Acid-induced Colitis In Rats Research Articles

The Effects of Mannyeon-hwan on Acetic Acid-induced Ulcerative Colitis in Rats

Objectives: This study was designed to verify the effects of Mannyeon-hwan (MNH) on acetic acid-induced ulcerative colitis in rats.Methods: Ulcerative colitis was induced in male Sprague-Dawley rats weighing approximately 250 g by injecting acetic acid through the anus. Rats were classified into four groups: normal group, control group (acetic-acid, AA), low concentration group (AA+MNH(L)), and high concentration group (AA+MNH(H)). Body weight, visual evaluation of the colonic mucosa, anatomical histological changes, and changes in the expression of proteins in colon tissue were compared and analyzed.Results: Compared to the control group, the MNH groups showed significant recovery from weight loss and mucosal damage. The expression of inflammatory proteins such as TNF-α, IL-6, IL-1β, NF-κB p65, MPO, and COX-2 were significantly decreased in the MNH groups compared to those in the AA group. In the MNH groups, significant changes in proteins involved in apoptosis such as caspase-3, BAX, and Bcl-2 were observed compared to those in the AA group. Additionally, changes in the expression of TNF-α, IL-6, IL-1β, NF-κB p65, BAX, and Bcl-2 were greater in the MNH(H) group than those in the MNH(L) group.Conclusion: Mannyeon-hwan was found to be effective in suppressing inflammation of the colonic mucosa in ulcerative colitis, inhibiting the expression of inflammation-related proteins, and suppressing damage to the colonic mucosa by regulating the expression of apoptosis-related proteins.

Protective effect of freeze-dried extract of Persicaria bistorta Samp. on acetic acid-induced colitis model in rats: Involvement of nitric oxide and opioid system.

Inflammatory bowel disease is a chronic inflammatory disorder accompanied by occasional flare-ups, abdominal pain, and rectal bleeding.Persicaria bistorta Samp. is a medicinal plant repeatedly mentioned in traditional Persian medicine for the treatment of bleeding and tissue damage in different organs, including the intestines. The current study aimed to evaluate the effect of bistort root in an animal model of colitis. Freeze-dried aqueous extract of the plant (PB) was prepared and analyzed using liquid chromatography-mass spectrometry and high-performance liquid chromatography. The anti-inflammatory effect of oral PB (300, 500, and 700mg/kg) was evaluated in acetic acid-induced colitis in Wistar rats compared with negative control and positive control (dexamethasone). The role of nitric oxide (NO), opioid receptors, Toll-like receptors (TLR-4), interleukin (IL)-1β, IL-6, TNF-α, NF-κB, myeloperoxidase, and intestinal tissue damage using immunohistochemistry staining for cyclooxygenase-2 (COX-2) were also assessed. A total of 29 compounds were identified in the extract. The gallic acid content of the extractwas 4.973 ± 1.102mg/g. PB significantly ameliorated the gross morphological damage from 4.66 ± 0.577 in negative control to 1.33 ± 0.56 in PB 700 (p < 0.001). Also, PB 700 lowered the levels of TNF-α (p < 0.01), TLR-4 (p < 0.001), NF-κB (p < 0.0001), IL-1β (p < 0.0001), and IL-6 (p < 0.0001) compared to the negative control. Additionally, while blocking NO and opioid pathways, the therapeutic effect of the extract was not significant, compared to the negative control, suggesting that PB 700 has exerted its therapeutic effect via these two pathways. However, further mechanistic and clinical studies are recommended to confirm PB as a natural treatment for colitis.

