Protective effect of alpha‐lipoic acid,aerobic or resistance exercise from colitis in second hand smoke exposed young rats

The role of second hand smoke (SHS) exposure on ulcerative colitis is not known. Our aim was to examine the effects of α‐lipoic acid (ALA), chronic aerobic (AE) or resistance exercise (RE) on SHS exposed rats with colitis. Sprague‐Dawley male rats (150‐200 g, n=54) were selected for colitis induction. Among the colitis groups, one group was exposed to SHS (6 d/wk, 4 cigarettes/d) and the other was not. The SHS group was divided into subgroups as follows: sedentary; AE (swimming; 3 d/wk); and RE (climbing with weight; 3 d/wk). After 5 weeks, colitis was induced by intrarectal acetic acid. All groups had subgroups that were given subcutaneously ALA (50 mg/kg per day) or vehicle for 3 days. Following decapitation, colon tissues were sampled to examine malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, luminol and lucigenin chemiluminenscence, macroscopic scoring and histologic examination. ANOVA and Student's t‐test were used for statistical analysis. The increased macroscopic and microscopic scores, MPO, MDA, luminol and lucigenin measurements in colitis and SHS‐colitis groups were decreased via ALA (P<.05‐.001). AE declined macroscopic and microscopic scores, MDA, lucigenin compared to colitis and SHS‐colitis groups (P<.01‐.001). RE reduced microscopic score, MPO, MDA, luminol, lucigenin (P<.05‐.001) that were increased with colitis. Decreased GSH levels (P<.01) in the SHS‐colitis group approached to control levels when given ALA. According to our results SHS and colitis induction increased inflammatory damage. SHS did not worsen it more than colitis. Our results suggest that ALA, AE or RE might be protective for SHS exposed ulcerative colitis conditions.     

Flaxseed extract exhibits mucosal protective effect in acetic acid induced colitis in mice by modulating cytokines,antioxidant and antiinflammatory mechanisms

New treatments for inflammatory bowel disease are of interest due to high rate of remission failure. Natural products have been effective in IBD therapeutics as they have multiple constituents. The aim of the present study was to evaluate the effect of Flaxseed extract (Fs.Cr) on ulcerative colitis and identify the possible mechanisms involved. Colitis was induced by intrarectal administration of 6% AA in BALB/c mice. Colonic mucosal damage was assessed after 24 h by calculating disease activity index (DAI), macroscopic and histological damage scores, biochemical measurement of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and total glutathione activities. Since cytokines are involved in exacerbating inflammatory cascade with emerging role of innate immune cytokines in IBD therapeutics, we hence assessed the effect on the levels of TNF-α, IFN-γ and IL-17, at 6, 12 and 24 h by ELISA.Fs.Cr ameliorated the severity of AA colitis as evident by improved DAI, macroscopic damage and the histopathological scores along with restoration of goblet cells. Fs.Cr decreased MDA and MPO activities and enhanced antioxidant activity compared to the AA group. Finally, Fs.Cr in doses (300 and 500 mg/kg) decreased TNF-α and IFN-γ levels at all time points with simultaneous increase in IL-17 levels at 24 h as compared to the AA group.These results suggest that Fs.Cr ameliorates the severity of AA colitis by reducing goblet cell depletion, scavenging oxygen-derived free radicals, reduce neutrophil infiltration that may be attributed due to decreasing IFN-γ and TNF-α and increasing IL-17 levels.     

Synthesis and evaluation of anti‐inflammatory properties of silver nanoparticle suspensions in experimental colitis in mice

The aim of our study was to investigate the effect of newly developed silver nanoparticle aqueous suspensions NanoAg1 and NanoAg2 in the mouse models mimicking ulcerative colitis and Crohn's disease. NanoAg1 and NanoAg2 were synthesized in aqueous medium with the involvement of tannic acid. To elucidate their anti‐inflammatory activity, semi‐chronic mouse models of inflammation induced by dextrane sulfate sodium addition to drinking water and intracolonic (i.c.) administration of 2,4,6‐trinitrobenzenesulfonic acid were used. NanoAg1 and NanoAg2 (500 mg/dm3, 100 μl/animal, i.c., once daily) significantly ameliorated colitis in dextrane sulfate sodium‐ and 2,4,6‐trinitrobenzenesulfonic acid‐induced mouse models of colonic inflammation, as indicated by reduced macroscopic, ulcer and microscopic scores. The anti‐inflammatory effect was dependent on the shape and diameter of silver nanoparticles, as indicated by weaker effect of NanoAg1 than NanoAg2. In addition, administration of NanoAg2, but not NanoAg1, modulated colonic microbiota, as indicated by reduced number of Escherichia coli and Clostridium perfringens, and increased number of Lactobacillus sp. Summarizing, NanoAg1 and NanoAg2 after administered i.c. effectively alleviate colitis in experimental models of ulcerative colitis and Crohn's disease in mice. Therefore, NanoAg1 and NanoAg2 administered i.c. have the potential to become valuable agents for the treatment of inflammatory bowel diseases.     

