Tissue Tumor Necrosis Factor Research Articles

Ameliorative Potential of Minocycline and/or Lactulose on Experimentally Induced Colitis

The aim of this study was to compare between the effect of minocycline or lactulose alone and in combination on experimentally-induced colitis in rats.Materials and methods:Seventy albino rats were divided into 7 equal groups: Control untreated group, trinitrobenzenesulphonic acid (TNBS) group, TNBS + lactulose group, lactulose group, TNBS + minocycline group, minocycline group and TNBS + lactulose+ minocycline group. A part of the colon was homogenized for determination of tissue tumor necrosis factor alpha, malondialdehyde, nitric oxide, reduced glutathione and myeloperoxidase. The other part of the colon was examined histopathologically. Also, disease activity index was measured.Results:Administration of each of lactulose or minocycline alone and in combination to TNBS-treated rats induced significant increase in tissue reduced glutathione with significant decrease in disease activity index, tissue tumor necrosis factor alpha, malondialdehyde, nitric oxide and myeloperoxidase and alleviated the histopathological changes compared to the group that received TNBS alone. Minocycline/lactulose combination produced significant improvement in the biochemical and histopathological parameters compared to the groups that received either minocycline or lactulose alone.Conclusion:Lactulose and minocycline had protective effects on TNBS-induced colitis in rats but minocycline/lactulose combination had the upper hand.

Ameliorative Potential of Different Doses of Indol-3-carbinol on Doxorubicin-induced Cardiotoxicity in Mice

Background: Doxorubicin (DOX) is a commonly used chemotherapeutic agent that is associated with serious dose-limiting cardiotoxicity. This cardiotoxicity was attributed to various mechanisms including induction of oxidative stress and inflammation together with inhibition of apoptosis. Indole-3-carbinol (I3C) is a phytochemical that was suggested to have potent anti-oxidant and anti-inflammatory properties. Aim: It was to detect the possible ameliorative effects of different doses of I3C on doxorubicin-induced cardiotoxicity in mice. Methods: Eighty mice were divided into four equal groups: control untreated group; DOX group; DOX + I3C 1000 ppm group and DOX + I3C 2000 ppm group. Survival rate, serum creatine kinase (CK-MB), lactate dehydrogenase (LDH) and troponin I were measured. Also, tissue malondialdehyde (MDA), tissue catalase (CAT), tissue glutathione peroxidase (GPx), and tissue tumor necrosis factor alpha (TNF-α) were determined. Parts of the heart were subjected to histopathological examination. Results: I3C produced dose-dependent significant increase in the survival rate, tissue GPx and CAT with significant decrease in serum CK-MB, LDH, troponin I, tissue MDA and TNF-α and improved the histopathological and immunohistochemical changes compared to DOX-treated group. Conclusion: I3C- in a dose dependent manner- had a protective effect against doxorubicin-induced cardiotoxicity in mice.

Investigation of the effect of crocin pretreatment on renal injury induced by infrarenal aortic occlusion

ObjectiveIschemia and reperfusion (IR) injury is an important complication of abdominal aortic surgery, and it mainly affects the lower extremities and remote organs. In the present study, we aimed to investigate the possible protective effect of crocin in IR-mediated kidney damage. Materials and methodsA total of 24 adult male Wistar–Albino rats were equally and randomly separated into three groups as follows: sham laparotomy, IR, and IR + crocin. Infrarenal aortic occlusion and reperfusion was applied for 1 and 2 h, respectively. Tissue samples were removed and collected. Biochemical and histopathologic analyses were performed. ResultsUrea, blood urea nitrogen, creatinine, renal tissue tumor necrosis factor α, interleukin (IL)-6, IL-18, interferon gamma, IL-1β, total oxidant status, and oxidative stress index levels were significantly higher in IR group, when compared with other groups. These improvements were also demonstrated with some parameters including total score of histopathologic damage, Tunel, Bax, and Caspase-3 expression levels, and these parameters were prominently higher in the IR group, when compared with the other groups. Nevertheless, Bcl2 expression degree was prominently lower in the IR group than those in the other two groups. ConclusionsData established from the present study suggest that crocin can preclude renal damage in infrarenal aortic occlusion models.

Neuroprotective effects of atomoxetine against traumatic spinal cord injury in rats.

