Acetic Acid-induced Colitis Research Articles

Effects of apple extract on the mechanism of apoptosis during acetic acid-induced colitis in Wistar rats

The aim of this study was to evaluate the immunoreactivity of Fas-L, Fas, FADD (Fas-associated protein with death domain), Smac/DIABLO, apoptosis-inducing factor (AIF), cytochrome c, and cleaved caspase 3 in the colon of rats with colitis and treated with apple extract. For this purpose, Wistar rats were submitted to the following experimental design: Group 1 (Sh) was kept as normal and received 1.0 mL of saline solution by intra-colonic injection. Group 2 (AE) only received the concentrated apple extract (CAE) treatment. Groups 3 (AA), 4 (CT), and 5 (PT) were subjected to the induction of experimental colitis by intra-colonic injection of 1 mL acetic acid (7%). Group 3 (AA) simulated as AA-colitis control. Group 4 (CT) was treated with CAE after AA-colitis induction for 7 days, and group 5 (PT) was treated 7 days before colitis induction and followed CAE treatment after colitis induction. The AE, CT, and PT groups received the CAE (1 mL) orally by gavage. All rats were euthanized on day 8 following the experiment. There were no significant statistical differences in the immunoreactivity of Fas-L, Fas, Smac/DIABLO, AIF, and cytochrome c. The expression of FADD in the PT group was similar to that of the AE group and three times greater than in the CT group. For this preventive group (PT), the expression of FADD was restored by apple extract. Our results demonstrated that concentrated apple extract was able to interfere with either intrinsic or extrinsic apoptotic pathways in the colon of rats with colitis.

An investigation of the anti-inflammatory effects of gabapentin on acetic acid-induced colitis in rats.

Inflammatory bowel disease (IBD) is considered a chronic inflammatory gastrointestinal disease with treatment options which exhibit low efficacies and lead to considerable side effects. Hence, the challenge to alleviate IBD complications is remained to be resolved. The purpose of this study is evaluating anti-inflammatory impacts of gabapentin on acetic acid-induced colitis in rats. Colitis was induced by the instillation of 2mL of 3% acetic acid solution into rat's colons. Rats were randomly allocated into six groups including normal group, colitis control group, gabapentin-treated groups (25, 50, and 100mg/kg; i.p.), and dexamethasone-treated group (1mg/kg; i.p.). Based on the macroscopic assessment besides histological and biochemical findings [myeloperoxidase (MPO), pro-inflammatory cytokines], the efficacy of gabapentin was investigated. Gabapentin (50 and 100mg/kg), and dexamethasone considerably reduced macroscopic and microscopic colonic lesions induced by acetic acid in rats in comparison with colitis control group. These results were confirmed by reduced levels of MPO activity and colonic concentrations of interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha, in inflamed colon tissue. Our data demonstrated that gabapentin exerts profitable impacts in experimental colitis that might be ascribed to its anti-inflammatory features and thus can be a potential therapeutic agent for IBD treatment.

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.

Methylene blue treatment on Alzheimer and inflammatory bowel disease

High-efficiency oxidative phosphorylation plays a key role in the progression of many diseases. There is growing evidence of methylene blue’s protective and reversing actions against neurodegenerative and inflammatory bowel diseases through different mechanisms. In Alzheimer’s disease (AD), oligomeric amyloid beta accumulates in the mitochondria and contributes to mitochondrial dysfunction, which occurs before significant plaque deposition. Methylene blue provides an alternative mitochondrial electron transfer pathway, switching from high-efficiency oxidative phosphorylation to the low-efficiency aerobic glycolysis pathway by receiving electrons from NADH in the presence of complex I and transferring them to cytochrome C. The second mechanism is the inhibition of active caspases, especially Caspase-6, a cysteinyl protease causing inflammation and cell death, which has been associated with age-dependent cognitive decline and the pathology of sporadic and familial AD. The third mechanism is the reversal of tau aggregation by oxidizing cysteine residues in tau and forming a more stable monomer, thus blocking tau-tau bindings as well as clearing tau pathology through increased autophagy. In regards to inflammatory bowel disease, reducing oxidative stress and attenuating inflammatory pathways inhibits epithelial destruction in acetic acid-induced colitis. Methylene blue has an anti-colitis effect, mainly relying on its mitochondrial efficacy-restoring, antioxidative, anti-inflammatory, and anti-apoptotic properties. In summary, methylene blue is a promising agent for both AD and inflammatory bowel disease due to its beneficial effects as well as its low cost and high accessibility.