Persicaria lanigera (Polygonaceae) leaf extract exhibits antiulcerogenic and antiproliferative activities against acetic acid-induced ulcerative colitis and cotton pellet-induced granuloma tissue in rats

Objective: To assess the effect of leaf extract of Persicaria lanigera on cotton pellet-induced granuloma tissue formation and acetic acid-induced ulcerative colitis. Methods: Rats were randomly divided into six groups: normal control, negative control, positive control (dexamethasone or sulfasalazine) as well as Persicaria lanigera (100-600 mg/kg)-treated groups. The effects of the extracts on body weight, antioxidant, and hematological parameters, as well as mast cell proliferation, were assessed. In addition, a histological evaluation was conducted. Results: Persicaria lanigera extract significantly decreased the mean exudate amount and suppressed granuloma tissue formation in a concentration-dependent manner in rats (P&lt;0.05). Additionally, the extract significantly increased body weight, improved hematological profile, reduced the disease activity index score and malondialdehyde level, as well as enhanced catalase and superoxide dismutase activities (P&lt;0.05). Histological evaluation showed Persicaria lanigera extract alleviated acetic acid-induced colonic damages, as evidenced by decreased cell necrosis, edema, and inflammatory cell infiltration. Conclusions: Persicaria lanigera extract possesses antiproliferative, antioxidative, and anti-colitis activities. However, its underlying mechanisms of action need further investigation.

Aspergillus awamori: potential antioxidant, anti-inflammatory, and anti-apoptotic activities in acetic acid-induced ulcerative colitis in rats

Ulcerative colitis (UC) is a chronic colonic inflammation with a significant health hazard. Aspergillus awamori (A. awamori) is a microorganism with various bioactive compounds with natural antioxidant and anti-inflammatory properties. The present work aimed to elucidate the protective and therapeutic effects of varying concentrations of A. awamori against acetic acid (AA)-induced ulcerative colitis (UC) in rats. Nine groups of albino male rats were established: a control negative group (G1), a control positive group (G2,AA), and preventive protocol groups (including G3A, G4A, and G5A) that received 100 mg, 50 mg, and 25 mg/kg b.w, respectively, of A. awamori orally and daily from the 1st day of the experiment and for 7 consecutive days. Then, they were subjected to one dose of AA intrarectally on day 8th. G3B, G4B, and G5B were termed as curative protocol groups that received one dose of AA on day 8th and then administered 100 mg, 50 mg, and 25 mg/kg b.w. of A. awamori, respectively, on day 9th and continued receiving these doses daily until day 16th. Rats in the AA group exhibited marked histopathological alterations of the distal colon, with an exaggeration of the DAI. In addition, a remarkable increase in oxidative stress was represented by the elevation of MDA and NO levels with a decline in SOD and GPx activities. In addition, upregulation of TNF-α, IL-6, and IL-1β mRNA expressions and downregulation of Muc2 and Nrf2 levels were detected. Unambiguously, a remarkable anti-inflammatory effect was noticed either in A. awamori prevented or treated groups expounded by reducing and regulating TNF-α, IL-6, and IL-1β with improved pathological lesion scoring. The Muc2, Nrf2, and bcl-2 gene levels were upregulated and restored also. In summary, the findings in this work reveal that A. awamori supplementation successfully alleviated the UC induced by AA, which had a better effect when administered before colitis induction.

Protective effects of Moringa oleifera against acetic acid-induced colitis in rat: Inflammatory mediators’ inhibition and preservation the colon morphohistology

Moringa oleifera decoction is used in folk medicine to alleviate various gastrointestinal ailments and has been shown in several studies to exhibit diverse biological activities: antioxidant, anti-inflammatory, and myorelaxant on intestine strips. However, its protective effect on pro-inflammatory cytokines in colitis remains to be ascertained. We investigated Moringa oleifera leaf aqueous extract activities on a rat model of acetic acid-induced colitis. Thirty-six rats were divided in random into six groups, and received either distilled water (10 mL/kg), the aqueous leaf extract of Moringa oleifera (25, 50, and 100 mg/kg) or the reference drug Loperamide (5 mg/kg) for 20 days. Animal body weight and food intake were followed-up. Colitis was induced on day 15, and daily stool weight was followed up. Animals were sacrificed (day 21), serum concentrations of pro-inflammatory cytokines MPO, IL-6, and TNF-α were evaluated, and the colon and liver preserved for histological examinations. After one-week pre-treatment, a significant (P < 0.05) weight increase was observed. At day 20, the extract significantly (P < 0.01) prevented weight loss. Food intake decreased by 36.33% in the colitis control, and by 4.34% in the extract (100 mg/kg) treated animals (P < 0.01). Moringa oleifera (100 mg/kg, day 20) decreased stool weights to 4.75±0.3 g (P < 0.05). The extract decreased (P < 0.01) MPO level. At 100 mg/kg, it significantly (P < 0.05) reduced IL-6 –0.58 ± 0.14 against 0.85 ± 0.00 ng/L in the colitis control. At the same dose, TNF-α levels decreased to 417.96 ± 0.17 ng/L (P < 0.001). Moringa oleifera alleviated colitis symptoms by reducing stool emission, alleviating inflammation, and preserving colon and liver cytoarchitecture.