Spinal cord injury (SCI) often causes serious and irreversible neurological deficit leading to disability or impairment of normal physical activity. Atomoxetine, a selective norepinephrine transporter (NET) inhibitor has gained much attention in the field of the neurodevelopmental disorder, but its effect on SCI has not been evaluated. The present study has been undertaken to investigate the neuroprotective effects of atomoxetine. Administration of atomoxetine 20 mg/kg IP was compared with methylprednisolone (MP) 30 mg/kg IP in traumatic spinal cord injured Wistar rats. Tissue samples were evaluated for apoptosis, inflammation, and oxidative stress, along with histopathological examination and neurological evaluation. There was no significant difference in the caspase-3 activity between the control and the sham groups or between the MP and the atomoxetine groups (P=0.811). The administration of atomoxetine significantly reduced tissue tumour necrosis factor alpha (TNF-α), and nitric oxide (NO) levels compared to the trauma group (P<0.001). Treatment with atomoxetine also decreased the tissue myeloperoxidase (MPO) activity (P=0.026) and increased the tissue superoxide dismutase (SOD) activity compared to the trauma group (P=0.001 and P=0.004, respectively). Histopathological examination showed less degenerated neurons in the atomoxetine group compared to trauma group. This is the first experimental evidence showing meaningful neuroprotective effects of atomoxetine over SCI through anti-apoptotic, anti-inflammatory, and antioxidant effects by reducing lipid peroxidation, which was confirmed by biochemical, histopathological and the functional evaluation.

Diabetes Worsens Ischemia-Reperfusion Brain Injury in Rats Through GSK-3β

:Background:Diabetes aggravates brain injury after cerebral ischemia/reperfusion (I/R).Objective:To investigate whether limb I/R causes cerebral injury in a rat diabetes model and whether glycogen synthase kinase-3β (GSK-3β) is involved.Methods:Male adult Sprague-Dawley rats were assigned into streptozotocin-induced diabetes (n = 30; blood glucose ≥16.7 mmol/L) or control (n = 20) groups, further subdivided into diabetes I/R (3-hour femoral artery/vein clamping), diabetes-I/R + TDZD-8 (I/R plus GSK-3β inhibitor), diabetes-sham, control-sham and control-I/R groups (n = 10 each). Cortical and hippocampal morphology (hematoxylin/eosin); hippocampal CA1 apoptosis (TUNEL assay); cleaved caspase-3 (apoptosis), and Iba1 (microglial activation) protein expression (immunohistochemistry); phosphorylated/total GSK-3β and nuclear factor-κB (NF-κB) protein levels (Western blotting); and serum and brain tissue tumor necrosis factor (TNF)-α levels (enzyme-linked immunosorbent assay) were analyzed.Results:The diabetes-I/R group showed greater cortical and hippocampal injury, apoptosis, cleaved caspase-3 expression and Iba1 expression than the control-I/R group; TDZD-8 reduced injury/apoptosis and cleaved caspase-3/Iba1 expressions. The diabetes-I/R group had lower p-GSK-3β and p-NF-κBp65 expression than the control-I/R group (P < 0.05); TDZD-8 increased p-GSK-3β expression but decreased p-NF-κBp65 expression (P < 0.05). The diabetes-I/R group showed higher elevation of serum and brain tissue TNF-α than the control-I/R group (P < 0.05); TDZD-8 reduced TNF-α production.Conclusions:Diabetes exacerbates limb I/R-induced cerebral damage and activates NF-κB and GSK-3β.

Effect of metformin and adriamycin on transplantable tumor model.

Adriamycin is a cytotoxic anthracycline antibiotic used in treatment of many types of cancer. Metformin is antidiabetic drug and is under investigation for treatment of cancer. The aim of this work was to study the effect of each of adriamycin and metformin alone and in combination on solid Ehrlich carcinoma (SEC) in mice. Eighty BALB/C mice were divided into four equal groups: SEC group, SEC+adriamycin, SEC+metformin, SEC+adriamycin+metformin. Tumor volume, survival rate, tissue catalase, tissue reduced glutathione, tissue malondialdehyde, tissue sphingosine kinase 1 activity, tissue caspase 3 activity and tissue tumor necrosis factor alpha were determined. A part of the tumor was examined for histopathological and immunohistochemical study. Adriamycin or metformin alone or in combination induced significant increase in the survival rate, tissue catalase, reduced glutathione and tissue caspase 3 activity with significant decrease in tumor volume, tissue malondialdehyde, tissue sphingosine kinase 1 activity and tumor necrosis factor alpha and alleviated the histopathological changes with significant increase in Trp53 expression and apoptotic index compared to SEC group. In conclusion, the combination of adriamycin and metformin had a better effect than each of these drugs alone against transplantable tumor model in mice.

