2015(35B-28) (original) (raw)
Related papers
Effects of statins on experimental colitis in normocholesterolemic rats
Scandinavian Journal of Gastroenterology, 2006
Objective . The results of previous studies suggest that statins have a direct anti-inflammatory effect that is not directly related to their cholesterol-lowering activity. The aim of this study was to investigate the effect of simvastatin (SIM) and fluvastatin (FLU) on trinitrobenzene sulfonic acid (TNBS)-induced colonic inflammation in rats. Material and methods . The drugs were given for 3 days (0.1 and 1 mg/kg day (1 ; intraperitoneally) after induction of colitis. The lesions in the distal colon were scored at the macroscopic and microscopic level. Tissue malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content were assessed and formation of reactive oxygen species and peroxynitrite was monitored by chemiluminescence (CL) assay. Trunk blood was collected for the measurement of serum tumor necrosis factor (TNF)-a level. Results .Treatment with SIM reduced the lesion score of the colitis group at macroscopic level (p B/0.05), but there was no effect of treatment with FLU. The increase in colonic MDA level of the colitis group was reduced by both drugs at all doses (p B/0.05 Á0.001). The decrease in GSH and the an increase in MPO activity in the colitis group were reversed by SIM at all doses (p B/0.01), but FLU had no effect. An increase in colonic lucigenin CL value in the colitis group was reduced by SIM and FLU at all doses (p B/0.001) and an increase in peroxynitrite ratio in the colitis group showed a significant reduction in SIM-treated groups; FLU reduced this effect at a dose of 1 mg/kg (p B/0.01). An increase in tissue collagen content and serum TNF-a level in the colitis group was reversed by both drugs at all doses (p B/0.001). Conclusions . SIM and FLU seemed to be beneficial in a TNBS-induced rat colitis model through the prevention of lipid peroxidation, superoxide generation, cytokine production and neutrophil accumulation.
Disease modifying effect of statins in dextran sulfate sodium model of mouse colitis
Inflammation Research, 2008
Objective: We evaluated the disease modifying effect of simvastatin and atorvastatin in Dextran Sulfate Sodium (DSS) model of colitis. Materials and methods: Thirty, 8-week old female Swiss-Webster mice were separated into 5 groups (n = 6/group). Colitis was induced by feeding 4 % DSS solution for 7 days. Following discontinuation of DSS, over the next 7 days, the groups orally received simvastatin (20 mg/kg/day), atorvastatin (60 mg/kg/day), vehicle only (0.75 % methylcellulose), subcutaneous 30 µg injections of anti-TNFα monoclonal antibody or intraperitoneal anti-mouse apolipoprotein A-I antibody respectively. Disease activity Index (DAI) was determined daily by a blinded investigator. Results: The mean reduction in DAI scores from day 7 to day 14 for anti-TNFα group, simvastatin and atorvastatin group were 74 %, 76 % and 64 %, respectively as compared to 41 % reduction in vehicle and anti-apolipoprotein A-I antibodytreated groups. Conclusions: This fi nding suggests that statins may have the ability to modify the disease activity in the DSS model of colitis and the disease modifying effect is comparable to anti-mouse TNFα treatment in this model.
Effect of acute Atorvastatin treatment in an experimental model of colitis
International Journal of Research in Pharmaceutical Sciences
Acute atorvastatin treatment in an experimental model of colitis was studied using the acetic acid induction modality for colitis in rats. This study was aimed to evaluate possible therapeutic effects of atorvastatin against acetic acid-induced colitis in a rat model and to find out the correlation between severity index with oxidative stress parameters and inflammatory markers. Experimental colitis was induced in rats by rectal administration of 4% acetic acid (vol/vol). Rats with colitis were received either atorvastatin 10mg/kg or sulfasalazine 100mg/kg orally for 7 days. Macroscopical and microscopical assessment and the measurement of the colonic cytokines (IL-6 and TNF-α), oxidative stress markers; myeloperoxidase (MPO) and malondialdehyde (MDA), and adhesion molecules (E-Selectin and ICAM-1). Both the macroscopical lesion area and histological colonic injury induced by acetic acid were reduced significantly by both atorvastatin and sulfasalazine. These were associated by atte...
Purpose: Based on studies that have attributed anti-inflammatory properties to statins, the aim of this work was to observe the effect of simvastatin in the attenuation of mucositis induced by methotrexate in the gastrointestinal tract in rats and its effects on cytokines. Methods: Twelve Wistar rats weighing 270±18 g were randomly distributed into two groups: methotrexate/saline (MTX/S n = 6) and methotrexate/simvastatin (MTX /SV n=6). In all animals, 3 mg / kg of methotrexate was injected subcutaneously for 3 consecutive days. In the MTX / SV simvastatin was administered orally one week before and during treatment with methotrexate. In the MTX/S, saline was administered at the same doses and schedules. We determined the plasma levels of TNF-α, IL-1β and IL-6 and the histological analysis by HE staining in segments of esophagus, stomach, duodenum, jejunum and colon. Results: The expression of TNF-α, IL-1β and IL-6 (14±91.7, 119.3±4 and 83.1±4, respectively) was lower in the MTX/SV ...
