title: Effects of mimic of manganese superoxide dismutase on 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats.
abstract: The mimic of manganese superoxide dismutase (MnSODm) has been synthesized and reported to have anti-inflammatory properties. However, whether MnSODm has anti-inflammatory effects on colitis and any underlying mechanisms are poorly understood. This study was to investigate therapeutic effects and mechanism of MnSODm on 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced colitis model in rats. Rats were intragastrically administered MnSODm (10, 20, and 40 mg/kg) per day for 7 days after colitis was induced by TNBS. After treated with MnSODm, the colonic macroscopic and microscopic damage scores and colonic weight/length ratios were significantly decreased compared with colitis model group. Myeloperoxidase (MPO) activity, malonyldialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 levels in colon tissues were also significantly decreased in MnSODm treatment groups. However, superoxide dismutase (SOD) activity significantly increased and phosphorylated inhibitory kappa B-alpha (IκBα), inhibitor kappa B kinase (IKKα/β), and nuclear factor-kappa Bp65 (NF-κBp65) as well as Toll-like receptor 4 (TLR4) and myeloid differentiation actor 88 (MyD88) in the colonic mucosa were significantly inhibited by MnSODm treatment. Thus, MnSODm was protective against colitis via antioxidant activity and by inhibiting inflammatory mediators by down-regulating TLR4/MyD88/NF-κB signaling pathways. These data suggest a potential therapeutic effect of MnSODm in colitis.
authors: Department of Pharmacy, Gansu Provincial Hospital, No. 204 Donggangxi Road, Lanzhou, 730000, Gansu, China.
authors: Yan-Hong
authors: YH
authors: Wang
authors: Outpatient Department of Xiaoxitian, 309 Hospital of the Chinese PLA, Agency for Offices Administration of the Central Military Commission, Beijing, 100082, China.
authors: Jiao
authors: J
authors: Dong
authors: Department of Pharmacy, Gansu Provincial Hospital, No. 204 Donggangxi Road, Lanzhou, 730000, Gansu, China.
authors: Jian-Xin
authors: JX
authors: Zhang
authors: Department of Pharmacy, Gansu Provincial Hospital, No. 204 Donggangxi Road, Lanzhou, 730000, Gansu, China.
authors: Jing
authors: J
authors: Zhai
authors: Department of Pharmacy, Gansu Provincial Hospital, No. 204 Donggangxi Road, Lanzhou, 730000, Gansu, China. gjy0630@126.com.
authors: Bin
authors: B
authors: Ge
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003092:Colitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018716:Molecular Mimicry; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity*
chemical_list: D014302:Trinitrobenzenesulfonic Acid; D013482:Superoxide Dismutase
keywords: 2,4,6-trinitrobenzenesulfonic acid; Anti-inflammatory; Colitis; Mimic of manganese superoxide dismutase; Nuclear factor-kappa B; TLR4