Effectiveness of sildenafil and U-74389G in a rat model of colitis

Crohn’s disease is still incurable. Compounds with anti-inflammatory and/or antioxidative effects are tested in various preclinical models of the disease. Our aim was to investigate the effects of sildenafil and lazaroid U-74389G on an experimental rat model with trinitrobenzenesulfonic acide-induced colitis. Trinitrobenzenesulfonic acid was instilled into the colon of all male Wistar rats except for those belonging to the first group. For some days, the animals in group 3 received daily sildenafil orally; the rats in group 4 received daily U-74389G intravenously, and the rats in group 5 were co-administered daily sildenafil orally and intravenous U-74389G. The rats in groups 1 and 2 were not given any treatment. During the study, the weight of the rats was recorded as a marker of their clinical condition. The colon damage was evaluated using the macroscopic colonic mucosa damage index (CMDI), microscopic (Geboes score), and biochemical methods (tissue tumour necrosis factor [TNF]-a and malondialdehyde [MDA]). Sildenafil reduced TNF-a tissue levels and increased the body weight. U-74389G reduced TNF-a, the macroscopic index of mucosal damage score (CMDI) and increased the body weight. The combined treatment with sildenafil and U-74389G reduced tissue levels of both TNF-a and MDA, lowered CMDI and microscopic Geboes score, and increased the body weight. U-74389G demonstrated a significant anti-inflammatory activity related to its ability to reduce colonic TNF-a, CMDI score, and improve weight change. We confirmed that sildenafil has an anti-inflammatory capacity in terms of reducing colonic TNF-a and improving body weight. Finally, the combined treatment showed superior effects by reducing colonic TNF-a, colonic MDA, the CMDI score, Geboes score, and by improving weight.

Hepatic Warm Ischemia-Reperfusion–Induced Increase in Pulmonary Capillary Filtration Is Ameliorated by Administration of a Multidrug Resistance–Associated Protein 1 Inhibitor and Leukotriene D4 Antagonist (MK-571) Through Reducing Neutrophil Infiltration and Pulmonary Inflammation and Oxidative Stress in Rats

BackgroundHepatopulmonary syndrome (HPS) is the major complication subsequent to liver ischemia and reperfusion (I/R) injury after resection or transplantation of liver. Hallmarks of HPS include increases in pulmonary leukotrienes and neutrophil recruitment and infiltrating across capillaries. We aimed to investigate the protective efficacy of MK-571, a multidrug resistance-associated protein 1 inhibitor and leukotriene D4 agonist, against hepatic I/R injury–associated change in capillary filtration. MethodsEighteen Sprague-Dawley male rats were evenly divided into a sham-operated group, a hepatic I/R group, and an MK-571–treated I/R group. MK-571 was administered intraperitoneally 15 min before hepatic ischemia and every 12 hours during reperfusion. Ischemia was conducted by occluding the hepatic artery and portal vein for 30 min, followed by removing the clamps and closing the incision. Forty-eight hours after hepatic ischemia, we assessed the pulmonary capillary filtration coefficient (Kfc) through the use of in vitro–isolated, perfused rat lung preparation. We also measured the lung wet-to-dry weight ratio (W/D) and protein concentration in broncho-alveolar lavage fluid (PCBAL). Lung inflammation and oxidative stress were evaluated by use of tissue tumor necrosis factor (TNF)-α and malondialdehyde levels and lavage differential macrophage and neutrophil cell count. ResultsHepatic I/R injury markedly increased Kfc, W/D, PCBAL, tissue TNF-α level, and differential neutrophil cell count (P < .05). MK-571 treatment reduced neutrophil infiltration and lung inflammation and improved pulmonary capillary filtration, collectively suggesting lung protection. ConclusionsTreatment with MK-571 before and during hepatic ischemia and reperfusion protects lung against pulmonary capillary barrier function impairment through decreasing pulmonary lung inflammation and lavage neutrophils.

Protective effects of colchicine in an experimental rat endometriosis model: histopathological evaluation and assessment of TNF-α levels.

