Therapeutic Mechanism and Effect of Camptothecin on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice

Camptothecin (CPT) is a cytotoxic quinoline alkaloid isolated from the bark and branches of the Chinese tree Camptotheca acuminata. CPT inhibits topoisomerase I. It possesses various antitumor activities and is mainly used in the treatment of colon, ovarian, liver, and bone cancers as well as leukemia. CPT inhibits the expressions of inflammatory genes and can prevent death from chronic inflammation. Therefore, we investigated the effect of CPT treatment in ulcerative colitis (UC) using DSS-induced UC mouse model; after that, we explored its potential mechanisms. Here, we found that CPT exerted protection on DSS-induced UC in rats. In addition, the administration prominently reduced the disease activity index as well as colon length of the model rats and remarkably reduced the inflammatory cytokines. Further, CPT significantly reduced several vital proinflammatory proteins in LPS-induced RAW264.7 cells. In summary, our findings demonstrate that CPT is hopefully to act as a therapeutic agent for UC.

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Efficacy of 5-Aminosalicylic Acid Enemas in the Treatment of Distal Ulcerative Colitis

Canadian Journal of Gastroenterology ◽

10.1155/1990/314931 ◽

1990 ◽

Vol 4 (7) ◽

pp. 468-471 ◽

Cited By ~ 3

Author(s):

MG Robinson ◽

DL Decktor

Keyword(s):

Ulcerative Colitis ◽

Disease Activity ◽

Activity Index ◽

Disease Activity Index ◽

First Episode ◽

High Dose ◽

Aminosalicylic Acid ◽

Open Label ◽

Distal Ulcerative Colitis ◽

The Mean

The efficacy of 4 g 5-aminosalicylic acid (5-ASA, mesalamine) enemas was assessed in 666 patients with distal ulcerative colitis. Patients were enrolled in an open-label compassionate use program. One 4 g 5-ASA enema was administered each night for a period of four weeks and the disease activity index was assessed at baseline and on days 14 and 28. On days 14 and 28, 78.0% and 88.1% of patients, respectively, demonstrated an improvement in disease activity index. The mean decline in disease activity index on day 14 was 40.7% (P=0.0001) and on day 28 it was 55.4% (P=0.0001). Efficacy was similar whether the disease was confined to or extended beyond 30 cm from the anus. There was no difference in efficacy in patients suffering their first episode of disease compared to patients suffering subsequent attacks. In conclusion, high dose 5-ASA enemas are a highly effective treatment for distal ulcerative colitis.

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Su1797 - Ultrasound for Assessing Disease Activity in Ulcerative Colitis Patients: Development of a Novel Ultrasonographic Disease Activity Index

Gastroenterology ◽

10.1016/s0016-5085(18)32143-7 ◽

2018 ◽

Vol 154 (6) ◽

pp. S-587-S-588

Author(s):

Steven Bots ◽

Kim Nylund ◽

Mark Löwenberg ◽

Krisztina Gecse ◽

Odd Helge Gilja ◽

...

Keyword(s):

Ulcerative Colitis ◽

Disease Activity ◽

Activity Index ◽

Disease Activity Index

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ROLE OF ANTIOXIDANT AND MYELOPEROXIDASE LEVELS IN 7, 12-DIMETHYLBENZ [A] ANTHRACENE INDUCED EXPERIMENTAL RAT MODEL: EVIDENCE FOR OXIDATIVE DAMAGE IN ACTIVE ULCERATIVE COLITIS.

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i3.16485 ◽

2017 ◽

Vol 9 (3) ◽

pp. 282

Author(s):

P. Geetha ◽

B. Lakshman Kumar ◽

U. Indra ◽

B. Pavithra Sheetal

Keyword(s):

Ulcerative Colitis ◽

Body Weight ◽

Antioxidant Status ◽

Activity Index ◽

Disease Activity Index ◽

The Body ◽

Unknown Etiology ◽

Steady Increase ◽

Tissue Samples ◽

Significant Change

Objective: Ulcerative colitis known as inflammatory bowel disease (IBD) of unknown etiology. We examined the antioxidant and myeloperoxidase status in a murine model of 7,12-dimethylbenz[a]anthracene induced colitis to elucidate the exact mechanism behind the inflammation.Methods: Male Wistar rats were exposed to ulcerative colitis using various concentration of DMBA (7,12-Dimethylbenz[A]anthracene) were periodically analysed on 4th, 8th, 12th, 24th and 32nd week from the date of induction. To determine the disease activity index changes in body weight, food consumption, the presence of gross blood in stool and consistency of feces and diarrhea were observed. Macroscopic characters were elucidated based on clinical features of the colon and rectum using scoring pattern. Tissue inflammation status was noted through myeloperoxidase (MPO) assay. The antioxidant status in tissue samples was analysed by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total reduced glutathione (GSH).Results: Gavage intubation of DMBA induced colitis showed significant changes from 4th week and severity on 32nd week. The body weight was gradually reduced. Macroscopic scoring showed severe scoring pattern the inflammation was significantly heavier by week 4; and by the end of 32 w, inflammation in rats was double that of the controls, tissue myeloperoxidase (MPO) activity showed the steady increase of neutrophil infiltration and inflammation rate every week. A significant change was noted in tissue antioxidant status and it showed the oxidation level. Statistically, significant change was recorded from 4th week till 32nd week.Conclusion: The conventional biochemical changes in colitis induced animal model revealed the association between the oxidative stress and ulcerative colitis.

