The antiprotozoal drug pentamidine ameliorates experimentally induced acute colitis in miceReport as inadecuate




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Journal of Neuroinflammation

, 9:277

First Online: 23 December 2012Received: 26 September 2012Accepted: 19 November 2012

Abstract

BackgroundIntestinal inflammation is partly driven by enteroglial-derived S100B protein. The antiprotozoal drug pentamidine directly blocks S100B activity. We aimed to investigate the effect of pentamidine on intestinal inflammation using an animal model of dextran sodium sulphate DSS-induced acute colitis.

MethodsMice were divided into: control group, colitis group 4% DSS for four days and two pentamidine-treated colitis groups 0.8 mg-kg and 4 mg-kg. Anti-inflammatory effect of pentamidine was assessed in colonic tissue by evaluating the disease activity index and the severity of histological changes. Colonic tissue were also used to evaluate cyclooxigenase-2, inducible nitric oxide synthase, S100B, glial fibrillary acidic protein, phosphorylated-p38 MAPkinase, p50, p65 protein expression, malondyaldheyde production, mieloperoxidase activity, and macrophage infiltration. Nitric oxide, prostaglandin E2, interleukin-1 beta, tumor necrosis factor alpha, and S100B levels were detected in plasma samples. Parallel measurements were performed in vitro on dissected mucosa and longitudinal muscle myenteric plexus LMMP preparations after challenge with LPS + DSS or exogenous S100B protein in the presence or absence of pentamidine.

ResultsPentamidine treatment significantly ameliorated the severity of acute colitis in mice, as showed by macroscopic evaluation and histological-biochemical assays in colonic tissues and in plasma. Pentamidine effect on inflammatory mediators was almost completely abrogated in dissected mucosa but not in LMMP.

ConclusionsPentamidine exerts a marked anti-inflammatory effect in a mice model of acute colitis, likely targeting S100B activity. Pentamidine might be an innovative molecule to broaden pharmacological tools against colitis.

KeywordsPentamidine Acute colitis S100B protein Enteric glia AbbreviationsCOX2cyclooxigenase-2

DAIdisease activity index

DSSdextran sodium sulphate

EGCenteric glial cells

GFAPglial fibrillary acidic protein

IL-1βinterleukin-1 beta

iNOSinducible nitric oxide synthase

LMMPlongitudinal muscle-myenteric plexus

LPSlipopolysaccharide

MDAmalonyldialdehyde

MPOmieloperoxidase

NF-κBnuclear factor-kappaB

NOnitric oxide

PGE2prostaglandin E2

p-p38 MAPKphosphorylated-p38 MAPkinase

RAGEreceptor for advanced glycation end products

TNF-αtumor necrosis factor alpha

UCulcerative colitis.

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Author: Giuseppe Esposito - Elena Capoccia - Giovanni Sarnelli - Caterina Scuderi - Carla Cirillo - Rosario Cuomo - Luca Steardo

Source: https://link.springer.com/



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