Endometriosis is an estrogen-dependent chronic inflammatory disease observed in reproductive period. The aim of the present study is to assess the efficacy of colchicine, widely used to treat many inflammatory diseases, in an experimental rat endometriosis model. Experimental endometriosis was constituted with implantation of autogenous endometrial tissue. Rats were divided randomly into 2 groups as colchicine group (n = 8) and control group (n =8). Although oral 0.1 mg/kg colchicine was administered 4 weeks to the colchicine group, the same amount of saline solution was administered to the control group. Before and after 30 days of treatment period, peritoneal and tissue tumor necrosis factor α (TNF-α), the volumes and histopathological properties of the implants were evaluated. Although the implant volume decreased significantly in the colchicine group (89.2 ± 13.4 mm(3) to 35.2 ± 4.5 mm(3), P < .05), the implant volume increased in the control group (85.1 ± 14.2 mm3 to 110.3 ± 10.5 mm(3), P < .05). When compared to the control group, the colchicine group had significantly lower histopathologic sores (1.4 ± 0.2 vs 2.6 ± 0.4, P < .001). Although peritoneal fluid TNF-α levels were significantly decreased in the colchicine group (45.2 ± 5.3 pg/mL vs 12.1 ± 5.2 pg/mL, P < .001), the peritoneal fluid TNF-α levels were significantly increased in the control group after the treatment (44.2 ± 3.5 pg/mL vs 61.3 ± 12.2 pg/mL; P < .001). Tissue TNF-α levels were significantly lower in the colchicine group when compared to the control group (45.4 ± 8.6 pg/mL vs 71.3 ± 11.2 pg/mL; P < .001). Colchicine resulted in regression of endometrial implant volumes in experimental rat endometriosis model and decreased peritoneal and tissue TNF-α levels.

Effectiveness of sildenafil and U-74389G in a rat model of colitis

BackgroundCrohn disease is still incurable. Compounds with anti-inflammatory and/or antioxidative effects are tested in various preclinical models of the disease. Our aim was to investigate the effects of sildenafil and lazaroid U-74389G in an experimental rat model of trinitrobenzenesulfonic acid–induced colitis. Materials and methodsTrinitrobenzenesulfonic acid was instilled into the colon of all male Wistar rats except for the rats belonging to the first group. For 6 days, the animals in group 3 were administered daily sildenafil orally, the rats in group 4 were administered daily U-74389G intravenously, and the rats in group 5 were coadministered daily sildenafil orally and intravenous U-74389G. The rats in groups 1 and 2 were not administered any treatment. During the study, the weights were recorded as a marker of clinical condition. The colon damage was evaluated using macroscopic colon mucosal damage index (CMDI), microscopic (Geboes score), and biochemical methods (tissue tumor necrosis factor [TNF]-α and malondialdehyde [MDA]). ResultsSildenafil reduced TNF-α tissue levels and increased body weight. U-74389G reduced TNF-α, the macroscopic index of mucosal damage score (CMDI) and increased body weight. The combined treatment with sildenafil and U-74389G reduced tissue levels of both TNF-α and MDA, lowered CMDI and microscopic Geboes score, and increased body weight. ConclusionsU-74389G demonstrated a significant anti-inflammatory activity related to its ability to reduce colonic TNF-α, CMDI score, and improve weight change. We confirmed that sildenafil has anti-inflammatory capacity by reducing colonic TNF-α and by improving body weight. Finally, the combined treatment showed superior effects by reducing colonic TNF-α, colonic MDA, CMDI score, Geboes score, and by improving weight.

Artemisinin prevents electric remodeling following myocardial infarction possibly by upregulating the expression of connexin 43.

Artemisinin has been demonstrated to exert beneficial effects on ventricular remodeling. The present study investigated whether artemisinin was able to decrease the ventricular fibrillation threshold (VFT) in rats following myocardial infarction (MI) and aimed to determine the possible underlying mechanisms. The rats were subjected to surgery to induce MI by ligation of the left anterior descending artery and were randomly allocated to receive vehicle or artemisinin (75 mg/kg/day) treatment for four weeks. Programmed electrical stimulation demonstrated a significantly increased VFT in the artemisinin-treated group compared with the vehicle-treated group. The electrophysiological improvement of the VFT was accompanied by increased immunofluorescence-stained connexin 43 (Cx43), myocardial Cx43 protein and mRNA levels in artemisinin-treated rats. The present study also demonstrated that artemisinin significantly decreased tissue tumor necrosis factor (TNF)-α levels at the infarcted border zone. Thus, artemisinin demonstrated a protective effect on ventricular arrhythmias following MI. Although the precise mechanism by which artemisinin modulates the dephosphorylation of Cx43 is unknown, it is likely that artemisinin increased the expression of Cx43 via the inhibition of TNF-α.