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.

Favourable effects of whey protein on acetic acid-induced ulcerative colitis in a rat model.

In the present study, we aimed to examine the effects of the administration of whey protein through rectal enema to rats with acetic acid-induced ulcerative colitis on the pathways of nuclear-related factor-2 (Nrf-2), haem oxygenase-1 (HO-1), nuclear factor κB (NF-κB), active protein kinase-1 (AP-1), tumour necrotising factor-α (TNF-α), and cyclooxygenase-2 (COX-2), IL-6, IL-10. Twenty-eight rats were employed for the trial. Ulcerative colitis was induced through the use of acetic acid. The therapeutic doses of whey protein were administered rectally. Ulcerative colitis was subjected to histopathological examination and protein levels in colon tissue were measured with the Western blot method. The significant increases observed in the levels of AP-1, COX-2, IL-6, IL-10, NF-κB, and TNF-α as markers of inflammation following the development of ulcerative colitis showed remarkable decreases along with the administration of whey protein (p < 0.05). On the other hand, we identified a decrease in the Nrf2-ARE signal pathway and HO-1 protein having protective roles in the colon inflammatory response along with the development of ulcerative colitis and activation of the Nrf2-HO-1 pathway by the whey protein. Whey protein modulates Nrf2/HO-1 and NF-kB pathways, thereby creating a therapeutic effect against colonic inflammation induced by acetic acid (AA) due to its anti-inflammatory effects.

Cinnamaldehyde targets TLR-4 and inflammatory mediators in acetic-acid induced ulcerative colitis model

Cinnamon and its bioactive ingredients such as cinnamaldehyde (CA), with broad pharmacological profiles, are important parts of daily diet in many cultures. Moreover, there are plenty motivating patents on efficacy of nutritional phytochemicals as novel anti-inflammatory drugs in patients with inflammatory bowel disease (IBD). This study intended to evaluate the effects of CA on inflammatory biomarkers in acetic acid-induced colitis rats. Colitis was induced in all animals, except in sham group, using acetic acid (4%). Following colitis induction, in 3 groups, CA was administrated orally at 2, 4 and 8 mg/kg/day for 2 days (once a day). Other groups were defined as the control (only treated with acetic acid), sham group (normal saline), and a standard group (Dexamethasone). To evaluate the inflammation sites, macroscopic and microscopic markers were assessed. Tissue concentrations of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF)-α, were assessed by ELISA assay kits, while myeloperoxidase (MPO) was measured spectrophotometrically. The mRNA expression of toll like receptor (TLR)-4 in colon tissue was assessed by Real time-PCR. CA at 4 mg/kg/day and 8 mg/kg/day significantly improved microscopic and macroscopic manifestations of colitis tissues. TNF-α, MPO, and IL-6 levels were significantly lower in CA treated groups at all the concentrations tested (P < 0.001). CA at 4 and 8 mg/kg/day significantly downregulated the mucosal gene expression of TLR-4. CA attenuated experimental colitis by means of colitis symptoms, reduction in inflammation cytokines, decline of neutrophil infiltration, and suppression of TLR-4 expression in acetic acid-induced colitis. CA improved colitis in animal model through suppression of inflammatory parameters and downregulation of TLR-4 mRNA expression.

Role of Oxidative Stress and Inflammatory Cytokines (TNF-α and IL-6) in Acetic Acid-Induced Ulcerative Colitis in Rats: Ameliorated by Otostegia fruticosa.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes irritation, inflammation, and ulceration in the linings of the colon and rectum. Otostegia fruticosa is traditionally used to treat various disorders in different parts of the Middle East and sub-Saharan Africa. In the present study, we evaluated the ameliorative effects of crude leaves extract of O. fruticosa (OF.Cr) on acetic acid (AA)-induced UC model in Wistar albino rats. Wistar rats were administered orally with either vehicle (10 mL/kg), OF.Cr (200 and 400 mg/kg), or prednisolone (2 mg/kg) once a day for 6 days. On day 6, UC was induced in rats by intrarectal administration of a single dose of 5% AA (1.0 mL). Disease activity index (DAI) was recorded after one day of colitis induction by assessing the symptoms of colitis and then the rats were euthanized by cervical dislocation, and colon tissues were isolated for the histopathological examination and biochemical analysis of oxidative stress parameters and cytokines (Interleukin-6 and Tumor Necrosis Factor-α). OF.Cr pretreatment exhibits significant prevention against UC, as confirmed by a significant decrease of DAI, colonic ulceration, and reduced inflammatory score as compared to the AA-induced colitis rats. Depletion of total glutathione (GSH) levels and catalase (CAT) activities in the colitis group was significantly restored in the OF.Cr treated groups, while increased lipid peroxidation in the colon tissues was significantly reduced. OF.Cr prevented the activation of the IL-6 and TNF-α pathways in the colonic tissues, which were clearly observed by the decreased levels of IL-6 and TNF-α in the OF.Cr treated animals. Hence, OF.Cr could be developed in the future for the treatment of UC.