Isoimperatorin alleviates acetic acid–induced colitis in rats

Objective: To investigate the effect of isoimperatorin on histopathological and biochemical changes in acetic acid-induced colitis rats. Methods: Colitis was induced by intracolonic administration of acetic acid solution (4% v/v) in rats. Rats were divided into six groups including the sham group, the negative control group, the dexamethasone-treated group, and the groups treated with isoimperatorin (0.1, 1, and 10 mg/kg/d by gavage). The treatments were administered for three days and then colonic status was assessed by macroscopic, histopathological, and biochemical analyses. Results: Isoimperatorin significantly alleviated colonic damage in a dose-dependent manner and improved histological changes in rats with acetic acid-induced colitis. It also significantly reduced myeloperoxidase, TNF-α, IL-1β, and malodialdehyde levels. Conclusions: Isoimperatorin alleviates acetic acid-induced colitis in rats and may be a potential therapeutic agent for the treatment of colitis.

Mimosa pudica leaf aqueous extract attenuates experimental ulcerative colitis in rats via suppression of MPO and IL-1β signaling pathways and improvement of the oxidative status

BackgroundColitis for so many years had been considered a disease exclusive only to developed countries; surprisingly, its incidence is now increasing worldwide. This study investigated Mimosa pudica leaf water extract anti-colitis potential on acetic acid-induced colitis in rats. MethodsFollowing 24 h fasting, 36 rats (both sexes) intrarectally received acetic acid (4%, 1 mL) to induce colitis. Afterward, they were separated into groups and treated twice a day (for 9 days) with distilled water; Mimosa pudica (25, 50, or 100 mg/kg); and Prednisolone (5 mg/kg). Body weight and quantity of feces were recorded. On day 9, animals were sacrificed, colon ulcerations number and weight/length ratio; GSH and MDA levels; MPO activity, and IL-1β were determined. ResultsColitis caused a significant drop in animals’ body weight - 30% decrease in colitis control against + 27% increase in the neutral control rats. Mimosa pudica at 25 mg/kg on day 9 brought a + 7% increase. Colitis led to an increase in the weight of feces in colitis rats with 14.28 ± 0.98 g (day 8). On this same day, the extract reduced feces weight (4.42 ± 0.31 g at 100 mg/kg), the number of colon ulcerations, and the mean colon weight/length ratio (P < 0.001). Colitis conditions increased MDA and decreased GSH. Mimosa pudica reversed these biomarkers. Colitis caused a marked increase in MPO activity and IL-1β concentration in colitis rats. This was reversed by the extract. ConclusionsOverall, our results proved the beneficial effects of Mimosa pudica leaf extract in protecting animals against colitis.

Tiron ameliorates acetic acid-induced colitis in rats: Role of TGF-β/EGFR/PI3K/NF-κB signaling pathway

