Acetic Acid-induced Colitis Model Research Articles

Therapeutic and prophylactic role of vitamin D and curcumin in acetic acid-induced acute ulcerative colitis model

Ulcerative Colitis (UC) is a disease that negatively affects quality of life and is associated with sustained oxidative stress, inflammation and intestinal permeability. Vitamin D and Curcumin; It has pharmacological properties beneficial to health, including antioxidant and anti-inflammatory properties. Our study investigates the role of Vitamin D and Curcumin in acetic acid-induced acute colitis model. To investigate the effect of Vitamin D and Curcumin, Wistar-albino rats were given 0.4 mcg/kg Vitamin D (Post-Vit D, Pre-Vit D) and 200 mg/kg Curcumin (Post-Cur, Pre-Cur) for 7 days and acetic acid was injected into all rats except the control group. Our results; colon tissue TNF-α, IL-1β, IL-6, IFN-γ and MPO levels were found significantly higher and Occludin levels were found significantly lower in the colitis group compared to the control group (p < 0.05). TNF-α and IFN-γ levels decreased and Occludin levels increased in colon tissue of Post-Vit D group compared to colitis group (p < 0.05). IL-1β, IL-6 and IFN-γ levels were decreased in colon tissue of Post-Cur and Pre-Cur groups (p < 0.05). MPO levels in colon tissue decreased in all treatment groups (p < 0.05). Vitamin D and Curcumin treatment significantly reduced inflammation and restored the normal histoarchitecture of the colon. From the present study findings, we can conclude that Vitamin D and Curcumin protect the colon from acetic acid toxicity with their antioxidant and anti-inflammatory potential. Brief synopsis: In this study; distal colon, distal ileum, jejunum and serum physiopathology in colitis induced by acetic acid and intestinal permeability were investigated. The roles of vitamin D and curcumin in this process were evaluated.

Evaluation of oral and topical bovine colostrum compared to mesalamine in the treatment of animal model of acetic acid-induced ulcerative colitis.

Oxidative activity and inflammatory responses have been shown to play a pivotal role in the pathogenesis of ulcerative colitis (UC). Colostrum is a natural product with anti-inflammatory and antioxidative properties. UC was induced in 37 Sprague Dawley rats by administration of a 2 mL enema of 3% acetic acid (AA). The control groups received no treatment during the study, while the experimental groups received either oral or rectal administration of 100 mg/kg 5-aminosalicylic acid, or oral or rectal administration of 300 mg/kg of colostrum. Histopathological and serological analyses were performed 7 days following treatment. A significant decrease in weight was seen in all rats except for the test groups receiving colostrum (P<0.001). After treatment, the level of superoxide dismutase increased more significantly in the test groups that received colostrum (P<0.05). All test groups had a reduction in C-reactive protein and white blood cell levels. The colostrum test groups also showed a decrease in inflammation rate, ulceration, destruction, disorganization, and crypt abscess of the colonic mucosa. The findings of this study show that the administration of colostrum can improve the pathological changes of the intestinal mucosa, as well as inflammatory responses, in animal models of UC. Further studies at both preclinical and clinical levels are suggested to confirm these findings.

Influence of laboratory-controlled ethanolic wheatgrass extract on acetic acid-induced changes in biochemical and antioxidant indices in the colitis of Wistar rats

