Intrarectal Administration Of Acetic Acid Research Articles

Immune-mediated impairment of tonic immobility defensive behavior in an experimental model of colonic inflammation.

Ulcerative colitis has been associated with psychological distress and an aberrant immune response. The immunomodulatory role of systemic cytokines produced during experimental intestinal inflammation in tonic immobility (TI) defensive behavior remains unknown. The present study characterized the TI defensive behavior of guinea pigs subjected to colitis induction at the acute stage and after recovery from intestinal mucosa injury. Moreover, we investigated whether inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-10, and prostaglandins) act on the mesencephalic nucleus, periaqueductal gray matter (PAG). Colitis was induced in guinea pigs by intrarectal administration of acetic acid. The TI defensive behavior, histology, cytokine production, and expression of c-FOS, IBA-1, and cyclooxygenase (COX)-2 in PAG were evaluated. Colitis reduced the duration of TI episodes from the first day, persisting throughout the 7-day experimental period. Neuronal c-FOS immunoreactivity was augmented in both columns of the PAG (ventrolateral (vlPAG) and dorsal), but there were no changes in IBA-1 expression. Dexamethasone, infliximab, and parecoxib treatments increased the duration of TI episodes, suggesting a modulatory role of peripheral inflammatory mediators in this behavior. Immunoneutralization of TNF-α, IL-1β, and IL-8 in the vlPAG reversed all effects produced by colitis. In contrast, IL-10 neutralization further reduced the duration of TI episodes. Our results reveal that peripherally produced inflammatory mediators during colitis may modulate neuronal functioning in mesencephalic structures such as vlPAG.

Neuroimmune response and oxidative stress in the prefrontal cortex mediate seizure susceptibility in experimental colitis in male mice.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder. Oxidative stress and inflammatory responses have a vital role in the pathophysiology of IBD as well as seizure. IBD is associated with extraintestinal manifestations. This study aimed to explore the relationship between colitis and susceptibility to seizures, with a focus on the roles of neuroinflammation and oxidative stress in acetic acid-induced colitis in mice. Forty male Naval Medical Research Institute mice were divided into four groups: control, colitis, pentylenetetrazole (PTZ), and colitis + PTZ. Colitis was induced by intrarectal administration of acetic acid, and seizures were induced by intravenous injection of PTZ 7 days postcolitis induction. Following the measurement of latency to seizure, the mice were killed, and their colons and prefrontal cortex (PFC) were dissected. Gene expression of inflammatory markers including interleukin-1β, tumor necrosis factor-alpha, NOD-like receptor protein 3, and toll-like receptor 4, as well as total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrite levels were measured in the colon and PFC. Histopathological evaluations were performed on the colon samples. Data were analyzed by t-test or one-way variance analysis. Colitis decreased latency to seizure, increased gene expression of inflammatory markers, and altered levels of MDA, nitrite, and TAC in both the colon and PFC. Simultaneous induction of colitis and seizure exacerbated the neuroimmune response and oxidative stress in the PFC and colon. Results concluded that neuroinflammation and oxidative stress in the PFC at least partially mediate the comorbid decrease in seizure latency in mice with colitis.

Electrical carotid sinus nerve stimulation attenuates experimental colitis induced by acetic acid in rats