BackgroundUlcerative colitis (UC), an ongoing inflammatory disorder of the colon, is marked by persistent mucosal surface irritation extending from the rectum to the near-proximal colon. Tiron is a synthetic analogue of vitamin E which is known to have antioxidant and anti-inflammatory effects in various animal models, so the goal of this study was to find out whether Tiron had any preventive impacts on UC inflicted by acetic acid (A.A) exposure in rats. MethodTiron (235 and 470 mg/kg) was administered intra-peritoneally for 2 weeks, and A.A (2 ml, 3 % v/v) was injected intra-rectally to cause colitis. Colon tissues and blood samples were then collected for measurement of various inflammatory and oxidative stress biomarkers. ResultsTiron administration significantly diminished lactate dehydrogenase (LDH), C-reactive protein (CRP), colon weight, and the weight/length ratio of the colon as compared to A.A-injected rats. Additionally, Tiron attenuated oxidative stress biomarkers. Tiron also enforced the levels of Glucagon-like peptide-1 (GLP-1) and trefoil factor-3 (TFF-3), while it greatly lowered the expression of nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), interferon-γ (IFN-γ), and transforming growth factor-1(TGF-β1), phosphorylated epidermal growth factor receptor (P-EGFR), phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT) expression in colonic cellular structures. Furthermore, colonichistopathologic damages, revealed by hematoxylin and eosin (H&E) and Alcian Blue stain, were significantly decreased upon Tiron administration. ConclusionTiron prevented A.A-induced colitis in rats via modulating inflammatory pathway TGF-β1/P-EGFR/PI3K/AKT/NF-κB, alongside managing the oxidant/antioxidant equilibrium, and boosting the reliability of the intestinal barrier.

Amelioration of acetic acid-induced ulcerative colitis in rats by cetirizine and loratadine via regulation of the PI3K/Akt/Nrf2 signalling pathway and pro-inflammatory cytokine release.

Ulcerative colitis is a chronic inflammatory bowel disease (IBD) that causes inflammation and ulcers in the rectum and the innermost layer of the large intestine. Our study aimed to elucidate the ameliorative effect of cetirizine (CTZ) and loratadine (LOR) against acetic acid-induced ulcerative colitis in rats via assessment of the PI3K/p-Akt/Nrf2 signaling pathway and proinflammatory cytokine release. Thirty-two rats were allocated into four groups (n=8). Group (I) was considered normal control. Acetic acid (AA) was injected intrarectally in groups (2-4). Group (2) was kept untreated. Group (3) was administered CTZ (20 mg/kg/day) for 7 days. Group (4) was administered LOR (10 mg/kg/day) for 7 days. AA showed severe macroscopic colonic lesions associated with increased ulcer number, area, and severity with significantly elevated PI3K, p-Akt, Nrf2, TNF-α, and IL-6 in colorectal tissue as compared to the normal control group. All the aforementioned indicators were greatly improved by CTZ and LOR therapy. This is the first study to elucidate the ameliorative effect of CTZ and LOR against AA-induced UC in rats. CTZ and LOR treatment mitigates UC via amelioration of the PI3K/p-Akt/Nrf2 pathway and proinflammatory cytokine release.

Phytochemical Properties of Crataegus azarolus Berries Decoction Extract and Evaluation of its Protective Activity Against Acetic Acid-Induced Ulcerative Colitis in Rats.

The present study aims to evaluate the protective effect of Crataegus azarolus berries decoction extract (CAB-DE) against acetic acid-induced ulcerative colitis as well as the mechanisms implicated in such protection. Adult male Wistar rats were separated into seven groups: Control (H2O), acetic acid (AA), AA + various doses of CAB-DE (100, 200, and 400mg/kg, b.w.,p.o.), and AA + sulfasalazine (100mg/kg, b.w.,p.o.) or gallic acid (50mg/kg, b.w.,p.o.) during 10days. All rats were kept fasting overnight and ulcerative colitis was induced by rectal infusion of AA (300mg kg-1, b.w.) (3%, v/v, 5mL kg-1 b.w), for 30s. The colon was rapidly excised and macroscopically examined to measure ulcerated surfaces and the ulcer index. In vitro, we found that CAB-DE exhibited a high antioxidant activity against DPPH radical (IC50 = 164.17 ± 4.78μg/mL). In vivo, pretreatment with CAB-DE significantly protected the colonic mucosa against AA-induced damage by stimulating mucus secretion, reducing ulcer index as well as histopathological changes. Also, CAB-DE limited the oxidative status induced by AA in the colonic mucosa, as assessed by MDA and H2O2 increased levels and the depletion of both enzymatic activities and non-enzymatic levels. In addition, AA intoxication increased iron and calcium levels in colonic mucosa and plasma, while CAB-DE pretreatment regulated all intracellular mediators deregulation and significantly reduced inflammatory markers such as CRP (1.175 ± .04 ─ .734 ± .06μg/dl) and ALP (161.53 ± 5.02 ─ 98.60 ± 4.21 UI/L) levels. We suggest that CAB-DE protected against AA-induced ulcerative colitis due in part to its antioxidant and anti-inflammatory properties.

