Anti-inflammatory effect of kaurenoic acid, a diterpene from Copaifera langsdorffi on acetic acid-induced colitis in rats

Kaurenoic acid, a diterpene from Copaifera langsdorffii (Leguminaceae), was evaluated on rat colitis induced by acetic acid. Rats were pretreated orally (15 and 2 h before) or rectally 2 h before induction of colitis with kaurenoic acid (50 and 100 mg/kg) or vehicle (1 ml, 3% DMSO). Colitis was induced by intracolonic instillation of a 2 ml of 4% (v/v) acetic acid solution and, 24 h later, the colonic mucosal damage was analysed macroscopically for the severity of mucosal damage, the myeloperoxidase (MPO) activity and the malondialdehyde (MDA) levels in the colon segments. A marked reduction in gross damage score (52% and 42%) and wet weight of damaged colon tissue (39% and 32%) were observed in rats that received 100 mg/kg kaurenoic acid, respectively, by rectal and oral routes. This effect was confirmed biochemically by a two- to three-fold reduction of colitis associated increase in MPO activity, the marker of neutrophilic infiltration and by a marked decrease in MDA level, an indicator of lipoperoxidation in colon tissue. Furthermore, light microscopy revealed the marked diminution of inflammatory cell infiltration and submucosal edema formation in the colon segments of rats treated with the test compound. These findings indicate the anti-inflammatory potential of kaurenoic acid in acetic acid-induced colitis.     

Ameliorative effect of pyrrolidinedithiocarbamate on acetic acid-induced colitis in rats

Ulcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. The present study examined the effect of NF-kappaB inhibitor and antioxidant, pyrrolidinedithiocarbamate (PDTC) on experimental ulcerative colitis in rats. Animals were randomly divided into 4 groups, each consisting of 6 animals; normal control group, acetic acid group, PDTC-treated group and sulfasalazine-treated group as a positive control group. Induction of colitis by intracolonic administration of 3% acetic acid produced severe macroscopic inflammation in the colon 24 h after acetic acid administration as assessed by the colonic damage score. Microscopically, colonic tissues showed ulceration, oedema and inflammatory cells infiltration. Biochemical studies revealed increased serum levels of lactate dehydrogenase (LDH), and nitrite/nitrate and colonic concentrations of tumor necrosis factor-alpha (TNF-alpha) and the neutrophil infiltration index, myeloperoxidase (MPO). Oxidative stress was indicated by elevated lipid peroxides formation and depleted reduced glutathione concentrations (GSH) in colonic tissues. Immunohistochemical studies of colonic sections revealed upregulation of inducible nitric oxide synthase (iNOS). Pretreatment with PDTC at a dose of (200 mg/kg/day, i.p.), three days before induction of colitis decreased serum LDH, nitrite/nitrate and TNF-alpha levels, colonic concentrations of MPO and lipid peroxides while increased colonic GSH concentration. Moreover, PDTC pretreatment attenuated colonic iNOS expression. Finally, histopathological changes were nearly restored by PDTC pretreatment. The findings of the present study provide evidence that PDTC may be beneficial in patients with inflammatory bowel disease.     

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.     

The effect of sodium valproate on acetic acid-induced colitis in rats

Ulcerative colitis is a chronic recurrent disease with incomplete treatment options. The current article evaluated the effect of sodium valproate on acetic acid-induced ulcerative colitis in rats. Rats were randomly distributed into six groups including Sham group, colitis control group, sodium valproate treatment groups (50, 100 and 300 mg/kg, i.p.) and dexamethasone-treatment group. Dexamethasone was used as a reference drug. Colitis was induced by intracolonic instillation of 2 mL of 3% acetic acid solution. The efficacy of sodium valproate was evaluated by macroscopical and histopathological scoring systems, hematocrit measurement as well as biochemical analysis including myeloperoxidase (MPO) and pro-inflammatory cytokines assessment. Sodium valproate, particularly with doses of 100 and 300 mg/kg significantly improved weight loss, and macroscopic damage, reduced ulcer area, colon weight, microscopic colitis index and elevated hematocrit level. Biochemical experiments showed elevated levels of colonic MPO activity, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in colitis control group. Treatment with sodium valproate at the doses of 100 and 300 mg/Kg) decreased the MPO activity and colonic concentrations of IL-1β, IL-6 and TNF-α. The results provide evidence that sodium valproate has a protective effect in acetic acid-induced ulcerative colitis which might be due to its anti-inflammatory activities, and it may be useful in patients with ulcerative colitis.     