The effect of U-74389G on pancreas ischemia–reperfusion injury in a swine model

BackgroundOxidative stress is a crucial factor in the pathophysiology of acute pancreatitis and its systemic complications. Lazaroids are a novel class of antioxidants that potently protect pancreatic acinar cells against oxidant attack. The aim of our study was to evaluate the therapeutic potential of 21-aminosteroid U-74389G in pancreatic injury after ischemia and reperfusion of the organ in a swine model. Materials and methodsTwelve pigs (weighing 28–35 kg) were randomized into the following two experimental groups: group A (control group, n = 6): ischemia of pancreas (30 min) followed by reperfusion for 120 min; and group B (n = 6): ischemia of pancreas (30 min), U-74389G intravenous injection (10 mg/kg) in the inferior vena cava, and reperfusion for 120 min. Tissue and blood sampling was conducted at 0, 30, 60, 90 and 120 min after reperfusion. Repeated measures analysis of variance was performed for the evaluation of differences between the two groups. ResultsHistopathologic evaluation did not reveal a statistically significant difference concerning hemorrhage (P = 0.193), leukocyte infiltration (P = 0.838), acinar necrosis (P = 0.183), and vacuolization (P = 0.185) in the pancreatic tissue between the two groups; nevertheless, edema seemed to be more pronounced in the U-74389G group (P = 0.020). Serum metabolic data in the control and therapy groups were not significantly different; accordingly, tissue malondialdehyde levels (P = 0.705) and tumor necrosis factor α values (P = 0.863) did not differ between the two groups. ConclusionsOn the basis of the histologic data and the absence of reduction in the malondialdehyde and tumor necrosis factor α levels, it is concluded that the administration of U-74389G does not seem to exert a sizable therapeutic effect in attenuating pancreatic damage from ischemia–reperfusion injury.

Ameliorative potential of gemfibrozil and silymarin on experimentally induced nephrotoxicity in rats

IntroductionAcute nephrotoxicity is a frequent complication of critical illness especially in the inpatient setting. Cisplatin is one of the most active anticancer drugs. Nephrotoxicity is the most common side effect associated with cisplatin treatment. Silymarin is widely used for hepatic disorders due to its antioxidant and anti-inflammatory properties. Gemfibrozil, a hypolipidemic drug, has also antioxidant and anti-inflammatory properties. ObjectiveTo detect the effect of gemfibrozil and silymarin either alone or in combination on cisplatin-induced nephrotoxicity in rats. Subjects and methodsFifty albino rats were divided into 5 equal groups: Control untreated group, cisplatin treated group, gemfibrozil+cisplatin treated group, silymarin+cisplatin treated group, gemfibrozil+silymarin+cisplatin treated group. Blood urea, serum creatinine, creatinine clearance, urinary N-acetyl beta-d-glucosaminidase, urinary protein, tissue superoxide dismutase, malondialdehyde, reduced glutathione, tumour necrosis factor alpha and mitochondrial complex I activity were determined. Kidneys were excised for histopathological examination. ResultsGemfibrozil and/or silymarin efficiently attenuated cisplatin-induced nephrotoxicity evidenced by significant decrease in blood urea, serum creatinine, urinary N-acetyl beta-d-glucosaminidase, urinary protein, tissue malondialdehyde and tissue tumour necrosis factor alpha with significant increase in creatinine clearance, tissue reduced glutathione, tissue superoxide dismutase and mitochondrial complex I activity simultaneous with reduction of the necrotic damage and progressively increasing apoptotic index assessed by renal histopathological examination compared to the cisplatin treated group. ConclusionThe combination of gemfibrozil and silymarin has protective effects against cisplatin-induced nephrotoxicity in rats better than each of these drugs alone due to anti-inflammatory and antioxidant properties of the used drugs.