Biochemical study on the effect of probiotic in experimentally induced ulcerative colitis in rats

In this study, potential protective and curative effect of probiotics on acetic acid-induced ulcerative colitis were evaluated. Ulcerative colitis was induced in rats by 2 ml of 3% glacial acetic acid (v/v) administered intracolonially for 3 successive days. Forty male albino rats were divided into Five equal groups. Group I: (Control group) rats received no drugs. Group II: Early UC-induced group, Group III: Late UC-induced group, Group IV: (Early UC + probiotics protected) rats received probiotics (135 mg/kg b. wt/day) orally for 21 days prior to acetic acid administration then sacrificed. Group V: (Late UC + probiotics treated) rats first administered with acetic acid then after 3 days probiotics was received for 21 days. A significant increase in L-MDA and Myeloperoxidase (MOP) and up-regulation of IL-1β, caspase-3 with down-regulation in Bcl-2 gene expression as well as marked decrease in GSH and CAT were observed in colon tissue of UC-induced rats. However, administration of probiotics to UC-induced rats caused a marked improvement and reverse all previous parameters near the average range. On conclusion, Probiotics protect colonic mucosa against ulcerative colitis and may be effective in enhances the healing of ulcerated colon via anti-inflammatory and anti-apoptotic activities and regenerating endogenous antioxidant mechanism.

Acrylamide exposure aggravates the development of ulcerative colitis in mice through activation of NF-κB, inflammatory cytokines, iNOS, and oxidative stress.

Objective(s):Acrylamide is a toxic compound that forms during food processing at high temperatures. Acrylamide has been shown to induce toxicity in various organs in the body. This study aimed to investigate the effect of acrylamide exposure on the susceptibility of the colon to ulcerative colitis in a mouse model. Materials and Methods:Mice were pretreated with acrylamide (oral, 20 and 30 mg/kg/day) for 21 consecutive days, and colitis was induced by intrarectal administration of acetic acid. Results:The results revealed that acrylamide-pretreatment significantly increased disease activity index (DAI), macroscopic damage, histological changes of the colonic mucosa and oxidative stress markers carbonyl protein, malondialdehyde (MDA), and nitric oxide (NO), whereas it decreased the levels of anti-oxidants glutathione (GSH), superoxide dismutase (SOD) and catalase. Moreover, induction of colitis in acrylamide-pretreated mice caused a higher increase in colonic levels of myeloperoxidase (MPO), matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-1, cytochrome-c, caspase-3, proinflammatory cytokine tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and interferon (IFN)-γ, whereas it reduced the level of IL-10. The mRNA expression of nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) were further increased in colon tissue of mice exposed to acrylamide.Conclusion:These findings suggest that acrylamide can accelerate the development of acetic acid-induced colitis. In conclusion, chronic acrylamide exposure may aggravate the severity of ulcerative colitis and increase colonic mucosal damage through oxidative stress and inflammatory responses.

Valorization of Algerian Grape Pomace Seeds: Extraction of Bioactive Compounds, Prevention and Treatment of Experimental Inflammatory Bowel Diseases

