Hypotensive effects of omentin-1 related to increased adiponectin and decreased interleukin-6 in intra-thoracic pericardial adipose tissue

BackgroundOmentin is an adipokine expressed in visceral adipose tissue (VAT). In vitro studies demonstrated that omentin induces vasorelaxation in isolated rat mesenteric arteries, and in vivo studies showed inhibition of agonist-induced increases in blood pressure, possibly mediated by nitric oxide (NO)-dependent mechanisms.MethodsWe investigated, in normotensive rats, the effects of subacute omentin-1 administration [8 μg/kg, intraperitoneally (ip), once daily for 14 days] on cardiac activity, blood pressure, plasma concentration of l-citrulline (as a marker of NO production from l-arginine), and the gene expression of adiponectin, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in intra-thoracic pericardial adipose tissue (PAT). Electrocardiography (ECG), heart rate (HR), mean blood pressure (MBP), pulse pressure (PP) were monitored before and after treatment with omentin-1 or vehicle.ResultsWith respect to baseline and vehicle, we found a significant decrease of MBP (p < 0.005) and PP (p < 0.05) after treatment with omentin-1, while ECG and HR were not modified. Omentin-1 significantly increased l-citrulline levels in plasma (p < 0.05), and the gene expression of adiponectin in PAT (p < 0.05). On the other hand, we found decreased gene expression of IL-6 (p < 0.005), while TNF-α mRNA in PAT was not affected.ConclusionWe conclude that the hypotensive effects of omentin-1 could be driven by stimulated production of NO in the vascular system, possibly related to increased adiponectin and decreased IL-6 mRNA in PAT.     

mRNA of cytokines in bone marrow and bone biomarkers in response to propranolol in a nutritional growth retardation model

BackgroundThe aim of this study was to assess mRNA of IL-6, TNFα and IL-10 cytokines in bone marrow, possible mediators involved in altered bone remodeling with detrimental consequences on bone quality in NGR (Nutritional growth retardation) rats.MethodsWeanling male Wistar rats were assigned either to control (C) or experimental group (NGR) (n = 20 each). C and NGR groups were assigned to 2 groups according to receiving saline solution (SS) or propranolol hydrochloride (P): C, C + P (CP), NGR or NGR + P (NGRP). For 4 weeks, NGR and NGRP rats received 80% of the amount of food consumed by C and CP, respectively, the previous day, corrected by body weight. P (7 mg/kg/day) was injected ip 5 days/week, for 4 weeks in CP and NGRP rats. Body weight and length were recorded. After 4 weeks, blood was drawn. Femurs were dissected for RNA isolation from bone marrow and mRNA of cytokines assays.ResultsFood restriction induced a significant negative effect on body growth in NGR and NGRP rats (p < 0.001). P had no effects on zoometric parameters (p > 0.05). CTX-I increased in NGR rats vs. C (p < 0.001), but diminished in NGRP (p < 0.01). Serum osteocalcin, PTH, calcium and phosphate levels remained unchanged between groups (p > 0.05). In NGR, bone marrow IL-6 mRNA and IL-10 mRNA levels were low as compared to other groups (p < 0.05). In contrast, bone marrow TNF-α mRNA levels were significantly high (p < 0.05).ConclusionsThis study provides evidences that NGR outcomes in a bone marrow proinflammatory microenvironment leading to unbalanced bone remodeling by enhancement of bone resorption reverted by propranolol.     

TLR4-HMGB1 signaling pathway affects the inflammatory reaction of autoimmune myositis by regulating MHC-I