AimsThe carotid bodies are sensors that detect physiological signals and convey them to the central nervous system, where the stimuli are processed inducing reflexes through efferent pathways. Recent studies have demonstrated that electrical stimulation of the carotid sinus nerve (CSN) triggers the anti-inflammatory reflex under different conditions. However, whether this electrical stimulation attenuates colitis was never examined. This study aimed to evaluate if the electrical CSN stimulation attenuates the experimental colitis induced by intrarectal administration of acetic acid in rats. MethodsElectrodes were implanted around the CSN to stimulate the CSN, and a catheter was inserted into the left femoral artery to record the arterial pressure. The observation of hypotensive responses confirmed the effectiveness of the electrical CNS stimulation. This maneuver was followed by a 4 % acetic acid or saline administered intrarectally. After 24 h, colons were segmented into distal and proximal parts for macroscopy, histological and biochemical assessment. Key findingsAs expected, the electrical CSN stimulation was effective in decreasing arterial pressure in saline and colitis rats. Moreover, electrical CSN stimulation effectively reduced colonic tissue lesions, colitis scores, and histopathologic parameters associated with colitis. In addition, the CSN stimulation also reduced the colonic mucosa pro-inflammatory cytokine interleukin-1 beta, and increased the anti-inflammatory interleukin-10, in rats submitted to colitis. SignificanceThese findings indicated that electrical CSN stimulation breaks the vicious cycle of local colon inflammation in colitis, which might contribute to its better outcome.

Topotecan alleviates acetic acid-induced ulcerative colitis in rats via attenuation of the RORγT transcription factor

AimsUlcerative colitis is characterized as a chronic immune-mediated inflammatory condition, affecting the intestinal gastroenteric tissue. Previous studies revealed that Th-17 cells are key players in the pathogenesis of ulcerative colitis. RORγT (Retinoic-acid-receptor-related orphan receptor-gamma T) is a lineage-specific transcription factor of Th-17 cells and thus has a role in their differentiation. Transient inhibition of RORγT has been reported to attenuate the differentiation of Th-17 cells and secretion of interleukin-17 (IL-17). Here, we investigated the efficacy of topotecan in ameliorating ulcerative colitis in rodents, via inhibition of the RORγT transcription factor. Main methods and key findingsExperimental ulcerative colitis was induced in rats by intrarectal acetic acid administration. Topotecan attenuated the severity of ulcerative colitis in rats by revoking neutrophils and macrophage infiltration to the colon. It also alleviated diarrhea and rectal bleeding and improved body weight. Further, attenuation of RORγT and IL-17 expression was observed in topotecan treated animals. Levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in the colon tissue were reduced by topotecan treatment. Significant reduction in malondialdehyde level, elevation of superoxide dismutase (SOD) and catalase activity was observed in the colon tissue of rats treated with topotecan compared to the diseased group. SignificanceThis study shows the therapeutic potential of topotecan in attenuating ulcerative colitis in rats probably via inhibition of the RORγT transcription factor and downstream mediators of Th-17 cells.

Levetiracetam attenuates experimental ulcerative colitis through promoting Nrf2/HO-1 antioxidant and inhibiting NF-κB, proinflammatory cytokines and iNOS/NO pathways

Ulcerative colitis (UC) is a serious inflammatory disease of the colon. The pathogenic mechanisms of UC involve the activation of inflammatory and oxidative stress responses in the colon. Levetiracetam is an antiepileptic drug with anti-inflammatory and antioxidant effects. The aim of this study was to investigate the potential protective effect of levetiracetam against UC in a mouse model. UC was induced in mice by intrarectal administration of acetic acid and then mice were treated with levetiracetam (50 or 100mg/kg/day, i.p.) for three days. The colonic tissue samples were dissected for biochemical, RT-PCR and immunofluorescence analysis. Results showed that levetiracetam treatment significantly decreased colonic mucosal injury as evidenced by the macroscopic and histopathological analysis. Levetiracetam induced Nrf2/HO-1 and antioxidants while reduced lipid peroxidation and myeloperoxidase activity in colon tissue. Levetiracetam treatment decreased NF-κB activity and the expression of proinflammatory mediators TNF-α, IL-6, IL-1β, IFN-γ, MCP-1 and ICAM-1. The colonic levels of anti-inflammatory cytokines IL-10 and TGF-β1 were increased by levetiracetam treatment. Furthermore, levetiracetam significantly diminished iNOS expression and NO production in colon tissue. These findings suggest that levetiracetam ameliorates the severity of UC in mice through the regulation of inflammatory and oxidative responses.