The global production of agroindustry wastes generate high amounts of wastes that represent an economical and environmental issues. Hence, the objective of this study was to characterize the phenolic composition profile recovered from Vitis vinifera waste and its related in vitro antioxidant and anti-inflammatory activities. In this study, we investigated the effects of different amounts of V. vinifera grape pomace seeds polyphenols (GPEs) on an experimental ulcerative colitis mouse model. We induced colitis using acetic acid and estimated disease activity index (DAI), which included weight loss, stool consistency and bleeding. The colonic mucosal injury was assessed by clinical, macroscopic, biochemical and histopathological examinations. Microscopic damage score and changes in weight and length of colon and digestive system segment were analyzed. Macroscopic activity of acetic acid-induced colitis was observed, the colon of acetic acid-treated mice showed severe inflammation characterized by marked ulceration, edema and erosions. The severity of acetic acid-induced colitis was assessed by macroscopic score analysis. Treatment with phenolic extract (0.15 and 0.1 mg) significantly (P < 0.001) reduced the disease index and significantly improved the macroscopic score. Histological analysis shows the therapeutic effect of GPEs (0.15 and 0.1 mg), with a decrease in the intensity and distribution of lesions in the duration of treatment. In conclusion, grape pomace seeds polyphenols may serve as a natural antioxidant and anti-inflammatory treatment for ulcerative colitis.

Strong protective effects of Salvia officinalis L. leaves decoction extract against acetic acid-induced ulcerative colitis and metabolic disorders in rat

• Salvia officinalis leaves decoction extract (SOLDE) increased the plasma scavenging activity. • SOLDE pre-treatment significantly reduced acetic acid (AA)-induced colonic mucosa lesions and histopathological changes. • SOLDE counteracted AA-induced oxidative stress, inflammation and intracellular mediator perturbations. We aimed in the present research to evaluate the ameliorative effect of Salvia officinalis leaves decoction extract (SOLDE) against ulcerative colitis (UC) induced by acetic acid intoxication in rat as well as the mechanisms implicated in such protection. The RP-HPLC-DAD analysis revealed the presence of 8 phenolic compounds with rosmarinic acid being the main major component. Results of the in vivo assay showed that SOLDE pre-treatment significantly reduced acetic acid (AA)-induced colonic mucosa lesion sand attenuates histopathological alterations. SOLDE counteracted AA-induced lipid peroxidation and antioxidant enzyme activities depletion. It also increased the plasma scavenging activity (PSA) and preserved the contents of non-enzymatic antioxidants. More importantly, acetic acid administration increased colonic hydrogen peroxide, free iron and calcium levels, while the SOLDE pre-treatment reversed all intracellular mediator perturbations. Also, SOLDE treatment significantly protected against inflammation. Our data suggest that the SOLDE exerted a potential protective effect against AA-induced colitis in rat.

Biochemical and histopathological effects of low dose vanadium in the healing of acetic acid-induced colitis in male wistar rats.

Vanadium has been reported to possess relevant therapeutic properties such as anti-diabetic and anti-tumoral. This study aimed at determining the effects of vanadium on experimentally induced colitis in rats. Forty-five male Wistar rats (103±3.90g, n=15) were used for this study and were divided into three groups. Group 1 (Untreated control) had nothing added to their drinking, while groups 2 and 3 received sodium metavanadate at a dose of 50 and 200mg/L respectively in their drinking water for 10weeks. Colitis was thereafter induced by intra colonic administration of 1.50mL of 6% acetic acid. Animals were sacrificed on day 0 (pre-induction), three- and seven-days post induction. Blood samples were collected for haematological variables and the distal 8cm of the colon was collected for macroscopic, histological and biochemical (malondialdehyde-MDA, superoxide dismutase-SOD, catalase-CAT, glutathione peroxidase- GPx and nitrite concentration- NO) assessment. Low dose vanadium proved beneficial in ameliorating acetic acid-induced colitis by improving both histopathological and haematological changes. Gross observation showed a faster healing rate in vanadium treated groups (50and 200mg/L) compared with untreated control at day 3 (40 and 26.20 vs. 2.50%) and day 7 (80 and 66.70 vs. 42%) respectively. Vanadium also appears to exert its beneficial effects on acetic acid-induced colitis via up regulation of antioxidant enzymes (SOD, CAT, GPx) and NO while decreasing the over production of MDA. Vanadium at small concentration functions as an essential trace element and may be able to promote healing process during ulcerative colitis.