Effects of Mannyeon-hwan on Acetic Acid-induced Colitis in Rats

Objectives: This study is designed to verify the effects of Mannyeon-hwan (MNH) on acetic acid-induced colitis in rats.Methods: Colitis was induced in male Sprague-Dawley rats weighing approximately 250 g by injecting acetic acid through the anus. The rats were classified into four groups: normal group, acetic acid (AA) group, AA+MNH (L) (low concentration) group, and AA+MNH (H) (high concentration) group. The body weight, visual evaluation of the colonic mucosa, anatomical histological changes, and changes in the expression of cytokines in the colon tissue were compared and analyzed.Results: Compared with the normal group, weight loss was observed in mice induced with colitis. Compared with the AA group, weight loss recovery occurred in the AA+MNH (L) and AA+MNH (H) groups, and significant changes were observed after the sixth day. In the visual evaluation of the colonic mucosa, a significant decrease in damage indicators was observed in the AA+MNH (L) and AA+MNH (H) groups compared with the AA group. In terms of anatomical histological changes and changes in the expression of tumor necrosis factor-α and interleukin-6 in colon tissue, a significant decrease was observed in the AA+MNH (L) and AA+MNH (H) groups compared with the AA group. A more pronounced decrease was observed in the AA+MNH (H) group compared with the AA+MNH (L) group.Conclusion: The effects of MNH on colitis were confirmed through research. MNH can be used as a first-line treatment for patients complaining of colitis who visit oriental medicine clinics.

Comparison of Antioxidant and Anti-Inflammatory Effects of Honey and Spirulina platensis with Sulfasalazine and Mesalazine on Acetic Acid-Induced Ulcerative Colitis in Rats

 Background: Antioxidant therapy has gained attention for the treatment of ulcerative coli­tis (UC). The excessive generation of reactive oxygen/nitrogen species in the gastrointestinal tract increases oxidative stress, thereby leading to antioxidant defense depletion, lipid perox­idation, inflammation, tissue damage, and ulceration. Spirulina platensis (SP) and honey are excellent sources of potent antioxidants such as polyphenols and other bioactive compounds. We aimed to investigate antioxidant and anti-inflammatory effects of honey and SP in com­parison with sulfasalazine (SSZ) and mesalazine on acetic acid-induced colitis (AA-colitis) in rats. Materials and Methods: Fifty-six Sprague Dawley male rats were allocated to sev­en groups, with each group comprising eight rats. UC was induced, except in normal con­trols (NC). All groups received oral treatments for seven days. The normal saline solution of 2 mL was intrarectally administered to the NC group. The AA-colitis and NC groups received 2 mL acetic acid intrarectally as a single dose and 2 mL normal saline for seven consecutive days orally. The mesalazine group received 100 mg/kg mesalazine, the SSZ group 360 mg/kg SSZ, the honey or H group 1 mL honey diluted with 1 mL distilled water, the SH group 1g/kg SP and 1 mL honey, and the SP group 1g/kg SP. After clinical activity score assessment, the rats were sacrificed. Colonic weight/length ratio, prostaglandin E2 (PGE2), myeloperoxidase (MPO), nitric oxide (NO), malondialdehyde (MDA), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), glutathione peroxidase (GPx), total antioxidant capacity (TAC), reduced glutathione (GSH), and superoxide dismutase (SOD) were measured. Colonic histopathological changes were observed microscopically. Results: Treatment of UC with SP, honey, and combination regimen significantly reduced TNF-α, IL-1β, IL-6, MDA, MPO, NO, and PGE2, and increased TAC, GSH, GPx, and SOD in interventional groups compared to the AA-colitis group (P&lt;0.05). Conclusion: Honey and SP might be beneficial food supple­ments for medical nutrition therapy in UC. [GMJ.2019;8:e1095]