Introduction and Aim: Triticum aestivum (wheatgrass) is a good source of mineral nutrients and antioxidant enzymes. It also acts as a detoxifying agent and helps to revive healthy cells. The present study aimed to assess the effects of acetic acid on biochemical and antioxidant indices in the colitis of Wistar rats using an ethanolic extract derived from the dried shoots of wheatgrass maintained under specified growth conditions.&#x0D; &#x0D; Materials and Methods: Aqueous and ethanolic extract of wheatgrass was subjected to preliminary phytochemical screening and in-vitro antioxidant activity. Effects of the ethanolic wheatgrass extract were investigated in the acetic acid-induced rat colitis model. Sulphasalazine was used as the standard anti-inflammatory drug. Malondialdehyde (MDA), myeloperoxidase (MPO), total antioxidant capacity (TAC), catalase (CAT), and reduced glutathione (GSH) levels were estimated in the rat blood. Colitis was quantified with a clinical score and colon length/weight index was measured. Histopathological analyses were also performed on the colon tissue of rats.&#x0D; &#x0D; Results: The presence of phytochemical elements such as saponins, tannins, alkaloids, and terpenes in aqueous and ethanolic wheatgrass extract was discovered. These compounds have the potential to boost antioxidant and anti-inflammatory effects. The ethanolic extract significantly reduced MDA, MPO, and antioxidant levels (TAC, CAT, and GSH) in colon tissue and blood. Biochemical measurements corroborated the conclusions of histopathological investigation.&#x0D; &#x0D; Conclusion: According to macroscopic, microscopic, histological, and other biochemical studies, ethanolic wheatgrass extract significantly inhibits experimental colitis in rats.

Protective and Therapeutic Effects of Betulinic Acid on Acetic Acid-Induced Experimental Colitis Model

Protective and Therapeutic Effects of Betulinic Acid on Acetic Acid-Induced Experimental Colitis Model

Dual role of melatonin as an anti-colitis and anti-extra intestinal alterations against acetic acid-induced colitis model in rats

The available ulcerative colitis drugs exhibit limited outcomes and adverse side effects. Therefore, our study aimed to investigate the therapeutic efficacy of melatonin in acetic acid (AA)-induced colitis to establish a possible treatment for colitis and its impacts on vital organs. Following colitis induction (2 ml 5% AA, rectally), rats were orally received melatonin (5 mg/kg) once per day for 6 days after colitis induction. Then, histopathological examination of colon, kidney, liver, and spleen was conducted, interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), and total antioxidant capacity (TAC) levels were assessed in colon tissue. Colitis induction in untreated rats caused necrotic effects in colon tissues, a significant increase in colonic IL-1β, TNF-α, MPO, and MDA levels, and a remarkable decrease in GSH and TAC levels in colon tissue in comparison to the control group. Meanwhile, melatonin treatment reversed these parameters by improving the microscopic and macroscopic colitis features and extra-intestinal (kidney, liver, and spleen) changes in all treated rats compared to the colitis control group. These results denote a reduction in colitis severity due to the anti-inflammatory and anti-oxidative effects of melatonin and its positive impact on the vital organs.

Linagliptin ameliorates acetic acid-induced colitis via modulating AMPK/SIRT1/PGC-1α and JAK2/STAT3 signaling pathway in rats

Ulcerative colitis is a chronic inflammatory disease, profoundly affecting the patient's quality of life and is associated with various complications. Linagliptin, a potent DPP- IV inhibitor, shows favorable anti-inflammatory effects in several animal model pathologies. To this end, the present study aimed to investigate the anti-inflammatory effect of linagliptin in a rat model of acetic acid-induced colitis. Moreover, the molecular mechanisms behind this effect were addressed. Accordingly, colitis was established by the administration of a 2 ml 6% acetic acid intrarectally and treatment with linagliptin (5 mg/kg) started 24 h after colitis induction and continued for 7 days. On one hand, the DPP-IV inhibitor alleviated the severity of colitis as evidenced by a decrease of disease activity index (DAI) scores, colon weight/length ratio, macroscopic damage, and histopathological deteriorations. Additionally, linagliptin diminished colon inflammation via attenuation of TNF-α, IL-6, and NF-κB p65 besides restoration of anti-inflammatory cytokine IL-10. On the other hand, linagliptin increased levels of p-AMPK, SIRT1, and PGC-1α while abolishing the increment in p-JAK2 and p-STAT3. In parallel linagliptin reduced mTOR levels and upregulated expression levels of SHP and MKP-1 which is postulated to mediate AMPK-driven JAK2/STAT3 inhibition. Based on these findings, linagliptin showed promising anti-inflammatory activity against acetic acid-induced colitis that is mainly attributed to the activation of the AMPK-SIRT1-PGC-1α pathway as well as suppression of the JAK2/STAT3 signaling pathway that might be partly mediated through AMPK activation.

