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Open Access Research

The antiprotozoal drug pentamidine ameliorates experimentally induced acute colitis in mice

Giuseppe Esposito1*, Elena Capoccia1, Giovanni Sarnelli2, Caterina Scuderi1, Carla Cirillo23, Rosario Cuomo2 and Luca Steardo1

Author Affiliations

1 Department of Physiology and Pharmacology ‘Vittorio Erspamer’, University SAPIENZA of Rome, P. le Aldo Moro 5, 00185, Rome, Italy

2 Department of Clinical and Experimental Medicine, University of Naples FEDERICO II, Via S. Pansini 5, 80131, Naples, Italy

3 Current address: Laboratory for Enteric NeuroScience (LENS), TARGID, KU Leuven, Herestraat 49, 3000, Leuven, Belgium

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Journal of Neuroinflammation 2012, 9:277  doi:10.1186/1742-2094-9-277

Published: 23 December 2012

Abstract

Background

Intestinal 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.

Methods

Mice 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.

Results

Pentamidine 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.

Conclusions

Pentamidine 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.

Keywords:
Pentamidine; Acute colitis; S100B protein; Enteric glia