The coumaric acid and syringic acid ameliorate acetic acid-induced ulcerative colitis in rats via modulator of Nrf2/HO-1 and pro-inflammatory cytokines

BackgroundUlcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes uncontrolled inflammation and ulcers in your digestive tract. The coumaric acid and syringic acid are phenolic derivative found in many fruits and vegetables and is widely recognized for the ability of anti-parasitic, anti-microbial, anti-viral, anti-inflammatory, and antioxidant. The purpose of this study was to investigate the anti-inflammatory and antioxidant properties of coumaric acid and syringic acid on acetic acid-induced colitis in rats. MethodsA total of 64 male Wistar rats were divided into eight equal groups (n = 8). Colitis was induced by intrarectal administration of acetic acid, and rats orally received coumaric acid (100 and 150 mg/kg), syringic acid (10, 25, and 50 mg/kg), and dexamethasone (2 mg/kg) once per day for four days after colitis induction. Then, HO-1, Nrf2, and NQO1 mRNA expression were quantified by real time-PCR. Finally, the tissue levels of TNF-α and IL-1β protein were measured by ELISA. ResultsColitis led to a decrease in HO-1, Nrf2, and NQO1 mRNA expression and an increase in the tissue levels of TNF-α and IL-1β protein in the colon tissue. Treatment with dexamethasone significantly increased HO-1, Nrf2, and NQO1 mRNA expression and decreased the tissue levels of TNF-α and IL-1β protein compared to the UC group. Treatment with 150 mg/kg of coumaric acid and 50 mg/kg of syringic acid significantly increased HO-1, Nrf2, and NQO1 mRNA expression compared to the UC group. Also, treatment with 100 and 150 mg/kg of coumaric acid and 10, 25, and 50 mg/kg of syringic acid significantly decreased the tissue levels of TNF-α and IL-1β protein compared to the UC group. ConclusionThe coumaric acid and syringic acid, especially at high doses, may be an alternative strategy for the treatment of UC by the reduction of TNF-α and IL-1β levels and upregulation of the Nrf2/HO-1 pathway.

Lactobacillus acidophilus regulates abnormal serotonin availability in experimental ulcerative colitis

ObjectivesProbiotics are known to play a beneficial role in curing irritable bowel syndrome such as ulcerative colitis. Commensal Lactobacillus species are thought to play a protective role against ulcerative colitis, as they restore homeostasis in intestinal disorders. Abnormal serotonin availability has been described in ulcerative colitis, but the underlying mechanism is still unclear. The aim of this study was to determine the anti-inflammatory role of Lactobacillus acidophilus (L. acidophilus) and its effect on serotonin expression. MethodsUlcerative colitis was created with the intrarectal administration of acetic acid. A total of 40 adult male rats were divided into five groups of eight rats as control, sham, experimental colitis, treatment (Colitis + L. acidophilus) and protective group (L. acidophilus + colitis). To evaluate the effects of L. acidophilus on serotonin expression in ulcerative colitis, this bacterial strain was administered orally to the rats with acetic acid-induced colitis. After oral administration of L. acidophilus for 14 days, serotonin content was biochemically measured and serotonin expression was evaluated immunohistochemically. ResultsThe expression of serotonin and its protein content was significantly increased in colitis compared to the control and sham groups. Abnormal serotonin availability in the rats with acetic acid-induced colitis was significantly reduced by the L. acidophilus. ConclusionsIn our study, it was observed that the amount of serotonin in the intestinal tissue increased excessively with ulcerative colitis. In addition, L.acidophilus has been found to reduce the abnormally increased amount of serotonin in the colon tissue, as well as reduce the inflammation in the intestinal tissue that occurs with ulcerative colitis. With our findings, it is predicted that probiotic application can be used as a treatment option in ulcerative colitis.

