for three days, on the fourth day animals were sacrificed, blood and kidney were collected for various biochemical and histopathological studies., Results: Glycerol treatment produced significant renal structural abnormalities and functional impairment (increased urea and creatinine). Increase in myeloperoxidase (MPO) and malondialdehyde (MDA) clearly suggested the involvement of oxidative stress and neutrophilic activity following glycerol administration. Quinacrine dose dependently attenuated glycerol induced structural and functional changes in kidney., Conclusion: The reversal of glycerol induced AKI by quinacrine points towards a role of phospholipase A2 (PLA2) in the pathogenesis of renal injury. The result of this study suggests that quinacrine may offer an alternative mode of treatment for AKI.

Objective: To analyse the relationship between paracetamol and asthma., Data Sources: An English literature search using electronic search engines (PubMed and EMBASE) was conducted., Study Selections: Articles published in peer-review journals, from 1990 to December 2015 were included. To perform the search for the most suitable and representative articles, keywords were selected ("asthma," "paracetamol" and "acetaminophen"). The evidence level was rated according to the criteria of the Oxford Centre For Evidence-Based Medicine., Results: The exposure to paracetamol during pregnancy was analysed in several cohort studies, showing an association between the prenatal exposure to paracetamol with suffering from asthma or presence of wheezing in childhood, especially for persistent wheezing. Nevertheless, a recent study concluded that the relationship between asthma and paracetamol is explained, at least in part, by confounding factors. Several works have also associated the exposure to paracetamol in the first years of life or in adults with the development of childhood asthma. Several pathophysiological mechanisms are known that could explain this relationship, such as the glutathione pathway, the decrease in the release of Th1 cytokines that are normally produced during febrile episodes, which would then lead to a predominance of Th2 cytokines, the cytotoxic effect of paracetamol for pneumocytes, a modulator effect on the activity of myeloperoxidase, as well as the possible antigenic effect of paracetamol, mediated by IgE., Conclusions: There are many arguments that suggest a relationship between the use of paracetamol with the appearance of asthmatic symptoms, however the evidence is inconclusive.

In this study, Eruca sativa (Rocket) seedlings were treated with different cadmium (Cd) concentrations (0, 150, 300 and 450 μg ∙ g -1 ). The effects of Cd on lipid peroxidation, enzymatic (APx, CAT, GPX, SOD) and non-enzymatic antioxidants (total ascorbate, dehydroascorbate, ascorbate, non-protein thiol), fresh and dry masses, water content were determined. Also, Cd content of the leaves and the roots were analysed. The highest cadmium accumulation of leaves was at 450 μg ∙ g -1 Cd treatment and the accumulation was 2.62 times greater than those in the roots. The translocation factor was 3.89 at 300 μg ∙ g -1 Cd treatment. Cd treatments caused decreases of fresh, dry mass and water content of leaves and roots. Malondialdehyde content, which is an index of lipid peroxidation, was increased in proportion with the increase in Cd. While there was not change in the activity of GPX according to control, a decrease in activities of SOD, CAT and APX were observed with the increase of cadmium concentration. Although a significant increase in the amounts of non-protein thiol groups and proline were observed in 450 μg ∙ g -1 Cd treated plants, Cd did not lead to a significant change in AsA, DHA and total AsA contents. According to the results of the research, E. sativa may be a Cd hyperaccumulator plant and we suggest that the plant may be a candidate plant for remediation of Cd-contaminated soil.

Excess catecholamine levels are suggested to be cardiotoxic and to underlie stress-induced heart failure. The cardiotoxic effects of norepinephrine and epinephrine are well recognized. However, although cardiac and circulating dopamine levels are also increased in stress cardiomyopathy patients, knowledge regarding putative toxic effects of excess dopamine levels on cardiomyocytes is scarce. We now studied the effects of elevated dopamine levels in H9c2 cardiomyoblasts. H9c2 cells were cultured and treated with dopamine (200 μM) for 6, 24, and 48 h. Subsequently, the effects on lipid accumulation, cell viability, flippase activity, reactive oxygen species (ROS) production, subcellular NADPH oxidase (NOX) protein expression, and ATP/ADP and GTP/GDP levels were analyzed. Dopamine did not result in cytotoxic effects after 6 h. However, after 24 and 48 h dopamine treatment induced a significant increase in lipid accumulation, nitrotyrosine levels, indicative of ROS production, and cell death. In addition, dopamine significantly reduced flippase activity and ATP/GTP levels, coinciding with phosphatidylserine exposure on the outer plasma membrane. Furthermore, dopamine induced a transient increase in cytoplasmic and (peri)nucleus NOX1 and NOX4 expression after 24 h that subsided after 48 h. Moreover, while dopamine induced a similar transient increase in cytoplasmic NOX2 and p47 phox expression, in the (peri)nucleus this increased expression persisted for 48 h where it colocalized with ROS. Exposure of H9c2 cells to elevated dopamine levels induced lipid accumulation, oxidative stress, and a proinflammatory status of the plasma membrane. This can, in part, explain the inflammatory response in patients with stress-induced heart failure., (Copyright © 2016 the American Physiological Society.)