Anti-inflammatory effect of kaurenoic acid, a diterpene from Copaifera langsdorffii on acetic acid-induced colitis in rats

Kaurenoic acid, a diterpene from Copaifera langsdorffii (Leguminaceae), was evaluated on rat colitis induced by acetic acid. Rats were pretreated orally (15 and 2 h before) or rectally 2 h before induction of colitis with kaurenoic acid (50 and 100 mg/kg) or vehicle (1 ml, 3% DMSO). Colitis was induced by intracolonic instillation of a 2 ml of 4% (v/v) acetic acid solution and, 24 h later, the colonic mucosal damage was analysed macroscopically for the severity of mucosal damage, the myeloperoxidase (MPO) activity and the malondialdehyde (MDA) levels in the colon segments. A marked reduction in gross damage score (52% and 42%) and wet weight of damaged colon tissue (39% and 32%) were observed in rats that received 100 mg/kg kaurenoic acid, respectively, by rectal and oral routes. This effect was confirmed biochemically by a two- to three-fold reduction of colitis associated increase in MPO activity, the marker of neutrophilic infiltration and by a marked decrease in MDA level, an indicator of lipoperoxidation in colon tissue. Furthermore, light microscopy revealed the marked diminution of inflammatory cell infiltration and submucosal edema formation in the colon segments of rats treated with the test compound. These findings indicate the anti-inflammatory potential of kaurenoic acid in acetic acid-induced colitis.     

Effects of hydro-ethanolic extract of leaves of Maesa lanceolata (Mursinaceae) on acetic acid-induced ulcerative colitis in rats

Inflammopharmacology - Ulcerative colitis is a form of inflammatory bowel disease that is characterized by acute and chronic inflammation. The aim of this work was to evaluate the efficacy of...     

Comparative study of D-002 versus sulfasalazine on acetic acid-induced colitis in rats

D-002 is a natural mixture of higher aliphatic primary alcohols purified from beeswax and has experimentally proven mild antiinflammatory and effective antiulcer effects. It reduces leukotrienes in the exudate of carrageenan-induced pleurisy and has a protective effect on the preulcerative phase of carrageenan-induced colonic ulceration in the guinea pig. This study was conducted to compare the effect of D-002 and sulfasalazine on acetic acid-induced colitis in rats administered at 1, 5.25 and 100 mg kg-1, 24 h before colitis induction. Significant reductions in wet weight, macroscopic injury, polymorphonuclear infiltration and wall thickness were observed in the colonic mucosa of D-002 and sulfasalazine-treated animals compared with controls, except at the dose of 1 mg kg-1. It was concluded that the effects of D-002 and sulfasalazine were comparable in this experimental model.     

Effect of D-002 on acetic acid-induced colitis in rats at single and repeated doses.

D-002 is a natural mixture of higher aliphatic primary alcohols purified from beeswax, with mild anti-inflammatory and effective antiulcer effects experimentally proved. Furthermore, it reduces leukotriene (LTB(4)) in the exudate of carrageenan-induced pleurisy and has a protective effect on the pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea pig. This study was conducted to determine the effect of D-002 on acetic acid-induced colitis in rats at single and repeated doses. In a first series, D-002 was orally administered at 25 and 50 mg kg(-1), 24 h before the induction of colitis, meanwhile, in a second series, it was administered 24 h after the induction of colitis. Two other series (III and IV) examined the protective and therapeutic effect of D-002 administered for 7 days at the same doses, before or after colitis induction. Significant reductions in wet weight, macroscopic injury, polymorphonuclear infiltration and wall thickness were observed in colonic mucosa of D-002-treated animals compared with controls in both protective and therapeutic alternatives. It is concluded that D-002 was effective to protect or prevent the damage associated to acetic acid-induced colitis.     