Protective effects of Rubus tereticaulis leaves ethanol extract on rats with ulcerative colitis and bio-guided isolation of its active compounds: A combined in silico, in vitro and in vivo study

The aim of this study was to evaluate the therapeutic effect of active ethanol extract obtained from the leaves of Rubus tereticaulis (RTME) against colitis, and to purify major compounds from this extract by bioassay-directed isolation. Rats with colitis induced via intra-rectal acetic acid administration (5%, v/v) received RTME or sulfasalazine for three consecutive days. On day four, all rats were decapitated, and the colonic tissue samples were collected for macroscopic score, colon weight, reduced glutathione (GSH), myeloperoxidase (MPO), and malondialdehyde (MDA) analyses. The active compounds and chemical composition of RTME were determined by bio-guided isolation and LC-MS/MS, respectively. Compared to the colitis group, the rats treated with RTME displayed significantly lowered macroscopic scores and colon wet weights (p < 0.001). These effects were confirmed biochemically by a decrease in colonic MPO activity (p < 0.001), MDA levels (p < 0.001), and an increase in GSH levels (p < 0.001). Kaempferol-3-O-β-d-glucuronide (RT1) and quercetin-3-O-β-d-glucuronide (RT2) were found to be the major compounds of RTME, as evidenced by in vitro anti-inflammatory and antioxidant activity-guided isolation. Their anti-inflammatory/antioxidant activities were also predicted by docking simulations. Additionally, quinic acid, 5-caffeoylquinic acid, quercetin pentoside, quercetin glucoside, quercetin-3-O-β-d-glucuronide, kaempferol-3-O-β-d-glucuronide, and kaempferol rutinoside were identified in RTME via using LC-MS/MS. RT2, along with other compounds, may be responsible for the observed protective action of RTME against colitis. This study represents the first report on the beneficial effects of RTME in an experimental model of colitis and highlights the potential future use of RTME as a natural alternative to alleviate colitis.

Chelerythrine Ameliorates Acetic Acid-Induced Ulcerative Colitis via Suppression of Inflammation and Oxidation

The incidence of ulcerative colitis (UC), an inflammatory bowel disease (IBD), is drastically increasing globally, leading to greater economic hardship and patient morbidity. This study evaluated the effects of chelerythrine on acetic acid (AA)-induced UC in a mouse model. Mice received chelerythrine (25, 50, and 100 mg/kg, i.g.) and sulfasalazine (SASP) (500 mg/kg, i.g.) for 7 consecutive days following the induction of colitis via the intrarectal administration of AA (5% v/v). Disease activity index (DAI), tissue morphology, tissue damage, oxidative stress (OS), and inflammatory markers were then evaluated. The results revealed that the colonic levels of total antioxidant capacity (T-AOC), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) had decreased, while colonic myeloperoxidase (MPO), malondialdehyde (MDA), lipid peroxide (LPO) activity, colonic and serum interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) levels, and serum lactate dehydrogenase (LDH) had all increased significantly in the colitis untreated group compared to that of the normal control. Treatment with chelerythrine considerably improved most of these parameters, and a dose of 100 mg/kg, was found to be comparable to that of 500 mg/kg SASP. This alkaloid also markedly reversed body weight (BW), clinical activity score, gross lesion score, mucosal edema, and colon weight/length in a dose-dependent manner. In conclusion, the protective effect of chelerythrine could be attributed to its anti-inflammatory and antioxidant activities.

Budesonide-Loaded Hyaluronic Acid Nanoparticles for Targeted Delivery to the Inflamed Intestinal Mucosa in a Rodent Model of Colitis.