Background: Inflammatory bowel disease (IBD) is an idiopathic, chronic inflammatory condition, which affects the gastrointestinal tract and has no curative treatment. The present study aimed to investigate the effect of different doses of Rosiglitazone alone and in combination with sulfasalazine in AA (acetic acid)-induced inflammatory bowel disease (IBD) in rats. Methods: A total of 36 animals were included in the study. Animals were divided into five groups (n = 6): group I-control (normal saline), group II-AA+ normal saline, group III-Sulfasalazine(360mg/kg) +AA, group IV A-Rosiglitazone (1 mg/kg), group IV B-Rosiglitazone 5 mg/kg + AA, group V-Rosiglitazone 5 mg/kg + Sulfasalazine (360 mg/kg) +AA. Group IV was divided into two subgroups, namely IVA and IVB, on the basis of different doses of Rosiglitazone used. After completion of one week of treatment, rats were sacrificed under ether anesthesia for assessment of intestinal inflammation using parameters namely colon weight change, macroscopic and histopathological evaluation. Results: There was a decrease in colonic weight, macroscopic scores and microscopic scores in groups treated with Rosiglitazone at a dose of 5 mg/kg i.e. high dose given alone and in combination with sulfasalazine .Combination treatment was more effective when compared to single drug treatment. Conclusion: The present study indicates the efficacy of Rosiglitazone in Acetic acid-induced IBD. The effects are more pronounced at higher dose i.e., 5 mg/kg. Combination of Rosiglitazone and Sulfasalazine has shown greater efficacy than single drug treatment.
A Novel Pre-treatment Approach to Ulcerative Colitis in a Mouse Model
Iranian Journal of Colorectal Research, 2023
Background: Inflammatory bowel disease (IBD) is a complex multifactorial condition that includes Crohn's disease and ulcerative colitis (UC). UC is characterized by inflammation, oxidative stress, and increased intestinal epithelial cell apoptosis. The present study investigated the protective potential of five safety products, namely bromelain (Br), silibinin (SB), alpha-lipoic acid (ALA), inulin (IN), and sodium butyrate (BU), against UC. Methods: Seventy-two male Balb/c mice were divided into nine groups and administered for 14 days with a minimum effective dose of Br, SB, ALA, IN, BU, or all five together (PAC). Mesalazine (MZ) was used to compare the therapeutic effects of the compounds. Colitis was induced by rectal injection of acetic acid (4%) on the 12 th day. Blood and colon tissue were collected, and the expression of inflammatory cytokines and oxidative stress indices were examined via ELISA. SPSS v.24 was used for data analysis. Results: All the individual therapeutic groups, including Br, IN, BU, ALA, and SB, partially improved histopathological changes due to colitis, but PAC treatment prior to colitis induction significantly (P<0.001) and more effectively improved colitis and alleviated the extent and intensity of the histological signs of cell damage including inflammation intensity and macroscopic and microscopic colon damage. A significant decrease in inflammatory cytokines and oxidative stress indices was also observed in the groups treated with ALA, SB, and PAC. Conclusion: This animal study suggests that the new drug combination (PAC) is more beneficial for the prevention of UC than MZ, a usual treatment of UC.
Iraqi Journal of Veterinary Sciences, 2020
Ulcerative colitis is a chronic and intermittent illness. The current treatment failed to cure the disease which requires to investigate other drug with minimal side effects. The goal of the research is to assess the histological outcome, antioxidant and anti-inflammatory effects of cinnarizine in comparison with that of sulfasalazine (salazosulfapyridine) in experimentally induced colitis in rats. Acetic acid 4% (vol/vol) was used rectally to induce experimental colitis in rats. After induction, rats were administered either sulfasalazine 100mg/kg or cinnarizine 20 mg/kg as a therapeutic dose in rats orally for one week. The duration of treatment was depended on previous studies. There were estimation of histopathological and clinical parameters also the expression of cytokines (tumor necrosis factor alpha (TNF-α) and interleukin-4 (IL-4)), oxidative stress markers (malondialdehyde (MDA) and myeloperoxidase (MPO)), and adhesion molecules (intercellular adhesion molecule-1 (ICAM-1) and endothelial (E)-Selectin) in the colonic tissue. Results showed that both cinnarizine and sulfasalazine significantly reduced the clinical and histological injury in colon that induced by acetic acid. In addition to the down regulation of the increased colonic cytokines, MDA, MPO parameters and adhesive molecules. These results concluded that cinnarizine had an effective therapeutic role which is comparable with sulfasalazine on the experimental colitis through anti-inflammatory and antioxidant actions with down regulation the colonic adhesion molecule.
European Journal of Pharmacology, 2009
This study investigated the possible mechanisms underlying the gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats. Rats were randomly assigned to vehicle-, simvastatin-, simvastatin + L-arginine-and simvastatin + N(G)-nitro-L-arginine methyl ester (L-NAME)-pretreated groups for two weeks. Pyloric ligation was performed for the collection of gastric juice, and gastric ulceration was induced by a single intraperitoneal injection of indomethacin (30 mg/kg). Gastric juice parameters (total acid output, pepsin activity and mucin concentration) were determined. The stomachs tissues were used for determination of gastric mucosal lipid peroxides, superoxide dismutase, catalase, total nitrites and prostaglandin E 2 levels. Pretreatment with simvastatin (10 mg/kg, orally, for 2 weeks) caused significant reduction in gastric mucosal lesions and lipid peroxides associated with a significant increase in gastric juice mucin concentration. Simvastatin significantly increased the gastric mucosal total nitrite and prostaglandin E 2 levels. Additionally, simvastatin attenuated the elevations in gastric mucosal superoxide dismutase observed with indomethacin. The gastroprotective effect afforded by simvastatin was significantly augmented by coadministration with L-arginine (a nitric oxide precursor) and inhibited by coadministration with L-NAME (a nitric oxide synthase inhibitor). Results confirm a gastroprotective effect for simvastatin, and indicate that the anti-ulcer effect of simvastatin is mediated by scavenging free radicals, increasing nitric oxide and prostaglandin E 2 levels, and increasing gastric juice mucin production. We conclude that simvastatin represents a more suitable antihyperlipidemic therapy for patients who are at risk of gastric ulcers that were induced by the use of nonsteroidal anti-inflammatory drugs (NSAIDs).