ObjectivesTo analyze the effects of TLR4 on the expression of the HMGB1, MHC-I and downstream cytokines IL-6 and TNF-α, and to investigate the biological role of the TLR4-HMGB1 signaling pathway in the development of the autoimmune myositis.MethodsWe built mice models with experimental autoimmune myositis (EAM) and used the inverted screen experiment to measure their muscle endurance; we also examined inflammatory infiltration of muscle tissues after HE staining; and we assessed the expression of MHC-I using immunohistochemistry. In addition, peripheral blood mononuclear cells (PBMC) were extracted and flow cytometry was utilized to detect the effect of IFN-γ on the expression of MHC-I. Furthermore, PBMCs were treated with IFN-γ, anti-TLR4, anti-HMGB1 and anti-MHC-I. Real-time PCR and western blotting were employed to examine the expressions of TLR4, HMGB1 and MHC-I in different groups. The ELISA method was also utilized to detect the expression of the downstream cytokines TNF-α and IL-6.ResultsThe expressions of TLR4, HMGB1 and MHC-I in muscle tissues from mice with EAM were significantly higher than those in the control group (all P < 0.05). After IFN-γ treatment, the expressions of TLR4, HMGB1, MHC-I, TNF-α and IL-6 in PBMCs significantly increased (all P < 0.05). The treatment of anti-TLR4, anti-HMGB1 and anti-MHC-I could significantly downregulate the expression of MHC-I (all P < 0.05). In addition, anti-TLR4 and anti-HMGB1 significantly reduced the expression of TNF-α and IL-6 (all P < 0.05).ConclusionsThe TLR4-HMGB1 signaling pathway affects the process of autoimmune myositis inflammation by regulating the expression of MHC-I and other pro-inflammatory cytokines.     

Tripterygium wilfordii polyglycosidium ameliorates pouchitis induced by dextran sulfate sodium in rats

BackgroundThe aim of this study was to investigate the therapeutic effects of Tripterygium wilfordii polyglycosidium (TWP) to rats with dextran sulfate sodium (DSS)-induced pouchitis and its possible mechanism.MethodsSprague-Dawley rats underwent surgery of ileal pouch anal anastomosis (IPAA) and pouchitis was induced by DSS. Rats were randomly divided into no intervention (NI), normal saline (NS) and TWP groups. Rats were lavaged with normal saline (3 ml/day in NS group) or TWP (12 mg/kg/day in TWP group) for 7 days. General conditions of animals and histopathological examinations were evaluated. Interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor (TNF)-α mRNA expression was measured. Levels of occludin and Zo-1 proteins were measured by immunohistochemistry. In addition, ALT and AST were assessed.ResultsTWP significantly attenuated the symptoms of pouchitis characterized by body weight loss, diarrhea, and bloody stool. Furthermore, TWP diminished histological damage compared with other groups. There was a significant reduction in levels of IL-1β, IL-6, and TNF-α, as well as an increase in IL-10 in the TWP group. The expression of tight junction proteins occludin and Zo-1 were increased in the TWP group. There were no statistical differences in serum ALT and AST among the three groups.ConclusionsTWP significantly ameliorated pouchitis and inhibited the production of IL-1β, IL-6, and TNF-α as well as increased the levels of IL-10, occludin, and Zo-1 protein in rats. These findings suggest TWP might be a potential therapeutic agent for patients with pouchitis.     

COX-2 inhibition attenuates lung injury induced by skeletal muscle ischemia reperfusion in rats

BackgroundSkeletal muscle ischemia reperfusion accounts for high morbidity and mortality, and cyclooxygenase (COX)-2 is implicated in causing muscle damage. Downregulation of aquaporin-1 (AQP-1) transmembrane protein is implicated in skeletal muscle ischemia reperfusion induced remote lung injury. The expression of COX-2 in lung tissue and the effect of COX-2 inhibition on AQP-1 expression and lung injury during skeletal muscle ischemia reperfusion are not known. We investigated the role of COX-2 in lung injury induced by skeletal muscle ischemia reperfusion in rats and evaluated the effects of NS-398, a specific COX-2 inhibitor.MethodsTwenty-four Sprague Dawley rats were randomized into 4 groups: sham group (SM group), sham + NS-398 group (SN group), ischemia reperfusion group (IR group) and ischemia reperfusion + NS-398 group (IN group). Rats in the IR and IN groups were subjected to 3 h of bilateral ischemia followed by 6 h of reperfusion in hindlimbs, and intravenous NS-398 8 mg/kg was administered in the IN group. In the SM and SN groups, rubber bands were in place without inflation. At the end of reperfusion, myeloperoxidase (MPO) activity, COX-2 and AQP-1 protein expression in lung tissue, PGE₂ metabolite (PGEM), tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels in bronchoalveolar lavage (BAL) fluid were assessed. Histological changes in lung and muscle tissues and wet/dry (W/D) ratio were also evaluated.ResultsMPO activity, COX-2 expression, W/D ratio in lung tissue, and PGEM, TNF-α and IL-1β levels in BAL fluid were significantly increased, while AQP-1 protein expression downregulated in the IR group as compared to that in the SM group (P < 0.05). These changes were remarkably mitigated in the IN group (P < 0.05). NS-398 treatment also alleviated histological signs of lung and skeletal muscle injury.ConclusionCOX-2 protein expression was upregulated in lung tissue in response to skeletal muscle ischemia reperfusion. COX-2 inhibition may modulate pulmonary AQP-1 expression and attenuate lung injury.     