The aim of the present study was to investigate the therapeutic potential of budesonide- (BDS-) loaded hyaluronic acid nanoparticles (HANPs) for treatment of inflammatory bowel disease (IBD) using an acute model of colitis in rats. The therapeutic efficacy of BDS-loaded HANPs in comparison with an aqueous suspension of the drug with the same dose (30 μg/kg) was investigated 48 h following induction of colitis by intrarectal administration of acetic acid 4% in rats. Microscopic and histopathologic examinations were conducted in inflamed colonic tissue. Tissue concentration of tumor necrosis factor (TNF)-α was assessed by ELISA assay kit, while the activity of myeloperoxidase (MPO) was measured spectrophotometrically. Results from in vivo evaluations demonstrated that administrations of BDS-HANPs ameliorated the general endoscopic appearance, quite close to the healthy animals with no signs of inflammation and reduced the cellular infiltration, as well as the TNF-α level, and the MPO activity. It was found that delivery by BDS-loaded HANPSs alleviated the induced colitis significantly better than the same dose of the free drug. These data further suggest the potential of HANPs as a targeted drug delivery system to the inflamed colon mucosa.

Curcumin-Loaded Microspheres Are Effective in Preventing Oxidative Stress and Intestinal Inflammatory Abnormalities in Experimental Ulcerative Colitis in Rats.

Curcumin’s role in the treatment of ulcerative colitis (UC) has been proven by numerous studies, but its preventive administration, with the aim of reducing the remission episodes that are characteristic of this disease, must be further investigated. This study investigates the effects of a novel curcumin-loaded polymeric microparticulate oral-drug-delivery system for colon targeting (Col-CUR-MPs) in an experimental model of UC. Male Wistar rats (n = 40) were divided into five groups (n = 8), which were treated daily by oral gavage for seven days with a 2% aqueous solution of carboxymethylcellulose sodium salt (CMCNa) (healthy and disease control), free curcumin powder (reference), Col-CUR-MPs (test) and prednisolone (reference) prior to UC induction by the intrarectal administration of acetic acid (AA), followed by animal sacrification and blood and colonic samples’ collection on the eighth day. Col-CUR-MPs exhibited an important preventive effect in the severity degree of oxidative stress that resulted following AA intrarectal administration, which was proved by the highest catalase (CAT) and total antioxidant capacity (TAC) levels and the lowest nitrites/nitrates (NOx), total oxidative status (TOS) and oxidative stress index (OSI) levels. Biochemical parameter analysis was supported by histopathological assessment, confirming the significant anti-inflammatory and antioxidant effects of this novel colon-specific delivery system in AA-induced rat models of UC. Thus, this study offers encouraging perspectives regarding the preventive administration of curcumin in the form of a drug delivery system for colon targeting.

Lycopodium Mitigates Oxidative Stress and Inflammation in the Colonic Mucosa of Acetic Acid-Induced Colitis in Rats.

Inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) and Crohn’s disease (CD) are diseases of the gastrointestinal system involving genetic and environmental factors attributed to oxidative stress and inflammation. Targeting oxidative stress and inflammation by novel dietary compounds of natural origin convincingly appears to be one of the important therapeutic strategies to keep the disease in remission. As there is no permanent cure for IBD except for chronic long-term treatment or surgery, it is therefore imperative to investigate plant-based agents that are receiving attention for their therapeutic benefits to overcome the debilitating clinical conditions of IBD. Lycopodium (LYCO), a plant of tropical and subtropical origin and known by numerous names such as ground pine, club moss, or devil’s claw, has been popularly used for centuries in traditional medicine including Chinese and Indian medicines. In the present study, the effect of LYCO has been investigated in an acetic acid (AA)-induced colitis model in Wistar rats. LYCO was orally administered at the dose of 50 mg/kg/day either 3 days before or 30 min after the induction of IBD and continued for 7 days by intrarectal administration of AA. The changes in body weight and macroscopic and microscopic analysis of the colon of rats of different experimental groups were observed on days 0, 2, 4, and 7. The levels of myeloperoxidase (MPO), reduced glutathione (GSH), and malondialdehyde (MDA) were measured. AA caused a significant reduction in body weight and increased macroscopic and microscopic ulcer scores along with a significant decline in antioxidant enzymes, superoxide dismutase (SOD), and catalase and antioxidant substrate, glutathione (GSH). There was a concomitant increased formation of malondialdehyde (MDA), a marker of lipid peroxidation, and raised myeloperoxidase (MPO) activity, a marker of neutrophil activation. Treatment with LYCO significantly improved IBD-induced reduction in body weight, improved histology, inhibited MDA formation, and restored antioxidants along with reduced MPO activity. AA also caused the release of proinflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-23 (IL-23). Furthermore, AA also increased the levels of calprotectin, a protein released by neutrophils under inflammatory conditions of the gastrointestinal tract. LYCO treatment significantly reduced the release of calprotectin and proinflammatory cytokines. The results demonstrate that LYCO treatment has the potential to improve disease activity by inhibiting oxidative stress, lipid peroxidation, and inflammation along with histological preservation of colonic tissues.