Solidagenone from Solidago chilensis Meyen inhibits skin inflammation in experimental models

Solidagenone (SOL) is a labdane‐type diterpenoid found in Solidago chilensis, a plant traditionally used to treat skin diseases, kidney pain and ovarian inflammation. In this study, the topical anti‐inflammatory activity of SOL was evaluated using in vivo and in silico assays. Croton oil‐, arachidonic acid (AA)‐ and phenol‐induced ear oedema mouse models were applied in the in vivo studies. Myeloperoxidase (MPO) and N‐acetyl‐β‐D‐glucosaminidase (NAG) activities and tumour necrosis factor alpha (TNF‐α), interleukin‐6 (IL‐6) and nitric oxide (NO) levels were determined, as well as histopathological analyses were conducted. Interaction profiles between SOL and cyclooxygenase‐1 (COX‐1), cyclooxygenase‐2 (COX‐2), glucocorticoid receptor, estradiol‐17‐β‐dehydrogenase and prostaglandin‐E(2)‐9‐reductase were established using molecular docking. SOL significantly inhibited croton oil‐, AA‐ and phenol‐induced ear oedema (P < .001) at doses of 0.1, 0.5 and 1.0 mg/ear. The MPO and NAG activities and TNF‐α, IL‐6 and NO levels were decreased (P < .001). The histopathological data revealed that inflammatory parameters (oedema thickness, leucocyte infiltration and vasodilatation) were reduced by treatment with SOL at doses of 0.1, 0.5 and 1.0 mg/ear. The docking study showed that SOL interacts with COX‐1 and prostaglandin‐E(2)‐9‐reductase through hydrogen bonding, inhibiting these enzymes. These results indicate that SOL may be a promising compound for the treatment of cutaneous inflammatory disorders and has potential as a topical anti‐inflammatory agent.     

Tauroursodeoxycholate improves 2,4,6-trinitrobenzenesulfonic acid-induced experimental acute ulcerative colitis in mice

Ulcerative colitis is a chronic nonspecific inflammatory disease of unknown cause. The aim of this study was to evaluate the anti-inflammatory effect of tauroursodeoxycholate in 2, 4, 6-trinitrobenzenesulfonic acid-induced experimental colitis in mice. After the induction of colitis for 24 h, the mice were administrated orally with tauroursodeoxycholate (20, 40 and 60 mg/kg) and sulfasalazine (500 mg/kg) by gavage for 7 consecutive days. The inhibition effects were evaluated by the body of weight change, survival rate, macroscopical and histological evaluations. Besides, myeloperoxidase (MPO) activity, interleukin (IL)-1β, interferon (IFN)-γ and tumour necrosis factor-α (TNF-α) in colon tissue were also determined by enzyme-linked immunosorbent assay. Treatment with different doses of tauroursodeoxycholate (20, 40 and 60 mg/kg) significantly improved the body weight change, decreased the macroscopic and histopathological scores. Compared with the model group, the accumulation of MPO activity, the colonic tissue levels of IL-1β, IFN-γ and TNF-α were significantly reduced in the tauroursodeoxycholate treated groups. Moreover, tauroursodeoxycholate assuaged the symptoms of colitis. These results suggested that tauroursodeoxycholate has an anti-inflammatory effect in TNBS-induced ulcerative colitis in mice.     