结肠缓释胶囊对乙酸诱导的大鼠急性溃疡型结肠炎的治疗作用

目的观察结肠缓释胶囊对乙酸诱导的大鼠急性溃疡型结肠炎(UC)的治疗作用。方法给大鼠注射乙酸,以复制大鼠UC模型,运用图象分析系统测定平均光密度、积分光密度、平均黑度。结果结肠缓释胶囊能减少大鼠炎症面积、抑制炎症反应,降低平均光密度、积分光密度和平均黑度。结论结肠缓释胶囊对大鼠UC有显著的治疗作用。     

葡萄籽原花青素提取物对大鼠乙酸性结肠炎的保护作用

目的:研究葡萄籽原花青素提取物(GSPE)对大鼠乙酸性结肠炎的治疗作用。方法:制备大鼠乙酸性结肠炎模型,分别设正常对照组、模型对照组、阳性对照组和GSPE低、中、高剂量组,共6组。每天给药1次,共7d。于给药d8时进行大鼠病变结肠大体及组织学评分;用邻联茴香胺法检测结肠组织中MPO活性以考察中性白细胞浸润程度。结果:实验1周时,模型对照组大鼠体重明显下降,结肠湿重明显增加,和模型对照组比较,GSPE低、中剂量组体重下降程度减轻(P<0.05),GSPE高剂量组体重呈增加趋势(P<0.01)。GSPE各剂量组结肠湿重增加幅度较模型对照组明显降低(P<0.05)。大体观察,模型对照组结肠粘膜大面积溃疡、坏死,和模型对照组比较,GSPE各剂量组结肠粘膜溃疡面积缩小,粘膜修复明显。光镜下观察,模型对照组结肠粘膜组织内可见大量炎性渗出物和组织坏死;GSPE各剂量组溃疡面可见多量再生上皮和新生腺体。模型对照组结肠粘膜组织内MPO含量较正常对照组明显升高(P<0.01),GSPE各剂量组MPO活性较模型对照组明显降低(P<0.05)。结论:GSPE对大鼠乙酸性结肠炎有明显的治疗作用,且呈剂量依赖性。     

Studies on the expression and function of beta-3-adrenoceptors in the colon of rats with acetic acid-induced colitis.

Ulcerative colitis is characterized by dysfunctional motility. Our main objective in this investigation was to study the effect of an acetic acid-induced ulcerative colitis on the expression and function of beta(3)-adrenoceptors in the rat colon. Inflammation was induced by administering acetic acid intrarectally into rats. Levels of myeloperoxidase activity and beta(3)-adrenoceptor mRNA were measured in colon samples taken following acetic acid administration. Relaxation responses to beta(3)-adrenoceptor agonists were also studied. Ulcerative colitis was associated with significantly elevated levels of myeloperoxidase activity in the colon segments. Levels of beta(3)-adrenoceptor mRNA as well as the relaxation responses to isoprenaline and BRL 37344 were however not significantly different between inflamed and control tissue. Acetic acid-induced ulcerative colitis in rats was not associated with changes in the expression and/or function of beta(3)-adrenoceptors in the rat colon. Therefore, the dysfunctional motility that is characteristic of ulcerative colitis, is not likely to be due to changes in beta(3)-adrenergic mechanisms in this model.     

Suprofen, a potent antagonist of acetic acid-induced writhing in rats.