Effect of atorvastatin and methotrexate on solid Ehrlich tumor

Hydroxymethyl glutaryl CoA reductase is the key enzyme in cholesterol synthesis. A relationship was found between cholesterol and the development of many types of cancer. Atorvastatin is a hypolipidemic drug that may have a role in treatment of cancer. Moreover, atorvastatin was reported to decrease the resistance of cancer cells to many chemotherapeutic agents. The aim of this work was to study the effect of each of methotrexate (MTX) and atorvastatin alone and in combination on solid Ehrlich carcinoma (SEC) in mice. Fifty BALB/c mice were divided into five equal groups: control untreated group, SEC, SEC+MTX, SEC+atorvastatin, SEC+MTX+atorvastatin. Tumor volume, tissue glutathione reductase (GR), catalase, malondialdehyde (MDA), cholesterol and tumor necrosis factor alpha (TNF-α) were determined. A part of the tumor was examined for histopathological and immunohistochemical study. MTX or atorvastatin alone or in combination induced significant increase in tissue catalase and GR with significant decrease in tumor volume, tissue MDA, cholesterol and TNF-α and alleviated the histopathological changes with significant increase in p53 expression and apoptotic index compared to SEC group. In conclusion, the combination of MTX and atorvastatin had a better effect than each of MTX or atorvastatin alone against solid Ehrlich tumor in mice.

Multipotent mesenchymal stromal cells protect against kidney injury

Multipotent mesenchymal stromal cells protect against kidney injury

Effects of Hydrogen Sulfide on Oxidative Stress, TNF- and #945; Level and Kidney Histological Changes in Cisplatin Nephrotoxicity in Rat

Cisplatin (CP) is an anticancer drug that enhances renal generation of reactive oxygen metabolites, lipid peroxidation and inflammation. This study examined the effect of hydrogen sulfide on lipid peroxidation content, tissue antioxidant enzyme activities and tumor necrosis factor (TNF-α) in cisplatin nephrotoxic rats. Thirty male Sprague-Dawley rats were divided into three groups of 10 rats in each group: control, nephrotoxic and nephrotoxic groups that received single dose 100 µmol/kg NaHS (i.p.). Nephrotoxicity was induced by a single intraperitoneally injection of cisplatin (6 mg/kg b.w.). Five days after cisplatin injection kidney tissue samples removed for laboratory analyses and light microscopy evaluation. Lipid peroxidation content and activities of catalase, superoxide dismutase, glutathione peroxidase and TNF-α were measured in kidney homogenate supernatants. Statistical differences were assessed with one-way ANOVA by SPSS followed by Tukey\'s t-test. P

Nilotinib-mediated mucosal healing in a rat model of colitis

To investigate the effects of nilotinib in a rat model of trinitrobenzene sulfonic acid (TNBS)-induced colitis. Twenty-one Wistar albino female rats obtained from Dokuz Eylul University Department of Laboratory Animal Science were categorized into a control (n = 7), TNBS (n = 7) and nilotinib group (n = 7). Saline was administered orally for 14 d to the control and the TNBS group. The TNBS group received rectal TNBS on the first day while saline was administered to the control group. The nilotinib group received 20 mg/kg nilotinib for 14 d in 2 divided doses, starting the same day as TNBS administration. For 14 d, the rats were fed a standard diet, and their weights were recorded daily. After sacrifice, colon tissue samples from each group were scored for macroscopic and microscopic pathology. Apoptotic indices were determined by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method. Platelet-derived growth factor receptor (PDGFR) alpha and beta levels were assessed through immunohistochemistry staining scores and compared among the groups. Tissue and serum tumor necrosis factor (TNF) alpha levels were determined by enzyme-linked immunosorbent assay. Between days 1 and 14, the nilotinib group rats lost significantly less weight than the TNBS group rats (-0.7 g vs -14.0 g, P = 0.047). The difference in weight between the control and nilotinib groups was also statistically significant (+8.3 g vs -0.7 g, P = 0.031). From day 7 to day 14, the weight differences of the control group vs the TNBS group, the TNBS group vs the nilotinib group, and the control group vs the nilotinib group were all statistically significant (+8.0 g vs -11.1 g, P = 0.007; -11.1 g vs +2.9 g, P = 0.015; +8.0 g vs +2.9 g, P = 0.042, respectively). Macroscopic and microscopic scores were significantly lower in the nilotinib group than in the TNBS group (0.00 ± 0.00 vs 1.43 ± 0.65, P = 0.009; 2.86 ± 0.55 vs 7.71 ± 1.48, P = 0.030, respectively). However, these scores were similar between the nilotinib and control groups. While no significant difference for the nilotinib vs control groups could be determined for PDGFR alpha and beta scores, PDGFR alpha and beta scores were lower in the nilotinib group than in the TNBS group. Furthermore, the TNF alpha levels in the serum, tissue and apoptosis scores were similar between the nilotinib and TNBS groups. Nilotinib prevents weight loss, facilitates mucosal healing by improving the pathological scores without introducing variation into the apoptotic scores or TNF alpha levels.