Effects of trimetazidine on acetic acid-induced colitis in female Swiss rats

Induction of colitis by acetic acid (AA) in the rat is widely used experimental model of inflammatory bowel disease (IBD) and ulcerations. AA as an irritant induces colitis involving infiltration of colonic mucosa with neutrophils and increased production of inflammatory mediators, such as hydrogen peroxide (H2O2), nitric oxide (NO), myeloperoxidase activity (MPO), and tumor necrosis factor (TNF-alpha). Trimetazidine (TMZ), an antianginal compound, was administered to investigate if its cytoprotective features in cardiac tissue are also effective in AA colitis where ischemic injury contributes to colitis. Administration of TMZ intraperitoneally improved the macroscopic and microscopic score alterations produced by AA. AA administration significantly elevated colonic MPO activity; however, treatment with TMZ significantly lowered this enzyme activity compared to AA. AA administration significantly enhanced superoxide dismutase (SOD) activities, except for AA + TMZ given rectally. TMZ treatment significantly lowered nitrate levels, but AA increased these levels. AA administration markedly lowered TNF-alpha levels, but TMZ treatment elevated these levels to control. These findings indicate that overproduction of NO may be involved in the immunosuppression observed during acute AA-induced rat colitis. In conclusion, TMZ treatment was more effective via the intraperitoneal than rectal route, and may be beneficial in therapy of colitis.     

Protective effect of curcumin,a Curcuma longa constituent,in early colonic inflammation in rats

Curcumin, a polyphenol derived from the plant, Curcuma longa, has a variety of pharmacological effects, including chemotherapeutic, anti‐inflammatory, antiangiogenic, and antioxidant activities. To gain a better understanding of the effects and mechanisms of action of curcumin on the acute injury caused by intra‐colonic administration of acetic acid (AA) in rats, inflammation was assessed by histology and myeloperoxidase activity (MPO; an index of neutrophil infiltration in the mucosa); Th1 and Th2 cytokine production; histological and histochemical analysis of the lesions; nitrite production in colon mucosa; and the expression of iNOS, COX‐1 and ‐2 using Western blotting and inmmunohistochemistry. We also studied the involvement of the p38 MAPK/JNK signalling pathway in the protective effect of curcumin in acute colonic inflammation. Curcumin (50–100 mg/kg/day) reduced the degree of colonic injury, the index of neutrophil infiltration and Th1 cytokine secretion, and increased IL‐10 production, reduced colonic levels of nitrites, and reduced COX‐2 and iNOS overexpression. A reduction in the activation of p38 and JNK MAPKs was also observed. Thus, we show that the widely used food additive, curcumin reduced the development of AA‐induced colitis and alleviated the inflammatory response. Inhibition of MAPK signalling by curcumin could explain the changes on the cytokine Th1/Th2 profile, the reduction of COX‐2 and iNOS signaling, as well as the decreased nitrite production in colonic mucosa, suggesting that curcumin may be useful in the treatment of ulcerative colitis. Drug Dev Res, 2009. © 2009 Wiley‐Liss, Inc.     

Kolaviron,a Natural Antioxidant and Anti‐Inflammatory Phytochemical Prevents Dextran Sulphate Sodium‐Induced Colitis in Rats

The beneficial effects of kolaviron, a natural biflavonoid from the seeds of Garcinia kola, have been attributed mainly to its antioxidant and anti‐inflammatory effects. This study investigated these effects on dextran sulphate sodium (DSS)‐induced ulcerative colitis in rats. Sulfasalazine served as standard reference in this study. Kolaviron and sulfasalazine were separately co‐administered orally at 200 mg/kg and 500 mg/kg, respectively, to dextran sulphate sodium‐exposed rats for 5 days. The result indicated that kolaviron or sulfasalazine significantly prevented DSS‐induced body weight loss as well as the incidence of diarrhoea and bleeding in DSS‐exposed rats. Kolaviron suppressed the DSS‐mediated increase in colonic nitric oxide concentration and myeloperoxidase activity and significantly prevented the increase in inflammatory mediators, interleukin‐1β and tumour necrosis factor alpha, in the colon of DSS‐treated rats. The significant depletion in colonic antioxidant status in rats exposed to DSS alone was evident by marked reduction in colonic catalase and glutathione S‐transferase activities as well as glutathione content, leading to elevated hydrogen peroxide and lipid peroxidation levels. Histopathologically, DSS alone resulted in severe epithelial erosion, total absence of goblet cells, destruction of the crypts, necrotic and distorted glands, accompanied by marked cellular mononuclear cells infiltration. However, administration of kolaviron and sulfasalazine ameliorated DSS‐induced colitis by increasing the antioxidant status decreased hydrogen peroxide and lipid peroxidation levels and attenuated the adverse effect of DSS on colon architecture. In conclusion, the anti‐colitis effect of kolaviron is related to its intrinsic anti‐inflammatory and anti‐oxidative properties.     

