title: Amelioration of severe TNBS induced colitis by novel AP-1 and NF- κ B inhibitors in rats.
abstract: AP-1 and NF-κ B inhibitors, namely, DTCM-G and DHMEQ, were investigated in male Wistar rats with severe colitis, induced by TNBS. The animals were randomized into 3 groups. The control group received 0.5 mL of 0.5% of the vehicle i.p., the DTCM-G group received 22.5 mg/kg body weight DTCM-G in 0.5% i.p., and the DHMEQ group received 15 mg/kg body weight DHMEQ i.p., all twice daily for 5 days. The body weight losses and mortality rates were significantly higher in the control group than those in DTCM-G-treated and DHMEQ-treated groups. The endoscopic inflammation scores in the control, DTCM-G-treated, and DHMEQ-treated groups were 6.3 ± 0.7, 1.0 ± 0.3, and 0.7 ± 0.3, respectively (P = 0.004 and 0.02, resp.). The inflammation scores as assessed by the macroscopic appearance were 4.3 ± 0.8, 0.7 ± 0.3, and 1.2 ± 0.4 in the control, DTCM-G-treated, and DHMEQ-treated groups, respectively (P = 0.01 and 0.009, resp.). The histopathological inflammation scores were 6.4 ± 0.7, 2.0 ± 1.0, and 2.2 ± 0.6 in the control, DTCM-G-treated, and DHMEQ-treated groups, respectively (P = 0.03 and 0.01, resp.). It was concluded that DTCM-G and DHMEQ exhibit strong anti-inflammatory and anticancer activities with no apparent toxicity, which make them excellent drug candidates for clinical use in inflammatory bowel diseases.
authors.affiliation: Section for Gastroenterology, Department of Medicine, Stord Helse-Fonna Hospital, P.O Box 4000, 54 09 Stord, Norway ; Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, P.O Box 7800, 5020 Bergen, Norway.
authors.forename: Magdy
authors.identifier: 0000-0003-3398-3288
authors.initials: M
authors.lastname: El-Salhy
authors.affiliation: Department of Molecular Target Medicine Screening, School of Medicine, Aichi Medical University, 1-1 Yazakokarimata, Aichi Nagakute, Aichi, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.affiliation: Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, P.O Box 7800, 5020 Bergen, Norway.
authors.forename: Odd Helge
authors.identifier: 0000-0002-0436-0383
authors.initials: OH
authors.lastname: Gilja
authors.affiliation: Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, P.O Box 7800, 5020 Bergen, Norway.
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hatlebakk
authors.affiliation: Department of Research, Helse-Fonna, Karmsundsgt. 120, 5528 Haugesund, Norway.
authors.forename: Doris
authors.initials: D
authors.lastname: Gundersen
authors.affiliation: Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, P.O Box 7800, 5020 Bergen, Norway.
authors.forename: Trygve
authors.initials: T
authors.lastname: Hausken
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*
chemical_list: D016328:NF-kappa B; D018808:Transcription Factor AP-1