Umbelliferone ameliorates ulcerative colitis induced by acetic acid via modulation of TLR4/NF-κB-p65/iNOS and SIRT1/PPARγ signaling pathways in rats.

Ulcerative colitis (UC) is a common chronic, idiopathic inflammatory bowel disease associated with inflammatory perturbation and oxidative stress. Umbelliferone (UMB) is a potent anti-inflammatory and antioxidant coumarin derivative.Depending on the possible mechanisms, we aimed to explore and elucidate the therapeutic potential of UMBon UC-inflammatory response and oxidative injury-induced via intrarectal administration of acetic acid (AA) in rats. Animals were assigned into four groups: control group, UMB (30mg/kg, oral)-treated group, AA-induced colitis model group (2ml of AA; 3% v/v), and colitis treated with UMB group. The results showed that UMB improved macroscopic and histological tissue injury caused by the AA. Mechanistically, UMB reduced the elevated colonic TNF-α, IL-6, MPO, and VCAM-1 and downregulated the gene and protein expression of TLR4, NF-κB, and iNOS signaling factors, exhibiting potent anti-inflammatory effects. Moreover, UMB upregulated the gene and protein expression of both SIRT1 and PPARγ signaling pathways, thereby inhibiting both oxidative injury and inflammatory response. Conclusively, UMB protected rats against AA-induced UC by suppressing the TLR4/NF-κB-p65/iNOS signaling pathway and promoting the SIRT1/PPARγ signaling. Our results showed the effectiveness of UMB in alleviating the pathogenesis of UC and introduced it as a possible therapeutic applicant for clinical application.

Immunomodulatory assessment of Portulaca oleracea L. extract in a mouse model of colitis

Ulcerative colitis (UC) is a gastrointestinal inflammatory disease with a multifactorial pathophysiology. This study aims to investigate the immunomodulatory effect of Portulaca oleracea leaf ethanolic extract (POE) on acetic acid (AA)-induced UC in mice. Experimental animals received oral doses of POE (200 mg/kg for 7 days) after an induction of colitis by intrarectal AA administration. In mice with AA-induced UC treated with POE, the results revealed a significant modulation in body weight and colon length. Moreover, treatment with POE downregulated the interleukin 1, 6, and 17, tumor necrosis factor-alpha, gamma interferon, and nuclear factor-kappa B levels compared with the colitis group. Furthermore, POE markedly inhibited histological damage, decreased myeloperoxidase activity and reduced fecal calprotectin level compared with the colitis group. These data are consistent with the reduction in total bacterial content in the colon. Taken together, treatment with POE may reduce colonic inflammation by alleviating the immune response and inhibiting the severity of colitis. The HPLC analysis of POE resulted in the identification of seven medicinal compounds comprising two phenolic acids (ferulic and caffeic acids) and five flavonoids (kaempferol, quercetin, rutin, narenginin and hesperidin). Subsequent analysis of POE by GC-MS revealed ten phytocomponents; the major percentages were hexadecenoic acid, methyl ester (29.8119%), α-linolenic acid (25.8431%), 16-octadecenoic acid, methyl ester (15.1578%) and α-tocopherol (10.7848%). Delta-lactams and alkanes were the minor components. Such natural plant-derived substances and their probable synergistic action appear to contribute to a promising therapeutic protocol for colitis.