The effect of methylsulfonylmethane on the experimental colitis in the rat

Methylsulfonylmethane (MSM), naturally occurring in green plants, fruits and vegetables, has been shown to exert anti-inflammatory and antioxidant effects. MSM is an organosulfur compound and a normal oxidative metabolite of dimethyl sulfoxide. This study was carried out to investigate the effect of MSM in a rat model of experimental colitis. Colitis was induced by intracolonic instillation of 1 ml of 5% of acetic acid. Rats were treated with MSM (400 mg/kg/day, orally) for 4 days. Animals were euthanized and distal colon evaluated histologically and biochemically. Tissue samples were used to measurement of malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), glutathione (GSH) and proinflammatory cytokine (TNF-α and IL-1β) levels. Results showed that MSM decreased macroscopic and microscopic colonic damage scores caused by administration of acetic acid. MSM treatment also significantly reduced colonic levels of MDA, MPO and IL-1β, while increased the levels of GSH and CAT compared with acetic acid-induced colitis group. It seems that MSM as a natural product may have a protective effect in an experimental ulcerative colitis.     

Caffeic acid phenethyl ester (CAPE) prevents methotrexate-induced hepatorenal oxidative injury in rats

Objectives This study aimed to investigate the antioxidant and anti‐inflammatory effects of caffeic acid phenethyl ester (CAPE) on the methotrexate (MTX)‐induced hepatorenal oxidative damage in rats. Methods Following a single dose of methotrexate (20 mg/kg), either vehicle (MTX group) or CAPE (10 µmol/kg, MTX + CAPE group) was administered for five days. In other rats, vehicle (control group) or CAPE was injected for five days, following a single dose of saline injection. After decapitation of the rats, trunk blood was obtained, and the liver and kidney tissues were removed for histological examination and for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and sodium potassium‐adenosine triphosphatase (Na⁺/K⁺‐ATPase) activity. TNF‐α and IL‐1β levels were measured in the blood. Key findings Methotrexate administration increased the tissue MDA levels, MPO activity and decreased GSH levels and Na⁺/K⁺‐ATPase activity, while these alterations were reversed in the CAPE‐treated MTX group. Elevated TNF‐α and IL‐1β levels were also reduced with CAPE treatment. Conclusions The results of this study revealed that CAPE, through its anti‐inflammatory and antioxidant actions, alleviates methotrexate‐induced oxidative damage, which suggests that CAPE may be of therapeutic benefit when used with methotrexate.     

Local administration of 4-Thiouridine,a novel molecule with potent anti-inflammatory properties,protects against experimental colitis and arthritis

Previous studies in a rat model of Sephadex induced lung inflammation showed that 4-Thiouridine (4SU), a thiol substituted nucleoside, was very effective in reducing edema, leukocyte influx and TNF levels in bronchoalvelolar lavage fluid. However, little is known about the factors and mechanisms underlying these effects. In the present study, we have used two separate mouse models of chronic inflammation, a model of dextran sulphate sodium (DSS) induced colitis and a model of antigen induced arthritis, to evaluate the anti-inflammatory effect of 4-thiouridine. We have analyzed a broad spectrum of inflammatory mediators in order to delineate the mechanisms behind a potential anti-inflammatory effect of 4SU. Colitis was induced in C57BL/6 mice by administration of 3.5% DSS in drinking water for 5 days and the potential anti-colitic effect of 4SU was assessed by monitoring the disease activity index (DAI), measurement of colon length and histopathological analysis of colon tissue. We analyzed tissue myeloperoxidase (MPO) activity, serum pro-inflammatory cytokines (IL-1β, IL-6 and TNF), mRNA and protein expression of pro-inflammatory cytokines, COX-2, and NF-κB activity in colitis tissue. Intracolonic administration of 4SU (5 mg/kg & 10 mg/kg.) significantly inhibited MPO activity and reduced the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF) as well as COX-2. Further, NF-κB activation was also blocked by attenuating the phosphorylation of IkB kinase (IKK α/β) in DSS-induced colitis tissues. Arthritis was induced by intra-articular injection of mBSA in the knee of NMRI mice pre-immunized with mBSA and 4SU was administered locally by direct injection into the knee joint. The antiarthritic potential of 4SU was calculated by histopathological scores and histochemical analysis of joint tissue. Further, immunohistochemistry was used to study inflammatory cell infiltration and expression of cytokines and adhesion molecules in the synovium. Local administration of 50–100 mg/kg 4SU at the time of arthritis onset clearly prevented development of joint inflammation and efficiently inhibited synovial expression of CD18, local cytokine production and recruitment of leukocytes to the synovium. Taken together, our data clearly demonstrates a potent anti-inflammatory effect of 4SU in two experimental models. In conclusion 4SU could be a new promising candidate for therapeutic modulation of chronic inflammatory diseases like ulcerative colitis and arthritis.     