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The protective effect of curcumin on rats with DSS-induced ulcerative colitis and its mechanisms

10.21203/rs.3.rs-191627/v1 ◽

2021 ◽

Author(s):

Jing Guo ◽

Yan-yan Zhang ◽

Mei Sun ◽

Ling-fen Xu

Keyword(s):

Ulcerative Colitis ◽

Th17 Cells ◽

Dextran Sulfate ◽

Activity Index ◽

Disease Activity Index ◽

Treg Cells ◽

Enzyme Linked Immunosorbent Assay ◽

T Helper ◽

T Helper 17 ◽

Inflammatory Bowel

Abstract Aim This study aimed to explore effect of curcumin on inflammatory bowel disease (IBD) in rats and its mechanism.Methods: A dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) rat model was established. The disease activity index (DAI) scores were calculated. The histopathological damage scores were determined by haematoxylin-eosin (H&E) staining. Regulatory T (Treg) cells and T helper 17 (Th17) cells in the spleen were analysed by flow cytometry. The levels of interleukin (IL)-10 and IL-17A were determined by enzyme-linked immunosorbent assay (ELISA). Results: Compared with the DSS model group, the curcumin group exhibited significantly reduced DAI scores and improvements in histopathological damage. The expression of CD4+IL-17+ Th17 cells was significantly lower and the expression of CD4+CD25+Foxp3+ Treg cells was significantly higher in the curcumin group than in the DSS group.Conclusion: Curcumin may be a new and effective treatment for IBD by regulating the balance of Treg/Th17 cells and the expression of IL-10 and IL-17A.

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Validation of the “German Inflammatory Bowel Disease Activity Index (GIBDI)”: An Instrument for Patient-Based Disease Activity Assessment in Crohn’s Disease and Ulcerative Colitis

Zeitschrift für Gastroenterologie ◽

10.1055/a-0605-4080 ◽

2018 ◽

Vol 56 (10) ◽

pp. 1267-1275 ◽

Cited By ~ 1

Author(s):

Angelika Hüppe ◽

Jana Langbrandtner ◽

Winfried Häuser ◽

Heiner Raspe ◽

Bernd Bokemeyer

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Activity Index ◽

Disease Activity Index ◽

Inflammatory Bowel ◽

Activity Indices

Abstract Introduction Assessment of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC) is usually based on the physician’s evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDICD) and UC (GIBDIUC) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians’ documented activity indices. Methods Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements. Results Rank correlations were 0.56 (pMS, GIBDIUC) and 0.57 (HBI, GIBDICD), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories). Discussion There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information.

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Novel Leucocyte/Thrombocyte Apheresis for Induction of Steroid-Free Remission in Ulcerative Colitis: A Controlled Randomized Pilot Study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz005 ◽

2019 ◽

Vol 13 (7) ◽

pp. 949-953 ◽

Cited By ~ 1

Author(s):

Wolfgang Kruis ◽

Phuong Nguyen ◽

Julia Morgenstern ◽

Wolfgang Ramlow ◽

Axel Dignaß ◽

...

Keyword(s):

Ulcerative Colitis ◽

Pilot Study ◽

Clinical Remission ◽

Activity Index ◽

Disease Activity Index ◽

Oral Prednisolone ◽

Serious Adverse Events ◽

Symptomatic Infection ◽

Reactive Protein ◽

Group A

Abstract Background and Aims In active ulcerative colitis [UC] refractory to mesalazine, escalation to either steroids or immunosuppression is common practice. The efficacy and safety of alternative escalation therapy with a novel leukocyte apheresis device were studied. Methods This was a prospective, randomized, controlled multicentre pilot study comparing leukocyte apheresis with prednisolone in refractory UC (disease activity index [DAI] ≥ 4 and ≤8). Group A received weekly apheresis over five consecutive weeks. Group P received oral prednisolone 40 mg/day tapered to 0 mg at week 6. The primary end point was steroid-free clinical remission [DAI ≤ 2] at week 12. Clinical response was also analysed. Results Twenty-four patients were enrolled, 13 of whom were randomized into group A and 11 into group P. Clinical remission off steroids at week 12 was achieved in 3/12 patients [25.0%] with apheresis and 2/10 [20.0%] with prednisolone [p = 1.0]. The response rate after 12 weeks was 75.0% in group A and 50.0% in group P. Mean DAI scores improved in both treatment groups [p = 0.008]. C-reactive protein decreased from 6.0 ± 5.3 to 3.8 ± 3.7 mg/L at 12 weeks in group A and increased from 5.2 ± 6.0 to 6.3 ± 7.9 mg/mL in group P. Both treatments were well tolerated. No unexpected serious adverse events were seen in group A. In group P one symptomatic infection with Clostridium difficile occurred. Conclusions In patients with active UC refractory to mesalazine a novel leukocyte apheresis showed promising results. A comparison with prednisolone revealed similar therapeutic effectivity and excellent safety, providing the chance to escalate without systemic steroids.