Parotoid glands of amphibians are known for the production of several biologically active compounds having pharmacological and toxic effects in mammals. In the present work, a protein fraction obtained from Rhinella schneideri parotoid gland (RsPP) was characterized to study its biological and toxic effects. Rhinella schneideri parotoid secretion is composed of up to 30% (w/w) of soluble proteins. Tandem mass spectrometric analysis of the RsPP identified 104 proteins, including actin, beta-actin, ribosomal proteins, catalase, galectin, and uncharacterized proteins; however, no peptidases were found, and this result was reinforced by the absence of proteolytic activity. In addition, RsPP did not exhibit pro-coagulant or antibacterial effects. However, pretreatment of mice with different doses of RsPP intraperitoneally inhibited carrageenan-induced paw edema and increased tissue myeloperoxidase activity. RsPP also reduced interleukin 1β levels in the peritoneal cavities and cell migration in the peritoneal cavities of an animal model of carrageenan-induced peritonitis. Subchronic treatment of animals with RsPP for 7 consecutive days did not alter the serum biochemical, renal, or liver parameters. However, a significant reduction in blood leukocyte count was observed. Our results showed that R. schneideri parotoid secretion contains proteins with anti-inflammatory and slight toxic effects., (© 2016 Wiley Periodicals, Inc.)

Duckweed can be used for bioremediation of selenium (Se) polluted water because of its capability of absorbing minerals from growing media. However, the presence of Se in the media may affect the growth of the duckweed. Landoltia punctata 7449 has been studied for its changes in chemical and biological properties with the presence of Se in the media. The duckweed was cultivated over a 12-day period at different initial concentrations of selenite (Na2 SeO3 ) from 0 to 80 μmol·l(-1) . The growth rate, the organic and total Se contents, the activity of antioxidant enzymes, the photosynthetic pigment contents, the chlorophyll a fluorescence OJIP transient, and the ultrastructure of the duckweed were monitored during the experiment. The results have shown that Se at low concentrations of ≤20 μmol·l(-1) promoted the growth of the L. punctata and inhibited lipid peroxidation. Substantial increases in duckweed growth rate and organic Se content in the duckweed were observed at low Se concentrations. The anti-oxidative effect occurred likely with the increases in guaiacol peroxidase, catalase and superoxide dismutase activities as well as the amount of photosynthetic pigments. However, negative impact to the duckweed was observed when the L. punctata was exposed to high Se concentrations (≥40 μmol·l(-1) ), in which the duckweed growth was inhibited by the selenium. The results indicate that L. punctata 7449 can be used for bioremediation of selenium (Se) polluted water when the Se concentration is ≤20 μmol·l(-1) ., (© 2016 German Botanical Society and The Royal Botanical Society of the Netherlands.)

Background: 5-aminosalicylic acid (5-ASA) is a classic anti-inflammatory drug for the treatment of ulcerative colitis. N-acetyltransferase (NAT) enzymes convert 5-ASA to its metabolite N-acetyl-5-ASA, and it is unresolved whether 5-ASA or N-acetyl-5-ASA is the effective therapeutic molecule. We previously demonstrated that colonic production of N-acetyl-5-ASA (NAT activity) is decreased in dextran sulfate sodium-induced colitis. Our hypothesis is that 5-ASA is the therapeutic molecule to improve colitis, with the corollary that altered NAT activity affects drug efficacy. Since varying clinical effectiveness of 5-ASA has been reported, we also ask if NAT activity varies with inflammation in pediatric or adult patients., Methods: Acute colonic inflammation was induced in C57BL/6 NAT wild-type (WT) or knockout mice, using 3.5% dextran sulfate sodium (w/v) concurrent with 5-ASA treatment. Adult and pediatric rectosigmoid biopsies were collected from control or patients with ulcerative colitis. Tissue was analyzed for NAT and myeloperoxidase activity., Results: Dextran sulfate sodium-induced colitis was of similar severity in both NAT WT and knockout mice, and NAT activity was significantly decreased in NAT WT mice. In the setting of colitis, 5-ASA significantly restored colon length and decreased myeloperoxidase activity in NAT knockout but not in WT mice. Myeloperoxidase activity negatively correlated with NAT activity in pediatric patients, but correlation was not observed in adult patients., Conclusions: Inflammation decreases NAT activity in the colon of mice and human pediatric patients. Decreased NAT activity enhances the therapeutic effect of 5-ASA in mice. A NAT activity assay could be useful to help predict the efficacy of 5-ASA therapy.