Concentration of Il-1β, Il-2, Il-6, TNFα in the blood serum in children with generalized epilepsy treated by valproate

BackgroundThe aim of the study was the comparison of concentrations of IL-1β, IL-2, IL-6 and TNFα before and after valproate (VPA) treatment in blood serum in patients with generalized seizures diagnosed and treated in the Department of Developmental Neurology, Poznan University of Medical Sciences from January 2006 to May 2007.MethodsThe analysis was conducted in a group of 21 patients with well controlled, generalized seizures (mean age 7.7 ± 4.7 years) before and after 4–6 months of VPA therapy. Quantitative determination IL-1β, IL-2, IL-6 and TNFα were performed with method of enzyme-linked immunosorbent assay (ELISA). The serum drug concentration was determined with the use of fluorescence-polarization-immunoassay system (FPIA).ResultsThe concentration of IL-6 in blood serum of patients decreased significantly (p < 0.001) after 4–6 months of VPA therapy, but concentration of IL-1β (p = 0.732), IL-2 (p = 0.865), TNFα (p = 0.079) did not change significantly. The serum concentration of VPA in all of patients was in therapeutic range (mean 77.53 ± 19.71 μg/ml).ConclusionsThe serum level of pro-inflammatory IL-6 in patients with generalized epilepsy decreased in statistically significant way during VPA therapy, so the anti-inflammatory properties of VPA are also important for the effective control of seizure. Due to the incompatibility of reports on the influence of VPA on cytokine system in patients with generalized epilepsy, this problem needs more investigations, especially in the group of children.     

Effects of taurocholic acid on immunoregulation in mice

ContextCurrently, there is a dramatically growing interest in Chinese traditional medicines, especially in the therapy of inflammatory diseases. Taurocholic acid (TCA), as a kind of natural bioactive substance of animal bile acid, has medicinal applications to treat a wide range of inflammatory diseases.ObjectiveThe study was designed to evaluate the effects of TCA on cytokine secretion, such as TNF-α and IL-1β and on the ratio of CD4⁺/CD8⁺, which is beneficial for understanding the mechanism of TCA on immunoregulation preliminarily, and also will benefit our further research.Materials and methodsThe gene and protein expressions of TNF-α and IL-1β were measured by real time RT-PCR and ELISA in serum, spleen and lymphocytes respectively. The ratio of CD4⁺/CD8⁺ in peripheral blood and lymphocytes was measured by flow cytometry.ResultsOur present study has shown that lipopolysaccharide (LPS) and cyclosporin A (CsA) could increase or decrease the gene and protein expressions of TNF-α and IL-1β respectively. TCA (0.25 g/kg, 0.125 g/kg) could recover the suppressed expressions of TNF-α and IL-1β and increase the ratio of CD4⁺/CD8⁺. In vitro, TCA (15 μg/mL) could inhibit the increased production of TNF-α and IL-1β; TCA (0.15 μg/mL–15 μg/mL) could inhibit the increased gene expressions of IL-1β and TNF-α. TCA (0.15 μg/mL) could recover the suppressed expressions of TNF-α and IL-1β.ConclusionThe function of immunoregulation of TCA may be accomplished through modulating the gene and protein expressions of TNF-α and IL-1β and elevating CD4⁺/CD8⁺ T-cell ratio.     