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 Study Between Virgin Coconut Oil and Omeprazole Drug on Ulcerative Colitis in Experimental Rats

This study aims to identify the curative effect of virgin coconut oil on ulcerative colitis(UC),the present study was carried (24) adult albino male rats Sprague –Dawley strain weighting 180 ±10g were classified into four groups,(6 rats each) the first group rats were fed on basal diet only control negative(-ve) group and three rat groups were injured of ulcerative colitisby intra colonic administration of acetic acid 4% given rectally by single dose ( 1 ml/ rat ) and reclassified into control positive (+ve) group (fed on basal diet only), group treated with (20 mg/kg b.w) of omeprazole drug and group treated with (2 ml per/ rat) daily of virgin coconut oil . The results revealed that, the control (+ve) group showed a significant decrease in final weight(FW) ,weight gain(WG) feed efficiency ratio (FER), organs weight of heart, kidney, and liver , catalase (CAT), superoxide dismutase (SOD), glutathione reduced (GSH), Glutathione reductase (GSR),Glutathione peroxidase (GPx(, glutathione-S-transferees (GST) and significant increase in malondialdehyde (MDA) , hydrogen peroxide (H2O2), C-reactive protein (CRP), interleukin-6 (IL-K) and prostaglandin (PG2) compared with control (- ve) group. The virgin coconut oil group showed a significant increase in (FW),(WG),(FI),(FER),organ stomach,(CAT),(SOD),(GSH),(GSR (GPx), (GST) but significant decrease in (MDA),(H2O2),(CRP),(ILK), (PG2) compared with control (+ve) group . the study clearly showed that consumption virgin coconut oil has a role in treating rats with acetic acid-induced ulcerative colitis. It can be recommended that virgin coconut oil should be consumed daily to reduce the incidence of ulcerative colitis.

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.

Anti-inflammatory effect of amitriptyline in a rat model of acetic acid-induced colitis: the involvement of the TLR4/NF-kB signaling pathway.

Inflammatory bowel disease (IBD) consists of ulcerative colitis and Crohn's disease, which affects gastrointestinal tract. The immune-mediated inflammation is mostly considered as the pathogenesis of IBD. It has been demonstrated that amitriptyline exerts anti-inflammatory influence; therefore, the aim of the current experiment is to evaluate the anti-inflammatory impact of amitriptyline on intestinal disorders following acetic acid-induced colitis in rats. Thirty male Wistar rats were randomly divided into five groups, including sham, control, dexamethasone (2mg/kg), and amitriptyline (10 and 20mg/kg). Intrarectal administration of acetic acid was applied to colitis induction in all study groups except for sham group. Animals were treated by oral administration of dexamethasone or amitriptyline. While macroscopic and microscopic lesions appeared after colitis induction treatment with dexamethasone and amitriptyline 10 and 20mg/kg significantly improved lesions. Moreover, Toll-like receptor 4 (TLR4) and nuclear factor binding kappa light-chain (NF-ĸB expression), tumor necrosis factor-alpha (TNF-α) level, and myeloperoxidase (MPO) activity were increased after colitis induction, whereas treatment with dexamethasone (2mg/kg) or amitriptyline (10 and 20mg/kg) caused a noticeable decrease in the TLR4 and pNF-ĸB expression, TNF-α level, and MPO activity. In conclusion, amitriptyline plays an anti-inflammatory role through the suppression of TLR4/pNF-ĸB signaling pathway in the rat model of acute colitis.

Protective effect of 6-paradol in acetic acid-induced ulcerative colitis in rats

BackgroundUlcerative colitis is a gut inflammatory disorder due to altered immune response to gut microbiome, with interplay of environmental and genetic factors. TNF-α activates inflammatory response through a cascade of immune responses, augmenting pro-inflammatory mediators and proteases, activating chemotaxis, and infiltration of inflammatory cells, leading to ulceration and haemorrhage through cytotoxic reactive oxygen species. 6-Paradol, a dietary component in several plants belonging to the Zingiberaceae family, has shown anti-inflammatory and antioxidant activities. Current study evaluates the effect of 6-paradol in amelioration of ulcerative colitis in rats for the first time.Methods6-Paradol (95% purity) was obtained from seeds of Aframomum melegueta. Rats were divided randomly into six groups (n = 8). Group one was administered normal saline; group two was treated with the vehicle only; group three, sulfasalazine 500 mg/kg; and groups four, five, and six, were given 6-paradol (50, 100, 200, respectively) mg/kg orally through gastric gavage for 7 days. Colitis was induced on 4th day by intrarectal administration of 2 ml acetic acid (3%), approximately 3 cm from anal verge. On 8th day, rats were sacrificed, and distal one-third of the colon extending proximally up to 4 cm from anal orifice was taken for biochemical and gross examination. Two centimetres of injured mucosal portion was taken for histopathological investigations. SPSS (ver.26) was used for statistical analysis.ResultsColonic and serum glutathione (GSH) levels decreased, while colonic and serum malondialdehyde (MDA), colonic myeloperoxidase (MPO) activity, serum interleukin-6 (IL-6), serum tumour necrosis factor-α (TNF-α) levels, and colon weight to length ratio were increased significantly in the colitis untreated group compared to normal control. Treatment with 6-paradol considerably improved all these parameters, especially at a dose of 200 mg/kg (p < 0.001), revealing non-significant differences with sulfasalazine 500 mg/kg and normal control (p = 0.998). Sulfasalazine and 6-paradol in a dose dependent manner also markedly reversed mucosal oedema, atrophy and inflammation, cryptic damage, haemorrhage, and ulceration. There were non-significant differences between low and medium doses and between medium and high doses of 6-paradol for IL-6 and serum MDA levels.Conclusion6-Paradol demonstrated protection against acetic acid-induced ulcerative colitis, probably by anti-inflammatory and antioxidant actions.