A new standardized acetic acid-induced writhing test in rats is described in detail and its methodology is discussed briefly. The described method has proved to be useful for evaluating the anti-writhing activity of narcotic analgesics, non-narcotic anti-inflammatory compounds and narcotic-antagonists with analgesic activity. A direct quantitative comparison of anti-writhing activity was made between orally administered acetyl-salicylic acid, phenylbutazone, indometacin, tolmetin, ketoprofen and alpha-methyl-4-(2-thienylcarbonyl)benzeneacetic acid (suprofen) in a specially designed experiment. Among the known non-narcotic, non-steroidal anti-inflammatory compounds suprofen appeared to be the most potent antagonist of acetic acid-induced writhing in rats, about 200 to 300 times as potent as acetyl-salicylic acid and phenylbutazone, 15 to 30 times as potent as indometacin and tolmetin, and about 6 times as potent as ketoprofen.     

Anti-inflammatory effects of sinapic acid on 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice

This study was conducted to evaluate the effect of sinapic acid, a cinnamic acid derivative, on inflammatory changes in a mouse model of colitis. Colitis was induced by intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Sinapic acid (10, 30, and 100 mg/kg) and dexamethasone (2 mg/kg) were orally administered to Balb/c female mice after TNBS instillation. The anti-inflammatory effect of sinapic acid on colonic injury or damage was assessed by clinical, macroscopic, microscopic, and biochemical analyses. Compared with TNBS control, treatment with sinapic acid significantly improved colonic weight and length and decreased the macroscopic and microscopic changes in TNBS-induced colitis. Furthermore, myeloperoxidase activity and the colonic tissue levels of malondialdehyde and tumor necrosis factor alpha were decreased by administration of sinapic acid. The findings of this study suggest that sinapic acid exerts anti-inflammatory effects on intestinal inflammation and can be selected as a novel therapeutic candidate in the treatment of inflammatory bowel disease.     

Evaluation of an interleukin-1 receptor antagonist in the rat acetic acid-induced colitis model.

The anti-inflammatory activity of the IL-1 receptor antagonist, IL-1ra, was evaluated in the acetic acid (HOAc)-induced model of colitis in rats. Animals treated with 10 mg/kg IL-1ra or vehicle were evaluated for general health, acute phase response, and colonic in flammation 24 hours after the initiation of inflammation. A significant decrease in the accumulation of neutrophils in the colonic mucosa as measured by myeloperoxidase activity was seen in animals with HOAc induced colitis that were treated intraperitoneally with IL-1ra when compared to animals with colitis that had been treated with vehicle. IL-1ra also reduced colonic necrosis measured grossly, although there was no effect on the histology IL-1ra had a modest effect on the HOAc-induced acute phase response, as indicated by changes in the serum iron, albumin and transferrin, but the results were not statistically significant. The number of circulating erythrocytes and neutrophils was significantly increased in animals with HOAc-induced colitis and treated with IL-1ra, suggesting that IL-1ra under these experimental conditions inhibited the migration of neutrophils to the injured colon and also the overall intestinal necrosis in the colon as assessed by gross pathology. IL-1ra may be useful as an intestinal anti-inflammatory agent.     

Effect of ethanolic extract of leaves of Paederia foetida Linn. on acetic acid induced colitis in albino rats

Objectives:

To evaluate the effect of ethanolic extract of leaves of Paederia foetida on acetic acid induced colitis in albino rats.

Materials and Methods:

Ethanolic extract of Paederia foetida (EEPF) was prepared by percolation method. Acute toxicity test was done by using Organization for Economic Cooperation and Development guidelines. Albino rats were divided into four groups of five animals each. Groups A and B received 3% gum acacia. Groups C and D received EEPF 500 mg/kg body weight (BW) and 5-aminosalisylic acid 100 mg/kg BW respectively. Colitis was induced by transrectal administration of 4% acetic acid on 5^th day. All animals were sacrificed after 48 h of colitis induction and distal 10 cm of the colon was dissected. Colon was weighed for disease activity index (DAI) and scored macroscopically and microscopically. Biochemical assessment of tissue myeloperoxidase (MPO), catalase (CAT) and superoxide dismutase (SOD) was done in colonic tissue homogenate and malondialdehyde (MDA) was estimated in serum.