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Anti-inflammatory Bifidobacterium strains prevent dextran sodium sulfate induced colitis and associated gut microbial dysbiosis in mice

Scientific Reports ◽

10.1038/s41598-020-75702-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Shashank Singh ◽

Ruchika Bhatia ◽

Pragyanshu Khare ◽

Shikha Sharma ◽

Sivasubramanian Rajarammohan ◽

...

Keyword(s):

Ulcerative Colitis ◽

Sodium Sulfate ◽

Activity Index ◽

Disease Activity Index ◽

Dextran Sodium Sulfate ◽

Raw 264.7 Cells ◽

Spleen Weight ◽

Lipocalin 2 ◽

Weight Percentage ◽

Microbial Dysbiosis

Abstract Crohn’s and ulcerative colitis are common inflammatory conditions associated with Inflammatory bowel disease. Owing to the importance of diet based approaches for the prevention of inflammatory gut conditions, the present study was aimed to screen the human isolates of Bifidobacterium strains based on their ability to reduce LPS-induced inflammation in murine macrophage (RAW 264.7) cells and to evaluate prioritized strains for their preventive efficacy against ulcerative colitis in mice. Twelve out of 25 isolated strains reduced the production of LPS-induced nitric oxide and inflammatory cytokines. Furthermore, three strains, B. longum Bif10, B. breve Bif11, and B. longum Bif16 conferred protection against dextran sodium sulfate induced colitis in mice. The three strains prevented shortening of colon, spleen weight, percentage body weight change and disease activity index relative to colitis mice. Lower levels of Lipocalin-2, TNF-α, IL-1β and IL-6 and improved SCFA levels were observed in Bifidobacterium supplemented mice relative to DSS counterparts. Bacterial composition of B. longum Bif10 and B. breve Bif11 fed mice was partly similar to the normal mice, while DSS and B. longum Bif16 supplemented mice showed deleterious alterations. At the genus level, Bifidobacterium supplementation inhibited the abundances of pathobionts such as Haemophilus, Klebsiella and Lachnospira there by conferring protection.

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POSITIVE CORRELATION BETWEEN DISEASE ACTIVITY INDEX AND MATRIX METALLOPROTEINASES ACTIVITY IN A RAT MODEL OF COLITIS

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032014000200007 ◽

2014 ◽

Vol 51 (2) ◽

pp. 107-112 ◽

Cited By ~ 8

Author(s):

Luiz Gustavo de OLIVEIRA ◽

André Luiz da CUNHA ◽

Amaury Caiafa DUARTE ◽

Maria Christina Marques Nogueira CASTAÑON ◽

Júlio Maria Fonseca CHEBLI ◽

...

Keyword(s):

Ulcerative Colitis ◽

Disease Activity ◽

Dextran Sulfate ◽

Tissue Injury ◽

Activity Index ◽

Disease Activity Index ◽

Blue Staining ◽

Control Group ◽

Alcian Blue Staining ◽

Increased Activity

ContextInflammatory bowel disease, including ulcerative colitis and Crohn’s disease, comprising a broad spectrum of diseases those have in common chronic inflammation of the gastrointestinal tract, histological alterations and an increased activity levels of certain enzymes, such as, metalloproteinases.ObjectivesEvaluate a possible correlation of disease activity index with the severity of colonic mucosal damage and increased activity of metalloproteinases in a model of ulcerative colitis induced by dextran sulfate sodium.MethodsColitis was induced by oral administration of 5% dextran sulfate sodium for seven days in this group (n=10), whereas control group (n=16) received water. Effects were analyzed daily by disease activity index. In the seventh day, animals were euthanized and hematological measurements, histological changes (hematoxylin and eosin and Alcian Blue staining), myeloperoxidase and metalloproteinase activities (MMP-2 and MMP-9) were determined.ResultsDextran sulfate sodium group showed elevated disease activity index and reduced hematological parameters. Induction of colitis caused tissue injury with loss of mucin and increased myeloperoxidase (P<0.001) and MMP-9 activities (45 fold) compared to the control group.ConclusionsIn this study, we observed a disease activity index correlation with the degree of histopathological changes after induction of colitis, and this result may be related mainly to the increased activity of MMP-9 and mieloperoxidase.

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