Methylene blue ameliorates colonic injury in acetic acid-induced colitis model

Methylene blue ameliorates colonic injury in acetic acid-induced colitis model

Histone deacetylase inhibitor givinostat has ameliorative effect in the colitis model.

ABSTRACTPurpose:To investigate the effect of givinostat treatment in acetic acid-induced ulcerative colitis model in rats.Methods:Thirty male Wistar albino rats were used. Rats were randomly divided into three equal groups, and colitis was induced on 20 rats by rectal administration of %4 solutions of acetic acid. Twenty rats with colitis were randomly divided into two groups. %0.9 NaCl (saline) solution was administered intraperitoneally to the first group of rats (saline group, n=10) at the dose of 1 mL/kg/day. Givinostat was administered intraperitoneally to the second group rats (Givinostat group, n=10) at the dose of 5 mg/kg/day. Samples were collected for biochemical analysis. Colon was removed for histopathological and biochemical examinations.Results:Plasma tumor necrosis factor-α (TNF-α), pentraxin-3 (PTX-3), and malondialdehyde levels were significantly decreased in the givinostat group compared to the saline group (p<0.05, p<0.001, and p<0.001 respectively; p<0.001, p<0.001, and p<0.001, respectively). Colon TNF-α and prostaglandin F2 alpha (PGF-2) levels were significantly decreased (p<0.05, and p<0.001, respectively). The givinostat group had a significantly lower histologic score than saline group (p<0.001, and p<0.001, respectively).Conclusions:Givinostat, a good protector and regenerator of tissue and an anti-inflammatory agent, may be involved in the treatment of colitis in the future.

Gisekia pharnaceoides Restores Colonic Mucosal Homeostasis by Regulating Antioxidant Enzyme System and Cytokines Signaling in Ulcerative Colitis Mice Model.

Gisekia pharnaceoides Linn. (Aizoaceae), traditionally known as baluka saag or sareli is commonly found in the deep Cholistan region of Pakistan. It is used by the native community for the mitigation of a range of diseases, including inflammatory disorders and gastric ulcers. This study is designed to evaluate the defensive impact of G. pharnaceoides in acetic acid-induced ulcerative colitis in mice and to discover the mechanism for anti-inflammatory action. The ethanolic crude extract of G. pharnaceoides (Gp.Cr) was prepared and evaluated for phytochemical substances by preliminary screening and HPLC analysis. Anti-inflammatory activity of Gp.Cr (300 and 500 mg/kg) was examined by administration of 200 μl of 7.5% acetic acid intra- rectally to induce ulcerative colitis and colonic mucosal injury, while mucosal homeostasis was evaluated by disease activity index, colonic ulcer score, and hematological parameters. The anti-inflammatory potential was quantified by assessing antioxidant enzymes (SOD, CAT, GPX-1), lipid peroxides, nitric oxide, and cytokines (IL-1β, IL-6, TNF-α) immunoassays and further analyzed by histological analysis of colon tissues. Phytochemical screening of Gp.Cr revealed the presence of alkaloids, phenols, flavonoids, steroids, tannins, and saponins, while HPLC analysis confirmed the presence of quercetin, gallic acid, coumaric and sinapic acid. In acetic acid-induced ulcerative colitis model, Gp.Cr (300 and 500 mg/kg) along with sulphasalazine (500 mg/kg) decreased disease activity index, ulcer scores, and hematological parameters. Gp.Cr showed a significant anti-inflammatory potential by increasing antioxidant enzymes and decreasing lipid peroxides, nitric oxide, and cytokines levels. Histopathological examination showed a significant decline in ulceration and tissue disruption. Hence, the findings confirmed the effectiveness of G. pharnaceoides crude extract in the treatment of ulcerative colitis and might be a promising remedy to manage inflammatory disorders.