The effect of ascorbic acid supplementation on brain oxidative events in experimental diabetes

Increased oxidant stress plays an important role in the etiopathogenesis of chronic complications of diabetes. This study aimed to examine the effects of ascorbic acid (vitamin C, AA) supplementation on the oxidant and antioxidant processes in the brain of diabetic rats. Wistar albino rats were divided into four groups: group 1 (control), group 2 (ascorbic acid, AA, vitamin C), group 3 (diabetes), and group 4 (diabetes + AA). The rats were treated with a single dose of streptozotocin (45 mg/kg, intraperitoneal) to induce diabetes. After 48 h, the rats whose fasting blood glucose levels exceeded 200 mg/100 mL were included in the diabetes groups. The rats in the AA and diabetes + AA groups were treated with AA (20 mg/kg/day), administered intragastrically for 21 days. At the end of the experiment, malondialdehyde (MDA), glutathione (GSH), AA, and total nitric oxide (NOx) levels in the liver tissues were determined. Analysis of variance (ANOVA) and Mann–Whitney U tests were used for statistical analyses. Whereas the MDA levels increased in the diabetes group, the NOx levels decreased. The NOx levels increased in the diabetes + AA group compared with the control subjects. There were no significant differences in the diabetes + AA group in terms of GSH levels. In conclusion, vitamin C or vitamin C preparations may be beneficial in the treatment of diabetic patients for maintenance of the brain cells against oxidative damage.     

Anti-inflammatory effects of phytosteryl ferulates in colitis induced by dextran sulphate sodium in mice

BACKGROUND AND PURPOSE: We have recently reported that phytosteryl ferulates isolated from rice bran inhibit nuclear factor-kappaB (NF-kappaB) activity in macrophages. In the present study, we investigated the effect of gamma-oryzanol (gamma-ORZ), a mixture of phytosteryl ferulates, cycloartenyl ferulate (CAF), one of the components of gamma-ORZ, and ferulic acid (FA), a possible metabolite of gamma-ORZ in vivo, on a model of colitis in mice. EXPERIMENTAL APPROACH: We induced colitis with dextran sulphate sodium (DSS) in mice and monitored disease activity index (DAI), histopathology score, tissue myeloperoxidase (MPO) activity, mRNA expressions of cytokines and COX-2, colon length, antioxidant potency and NF-kappaB activity in colitis tissue. KEY RESULTS: Both DAI and histopathology score revealed that DSS induced a severe mucosal colitis, with a marked increase in the thickness of the muscle layer, distortion and loss of crypts, depletion of goblet cells and infiltration of macrophages, granulocytes and lymphocytes. MPO activity, pro-inflammatory cytokines and COX-2 levels, NF-kappaB p65 nuclear translocation and inhibitory protein of nuclear factor-kappaB-alpha degradation levels were significantly increased in DSS-induced colitis tissues. gamma-ORZ (50 mg kg(-1) day(-1) p.o.) markedly inhibited these inflammatory reactions and CAF had a similar potency. In vitro assay demonstrated that gamma-ORZ and CAF had strong antioxidant effects comparable to those of alpha-tocopherol. CONCLUSIONS AND IMPLICATIONS: Phytosteryl ferulates could be new potential therapeutic and/or preventive agents for gastrointestinal inflammatory diseases. Their anti-inflammatory effect could be mediated by inhibition of NF-kappaB activity, which was at least partly due to the antioxidant effect of the FA moiety in the structure of phytosteryl ferulates.     

