title: Anti-inflammatory effects of novel AP-1 and NF-κB inhibitors in dextran-sulfate-sodium-induced colitis in rats.
abstract: The aim of the present study was to elucidate the anti-inflammatory effects of the two novel anti-inflammatory substances, 3-[(dodecylthiocarbonyl)‑methyl]-glutarimide (DTCM-G) and dehydroxymethylepoxyquinomicin (DHMEQ), on DSS-induced colitis in rats. For this purpose, rats with dextran sulfate sodium (DSS)-induced colitis were randomly divided into 3 groups with 10 animals in each group as follows: i) the control group, which received 0.5 ml of 0.5% carboxymethyl cellulose (CMC; vehicle), ii) rats that received DTCM-G (20 mg/kg body weight in 0.5% CMC; the DTCM-G group), and iii) rats that received DHMEQ (15 mg/kg body weight in 0.5% CMC; the DHMEQ group). The animals were sacrificed after the 5-day treatment period, and tissue samples were taken from their colons and sectioned for histological evaluation. The tissue sections were stained with hematoxylin and eosin, and immunostained for leukocytes, lymphocytes, macrophages/monocytes and mast cells. The disease activity index (DAI), histological grading of colitis, and densities of several types of submucosal immune cells were compared between the controls, and the DTCM-G and DHMEQ groups. The DAI values were significantly lower in both the DTCM-G and DHMEQ groups than in the control group. The total scores for the histological grading of colitis were also significantly lower in the DTCM-G and DHMEQ groups than in the control group. The submucosal densities of leucocytes, lymphocytes, macrophages/monocytes and mast cells were significantly lower in the DTCM-G and DHMEQ groups than in the control group. Our findings indicate that the anti-inflammatory and anticancer effects of DTCM-G and DHMEQ, and the absence of any associated toxicity render them excellent therapeutic candidates for clinical use in the treatment of colitis.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Stord Helse-Fonna Hospital, 5416 Stord, Norway.
authors.forename: Magdy
authors.initials: M
authors.lastname: El-Salhy
authors.affiliation: Department of Molecular Target Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D003512:Cyclohexanones / Q000494:pharmacology*; D016264:Dextran Sulfate; D005786:Gene Expression Regulation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D010881:Piperidones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome
chemical_list: C573776:3-((dodecylthiocarbonyl)methyl)glutarimide; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001549:Benzamides; D003512:Cyclohexanones; D016328:NF-kappa B; D010881:Piperidones; D018808:Transcription Factor AP-1; C464444:dehydroxymethylepoxyquinomicin; D016264:Dextran Sulfate; D002266:Carboxymethylcellulose Sodium