Prednisolone Loaded Tamarind Gum Microspheres for Colonic Delivery

The aim of this work was to formulate a novel multiparticulate system having pH sensitive property and specific enzyme biodegradability for colon specific drug delivery of Prednisolone (PD). Natural polysaccharide, Tamarind gum is used for microsphere preparation and Eudratit S- 100 for coating to provide pH controlled drug release. The formulation aims at minimal degradation and optimum delivery of the drug with relatively higher local concentration, which may provide more effective therapy for inflammatory bowel disease including Crohn disease and ulcerative colitis. Tamarind gum microspheres were prepared by emulsion dehydration technique using polymer in ratio of 1:1 to 1: 9. These microspheres were coated with Eudragit S-100 by oil in oil solvent evaporation method using core: coat ration (5:1). Tamarind gum microspheres and Eudragit coated tamarind gum microspheres were evaluated for surface morphology, particle size and size distribution, percentage drug entrapment, surface accumulation studies, in vitro drug release in simulated gastrointestinal fluids. The effect of various formulation variables were studied the prepared microspheres were spherical in shape in the size range of 64 µm to 113 µm, the encapsulation efficiency was in range of 30-72% depending upon the concentration of gum. The drug release was about 14-20% in first four hours of study gradually rises in 5th hour and 85% drug release occurs in 10-12% hr thus showing desirable drug release in the colonic simulated environment. PD tamarind gum microspheres are thought to have the potential to maintain drug concentration within target ranges for a long time, decreasing the side effects caused by concentration fluctuation, ensuring the efficiency of treatment and improving patient compliance by reducing dosing frequency. The animal study done using acetic acid induced colitis model on rats also suggest the anti inflammatory activity of the formulation.

Nerolidol, a sesquiterpene, attenuates oxidative stress and inflammation in acetic acid-induced colitis in rats.

Targeting oxidative stress and inflammation by novel dietary compounds of natural origin convincingly appears to be one of the most important therapeutic strategies to keepinflammatory bowel diseases (IBD) such as ulcerative colitis disease in remission. It is imperative to investigate naturally occuringplant-derived dietary phytochemicals that are receiving attention for their therapeutic benefits to overcome the debilitating conditions of IBD. In the present study, the effect of nerolidol (NRD), a monocyclic sesquiterpene found in German Chamomile tea, was investigated in acetic acid-induced colitis model in Wistar rats. NRD was orally administered at a dose of 50mg/kg/day either for 3days before or 30min after induction of IBD for 7days, afterintrarectal administration of acetic acid. The body weight, macroscopic, and microscopic analyses of the colon in different experimental groups were observed on days 0, 2, 4, and 7. Acetic acid caused significant reduction in body weight and induced macroscopic and microscopic ulcer along with a significant decline of antioxidants, concomitant to increased malondialdehyde (MDA), a marker of lipid peroxidation, and myeloperoxidase (MPO) activity, a marker of neutrophil activation. Treatment with NRD significantly improved IBD-induced reduction in body weight, improved histology, inhibited MDA formation, and restored antioxidants along with reduced MPO activity. Acetic acid also induced the release of pro-inflammatory cytokines and increased calprotectin, released by neutrophils under inflammatory conditions. NRD treatment significantly reduced calprotectin and pro-inflammatory cytokines. NRD treatment showed potential to improve disease activity and inhibit oxidative stress, lipid peroxidation, and inflammation along with histological preservation of the colontissues.

Protective Effect of a Formulation Containing Pistacia atlantica Oleo-Gum-Resin and Honey on Experimental Model of Acetic Acid-Induced Colitis in Rats