Anti‐inflammatory Effect of Rosmarinic Acid and an Extract of Rosmarinus officinalis in Rat Models of Local and Systemic Inflammation

Rosmarinic acid is a polyphenolic compound and main constituent of Rosmarinus officinalis and has been shown to possess antioxidant and anti‐inflammatory properties. We aimed to evaluate the anti‐inflammatory properties of rosmarinic acid and of an extract of R. officinalis in local inflammation (carrageenin‐induced paw oedema model in the rat), and further evaluate the protective effect of rosmarinic acid in rat models of systemic inflammation: liver ischaemia–reperfusion (I/R) and thermal injury models. In the local inflammation model, rosmarinic acid was administered at 10, 25 and 50 mg/kg (p.o.), and the extract was administered at 10 and 25 mg/kg (equivalent doses to rosmarinic acid groups) to male Wistar rats. Administration of rosmarinic acid and extract at the dose of 25 mg/kg reduced paw oedema at 6 hr by over 60%, exhibiting a dose–response effect, suggesting that rosmarinic was the main contributor to the anti‐inflammatory effect. In the liver I/R model, rosmarinic acid was administered at 25 mg/kg (i.v.) 30 min. prior to the induction of ischaemia and led to the significant reduction in the serum concentration of transaminases (AST and ALT) and LDH. In the thermal injury model, rosmarinic acid was administered at 25 mg/kg (i.v.) 5 min. prior to the induction of injury and significantly reduced multi‐organ dysfunction markers (liver, kidney, lung) by modulating NF‐κB and metalloproteinase‐9. For the first time, the anti‐inflammatory potential of rosmarinic acid has been identified, as it causes a substantial reduction in inflammation, and we speculate that it might be useful in the pharmacological modulation of injuries associated to inflammation.     

苦参素对溃疡性结肠黏膜细胞NF-κB表达的影响

目的探讨苦参素对溃疡性结肠黏膜细胞中NF-κB mRNA表达的影响机制。方法 SPF级SD大鼠随机分成正常对照组,UC模型组,UC+苦参素组,UC+柳氮磺胺吡啶组,实验结束时,剖取病灶结肠,RT-PCR方法检测各实验组动物结肠黏膜细胞中NF-κB mRNA表达水平。结果苦参素可显著抑制NF-κB mRNA在溃疡性结肠炎症细胞中的表达(P<0.01)。结论苦参素可干预NF-κB mRNA在炎症性结肠黏膜细胞中的表达,进而抑制溃疡性结肠炎症反应。     

心理应激对溃疡性结肠炎病情及疗效的影响

目的:通过观察心理应激对溃疡性结肠炎大鼠产生的影响并探讨其影响的机制;同时观察抗焦虑药物对处于应激状态下溃疡性结肠炎大鼠症状的干预作用及其作用机制。方法:80只Wistar大鼠随机分为UC对照组、UC应激组、UC+氯硝西泮组和UC应激+氯硝西泮组各20只,用免疫接种法建立溃疡性结肠炎大鼠模型后,用猫恐吓的方法建立心理应激模型。建立心理应激模型期间分别给予各组生理盐水、氯硝西泮(2 mg.kg-1)灌胃。15 d后处死大鼠,以组织损伤评分、结肠组织MPO和NO活性等指标来评价其炎症和损伤程度。结肠组织损伤评分通过显微镜观察得出。并用分光光度分析法测定结肠组织MPO、NO活性,放射免疫分析法(RIA)检测大鼠血清中皮质醇的含量。结果:应激模型组的血清皮质醇、肠组织MPO、NO含量及结肠组织损伤评分较UC对照组明显增高;UC应激+氯硝西泮组上述指标明显低于UC应激组;而UC+氯硝西泮组上述指标与UC对照组无明显区别。结论:心理应激可以明显加重溃疡性结肠炎的症状。苯二氮卓类药物本身无抗炎作用,但可通过影响边缘系统和网状结构,减轻了心理应激对内脏的影响,缓解炎性肠病症状的加重。     

Ascorbic acid supplementation ameliorates testicular hormonal signaling,sperm production and oxidative stress in male rats exposed to rosuvastatin during pre‐puberty