Results:

P. foetida showed significant (P < 0.05) reduction in DAI, macroscopic and microscopic lesion score as well as significant (P < 0.05) improvement in MPO, MDA, CAT, and SOD level as compared to Group B.

Conclusions:

The ethanolic extract of leaves of P. foetida showed significant amelioration of experimentally induced colitis, which may be attributed to its anti-inflammatory and antioxidant property.KEY WORDS: Antioxidant, colitis, Paederia foetida     

Nicotine withdrawal alleviates acetic acid-induced gastric injury in rats

Epidemiological and experimental studies have demonstrated that cigarette smoking intensifies gastric ulceration. Although nicotine can act as an anxiolytic and antidepressant, its withdrawal may also lead to increased anxiety and depression. In order to associate the toxic actions of nicotine on gastric mucosa with alterations of anxiety level and to evaluate the impact of nicotine withdrawal on the anxiety level and the severity of ulcer, an acetic acid-induced ulcer model was used. Male Sprague-Dawley rats were given either tap water or nicotine bitartarate (50μg/ml in drinking water) for 15 days, while another group of rats had 5 days of withdrawal following 10 days of nicotine treatment. Ulcer was induced by acetic acid on the 15th day of the treatments, and the rats were followed for 3 days until they were decapitated and the gastric tissues were obtained. Using the hole-board test, basal anxiety levels measured on the first day of the treatments were compared with the measurements made at the early and late phases of ulcer induction. Chronic administration of nicotine did not have a potentiating effect on acetic acid-induced gastric ulcer, since the gastric injury, as assessed by both macroscopic and microscopic evaluation and increased gastric myeloperoxidase activity indicating neutrophil recruitment, was not exaggerated or attenuated by nicotine intake. On the other hand, nicotine withdrawal attenuated gastric mucosal injury, despite an increased level of anxiety. Smoking cessation, which triggers the onset of depressive symptoms with nicotine withdrawal, still has a worthwhile positive effect on the gastric mucosa.     

Protective effect of Periplaneta americana extract in ulcerative colitis rats induced by dinitrochlorobenzene and acetic acid

Context: Periplaneta americana L. (Dictyoptera; Blattaria) has been traditional used to treat ulcers, burns and heart disease in southwestern China. Recent reports indicate that P. americana can be used as an alternative medicine in therapy of ulcerative colitis, but the mechanism involved remains obscure.

Objective: This study investigated the therapeutic effect of P. americana extract (PAE) in rat colitis and elucidated its potential mechanism.

Materials and methods: Dinitrochlorobenzene and acetic acid-induced colitis rat model was applied. Colitis rats were treated with PAE for 10 d and estimated disease activity index daily. Rectal inflammation was assessed by myeloperoxidase activity and histological changes. Another colitis rats were treated with PAE for 4 d, meanwhile gavage with Escherichia coli labelled with green fluorescent protein. Mesenteric lymph nodes, colon, liver, spleen and kidney were harvested for bacteria culture. PAE was suspended in distilled water then partitioned with ethyl acetate and n-butanol to obtain ethyl acetate fraction, n-butanol fraction and water fraction, respectively. Fibroblasts proliferation and collagen accumulation of each fraction was determined.

Results: PAE treatment reduced the severity of colitis and tissue myeloperoxidase accumulation (p?<?0.001). Also, PAE at 80?mg/kg significantly inhibited labelled E. coli from translocating to distant organs, especially to MLN and liver. Additionally, PAE significantly stimulated fibroblasts proliferation (126.9%) and collagen accumulation (130.8%) for 48?h incubation. Among the partitions, ethyl acetate fraction generally had higher fibroblast viability enhanced-activity.

Conclusions: PAE can protect against ulcerative colitis and this protection is attributed to anti-inflammation and fibroblasts viability.