Preventive effects of interleukin-6 in lipopolysaccharide/d-galactosamine induced acute liver injury via regulating inflammatory response in hepatic macrophages

Lipopolysaccharide/d-Galactosamine (LPS/d-Gal)-induced acute liver injury is characterized by significant inflammatory responses including TNF-α and interleukin-6 (IL-6) and is a widely applied experimental model for inflammation research. TNF-α is critical in the progression of LPS/d-Gal-induced liver injury. However, the role of IL-6 in this model is still unknown. In the present study, we aim to elucidate the involvement of IL-6 in the pathogenesis of acute liver injury induced by LPS/d-Gal in mice and its underlying mechanism. To induce acute liver injury, LPS (50 μg/kg body weight) and d-Gal (400 mg/kg body weight) were injected intraperitoneally in the C57BL/6 mice. The vehicle (saline) or a single dose of recombinant IL-6 (200 μg/kg body weight) was administered 2 h prior to LPS/d-Gal injection. Mice were sacrificed 2 h and 6 h after LPS/d-Gal injection. The results indicated that IL-6 treatment could protect mice from LPS/d-Gal-induced tissue damage, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation, as well as hepatocyte apoptosis and inflammation. Furthermore, in vitro study showed that IL-6 treatment could significantly suppress LPS-triggered expression of proinflammatory cytokines and chemokines, TNF-α, RANTES and MCP-1 in macrophages while promoting the expression of M2 markers, such as Arg-1 and Mrc-1 in macrophages. Taken together, these findings revealed a novel and unexpected role of IL-6 in ameliorating LPS/d-Gal-induced acute liver injury via regulating inflammatory responses in hepatic macrophages.     

Physiological interactions between the hypothalamic-pituitary-gonadal axis and spleen in rams actively immunized against GnRH

Hypothalamic-pituitary-gonadal (HPG) axis is strongly implicated in the regulation of immune system. The objective was to determine the effects of immunocastration on splenic reproduction- and immunity-related gene expressions, and serum cytokine profiles in rams. Forty rams were randomly allocated into three groups: control (n = 14); surgically castrated (n = 13); or immunized (n = 13) against 100 μg D-Lys6-GnRH-tandem-dimer peptide conjugated to ovalbumin in Specol adjuvant at 6 months of age (with a booster 2 months later). Blood samples (for hormone and immune cytokine profiles) were collected at 1-month intervals until rams were slaughtered (10 months). Compared to intact controls, anti-GnRH immunization reduced (P < 0.05) serum concentrations of LH, FSH, and testosterone. Reduced testosterone abrogated its inhibitor feedback effect on the synthesis of GnRH in spleen, as evidenced by increased (P < 0.05) protein content and mRNA expressions of GnRH, and simultaneously decreased (P < 0.05) mRNA expressions of androgen receptor in spleen. In parallel with the increased GnRH production in spleen, the mRNA expressions of interleukin (IL)-2, IL-4, IL-6 and tumor necrosis factor alpha (TNF-α) as well as lymphocyte marker CD4, CD8 and CD19 molecules were increased (P < 0.05) in spleen. Consistently, serum concentrations of IL-2, IL-4, IL-6, TNF-α were increased (P < 0.05) in rams following immunization. Similarly, deprivation of testosterone by surgical castration also increased (P < 0.05) GnRH and thus immune cytokine expressions in spleen. Collectively, our data suggested that immunocastration increased GnRH production in spleen by abrogating the inhibitory feedback effects from testosterone, consequently improving the immune markers of spleen and serum immune cytokines in rams.     

Effect of cadmium-polluted water on plasma levels of tumor necrosis factor-α, interleukin-6 and oxidative status biomarkers in rats: Protective effect of curcumin

The present study was designed to investigate the effect of CdCl₂-polluted drinking water (40 mg CdCl₂/L) on the level of TNF-α and IL-6, as well as oxidative status biomarkers in plasma of rats. The possible protective effect of oral administration of curcumin (50 mg/kg body weight/day) was assessed. Results illustrated that Cd exposure significantly elevated the plasma levels of TNF-α and IL-6 (p < 0.001) as compared to normal rats. Also, Cd administration resulted in a significant elevation in the lipid peroxidation and markedly reduction in the activities of SOD and catalase as well as the level of glutathione and total antioxidant capacity in plasma. The co-treatment of Cd with curcumin significantly reduced the levels of TNF-α and IL-6 and ameliorated the alteration in oxidative status biomarkers induced by Cd. Negative correlation between IL-6 or TNF-α was and the plasma activities of catalase, SOD and the level of total antioxidant capacity were found in rats exposed to Cd. Conclusion: Cadmium toxicity induced the release of TNF-α and IL-6 which is associated with systemic oxidative stress. This may be involved in the mechanism of the Cd toxicity. On the other hand, the findings suggest the curative action of curcumin against Cd toxicity.     