Statins possess a wide variety of pleiotropic properties that are independent of their lipid-lowering abilities such as attenuating inflammation, oxidative stress, coagulation, platelet aggregation and stimulating bone formation. The aim of the study is to evaluate the effect of statins on clinical periodontal parameters and gingival crevicular fluid (GCF) levels of IL-1β, IL-10, and myeloperoxidase (MPO) in inflammatory periodontal diseases. Seventy-nine subjects with hyperlipidemia and 48 systemically healthy controls (C) were included. Hyperlipidemic patients were either given a diet (HD) or prescribed statin (HS). Patients were classified into three subgroups as those who were periodontally healthy (h), who had gingivitis (g), or who had chronic periodontitis (p). Blood samples were collected for the measurement of lipid profiles. Plaque index (PI), gingival index (GI), probing pocket depth (PD), clinical attachment level (CAL), and percentage of bleeding on probing (BOP) were recorded. Gingival crevicular fluid levels of IL-1β, IL-10, and MPO were measured in order to determine the anti-inflammatory and antioxidant effects of statins. Probing depth values of the HSp group were significantly lower than those of the Cp group. Percentage of BOP of the HSg group was significantly lower than those of the HDg and Cg groups. While the IL-1β level of the HSp group was significantly lower than that of the HDp group, IL-10 levels of the HSg group were significantly higher than those of the HDg group. MPO levels were significantly lower in the HSg group when compared to those in the HDg and Cg groups. Statin use decreased the IL-1β and MPO levels and enhanced IL-10 in GCF. It can be suggested that statins may attenuate periodontal inflammation and progression of periodontal inflammation.

Objective: To investigate the effects of cigarette smoking in different manners on acute lung injury in rats. Methods: The commercially available cigarettes with tar of 1,5, 11 mg were smoked in Canada depth smoking (health canada method, HCM) manner, and those with tar of 11 mg were also smoked in international standard (ISO) smoking manner. Rats were fixed and exposed to mainstream in a manner of nose-mouth exposure. After 28 days, the bronchoalveolar lavage fluids from left lung were collected for counting and classification of inflammatory cells and determination of pro-inflammatory cytokines IL-1β and TNF-α. The right lungs were subjected to histological examination and determination of myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and glutathione, reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Results: In both HCM and ISO manners, the degree of lung injury was closely related to the tar content of cigarettes, and significant decrease in the body weight of rats was observed after smoking for one week. In a HCM manner, smoking with cigarette of 11 mg tar resulted in robust infiltration of macrophages, lymphocytes and neutrophils into lungs, significant increase in IL-1β and TNF-α levels and MPO activities, and significant decrease in GSH levels and SOD activities and increase in ROS and MDA levels (all P <0.05). Smoking with cigarette of 5 mg tar led to moderate increase in IL-1β and TNF-α levels, and MPO activities (all P <0.05), and moderate decrease in GSH levels and SOD activities and increase of ROS and MDA levels (all P <0.05). However, smoking with cigarette of 1 mg tar affected neither inflammatory cell infiltration nor IL-1β and TNF-α levels. Conclusion: Cigarette smoking in nose-mouth exposure manner can induce acute lung injury in rats; and the degree of lung injury is closely related to the content of tar and other hazards in cigarettes.

