Effectiveness of mesalamine and propolis in experimental colitis (original) (raw)
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Evidence-Based Complementary and Alternative Medicine, 2013
This study focused on the therapeutic effect of a propolis SLNC 106 PI extract on experimental colitis. Wistar adult rats received 0.8 mL rectal dose of one of the following solutions: saline (group S), 20 mg TNBS in 50% ethanol (group TNBS), 20 mg TNBS in 50% ethanol and propolis extract in saline (group TNBS-P), propolis extract in saline (group SP), and 20 mg TNBS in 50% ethanol and 50 mg/kg mesalazine (group TNBS-M). The animals were euthanized 7 or 14 days after the colitis induction. Samples of the distal colon were harvested for the analysis of myeloperoxidase (MPO) enzyme activity and for morphometric analysis in paraffinembedded histological sections with hematoxylin-eosin or histochemical staining. The animals treated with TNBS exhibited the typical clinical signs of colitis. Increased MPO activity confirmed the presence of inflammation. TNBS induced the development of megacolon, ulceration, transmural inflammatory infiltrate, and thickened bowel walls. Treatment with propolis moderately reduced the inflammatory response, decreased the number of cysts and abscesses, inhibited epithelial proliferation, and increased the number of goblet cells. The anti-inflammatory activity of the propolis SLNC 106 extract was confirmed by the reductions in both the inflammatory infiltrate and the number of cysts and abscesses in the colon mucosa.
Antioxidant effect of mesalazine in the experimental colitis model induced by acetic acid
Journal of Coloproctology, 2016
Introduction Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the gastrointestinal tract, without specific cause or pathogen.Objective The effect of mesalazine in a colitis model induced by acetic acid (AA) was evaluated.Methods We used 40 Wistar rats, ±350 g, divided into 4 groups: control (CO); control + mesalazine (CO + M); colitis (CL) and colitis + M (CL + M) at 24 and 48 h of treatment. The animals received the substances by an intracolonic enema of AA 4% and treatment with mesalazine PO 20 mg/kg after colitis induction.Results Mesalazine reduced tissue damage in the gut, normalized sphincter anal pressure levels and decreased lipid peroxidation, metabolites of nitric oxide and iNOS and NF-kB expression in the treated groups in both treatment time points (24 and 48 h), as well as the activity of antioxidant enzymes.Conclusion Mesalazine was effective in reducing tissue damage and oxidative and inflammatory damage, restored antioxidant capacity and...
Biomedicine & Pharmacotherapy, 2019
Fish oil (FO) and mesalazine have well-known anti-inflammatory and antioxidant effects; on the other hand, information related to combined intrarectal administration of FO and mesalazine is limited. The present study was conducted to make comparison on therapeutic effectiveness of rectally administered FO and mesalazine in rats with trinitrobenzenesulfonic acid (TNBS)-induced colitis. Methods: Wistar rats were randomly assigned to 5 groups as (1) Control, (2) Colitis, (3) Colitis + Mesalazine (Colitis + M), (4) Colitis + Fish Oil (Colitis + F), and (5) Colitis + Mesalazine + Fish Oil (Colitis + M + F). Intrarectally administered TNBS induced colitis. At the end of the trial, the rats' macroscopic and histopathologic lesions were rated and tumour necrosis factor (TNF)-α, Interleukin 6 (IL6), glutathione reductase (GR), glutathione peroxidase (GP), myeloperoxidase (MPO), malondialdehyde (MDA), Superoxide dismutase (SOD), Total nitrate and nitrite, and catalase (CAT) in serum and tissue were detected. Results: As a result of macroscopic and microscopic examination, although separate administrations of FO and mesalazine partly decreased the damage, their combined administration decreased the damage scores significantly (p < 0.01). It was observed that separate and combined administrations of FO and mesalazine decreased the increase in the serum and tissue TNF-α and IL-6 levels caused by colitis (p < 0.05). It was observed that the serum MPO, serum GR, tissue SOD, tissue nitrite/nitrate values of both Colitis + M and Colitis + F groups were close to the control in terms of all the parameter values in Colitis + M + F group (p > 0.05). Also based on the histological results, the inflammation damage in the tissue caused by colitis in the Colitis + M + F group recovered significantly. Conclusions: We found that microscopic and macroscopic damage, serum IL-6 level decreased and increased serum and tissue GP and tissue GR values in Colitis + M + F group compared to Colitis + M and Colitis + F groups. Combined intrarectal administration of FO and mesalazine may bring a new insight concerning the treatment of ulcerative colitis.