Interleukin-23 mediates the pathogenesis of LPS/GalN-induced liver injury in mice

BackgroundInterleukin-23 (IL-23) is required for T helper 17 (Th17) cell responses and IL-17 production in hepatitis B virus infection. A previous study showed that the IL-23/IL-17 axis aggravates immune injury in patients with chronic hepatitis B virus infection. However, the role of IL-23 in acute liver injury remains unclear.ObjectiveThe purpose of this study was to determine the role of the inflammatory cytokine IL-23 in lipopolysaccharide/d-galactosamine (LPS/GalN)-induced acute liver injury in mice.MethodsSerum IL-23 from patients with chronic hepatitis B virus (CHB), acute-on-chronic liver failure (ACLF) and healthy individuals who served as healthy controls (HCs) was measured by ELISA. An IL-23p19 neutralizing antibody or an IL-23p40 neutralizing antibody was administered intravenously at the time of challenge with LPS (10 μg/kg) and GalN (400 mg/kg) in C57BL/6 mice. Hepatic pathology and the expression of Th17-related cytokines, including IL-17 and TNF-α; neutrophil chemoattractants, including Cxcl1, Cxcl2, Cxcl9, and Cxcl10; and the stabilization factor Csf3 were assessed in liver tissue.ResultsSerum IL-23 was significantly upregulated in ACLF patients compared with CHB patients and HCs (P < 0.05 for both). Serum IL-23 was significantly upregulated in the non-survival group compared with the survival group of ACLF patients, which was consistent with LPS/GalN-induced acute hepatic injury in mice (P < 0.05 for both). Moreover, after treatment, serum IL-23 was downregulated in the survival group of ACLF patients (P < 0.001). Compared with LPS/GalN mice, mice treated with either an IL-23p19 neutralizing antibody or an IL-23p40 neutralizing antibody showed less severe liver tissue histopathology and significant reductions in the expression of Th17-related inflammatory cytokine, including IL-17 and TNF-α; neutrophil chemoattractants, including Cxcl1, Cxcl2, Cxcl9, and Cxcl10; and stabilization factors Csf3 within the liver tissue compared with LPS/GalN mice (P < 0.05 for all).ConclusionHigh serum IL-23 was associated with mortality in ACLF patients and LPS/GalN-induced acute liver injury in mice. IL-23 neutralizing antibodies attenuated liver injury by reducing the expression of Th17-related inflammatory cytokines, neutrophil chemoattractants and stabilization factors within the liver tissue, which indicated that IL-23 likely functions upstream of Th17-related cytokine and chemokine expression to recruit inflammatory cells into the liver.     

Lectin from Abelmoschus esculentus reduces zymosan-induced temporomandibular joint inflammatory hypernociception in rats via heme oxygenase-1 pathway integrity and tnf-α and il-1β suppression

Temporomandibular joint (TMJ) disorders show inflammatory components, heavily impacting on quality of life. Abelmoschus esculentus is largely cultivated in Northeastern Brazil for medicinal purposes, having it shown anti-inflammatory activity. We evaluated A. esculentus lectin (AEL) efficacy in reducing zymosan-induced temporomandibular joint inflammatory hypernociception in rats along with the mechanism of action through which it exerts anti-inflammatory activity. Animals were pre-treated with AEL (0.01, 0.1 or 1 mg/kg) before zymosan (Zy) injection in the TMJ to determine anti-inflammatory activity. To analyse the possible effect of the hemeoxygenase-1 (HO-1) and the nitric oxide (NO) pathways on AEL efficacy, animals were pre-treated with ZnPP-IX (3 mg/kg), a specific HO-1 inhibitor, or aminoguanidine (30 mg/kg), a selective iNOS inhibitor, before AEL administration. Von Frey test evaluated inflammatory hypernociception, synovial fluid collection was performed to determine leukocyte counting and myeloperoxidase (MPO) activity 6 h after Zy injection, and Evans Blue extravasation determined vascular permeability. TMJ tissue was collected for histopathological analysis (H&E) and immunohistochemistry (TNF-α, IL-1β, HO-1). In addition, TMJ tissue and trigeminal ganglion collection was performed for TNF-α and IL-1β dosage (ELISA). AEL increased inflammatory nociceptive threshold, reduced leukocyte influx along with MPO activity, leukocyte influx into the synovial membrane, and Evans Blue extravasation. It promoted HO-1 overexpression whilst decreased TNF-α and IL-1β expression in the TMJ tissue. AEL reduced TNF-α and IL-1β levels in TMJ tissue and trigeminal ganglion. AEL effects, however, were not observed in the presence of ZnPP-IX. These findings suggest that AEL efficacy depends on TNF-α/IL-1β inhibition and HO-1 pathway integrity.     

Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human inflammatory bowel disease whole-blood model

Standard treatment for inflammatory bowel diseases (IBD) necessitates frequent intake of anti-inflammatory and/or immunosuppressive drugs, leading to significant adverse events.To evaluate the role solid lipid nanoparticles (SLN) play as drug delivery system in enhancing anti-inflammatory activity for drugs such as dexamethasone and butyrate in a human inflammatory bowel diseases whole-blood model. ELISA assay and the peripheral blood mononuclear cell (PBMC) cytokine mRNA expression levels were evaluated by quantitative SYBR Green real-time RT-PCR to determine the IL-1β, TNF-α, IFN-γ and IL-10 secretion in inflammatory bowel diseases patients’ PBMC culture supernatants. There was a significant decrease in IL-1β (p < 0.01) and TNF-α (p < 0.001) secretion, whilst IL-10 (p < 0.05) secretion significantly increased after cholesteryl butyrate administration, compared to that of butyrate alone at the highest concentration tested (100 μM), at 24 h exposure. There was a significant decrease in IL-1β (p < 0.01), TNF-α (p < 0.001) and IL-10 (p < 0.001) secretion after dexamethasone loaded SLN administration, compared to dexamethasone alone at the highest concentration tested (250 nM) at 24 h exposure. No IFN-γ was detected under any conditions and no cytotoxic effects observed even at the highest concentration tested.The incorporation of butyrate and dexamethasone into SLN has a significant positive anti-inflammatory effect in the human inflammatory bowel disease whole-blood model.     

1-Methylnicotinamide protects against liver injury induced by concanavalin A via a prostacyclin-dependent mechanism: A possible involvement of IL-4 and TNF-α

We have recently demonstrated that concanavalin A (Con A)-induced hepatitis is associated with the release of endogenous 1-methylnicotinamide (MNA). Here we study the mechanism by which exogenous MNA alleviates Con A-induced liver inflammation and injury in vivo.The involvement of prostacyclin (PGI₂) in hepatoprotective action of MNA (30–100 mg kg^− 1; i.v.) was studied by the use of IP receptor antagonist RO3244794 (10 mg kg^− 1; p.o.) given prior to Con A (5–20 mg kg^− 1; i.v.). Liver damage was assessed by measurements of: liver specific transaminases in plasma (alanine aminotransferase; aspartate aminotransferase); cytokines release (IL-4, IFN-γ and TNF-α); liver histopathology; and 24 h survival rates. Additionally, the effect of a stable analog of prostacyclin (carbaprostacyclin) on IL-4, IFN-γ and TNF-α production by isolated spleen lymphocytes in response to Con A was analyzed.MNA diminished Con A-induced rise in liver specific transaminases, alleviated histopathological injury and improved 24 h survival rates, the latter effect in a degree comparable with the pretreatment of animals with dexamethasone (0.5 mg kg^− 1; i.p.). MNA inhibited also a rise in IL-4 and TNF-α concentration in plasma measured 2 h after Con A administration, while IFN-γ was less affected. The effects of MNA were reversed by pretreatment with IP antagonist RO3244794. In isolated spleen lymphocytes, carbaprostacyclin profoundly decreased production of IL-4, the effect on TNF-α was modest with no effect on IFN-γ production.In conclusion, MNA attenuated Con A-induced hepatitis by a prostacyclin-dependent mechanism involving the inhibition of lymphocytes-derived IL-4 and the inhibition of Kuppfer-cells derived TNF-α.     