Dyslipidemias are occurring earlier in the population due to the augmentation of obesity. Rosuvastatin reduces cholesterol and triglycerides; however, previous studies have shown that it may affect male reproduction. Ascorbic acid (AA), an antioxidant compound, plays a protective role in the male reproductive system. This study aimed to evaluate whether pre‐pubertal exposure to rosuvastatin may impair testicular structure and antioxidant status in male rats and if supplementation with AA may alleviate these damages. Male rats were randomly divided into six experimental groups (n = 10) on postnatal day (PND) 23 and received the different treatments by gavage from PND 23 to 53. The experimental groups received vehicle (saline solution 0.9%), 3 or 10 mg/kg/day of rosuvastatin diluted in saline solution 0.9%, supplementation with 150 mg/day of AA, 3 mg/kg/day of rosuvastatin in association with 150 mg/day of AA or 10 mg/kg/day of rosuvastatin associated with 150 mg/day of AA. Testicular parameters were assessed on PND 53 and 110. There were diminished androgen receptors staining in the Sertoli cells and increased germ cell death in rosuvastatin‐exposed groups, in both periods. Spermatids showed lower estrogen alpha‐receptors staining in the group exposed to 10 mg of statin at adulthood. There were androgen depletion and increased lipid peroxidation and catalase activity in statin‐exposed groups. Rosuvastatin exposure during pre‐puberty impaired testicular structure, steroid receptor distribution and increased oxidative stress; however, AA was able to ameliorate the impairment provoked by statin exposure.     

Protective effect of taurohyodeoxycholic acid from Pulvis Fellis Suis on trinitrobenzene sulfonic acid induced ulcerative colitis in mice

Ulcerative colitis is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration and up-regulation of pro-inflammatory cytokines. The aim of this study is to evaluate the effect of taurohyodeoxycholic acid (THDCA) isolated from Pulvis Fellis Suis on acute ulcerative colitis model induced by trinitrobenzene sulfonic acid (TNBS) in mice. The efficacy of THDCA was studied by macroscopical and histological scoring systems as well as myeloperoxidase (MPO) activity. Serum levels, including tumor necrosis factor (TNF)-α and interleukin (IL)-6 were assayed by enzyme-linked immunoassay. The expression of cyclooxygenase (COX)-2 in the colons was assessed by immunohistochemical analysis. Treatment with THDCA in doses of 25, 50 and 100 mg/kg/day and sulfasalazine in a dose of 500 mg/kg/day used as reference for 7 consecutive days after the induction of colitis, significantly decreased colonic MPO activity, TNF-α, IL-6 serum levels and the expression of COX-2 in colon compared with TNBS induced ulcerative colitis model group. Moreover, THDCA attenuated the macroscopic colonic damage and the histopathological changes induced by TNBS. All the effects of these parameters were comparable to that of the standard sulfasalazine, especially at the highest dose level. The results suggested that THDCA from Pulvis Fellis Suis has a protective effect in TNBS-induced ulcerative colitis which might be due to its anti-inflammatory activities, and that it may have therapeutic value in the setting of inflammatory bowel disease.     

Efficacy and tolerability of oral iron therapy in inflammatory bowel disease: a prospective, comparative trial

BACKGROUND: In patients with inflammatory bowel disease, oral iron is anecdotally reported to be less effective and less well tolerated than in those without inflammatory bowel disease, and to increase disease activity. AIM: To study prospectively the effects of oral iron in patients with and without inflammatory bowel disease. METHODS: Patients with ulcerative colitis, Crohn's disease and non-inflammatory bowel disease controls, all with iron deficiency anaemia, were assessed with symptom diaries, a quality of life questionnaire (Inflammatory Bowel Disease Questionnaire; inflammatory bowel disease patients only) and blood tests to measure iron repletion, disease activity and antioxidant capacity before and after starting 4 weeks of oral iron. In patients with ulcerative colitis, sigmoidoscopic scoring and rectal biopsies for reactive oxygen metabolite production were performed before and after iron therapy. RESULTS: All groups showed increases in haemoglobin and ferritin. Iron intolerance occurred in about a quarter of patients in each group. Two of 33 (6%) of inflammatory bowel disease patients had a relapse during treatment. Symptoms worsened in ulcerative colitis, but not in Crohn's disease or non-inflammatory bowel disease patients; Inflammatory Bowel Disease Questionnaire scores improved in ulcerative colitis. Laboratory markers of disease activity, sigmoidoscopic scores, histological scores, antioxidant capacity levels and reactive oxygen metabolite production did not change. CONCLUSIONS: Oral iron is equally efficacious and well tolerated in inflammatory bowel disease and non-inflammatory bowel disease patients. A tiny minority of inflammatory bowel disease patients relapse in association with use of oral iron therapy.