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.

Bupropion Ameliorates Acetic Acid-Induced Colitis in Rat: the Involvement of the TLR4/NF-kB Signaling Pathway.

Inflammatory bowel disease composed of ulcerative colitis and Crohn's disease is a disorder that may involve entire gastrointestinal tract. Its pathogenesis is mainly an immune-mediated inflammation. Recently, it has been indicated that bupropion possesses anti-inflammatory properties; hence, the objective of this experiment is the investigation of the anti-inflammatory influence of bupropion on colonic lesions that emerged following the intrarectal administration of acetic acid. Thirty-six male Wistar rats were allocated randomly into six groups, including control, acetic acid, dexamethasone (2mg/kg), and bupropion (40, 80, and 160mg/kg). Colitis was induced by intrarectal administration of acetic acid in all study groups except control group, and animals were treated by oral administration of dexamethasone and bupropion. While macroscopic and microscopic lesions were observed after colitis induction, administration of dexamethasone and bupropion 160mg/kg led to the remarkable improvement in lesions. In addition, the expression of TLR4 and NF-ĸB was decreased after colitis induction; however, treatment with dexamethasone (2mg/kg) and bupropion (160mg/kg) resulted in a significant decrease in their expression. Regarding biochemical factors, following colitis induction, TNF-α level and MPO activity were increased; nevertheless, dexamethasone (2mg/kg) and bupropion (160mg/kg) decreased the TNF-α and MPO activity. In conclusion, bupropion exerts anti-inflammatory influence through suppressing the TLR4 and NF-ĸB expression in the rat model of acute colitis.

Anti-inflammatory effect of Adiantum capillus-veneris hydroalcoholic and aqueous extracts on acetic acid-induced colitis in rats.

Colitis is an inflammatory bowel disease with unknown etiology where many factors might play a role. Adiantum capillus-veneris may have beneficial effects in colitis because of its anti-inflammatory, antioxidant, wound healing and antimicrobial effects. The aim of this study was to explore the anti-inflammatory and anti-ulcerative effects of A. capillus-veneris on acetic acid-induced colitis in a rat model. A. capillus-veneris aqueous (ACAE; 150, 300, and 600 mg/kg) and hydroalcoholic extract (ACHE; 150, 300, and 600 mg/kg) were given orally (p.o.) to male Wistar rats 2 hr before induction of colitis by intra-rectal administration of acetic acid 3%, and continued for 4 days. Prednisolone (4 mg/kg) and mesalazine (100 mg/kg) were applied p.o., as reference drugs for comparison. On day five, colitis indices of tissue specimens were evaluated and levels of biochemical markers including myeloperoxidase (MPO) and malondialdehyde (MDA) were determined. In all groups treated with ACAE and ACHE with the exception of ACAE (150 mg/kg), ulcer index and wet weight of colon as parameters of macroscopic injuries, total colitis index as marker of microscopic features and MPO activity were significantly reduced in comparison to the control group; however, MDA value was only diminished in ACAE (300 and 600 mg/kg) and ACHE (300 mg/kg) groups significantly. This research showed that ACAE and ACHE had dose-related beneficial effects on acetic acid-induced colitis and these effects could be attributed to anti-inflammatory, ulcer healing and antioxidant activities of these extracts.

Efficacy of Pyrus elaeagnifolia subsp. elaeagnifolia in acetic acid–induced colitis model

