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Preventive effects of guanosine on intestinal inflammation in 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats

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Abstract

Background

Guanosine, a guanine-based purine, is an extracellular signaling molecule exerting anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. We aimed to investigate its protective effects on 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rat.

Methods

Rats were divided into five groups and colitis was induced by intracolonic instillation of DNBS (15 mg/rat). Guanosine (4 or 8 mg/kg) was administered for 6 days i.p. starting the day of the colitis induction. Body weight loss, stool consistency, colon weight/length, histological analysis, myeloperoxidase activity (MPO) and pro-inflammatory cytokine levels were assessed. Immunoblotting of nuclear factor-κB (NF-κB) p65 protein levels and detection of oxidative and nitrosative stress markers were also performed.

Results

Guanosine, in a dose-dependent manner, significantly ameliorated the severity of DNBS-induced colitis, reducing body weight loss and diarrhea incidence, preventing the DNBS-induced macroscopic and microscopic damage to the colonic mucosa, and the MPO increase. Guanosine treatment also lowered interleukin-1β, interleukin-6, and tumor necrosis factor-α mRNA levels. Importantly, guanosine in DNBS rats down-regulated the expression of NF-κB p65 and the levels of reactive oxygen species and nitrite.

Conclusions

In conclusion, guanosine exerts beneficial effects in DNBS-induced colitis in rats, through modulation of colonic inflammation, downregulating of NFκB-mediated signaling.

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Funding

This work was supported by a grant (FFR 2012/2013) from the University of Palermo, Italy.

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Authors and Affiliations

  1. Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Laboratorio di Fisiologia generale, Università di Palermo, Viale delle Scienze, 90128, Palermo, Italy

    Maria Grazia Zizzo, Gaetano Caldara & Rosa Serio

  2. ATeN (Advanced Technologies Network) Center, Università di Palermo, Viale delle Scienze, 90128, Palermo, Italy

    Maria Grazia Zizzo & Annalisa Bellanca

  3. Istituto di Biomedicina ed Immunologia Molecolare (IBIM) “Alberto Monroy”, CNR, 90146, Palermo, Italy

    Domenico Nuzzo & Marta Di Carlo

Authors
  1. Maria Grazia Zizzo
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  2. Gaetano Caldara
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  3. Annalisa Bellanca
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  4. Domenico Nuzzo
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  5. Marta Di Carlo
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  6. Rosa Serio
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Contributions

All authors approved the final manuscript. MGZ designed the study, performed the experiments, analyzed as well as interpreted data, and prepared the manuscript. GC and AB performed the experiments, analyzed as well as interpreted data. DN and MDC contributed to biomolecular studies, interpreted data, and critically revised the manuscript. RS designed the study, supervised the interpretation of the data and the preparation of the manuscript.

Corresponding author

Correspondence to Maria Grazia Zizzo.

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Zizzo, M.G., Caldara, G., Bellanca, A. et al. Preventive effects of guanosine on intestinal inflammation in 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats. Inflammopharmacol 27, 349–359 (2019). https://doi.org/10.1007/s10787-018-0506-9

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  • DOI: https://doi.org/10.1007/s10787-018-0506-9

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