Background and objectives: Inflammatory bowel disease (IBD) is a recurrent chronic inflammatory disease of the gastrointestinal tract. In Iranian traditional medicine, the oleo-gum-resin of the genus Pistacia is recommended for treatment of various diseases including gastrointestinal disorders. The present study investigated the therapeutic action of a combination of Pistacia atlantica subspecies kurdica oleo-gum-resin and honey in acetic acid-induced colitis in rats. Methods: Pistacia atlantica oleo-gum-resin was mixed with honey. The mixture was suspended in distilled water. Following induction of colitis with 4% acetic acid in all animals, except in sham group,themixture was orally administered for two consecutive days at the concentrations of 100, 200, 400 mg/kg. Other groups included the control, sham and a standard group (dexamethasone). Microscopic and histopathologic examinations were conducted in inflamed colonic tissue. The inflammatory biomarkers of colitis including interleukin 6 (IL-6), tumor necrosis factor (TNF-α), and myeloperoxidase (MPO) and the gene expression level of toll like receptor-4 (TLR-4) were assessed. Results: Pistacia atlantica oleo-gum-resin+ honey induced significant progress in macroscopic and microscopic scores. Colonic levels of MPO, IL-6, and TNF-α significantly declined in rats treated with the mixture; while significant decrease in mucosal gene expression of TLR-4 and significant improvement of colitis were observed. Pistacia atlantica oleo-gum-resin (400 mg/kg) + honey (400 mg/kg)reduced inflammation of the bowel and colonic ulcer severity shown by downregulation of inflammation cytokines, reduction of neutrophil infiltration, and suppression of TLR-4 expression. Conclusion: The combination might be a promising supplement for treatment of inflammatory disorders.

Regulation of IL-6/STAT-3/Wnt axis by nifuroxazide dampens colon ulcer in acetic acid-induced ulcerative colitis model: Novel mechanistic insight

AimUlcerative colitis (UC) is a common intestinal problem characterized by the diffusion of colon inflammation and immunity dysregulation. Nifuroxazide, a potent STAT-3 inhibitor, exhibits diverse pharmacological properties. The present study aimed to elucidate a novel anti-colitis mechanism of nifuroxazide against the acetic acid-induced UC model. MethodsRats were grouped into control (received vehicle), UC (2 ml of 5% acetic acid by intrarectal infusion), UC plus sulfasalazine (100 mg/kg/day, P.O.), UC plus nifuroxazide (25 mg/kg/day, P.O.), and UC plus nifuroxazide (50 mg/kg/day, P.O.) and lasted for 6 days. ResultsThe present study revealed that nifuroxazide significantly reduced UC measures, hematological changes, and histological alteration. In addition, treatment with nifuroxazide significantly down-regulated serum CRP as well as the colonic expressions of MPO, IL-6, TNF-α, TLR-4, NF-κB-p65, JAK1, STAT-3, DKK1 in a dose-dependent manner. Besides, our results showed that the colonic Wnt expression was up-regulated with nifuroxazide treatment. In a dose-dependent manner, nifuroxazide markedly alleviated acetic acid-induced cellular infiltration and improved ulcer healing by increasing intestinal epithelial cell regeneration. SignificanceOur results collectively indicate that nifuroxazide is an effective anti-colitis agent through regulation of colon inflammation and proliferation via modulation IL-6/STAT-3/Wnt signaling pathway.

Effect of escitalopram on an acetic acid-induced ulcerative colitis model.

Ulcerative colitis (UC) is a chronic and recurrent gastrointestinal (GI) disorder with an unknown aetiology and pathogenesis. Regarding the effectiveness of antidepressants on UC in animal models of depression and the known anti-inflammatory effects of escitalopram this study was conducted to evaluate the beneficial effects of escitalopram on an acetic acid-induced UC model without depression. UC model was induced by intra rectal (i.r.) administration of 4% acetic acid in rats after 24 hours of fasting. Animals were treated with three doses of escitalopram (5, 10 and 20mg/kg). Prednisolone (4mg/kg) was used as a reference drug in UC. Histological and oxidative stress markers were measured in all groups. Results showed significant increase in superoxide dismutase (SOD) activity and glutathione (GSH) levels, as well as significant decrease in myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, macroscopic factors (ulcer surface area, ulcer severity and weight-to-colon ratio) and microscopic and histological parameters (severity and extent of inflammation, cryptic destruction and severity of tissue involvement) in escitalopram treated rats (10, 20mg/kg) compared to the UC group. In conclusion, the results of our study are in support of beneficial anti-inflammatory and antioxidant effects of escitalopram in UC.