Perfluorocarbon attenuates inflammatory cytokines,oxidative stress and histopathologic changes in paraquat-induced acute lung injury in rats

The effects of perfluorocarbon (PFC) on paraquat (PQ) induced acute lung injury (ALI) was evaluated among rats.Twenty four Wistar rats were divided into 4 groups: control group injected by saline physiologic 0.9%, PFC group injected by Perfluorocarbon, PQ group injected by PQ and PQ + PFC group injected by PFC one hour after receiving paraquat. Bronchoalveular fluid content, inflammatory cytokines, oxidative and histopathologic changes were measured after 72 h.The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1(TGF-β1) in the PQ group were increased compared to either control or PFC groups, but their levels decreased in PQ + PFC group significantly (p < 0.05). Also, histopathologic evaluation revealed an increase in malondialdehyde (MDA) and hydroxyproline (HP) in the PQ group but a decrease in PQ + PFC group significantly (p < 0.01).PFC emulsion by its anti-inflammatory, anti-oxidative and anti-fibrotic properties can reduce the inflammatory and fibrotic alterations, pulmonary oedema, and pulmonary histopathologic changes created by PQ.     

Comparative evaluation of different doses of PPAR-γ agonist alone and in combination with sulfasalazine in experimentally induced inflammatory bowel disease in rats

BackgroundInflammatory bowel disease (IBD) is an idiopathic, chronic inflammatory condition, which affects the gastrointestinal tract and has no curative treatment. The present study aimed to investigate the effect of different doses of pioglitazone alone and in combination with sulfasalazine in TNBS (trinitrobenzenesulfonic acid)-induced inflammatory bowel disease (IBD) in rats.MethodsA total of 36 animals were included in the study. Animals were divided into five groups (n = 6): group I – vehicle (ethanol), group II – TNBS + ethanol, group IIIA–TNBS + pioglitazone (15 mg/kg), group IIIB – TNBS + pioglitazone (30 mg/kg), group IV – TNBS + sulfasalazine (360 mg/kg), group V – TNBS + sulfasalazine (360 mg/kg) + pioglitazone (least effective dose found in group III). Group III was divided into two subgroups, namely ULA and IIIB, on the basis of different doses of pioglitazone used. After completion of two weeks of treatment, rats were sacrificed under ether anesthesia by cervical dislocation for assessment of intestinal inflammation, histological analysis, myeloperoxidase assay, malondialdehyde assay and TNF-α estimation.ResultsAll the drug-treated groups showed both gross morphological and microscopic score either 1 or 2. None of them showed score of > 2 on both gross and microscopic morphological examination. Both MDA levels and MPO activity were significantly re-duced in the drug-treated groups, with maximum reduction seen in the combination group. TNF-α was reduced in pioglitazone group. It was highly reduced in sulfasalazine group (group V) as compared to TNBS group thereby indicating that pioglitazone is protective in TNBS-induced inflammatory bowel disease.ConclusionThe present study showed reduction in lipid peroxidation, malondialdehyde levels and TNF-α levels in pioglitazone-treated group and hence, there was significant improvement in gross and microscopic features, too. However, combination of pioglitazone and sulfasalazine has shown greater efficacy.     

Chicken egg yolk antibodies (IgY) modulate the intestinal mucosal immune response in a mouse model of Salmonella typhimurium infection

This study determined the effects of chicken egg yolk antibodies (IgY) on immune responses in the intestinal mucosal of mice infected with Salmonella typhimurium. Sixty, 28-day-old mice were divided into 4 groups and treated with streptomycin or sterile water for 2 days followed by 1 day without treatment. The control group was unchallenged whereas the mice in the other three groups were treated twice with 10⁹ CFU mL^− 1 S. typhimurium. For the next 3 days, control mice continued to receive no treatment whereas the mice in the remaining three groups were orally administered with 20 mg mL^− 1 of specific IgY, 20 mg mL^− 1 of nonspecific IgY or PBS. S. typhimurium activated gut-associated lymphoid tissue, increasing the release of IFN-γ and TNF-α in the mucosa and increased the number of activated T-lymphocytes and cytotoxic T-γδ. Specific IgY attenuated the increase in IFN-γ and TNF-α and the decrease in IL-10. S. typhimurium induced mobilization of CD8⁺ and CD8⁺ TCRγδ T cells in the epithelium and CD4⁺ and CD8⁺ T cells in the lamina propria reflecting an inflammatory process that was attenuated by IgY. These results suggest that specific IgY modulates intestinal mucosal immune responses during a S. typhimurium infection.