Ameliorative effects of androstenediol against acetic acid-induced colitis in male wistar rats via inhibiting TLR4-mediated PI3K/Akt and NF-κB pathways through estrogen receptor β activation

5-androstenediol (ADIOL) functions as a selective estrogen receptor β (ERβ) ligand with a protective effect against many diseases. So, we conducted a novel insight into its role in acetic acid (AA)-induced colitis and investigated its effect on TLR4-Mediated PI3K/Akt and NF-κB Pathways and the potential role of ERβ as contributing mechanisms. Methods: Rats were randomized into 5 Groups; Control, Colitis, Colitis + mesalazine (MLZ), Colitis + ADIOL, and Colitis + ADIOL + PHTPP (ER-β antagonist). The colitis was induced through a rectal enema of acetic acid (AA) on the 8th day. At the end of treatment, colons were collected for macroscopic assessment. Tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), nuclear factor kappa b (NF-κB), toll-like receptor (TLR4), and phosphorylated Protein kinase B (pAKT) were measured. Besides, Gene expression of interleukin-1beta (IL-1β), metalloproteases 9 (Mmp9), inositol 3 phosphate kinase (PI3K), Neutrophil gelatinase-associated lipocalin (NGAL), ERβ and NLRP6 were assessed. Histopathological and immunohistochemical studies were also investigated. Results: Compared to the untreated AA group, the disease activity index (DAI) and macroscopic assessment indicators significantly decreased with ADIOL injections. Indeed, ADIOL significantly decreased colonic tissue levels of MDA, TLR4, pAKT, and NF-κB immunostainig while increased SOD activity and β catenin immunostainig. ADIOL mitigated the high genetic expressions of IL1β, NGAL, MMP9, and PI3K while increased ERβ and NLRP6 gene expression. Also, the pathological changes detected in AA groups were markedly ameliorated with ADIOL. The specific ERβ antagonist, PHTPP, largely diminished these protective effects of ADIOL. Conclusion: ADIOL could be beneficial against AA-induced colitis mostly through activating ERβ.

Impact of Eugenol on Acetic Acid-induced Colitis in Rats

Background: Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease, are immune-mediated chronic relapsing intestinal disorders characterized by the presence of an acute or chronic inflammatory process in the bowel wall. Eugenol essential oil is used in traditional medicine to treat digestive disorders such as gastrointestinal ulcers, indigestion, and inflammation of the intestines. Aim: To investigate the effects of Eugenol on colitis in rat models. Methods: Eugenol was administered per rectum (5 and 10 mg/kg) and intraperitoneally (0.25 and 0.5 mg/kg) for 6 days after induction of colitis by acetic acid. The changes were examined macroscopically, histologically, and biochemically and compared with Dexamethasone. Results: Results showed a significant decrease in the macroscopic damage score (P &lt; 0.05), and reduction in the weight ratio of the colon (P &lt; 0.01), the histological signs of inflammation (P &lt; 0.01) such as infiltration of lymphocytes and macrophages into the mucosa, mucin depletion, crypt abscess, edema, and tissue damage, as well as leukocyte accumulation and myeloperoxidase level in compare with the colitis control group. Conclusion: This animal trial demonstrates the beneficial anti-inflammatory and wound-healing effects of Eugenol in the treatment of acetic acid-induced colitis in rats. Eugenol can potentially be advantageous as a supplemental remedy for the treatment of IBD.

Preventive Anti-inflammatory Effects of Apocynin on Acetic Acid-Induced Colitis in Rats.