Antioxidant effects of N-acetylcysteine in a neonatal rat model of necrotizing enterocolitis

Background/PurposeHypoxia and ischemia appear to play an important role in the pathogenesis of necrotizing enterocolitis (NEC), which may be related to oxygen-derived free radical formation. This study was designed to evaluate the role of oxidative stress and potentially beneficial effects of N-acetylcysteine (NAC) in a neonatal rat model of NEC. MethodsThirty Wistar albino rat pups were randomly divided into 3 groups: group 1, control; group 2, NEC and saline; and group 3, NEC and NAC treatment. Necrotizing enterocolitis was induced by hyperosmolar enteral formula feeding and exposure to hypoxia after cold stress at 4°C and oxygen. The pups were killed on the fourth day, and their intestinal tissues were harvested for biochemical and histopathologic analysis. ResultsMucosal injury scores and intestinal malondialdehyde levels in group 2 were found to be significantly higher than that in other groups (P ≤ .05). Intestinal superoxide dismutase activities in group 3 were significantly higher than that in group 2 (P = .018). Intestinal tissue tumor necrosis factor α levels were significantly reduced with NAC treatment in group 3 compared with group 2 (P < .003). ConclusionsIt is likely that oxidative stress and inflammatory mediators contribute to the pathogenesis of NEC and that NAC has a protective effect on intestinal injury through its antiinflammatory and antioxidant properties.

Antioxidant and anti-inflammatory activities of aqueous extracts of Schizonepeta tenuifolia Briq.

This study investigated the antioxidative and anti-inflammatory activities of aqueous extracts of Schizonepeta tenuifolia Briq. (STE). The results showed that STE displayed radical scavenging and reducing activity, as well as liposome protection activity. In addition, the implementation of an HPLC with a photodiode array detector helped to identify polyphenolic components including hesperidin, luteolin, and diosmetin. STE administration in the range of 125–500mg/kg showed concentration dependent inhibition on carrageenan induced inflammatory response in mice. The anti-inflammatory effects of STE could be related to tissue NO and tumor necrosis factor a (TNF-α) suppression, and associated with the reduction of lipid peroxidation and an increase in antioxidant enzyme activities including catalase, superoxide dismutase, and glutathione peroxidase in vivo. Overall, the results showed that STE might serve as a natural inhibitor of oxidation and inflammation.

Characterization of the Cysteinyl Leukotriene 2 Receptor in Novel Expression Sites of the Gastrointestinal Tract

Cysteinyl leukotrienes (cysLTs: LTC₄, LTD₄, and LTE₄) are pro-inflammatory lipid molecules synthesized from arachidonic acid. They exert their actions on at least two cysLT receptors (CysLT₁R and CysLT₂R). Endothelial expression and activation of these receptors is linked to vasoactive responses and to the promotion of vascular permeability. Here we track the expression pattern of CysLT₂R in a loss-of-function murine model (CysLT₂R-LacZ) to neurons of the myenteric and submucosal plexus in the small intestine, colonic myenteric plexus, dorsal root ganglia, and nodose ganglion. Cysteinyl leukotriene (LTC₄/D₄) stimulation of colonic submucosal venules elicited a greater permeability response in wild-type mice. In a dextran sulfate sodium-induced colon inflammation model, the disease activity index and colonic edema (measured by wet:dry weights and submucosal thickness) were significantly reduced in knockout (KO) mice compared to controls. Tumor necrosis factor-α levels in colon tissue were significantly lower in KO mice; however, myeloperoxidase activity was similar in both the KO and wild-type groups. Finally, patch-clamp recordings of basal neuronal activity of colonic-projecting nociceptive neurons from dorsal root ganglia (T9-13) revealed significantly higher excitability in KO neurons compared to wild type. These results suggest that a lack of neuronal expression of CysLT₂R in the murine colonic myenteric plexus attenuates colitis disease progression via a reduction in inflammation-associated tissue edema and increases neuronal sensitivity to nociceptive stimuli.