Comparative characteristics of chronic colitis experimental models reproduced in vivo

The review presents modern ideas about the prevalence and etiopathogenesis of the gastrointestinal tract inflammatory diseases, in particular, colitis. The factors that determine their high medical and social significance and the main complications that could develop under these conditions are identified. According to the literature, chronic colitis of various etiologies provoke significant pathological changes in the qualitative and quantitative of the small intestinal microflora composition, which leads to disturbances of a number of biologically active compounds synthesis and immune system pathological changes. Unfortunately, in a significant number of patients with chronic enterocolitis develop serious complications, and approximately in 10% of patients develop colorectal cancer, which has an unfavorable prognosis. The article presents a comparative analysis of colitis experimental models with different etiology (spontaneous, induced, colitis model with using genetically modified animals, etc.). Different courses (acute and chronic), different histological and biochemical changes are typical for colitis different models. Each experimental model has features of reproduction in laboratory animals. Therefore, it is necessary to take into account pathologies features and choose an experimental model depending on the purpose of the study. In particular, the model of formalin-induced colitis or acetic acid-induced colitis is optimal for the study of the pathogenesis proinflammatory component, the model of peptidoglycan-polysaccharide-induced colitis or dextran sodium sulfate-induced colitis is preferable model for chronic ulcerative colitis evaluation. Keywords: experimental model, colitis, gastrointestinal tract inflammatory diseases.

Antioxidant and anti-inflammatory effects of hesperidin methyl chalcone in experimental ulcerative colitis

Neutrophil infiltration, pro-inflammatory cytokines, and reactive oxygen species (ROS) production have been implicated in development and progression of ulcerative colitis (UC), an inflammatory bowel disease (IBD) characterized by ulcerating inflammation of the mucosal layer generally restricted to the colon. The side effects, safety and human intolerance are limitations of the currently approved treatments for UC. Hesperidin methyl chalcone (HMC) is a flavonoid used to treat chronic venous disease, which shows anti-inflammatory, analgesic, and antioxidant properties in pre-clinical studies, however, its effects on colitis have never been described. Therefore, we aimed to evaluate the protective effects of HMC in a mouse model of acetic acid-induced colitis. Treatment with HMC significantly reduced neutrophil infiltration, edema, colon shortening, macro and microscopic damages induced by intracolonic administration of acetic acid. The improvement of colitis after HMC treatment is related to the increase in colon antioxidant status, and the inhibition of pro-inflammatory cytokines TNF-α, IL-6, IL-1β, and IL-33 in the colon. We observed, moreover, that HMC inhibited NF-κB activation in the colon, which might explain the reduction of the cytokines we observed. Finally, these results demonstrate a novel applicability of HMC to increase antioxidant response and reduce inflammation during acetic acid-induced colitis suggesting it as a promising therapeutic approach for the treatment of ulcerative colitis.

Lycopene mitigates experimental colitis in rats by inhibiting oxidative stress-mediated inflammation and apoptosis

Objective: The potential protective and beneficial effects of Lycopene (LYC) in a rat model of acetic acid-induced ulcerative colitis (UC) were evaluated. Methods: Forty male albino rats were divided into five equal groups. Group I: (Control normal) rats received no drugs. Group II: (Early ulcerative colitis): rats received 2 ml (3% v/v) glacial acetic acid intracolonially at 21 th day of experiment and sacrificed 3 days later. Group III:(Early ulcerative colitis + Lycopene protected) rats received Lycopene (10 mg/kg body weight/day, orally) for 21 days prior to acetic acid administration. Group IV: (Late ulcerative colitis) rats received acetic acid similar to group II for 3 successive days and sacrificed after 21 days. Group V: (Late ulcerative colitis+ Lycopene treated) rats first administered with acetic acid then after 3 days Lycopene was administered for 21 days. Results: A significant increase in L-Malondialdehyde (L-MDA) with marked decrease in reduced glutathione (GSH) level and Catalase (CAT) activity were observed in colon tissue of UC-induced rats. Additionally, a significant up-regulation of nuclear factor kappa B (NF-κB), caspase-3 and Transforming growth factor-β1 (TGF-β1) and down-regulation of Interleukin -10 (IL-10) and Beta cell lymphoma-2 (Bcl-2) gene expression levels of were observed in colon of UC induced rats. However, a significant depletion of colon tissue L-MDA and down-regulation of NF-κB, caspase-3 and TGF-β1 in addition to marked increase in GSH concentration and CAT activity and up-regulation of IL-10 and Bcl-2 were observed after LYC treatment. Conclusions: Lycopene has powerful antioxidants, anti-inflammatory and anti-apoptotic effects against ulcerative colitis.