Vildagliptin attenuates acetic acid-induced colitis in rats via targeting PI3K/Akt/NFκB, Nrf2 and CREB signaling pathways and the expression of lncRNA IFNG-AS1 and miR-146a

Inflammatory processes, including ulcerative colitis (UC), are associated with the increase in synthesis and release of pro-inflammatory cytokines. The release of these cytokines is regulated by phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor-kappa B (NFκB) and cAMP response element-binding protein (CREB) signaling pathways as well as over expression of microRNA 146a (miR-146a) and long non-coding RNA interferon gamma antisense 1 (lncRNA IFNG-AS1). Vildagliptin (Vilda), a dipeptidyl peptidase IV (DPP-IV) inhibitor, has an anti-inflammatory, antioxidant and anti-apoptotic effects which were established in various models. However, its possible protective effect in UC has not been clarified. Hence, the current study aimed to explore the possible prophylactic effect of different doses of Vilda against acetic acid (AA)-induced colitis in rats. Forty-eight adult Wistar rats were divided into six groups: control, Vilda (10 mg/kg/day; p.o.), AA, AA + Vilda (5 mg/kg/day; p.o.), AA + Vilda (10 mg/kg/day; p.o.) and AA + sulfasalazine (Sulfa) (100 mg/kg/day; p.o.).Low- and high-dose Vilda showed significant improvement in the disease activity index (DAI) and macroscopic assessment markers. Vilda has markedly inhibited the expression of lncRNA IFNG-AS1 and miR-146a, as well as PI3K/Akt/NFκB pathway, while activated CREB and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways, and this was reflected in alleviated oxidative stress, inflammation and apoptosis. Such outcomes were more prominent with the high-dose Vilda versus low-dose Vilda and Sulfa. Moreover, the histological examination showed almost intact histological features in Vilda-treated groups when compared to AA group treated with saline. In conclusion, Vilda can be regarded as a new promising therapeutic alternative against UC.

Bunium persicum essential oil reduced acetic acid-induced rat colitis through suppression of NF-κB pathway.

Objective:The aim of this study was to evaluate the anti-inflammatory effect of B. persicum essential oil on colonic inflammation and the role of suppression of NF-κB pathway in rat colitis induced by acetic acid solution.Materials and Methods:Induction of acute colitis was done by intra-luminal instillation of 2 ml of acetic acid (4%) diluted in normal saline. Two hours after colitis induction, 0.2% tween 80 in normal saline, prednisolone (4 mg/kg) or B. persicum essential oil (100, 200, and 400 mg/kg) were administered to the rats orally and continued for 5 consecutive days. The severity of macroscopic and microscopic damages was assessed. Myeloperoxidase and TNF-α activity was evaluated by biochemical analysis and ELISA respectively and protein expression of p-NF-κB was assessed by immunohistochemistry (IHC).Results:Prednisolone and B. persicum essential oil (100, 200, and 400 mg/kg) decreased macroscopic and microscopic injuries compared to the acetic acid group. On the other hand, prednisolone and B. persicum essential oil (200 and 400 mg/kg) decreased the activity of MPO and TNF-α in the colon tissue of rats compared with the acetic acid group. Furthermore, they suppressed the expression of p-NF-κB protein induced by acetic acid administration. Conclusion:It is suggested that the anti-inflammatory effect of B. persicum essential oil on acetic acid-induced colitis in rats may be due to the suppression of NF-κB pathway.