AbstractIn Turkish folk medicine, the fruits ofPyrus elaeagnifoliasubsp.elaeagnifoliahave been used to treat diarrhea and detoxify poisonous snake bites by enlarging the wound. The aim of the study was to confirm the ethnopharmacological usage of the plant usingin vivoandin vitromodels. Experimental colitis was performed under anesthesia by intrarectal administration of acetic acid in rats, and the extracts were administered orally. The colonic malondialdehyde (MDA), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and nitrite levels, in addition to the myeloperoxidase (MPO) and caspase-3 activities, were measured to determine the effects of the plant extracts. The methanol (MeOH) extract revealed a significant decrease in MPO and caspase-3 levels. The MeOH extract was found to have the highest total tannin content. It was also found to have significant antioxidant (p˂ 0.01) and anti-inflammatory activities (p˂ 0.05) in acetic acid induced colitis rat model . According to our results, the present study exhibited a decrease in MDA, nitrite, IL-6, and TNF-αlevels in the colon tissue and blood in the MeOH extract treated group. The findings of this study can help in treating various disorders, such asClostridium difficileinfection, irritable bowel syndrome, and inflammatory bowel diseases.

Involvement of central opioid receptors in protective effects of methadone on experimental colitis in rats.

There are several lines of evidence on the protective roles of opioids in gastrointestinal inflammatory conditions. This study aims to distinguish the central and peripheral roles of methadone, a non-selective opioid receptor agonist, in an acute model of ulcerative colitis in male rats. Ulcerative colitis was induced by intrarectal administration of acetic acid 4%. Methadone was injected subcutaneously (s.c.), 5 and 10mg/kg, and intracerebroventricular (i.c.v.), 50 and 300ng/rat. Opioid antagonists were employed. Methylnaltrexone (MNTX; 5mg/kg, i.p.), a peripherally acting opioid receptor antagonist, and naltrexone (NTX; 5mg/kg, i.p. and 10ng/rat, i.c.v.), a peripherally and centrally acting opioid receptor antagonist were injected before methadone (10mg/kg, s.c. and or 300ng/rat, i.c.v.) administration. NTX (5mg/kg, i.p. and 10ng/rat, i.c.v.) were administered 30min prior to administration of methadone (10mg/kg, s.c. and 300ng/rat, i.c.v.), respectively. MNTX (5mg/kg, i.p.) was injected 30min prior to methadone (10mg/kg, s.c.). Seventy-two hours following colitis induction, macroscopic and microscopic mucosal lesions, and the colonic levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were determined. Methadone (300ng/rat, i.c.v.) and Methadone (5 and 10mg/kg, s.c.) improved the macroscopic and microscopic scores through opioid receptors. Also, a significant reduction in TNF-α and IL-1β was observed. Peripherally and centrally injected NTX significantly reversed methadone 10mg/kg s.c. anti-inflammatory effects while MNTX could not completely reverse this effect. Moreover, centrally administered methadone (300ng/rat) showed the anti-inflammatory effect which was reversed by central administration of NTX (10ng/rat). Theopioid receptors mainly the central opioid receptors maymediate the protective actions of methadone on the experimental model of inflammatory bowel disease in rat.

Protective effect of carvacrol on acetic acid-induced colitis

The pharmacological therapy for inflammatory bowel diseases continues to be problematic, and requires new alternative options. In this study, we tested the hypothesis that carvacrol (CAR), a phenolic monoterpene with anti-inflammatory and antioxidant activities, can treat experimental colitis in mice. C57BL/6 mice (n=8/group) were subjected to intrarectal administration of acetic acid (5%) to induce colitis. Mice were pretreated with CAR (25, 50 or 100mg/kg, p.o.) every 12h for three days prior to the induction. Abdominal hyperalgesia, macroscopic and microscopic colon damage, myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels, oxidative stress markers, and antioxidant enzyme activities were evaluated. Pretreatment with all doses of CAR significantly decreased abdominal hyperalgesia and colon MPO activity and TNF-α and IL-1β levels. A reduction in macroscopic and microscopic damage (p<0.05) was observed at doses of 50 and 100mg/kg CAR. Pretreatment with CAR significantly reduced lipid peroxidation (for all doses) and increased sulfhydryl groups (at 100mg/kg). This effect was accompanied by a significant increase in catalase, superoxide dismutase, and glutathione peroxidase activities. These findings indicate that CAR protected mice from acetic acid-induced colitis by reducing inflammatory, nociceptive, and oxidative damages.