Trinitrobenzene sulfonic acid (TNBS)-induced colitis is one of the most common methods for studying inflammatory bowel disease in animal models. Several factors may, however, affect its reproducibility, rate of animal mortality, and macroscopic and histopathological outcomes. Our aim was to validate the main contributing factors to this method and compare the effects of different reference drugs upon remission of resultant colon injuries. TNBS was dissolved in 0.25 ml of ethanol (50% v/v) and instilled (25, 50, 100 and 150 mg/kg) intracolonically to the male Wistar rats. After determination of optimum dose of TNBS in male rats and assessment of this dose in female rats, they were treated with reference drugs including dexamethasone [1 mg/kg, intraperitoneally (i.p.) and 2 mg/kg, orally (p.o.)], Asacol (mesalazine, 100 mg/kg, p.o.; 150 mg/kg, enema) and hydrocortisone acetate (20 mg/kg, i.p.; 20 mg/kg, enema) which started 2 h after colitis induction and continued daily for 6 consecutive days. Thereafter, macroscopic and microscopic parameters and clinical features were assessed and compared in different groups. We found that the optimum dose of TNBS for the reproducibility of colonic damage with the least mortality rate was 50 mg/kg. Amongst studied reference drugs, hydrocortisone acetate (i.p.), dexamethasone (i.p. and p.o.) and Asacol (p.o.) significantly diminished the severity of macroscopic and microscopic injuries and could be considered effective for experimental colitis studies in rats. Our findings suggest that optimization of TNBS dose is essential for induction of colitis under the laboratory conditions; and gender exerts no impact upon macroscopic and histological characteristics of TNBS-induced colitis in rats. Furthermore, the enema forms of hydrocortisone and Asacol are not appropriate reference drugs.
Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity
Gut, 1995
Enhanced nitric oxide (NO) generation by stimulated NO synthase (NOS) activity may, through its oxidative metabolism contribute to tissue injury in experimental colitis. In this study the possible amelioration of experimental colitis by NG-nitro-Larginine methyl ester (L-NAME), an inhibitor of NOS activity, was evaluated. Colitis was induced in rats by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB) dissolved in 0.25 ml 50%/o ethanol or by flushing the colon of capsaicin pretreated rats with 2 ml of 50/0 acetic acid. In several experiments, L-NAME 0-1 mg/ml was added to the drinking water at the time of colitis induction with TNB or seven days before acetic acid treatment. Rats were killed at various time intervals after induction of colitis. A 10 cm distal colonic segment was isolated, weighed, lesion area measured, and explants organ cultured for 24 hours for determination of NO generation by the Greiss reaction. The rest of the mucosa was scraped for determination of myeloperoxidase and NOS activities and leukotriene generation. In TNB treated rats mean arterial pressure was also determined up to 72 hours after damage induction, with or without cotreatment with nitroprusside. L-NAME significantly decreased the extent of tissue injury in TNB treated rats. Seven days after TNB treatment lesion area was reduced by 55°/0, colonic weight by 37%, and myeloperoxidase and NOS activity by 590/o and 42%, respectively. Acetic acid induced colitis in capsaicin pretreated rats was also significantly decreased by L-NAME. Twenty four hours after acetic acid treatment lesion area was reduced by 61%/ colonic weight by 21%, and NOS activity by 39%. Mean (SEM) arterial blood pressure in TNB+L-NAME treated rats was 37.6 (8.1) mm Hg higher than in TNB treated rats, an effect that was only partially abolished by nitroprusside. These results show that inhibition of NO synthesis by an L-arginine analogue significantly ameliorates the extent of tissue injury in two models of experimental colitis, an effect that is not due only to its vasoconstrictor properties. Modulation of NO generation may be a novel therapeutic approach in inflammatory bowel disease. (Gut 1995; 37: 247-255)