Ulcerative colitis is an inflammatory bowel disease with a complex aetiology characterised by abnormal immune responses and oxidative stress-induced tissue injury. Inflammatory cells play an important role in the progression of this pathology through the overproduction of reactive oxygen species (ROS) from various sources including the NADPH oxidases (NOXs). The aim of this study was to investigate the preventive effect of apocynin, a natural antioxidant molecule and a selective inhibitor of NOXs, on acetic acid (AA)-induced ulcerative colitis in rats. Our results first confirmed that apocynin has a high free radical scavenging capacity as well as a potent iron chelating ability. Oral pretreatment of rats with apocynin (200mg/kg and 400mg/kg) for 7days prior to AA-induced colitis suppressed the increase in pro-oxidant markers in colonic homogenates and preserved colonic cytoarchitecture from acetic acid-induced damage. Oral administration of apocynin (200mg/kg and 400mg/kg) also reduced several systemic inflammatory markers such as alkaline phosphatase, iron, pro-inflammatory cytokines, C-reactive protein and myeloperoxidase. This study shows that apocynin protects rats from acetic acid-induced colonic inflammation and suggests that apocynin may have a promising beneficial effect in the prevention of ulcerative colitis.

Biochemical and histopathological evidence for beneficial effects of Empagliflozin pretreatment on acetic acid-induced colitis in rats

BackgroundUlcerative Colitis (UC) is a disorder which oxidative stress plays a critical role in its pathogenesis. Empagliflozin (EMPA) is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that has been shown to have anti-inflammatory and antioxidative effects. The aim of this study was to investigate the protective effects of EMPA on acetic acid (AA) induced colitis in rats.MethodsA total of twenty-four rats were divided into four groups (six animals in each group) as follows: (1) Control group; (2) acetic acid (AA)-induced colitis group (AA); (3) EMPA treatment group (AA + EMPA); (4) Dexamethasone (Dexa) treatment group (AA + Dexa). Animals in pre-treatment groups received EMPA (10 mg/kg, i.p.) or dexamethasone (4 mg/kg, i.p. as reference drug) for four consecutive days before induction of colitis by intra-rectal acetic acid (4% v/v) administration. Twenty-four hours after AA administration, rats were sacrificed and the colon tissues were removed for histopathological and biochemical evaluations.ResultsPretreatment with EMPA significantly decreased colon weight/length ratio (81.00 ± 5.28 mg/cm vs. 108.80 ± 5.51 mg/cm) as well as, macroscopic (2.50 ± 0.57 vs. 3.75 ± 0.25) and histological scores (3.3 ± 0.14 vs. 1.98 ± 0.14) compared to the AA-induced colitis group (p < 0.01). Pretreatment with EMPA significantly reduced malondialdehyde (MDA) (324.0 ± 15.93 vs. 476.7 ± 32.26 nmol/mg p < 0.001) and increased glutathione level (117.5 ± 4.48 vs. 94.38 ± 3.950 µmol/mg, p < 0.01) in comparison to the AA-induced colitis group. Furthermore, a significant increase in catalase (44.60 ± 4.02 vs.14.59 ± 2.03 U/mg, P < 0.01), superoxide dismutase (283.9 ± 18.11 vs. 156.4 ± 7.92 U/mg, p < 0.001), and glutathione peroxidase (10.38 ± 1.45 vs. 2.508 ± 0.37, p < 0.01) activities were observed by EMPA pretreatment when compared to the AA-induced colitis group. These results were in line with those of the reference drug.ConclusionsIt is concluded that EMPA could effectively reduce the severity of tissue injury in experimental colitis. This protective effect may be related to the antioxidative effects of EMPA drug.

Protective effects of topiramate on acetic acid-induced colitis in rats through the inhibition of oxidative stress.

Ulcerative colitis is an intestinal inflammatory condition characterized by a rise in inflammatory mediator production and oxidative stress. Topiramate is an anticonvulsant agent with effectiveness on a wide range of seizures, which is anti-oxidative. This study aims to examine the protective effects of topiramate on acetic acid-induced ulcerative colitis in rats. Rats were randomly divided into four groups as follows: control, acetic acid, acetic acid + topiramate, and acetic acid + dexamethasone groups. Topiramate (100 mg/kg/day) or dexamethasone (2 mg/kg/day) was administered for six consecutive days, and ulcerative colitis was induced on the first day of the study by transrectal administration of 4% acetic acid. Four hours after the last dose of treatments, animals of each group were sacrificed, and colon tissues were removed for further macroscopic, histopathologic, and biochemical analyses. Treatment with topiramate markedly decreased colonic lesions and macroscopic scores as well as the improvement of histopathologic changes. Topiramate also effectively decreased the levels of malondialdehyde and upregulated the activity of anti-oxidative enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. Our results reveal that the administration of topiramate ameliorates acetic acid-induced colitis in rats via anti-oxidative properties, and further studies may introduce it as an effective therapeutic candidate to decrease ulcerative colitis severity.