Antiulcerogenic effect of melittin via mitigating TLR4/TRAF6 mediated NF-κB and p38MAPK pathways in acetic acid-induced ulcerative colitis in mice

Ulcerative colitis (UC) is a chronic disease driven primarily by uncontrolled pervasive inflammatory responses affecting the colon and rectum. Currently available medications carry multiple detrimental adverse effects, which have emphasized the mandatory need for safer and more efficient novel therapeutic alternatives. Melittin is the main constituent of bee venom and exhibits potent anti-inflammatory properties. The antiulcerogenic effect of oral melittin (40 μg/kg) was explored in the current study using the acetic acid-induced colitis model. Increase in body weight and decrease in colon mass index were observed in the melittin group. Microscopically, melittin ameliorated acetic acid-induced histological damage. Melittin administration has efficiently amended the elevated levels of the cytokines, tumor necrosis factor (TNF-α) and interleukin 6 (IL-6) seen in the colitis group. This was accompanied by inhibition of the upstream signaling molecules, Toll-like receptor 4 (TLR4), tumor necrosis factor receptor (TNF-R)-associated factor (TRAF6), mitogen-activated protein kinase 38 (p38 MAPK), and nuclear factor kappaB (NF-κB) in the melittin group. Moreover, treatment with melittin resulted in marked decrease in colonic level of prostaglandin E2 (PGE2) together with the enzymes involved in its synthesis, secretory phospholipase A2 (sPLA2) and cyclooxygenase 2 (COX-2). Additionally, melittin has attenuated acetic acid-induced oxidative stress as manifested by the significant diminishment in malondialdehyde (MDA) as well as the increase in superoxide dismutase (SOD) and reduced glutathione (GSH) levels. Therefore, melittin mitigated UC pathogenesis and could be considered as a potent and promising therapeutic alternative for UC treatment.

Can Rodent Model of Acetic Acid-Induced Colitis be Used to Study the Pathogenesis of Colitis-Associated Intestinal Fibrosis?

In 1978, MacPherson and Pfeiffer performed a landmark experiment in which they administered diluted acetic acid intrarectally to rodents. They found that this approach induced mucosal inflammation ...

Cilostazol protects against acetic acid-induced colitis in rats: Possible role for cAMP/SIRT1 pathway

The phosphodiesterase-3 inhibitor, cilostazol has been recently shown to protect against chemically induced colitis in animal models. However, whether cyclic adenosine monophosphate (cAMP) contributes to the anti-inflammatory activity of cilostazol in colitis is still unknown. In the current study, we investigated the role of cAMP/silent information regulator-1 (SIRT-1) pathway in the protective effect of cilostazol using rat model of acetic acid-induced colitis. Upregulation of SIRT1 activity and expression has been recently shown to protect against chemically induced colitis. Our results demonstrated that cilostazol alleviated the histopathological changes associated with acetic acid-induced colitis. Interestingly, pre-administration of cilostazol increased cAMP concentration and SIRT1 expression in colonic mucosa to levels similar to that observed in control animals without induction of colitis. In addition, cilostazol inhibited the SIRT1 targets; NF-κB, Akt and MAPK inflammatory pathways as demonstrated by suppression of acetic acid-induced upregulation of NF-κB activity, p-AKT levels and the expression of p38 MAPK. NF-κB activity and the levels of p-AKT, tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) were similar in rats pretreated with cilostazol prior to induction of colitis and the control rats without colitis. Furthermore, cilostazol reduced acetic acid-induced oxidative stress and apoptosis. In conclusion, the protective effect of cilostazol against acetic acid-induced colitis may be attributed to activation of SIRT1 expression by cAMP. SIRT1 is suggested to contribute to cilostazol-induced suppression of NF-κB, Akt and MAPK inflammatory pathways, oxidative stress and apoptosis.