Objective: In this study, we evaluated whether budlein A modulates the activation of innate and adaptive immune cells such as neutrophils and lymphocytes., Material and Methods: Our research group has investigated several plant species and several compounds have been isolated, identified, and their medical potential evaluated. Budlein A is a SL isolated from the species Aldama buddlejiformis and A. robusta (Asteraceae) and shows anti-inflammatory and anti-nociceptive activities. Advances in understanding how plant-derived substances modulate the activation of innate and adaptive immune cells have led to the development of new therapies for human diseases., Results: Budlein A inhibited MPO activity, IL-6, CXCL8, IL-10, and IL-12 production and induces neutrophil apoptosis. In contrast, budlein A inhibited lymphocyte proliferation and IL-2, IL-10, TGF-β, and IFN-γ production, but it did not lead to cell death., Conclusions: Collectively, our results indicate that budlein A shows distinct immunomodulatory effects on immune cells.

Cisplatin (CIS) provides oxidative stress and inflammations in testicular tissues. Fenugreek seed extract (FSE) is a widely used herbal medicine with potent antioxidant and anti-inflammation properties. The purpose of this study was to investigate the protective effects and the possible mechanisms of FSE against CIS-induced testicular damage in rats. Adult male Wistar rats were given vehicle, single dose of CIS alone (10 mg kg(-1)), single dose of FSE alone or single dose of CIS followed by FSE (50, 100 or 200 mg kg(-1)) every day for 5 days. On day 6, oxidative stress and apoptotic testicular toxicity were evaluated. FSE attenuated both germ cell degenerations and apoptosis in seminiferous tubules in CIS-treated rats. Furthermore, FSE counteracted CIS-induced oxidative stress in rats as assessed by the restoration of superoxide dismutase and catalase activities and reduction in the myeloperoxidase activity and malondialdehyde levels in testes. CIS increased expressions of inducible nitric oxide synthase and nuclear factor-kappa B in testicular tissues. Importantly, treatment with FSE at all doses effectively alleviated all of these inflammatory parameters in testes. Based on these results, we concluded that FSE reduces CIS-induced reproductive toxicity in rats by the suppression of testicular oxidative stress, apoptosis and inflammations., (© 2015 Blackwell Verlag GmbH.)

Purpose: To investigate the effects of thiamine pyrophosphate (TPP) against desflurane induced hepatotoxicity., Methods: Thirty experimental animals were divided into groups as healthy (HG), desflurane control (DCG) , TPP and desflurane group (TDG). 20 mg/kg TPP was injected to intraperitoneally TDG. After one hour of TPP administration, desflurane was applied for two hours. After 24 hours, liver tissues of the animals killed with decapitation were removed. The oxidant/antioxidant levels and ALT, AST and LDH activities were measured. The histopathological examinations were performed in the liver tissues for all rats., Results: Notwithstanding the levels of oxidants and liver enzymes were significantly increased (p<0.0001), antioxidant levels were significantly decreased in DCG (p<0.0001). On contrary to the antioxidant parameters were increased (p<0.05) the oxidant parameters and liver enzymes were decreased in TDG (p<0.0001). Whereas multiple prominent, congestion, hemorrhage and dilatation were observed in sinusoids and lymphocyte-rich inflammation results in the centrilobular and portal areas of liver tissue in DCG, these findings were observed less frequently in TDG. CONCLUSİON : Thiamine pyrophosphate prevented liver oxidative damage induced with desflurane and may be useful in prophylaxis of desflurane induced hepatotoxicity.

Purpose: To investigate the effects of medical ozone theraphy on the colon anastomosis of peritonitis model in rats., Methods: Eighteen rats were randomly assigned into three equal groups; control, cecal punctuation and colon anastomosis and ozone theraphy. Sepsis was performed with a cecal punctuation in groups 2 and 3. The medical ozone theraphy was administered intraperitonealy for three weeks in group 3 while the other rats received saline injection. At the twenty second day serum were obtained for TNF-α and IL-1β, the colonic burst pressures were measured and colonic tissue samples were obtained for MDA and MPO levels. Histolopatological examination was evaluated with H&E stain, and Ki-67, IL-1β and the VEGF immunostaining densities were also compared., Results: Intraperitoneal ozone administration reversed TNF-α, IL-1β, MDA and MPO levels and the colonic burst pressures. There was also a significant difference at immunostaining densities of histopathological examination., Conclusion: Medical ozone therapy may contribute to tissue healing by affecting the proliferation and the vascularization thus has benefits on colonic anastomosis at peritonitis in rats.