Investigation of In vitro and In vivo Pursuits of Laurus nobilis Extract on Acetic Acid-induced Ulcerative Colitis in Wistar Rats

Investigation of In vitro and In vivo Pursuits of Laurus nobilis Extract on Acetic Acid-induced Ulcerative Colitis in Wistar Rats

Quinic acid ameliorates ulcerative colitis in rats, through the inhibition of two TLR4-NF-κB and NF-κB-INOS-NO signaling pathways.

In this study, the therapeutic effect of quinic acid (QA), which has anti-inflammatory activity, was investigated on acetic acid-induced colitis in male Wistar rats. Ulcerative colitis (UC) was induced in rats by acetic acid intrarectally, and the protective effects of QA in 10, 30, 60, and 100 mg/kg doses were investigated. Rats were treated for 5 days and their colon tissues were dissected out at the end. Macroscopic and histopathological examinations were performed in colon tissues. Also, the expression of inflammatory and apoptotic genes, including TLR4, IL-1β, INOS, IL-6, TNF-α, NF-κB, Caspase-3, Caspase-8, Bax, and Bcl-2, was measured. Biochemistry indices, such as malondialdehyde (MDA) and nitrite oxide (NO) content, in addition to, total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), and enzymes activities were also assessed. Colitis increased the levels of MDA and NO, and enhanced the inflammatory and apoptotic gene expressions, while reducing the SOD and CAT enzymes activity, and TAC levels in the colitis rats. Also, results showed that colitis was associated with the infiltration of inflammatory cells, epithelium damage, and edema in colon tissue. QA significantly ameliorated histopathological indices, oxidative stress, inflammation, and apoptosis in colitis rats. QA ameliorated UC through the inhibition of two TLR4-NF-κB and NF-κB-INOS-NO signaling pathways, which results in the reduction of colitis complications, including oxidative stress, inflammation, apoptosis and histopathological injuries in rats. Therefore it can be concluded, that QA exerts its therapeutic effects through antiapoptotic, antioxidant, and anti-inflammatory properties.

Prevention of Inflammation Initiation on Acetic Acid-Induced Ulcerative Colitis in Rats by Malva nicaeensis All.

Aerial parts of Malva nicaeensis All. are preferred in the prevention and treatment of intestinal infections and hemorrhoids in Turkish traditional medicine. This study is planned to evaluate the pharmacological activity of M. nicaeensis extracts on rats with acetic acid-induced colitis. The plant material was subsequently extracted with n-hexane, ethanol, and water, respectively. All of these extracts were tested for efficacy in the acetic acid-induced rat colitis model. The aqueous and polysaccharide extracts regulated cytokine levels and antioxidant parameters. Furthermore, the aqueous extract in particular regulated myeloperoxidase and caspase-3 levels in this rat model. In addition, the polysaccharide-rich fraction was separated from the aqueous extract. The polysaccharide-rich fraction and aqueous extract regulated cytokine levels and antioxidant parameters. The aqueous extract also positively affected myeloperoxidase and caspase-3 levels. The phytochemical studies revealed that the aqueous extract had the highest phenolic content. In addition, the polysaccharide fraction was found to contain total sugars, sulfated groups, uronic acids, and total proteins in 78.4%, 0.9%, 1.5%, and 14.7%, respectively, and was rich in monosaccharide-type compounds, especially galactose (36.4%). M. nicaeensis was discovered to be a drug lead in the future treatment of irritable bowel diseases or as a complementary therapeutic agent that aided conventional treatments.