Enhanced anti-inflammatory effects of a nitric oxide–releasing derivative of mesalamine in rats
Gastroenterology, 1999
Background & Aims: Nitric oxide (NO)-releasing derivatives of cyclooxygenase inhibitors exhibit enhanced anti-inflammatory activity and greatly reduced gastrointestinal toxicity. We evaluated whether a similar derivatization of mesalamine (5-aminosalicylic acid) would improve its anti-inflammatory activity. Methods: Effects of an NO-releasing derivative of mesalamine (NCX-456; NO-mesalamine) were compared with those of mesalamine itself and 2 other NO donors in a rat model of colitis. These drugs were compared for their ability to inhibit leukocyte adherence to the vascular endothelium in vivo, interleukin (IL)-1β and interferon (IFN)-γ release in vitro (splenocytes and colon), and messenger RNA expression in the inflamed colon. Results: NO-mesalamine was significantly more effective than mesalamine in reducing the severity of colitis (damage and granulocyte infiltration). Unlike mesalamine, NO-mesalamine significantly suppressed leukocyte adherence to the vascular endothelium in vivo. NO-mesalamine inhibited IL-1β and IFN-γ release and caspase 1 activity in splenocytes; such effects were not found in the inflamed colon. Conclusions: These studies show that an NO-releasing derivative of mesalamine has significantly enhanced anti-inflammatory activity, including improved efficacy in a rat model of colitis. The improved efficacy of this derivative is most likely caused by its enhanced ability to suppress leukocyte infiltration and possibly to scavenge peroxynitrite.GASTROENTEROLOGY 1999;117:557-566
2021
Background:Ulcerative colitis (UC) is a chronic inflammatory disease of large intestine. Overproduction of free radicals, lowered antioxidant capacity, inflammation and abnormal apoptosis are involved in its pathogenesis. Propranolol and carvedilol, βblockers with antioxidant and anti-inflammatory effects which may have a protective role in UC. The study aimed to evaluate and compare the effects of propranolol and carvedilol on UC development and to distinguish which of them have greater beneficial effect on experimentally-induced UC in male albino rats. Methods: Fifty male albino rats were randomly allocated to five groups with each group comprising eleven rats except control group composed of six rats. Group (1): control group, Group (2): ulcerative colitis group, Group (3): propranolol-pretreated (30 mg/kg/d), Group (4): carvedilol-pretreated (30 mg/kg/d) and Group (5): mesalazinepretreated (300 mg/kg/d). Treated groups received drugs by oral gavage for seven days before and thre...
Redox Biology, 2019
Inflammatory bowel disease (IBD) is a chronic condition characterised by leukocyte recruitment to the gut mucosa. Leukocyte myeloperoxidase (MPO) produces the two-electron oxidant hypochlorous acid (HOCl), damaging tissue and playing a role in cellular recruitment, thereby exacerbating gut injury. We tested whether the MPO-inhibitor, 4-Methoxy-TEMPO (MetT), ameliorates experimental IBD. Colitis was induced in C57BL/6 mice by 3% w/v dextran-sodium-sulfate (DSS) in drinking water ad libitum over 9-days with MetT (15 mg/kg; via i. p. injection) or vehicle control (10% v/v DMSO+90% v/v phosphate buffered saline) administered twice daily during DSS challenge. MetT attenuated bodyweight loss (50%, p < 0.05, n = 6), improved clinical score (53%, p < 0.05, n = 6) and inhibited serum lipid peroxidation. Histopathological damage decreased markedly in MetT-treated mice, as judged by maintenance of crypt integrity, goblet cell density and decreased cellular infiltrate. Colonic Ly6C + , MPO-labelled cells and 3-chlorotyrosine (3-Cl-Tyr) decreased in MetT-treated mice, although biomarkers for nitrosative stress (3-nitro-tyrosine-tyrosine; 3-NO 2-Tyr) and low-molecular weight thiol damage (assessed as glutathione sulfonamide; GSA) were unchanged. Interestingly, MetT did not significantly impact colonic IL-10 and IL-6 levels, suggesting a non-immunomodulatory pathway. Overall, MetT ameliorated the severity of experimental IBD, likely via a mechanism involving the modulation of MPO-mediated damage.