Background: Chronic visceral pain is a defining feature of irritable bowel syndrome (IBS). IBS patients often show alterations in innate and adaptive immune function which may contribute to symptoms. Immune mediators are known to modulate the activity of viscero-sensory afferent nerves, but the focus has been on the innate immune system. Interleukin-2 (IL-2) is primarily associated with adaptive immune responses but its effects on colo-rectal afferent function in health or disease are unknown., Methods: Myeloperoxidase (MPO) activity determined the extent of inflammation in health, acute trinitrobenzene-sulfonic acid (TNBS) colitis, and in our post-TNBS colitis model of chronic visceral hypersensitivity (CVH). The functional effects of IL-2 on high-threshold colo-rectal afferents and the expression of IL-2R and NaV 1.7 mRNA in colo-rectal dorsal root ganglia (DRG) neurons were compared between healthy and CVH mice., Key Results: MPO activity was increased during acute colitis, but subsided to levels comparable to health in CVH mice. IL-2 caused direct excitation of colo-rectal afferents that was blocked by tetrodotoxin. IL-2 did not affect afferent mechanosensitivity in health or CVH. However, an increased proportion of afferents responded directly to IL-2 in CVH mice compared with controls (73% vs 33%; p < 0.05), and the abundance of IL-2R and NaV 1.7 mRNA was increased 3.5- and 2-fold (p < 0.001 for both) in colo-rectal DRG neurons., Conclusions & Inferences: IL-2, an immune mediator from the adaptive arm of the immune response, affects colo-rectal afferent function, indicating these effects are not restricted to innate immune mediators. Colo-rectal afferent sensitivity to IL-2 is increased long after healing from inflammation., (© 2015 John Wiley & Sons Ltd.)

Objectives: Although intensive therapy for type 2 diabetes (T2D) prevents microvascular complications, 10% of well-controlled T2D patients develop microangiopathy. Therefore, the identification of risk markers for microvascular complications in well-controlled T2D patients is important. Recent studies have demonstrated that high-dose glucose induces neutrophil extracellular trap (NET) formation, which can be a risk for microvascular disorders. Thus, we attempted to determine the correlation of circulating NET levels with clinical/laboratory parameters in well-controlled T2D patients and to reveal the mechanism of NET formation induced by high-dose glucose., Methods: Circulating NET levels represented by myeloperoxidase (MPO)-DNA complexes in the serum of 11 well-controlled T2D patients and 13 healthy volunteers were determined by enzyme-linked immunosorbent assay. The pathway involved in the NET formation induced by high-dose glucose was determined using specific inhibitors., Results: Serum MPO-DNA complex levels were significantly higher in some well-controlled T2D patients in correlation with the clinical/laboratory parameters which have been regarded as risk markers for microvascular complications. The aldose reductase inhibitor, ranirestat, could inhibit the NET formation induced by high-dose glucose., Conclusions: Elevated levels of circulating NETs can be a risk marker for microvascular complications in well-controlled T2D patients. The polyol pathway is involved in the NET formation induced by high-dose glucose., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Background: Puerarin, the main isoflavone glycoside extracted from the root of Pueraria lobata, is widely prescribed for patients with cardiovascular disorders in China. This study investigates the effect of puerarin on severe burn-induced acute myocardial injury in rats and its underlying mechanisms., Materials and Methods: Healthy adult Wistar rats were divided into three groups: (1) sham group, sham burn treatment; (2) burn group, third-degree burns over 30% of the total body surface area (TBSA) with lactated Ringer's solution for resuscitation; and (3) burn plus puerarin group, third-degree burns over 30% of TBSA with lactated Ringer's solution containing puerarin for resuscitation. The burned animals were sacrificed at 1, 3, 6, 12, and 24 h after burn injury. Myocardial injury was evaluated by analyzing serum creatine kinase MB fraction (CK-MB) activity and cardiac troponin T (cTNT) level. Changes in cardiomyocyte ultrastructure were also determined using a transmission electron microscope. Tumor necrosis factor (TNF)-α concentration in serum was measured by radioimmunoassay. Cardiac myeloperoxidase (MPO) activity and malondialdehyde (MDA) concentration were measured to determine neutrophil infiltration and oxidative stress in the heart, respectively. The expression of p38 mitogen-activated protein (MAP) kinase in the heart was determined by Western blot analysis., Results: After the 30% TBSA full-thickness burn injury, serum CK-MB activities and cTnT levels increased markedly, both of which were significantly decreased by the puerarin treatment. The level of serum TNF-α concentration in burn group at each time-point was obviously higher than those in sham group (1.09±0.09 ng/ml), and it reached the peak value at 12 h post burn. Burn trauma also resulted in worsen ultrastructural condition, elevated MPO activity and MDA content in heart tissue, and a significant activation of cardiac p38 MAP kinase. Administration of puerarin improved the ultrastructural changes in cardiomyocytes, decreased TNF-α concentration in serum as well as suppressed cardiac MPO activity and reduced MDA content, and abolished the activation of p38 MAP kinase in heart tissue after severe burn., Conclusions: These results suggest that puerarin attenuates inflammatory responses, reduces neutrophil infiltration and oxidative stress in the heart, and protects against acute myocardial injury induced by severe burn., (Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.)

Curcumin has a wide spectrum of biological and pharmacological activities including anti-inflammatory, antioxidant, antiproliferative, antimicrobial and anticancer activities. Complexation of curcumin with metals has gained attention in recent years for improvement of its stability. In this study, the effect of gallium curcumin and gallium diacetylcurcumin on the structure, function and oxidative stability of horseradish peroxidase (HRP) enzyme were evaluated by spectroscopic techniques. In addition to the enzymatic investigation, the cytotoxic effect of the complexes was assessed on bladder, MCF-7 breast cancer and LNCaP prostate carcinoma cell lines by MTT assay. Furthermore, antibacterial activity of the complexes against S. aureus and E. coli was explored by dilution test method. The results showed that the complexes improve activity of HRP and also increase its tolerance against the oxidative condition. After addition of the complexes, affinity of HRP for hydrogen peroxide substrate decreases, while the affinity increases for phenol substrate. Circular dichroism, intrinsic and synchronous fluorescence spectra showed that the enzyme structure around the catalytic heme group becomes less compact and also the distance between the heme group and tryptophan residues increases due to binding of the complexes to HRP. On the whole, it can be concluded that the change in the enzyme structure upon binding to the gallium curcumin and gallium diacetylcurcumin complexes results in an increase in the antioxidant efficiency and activity of the peroxidise enzyme. The result of anticancer and antibacterial activities suggested that the complexes exhibit the potential for cancer treatment, but they have no significant antibacterial activity.

C5a plays a central role in antineutrophil cytoplasmic antibody (ANCA)-mediated neutrophil recruitment and activation. A previous study showed that C5a played a crucial role in the regulation of high mobility group box 1 (HMGB1) release from human neutrophils. The current study further investigated the interaction between C5a and HMGB1 in ANCA-induced neutrophil activation. The effects of HMGB1 inhibitors on the translocation of ANCA antigens, ANCA-induced respiratory burst and degranulation of C5a-primed neutrophils were tested. We found that blocking HMGB1 decreased C5a-mediated translocation of ANCA antigens, as well as ANCA-induced respiratory burst and degranulation of C5a-primed neutrophils. Further study showed that supernatant of C5a-primed neutrophils, which contained HMGB1, also caused translocation of ANCA antigens of primary neutrophils, whereas blocking HMGB1 decreased the translocation. In conclusion, blocking HMGB1 may attenuate ANCA-induced activation of C5a-primed neutrophils. The interaction between HMGB1 and C5a might play an important role in ANCA-induced neutrophil activation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Earlier studies showed that the compatible solute ectoine (1) given prophylactically before induction of colitis by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats prevented histological changes induced in the colon and the associated rise in inflammatory mediators. This study was therefore conducted to investigate whether ectoine (1) and its 5α-hydroxy derivative (2) would also be effective in treating an already established condition. Two days after inducing colitis in rats by instilling TNBS/alcohol in the colon, animals were treated orally once daily for 1 week with either 1 or 2 (50, 100, 300 mg/kg). Twenty-four hours after the last drug administration rats were sacrificed. Ulcerative lesions and colon mass indices were reduced by 1 and 2 in a bell-shaped manner. Best results were obtained with 100 mg/kg ectoine (1) and 50 mg/kg 5α-hydroxyectoine (2). The solutes normalized the rise in myeloperoxidase, TNFα, and IL-1β induced by TNBS but did not affect levels of reduced glutathione or ICAM-1, while reducing the level of fecal calprotectin, an established marker for inflammatory bowel disease. The findings indicate that the naturally occurring compatible solutes ectoine (1) and 5α-hydroxyectoine (2) possess an optimum concentration that affords maximal intestinal barrier stabilization and could therefore prove useful for better management of human inflammatory bowel disease.