Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Oct 20;8(10):438.
doi: 10.3390/biomedicines8100438.

Combined Treatment with Polynucleotides and Hyaluronic Acid Improves Tissue Repair in Experimental Colitis

Giovanni Pallio  1 , Alessandra Bitto  1 , Antonio Ieni  2 , Natasha Irrera  1 , Federica Mannino  1 , Socrate Pallio  1 , Domenica Altavilla  3 , Francesco Squadrito  1 , Carmelo Scarpignato  4   5 , Letteria Minutoli  1
Affiliations

Combined Treatment with Polynucleotides and Hyaluronic Acid Improves Tissue Repair in Experimental Colitis

Giovanni Pallio et al. Biomedicines. .

Abstract

Inflammatory bowel diseases (IBDs) are chronic conditions that can benefit from the combined treatment of adenosine receptor agonists and hyaluronic acid (HA), which, binding the CD44, has pro-survival effects. Therefore, this study investigated the effects of a mixture of polynucleotides and HA in an experimental model of dinitrobenzenesulfonic acid (DNBS)-induced colitis. A group of 40 rats received a single intra-colonic instillation of DNBS, and after 6 h, animals were randomized to receive daily: (i) saline solution; (ii) polynucleotides (Poly; 8 mg/kg); (iii) polynucleotides (8 mg/kg) plus hyaluronic acid (HA; 15 mg/kg); and (iv) hyaluronic acid (HA; 15 mg/kg). Rats in the control group (n = 10) received saline solution only. Seven days after induction, animals receiving Poly plus HA showed reduced clinical signs, weight loss and colon shortening, ameliorated macroscopic and histological damage, and apoptosis. Moreover, the combined treatment reduced the positivity in the colonic infiltrate of CD3 positive T cells, CD20 positive B cells and CD44. Furthermore, Poly plus HA reduced colonic myeloperoxidase activity and malondialdehyde, indicating a dampening of the inflammatory infiltrate and oxidation products. Our research demonstrated that a combined treatment of polynucleotides with hyaluronic acid had a protective effect in a model of ulcerative colitis, suggesting that this association deserves further attention for the treatment of IBDs.

Keywords: CD20; CD3; CD44; IBD; colitis; hyaluronic acid; polynucleotides.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Food intake and body weight evaluated during the experimental period. Values were obtained from 10 animals per group and are expressed as means and SD. Food intake (A) * p < 0.0001 vs. control group; # p < 0.0001 vs. dinitrobenzenesulfonic acid (DNBS) + Drug vehicle group. Weight loss (B) * p < 0.0001 vs. control group; # p < 0.0001 vs. DNBS + Drug vehicle group; ° p < 0.001 vs. DNBS + hyaluronic acid (HA); ^ p < 0.001 vs. DNBS + polynucleotides (Poly).
Figure 2
Figure 2
Macroscopic appearance of colon tissues (A) from Control (1), DNBS + Drug vehicle (2), DNBS + Poly (3), DNBS + HA (4), DNBS + Poly + HA (5). The graphs represent macroscopic damage scores (B) and colon length (C). Values were obtained from 10 animals per group and are expressed as the means and SD. * p < 0.0001 vs. control group; # p < 0.0001 vs. DNBS + Drug vehicle group; ° p < 0.001 vs. DNBS + HA; ^ p < 0.001 vs. DNBS + Poly.
Figure 3
Figure 3
Representative haematoxylin and eosin (H&E) images (original magnification 10×) of tissues derived from control (A), DNBS + Drug vehicle (B), DNBS + Poly (C), DNBS + Poly + HA (D). The graph in (E) represents the microscopic damage score. Values are expressed as the means and SD of 10 animals. * p < 0.0001 vs. control group; # p < 0.0001 vs. DNBS + Drug vehicle group. The blue arrow indicates mucosal ulceration; the red arrow indicates granulation tissue; the arrow head indicates pseudopolyps.
Figure 4
Figure 4
Representative CD3 immunostaining (original magnification ×20) of tissues derived from control (A), DNBS + Drug vehicle (B), DNBS + Poly (C), and DNBS + Poly + HA (D).
Figure 5
Figure 5
Representative CD20 immunostaining (original magnification ×20) of tissues derived from control (A), DNBS + Drug vehicle (B), DNBS + Poly (C), and DNBS + Poly + HA (D).
Figure 6
Figure 6
Representative CD44 immunostaining (original magnification ×20) of tissues derived from control (A), DNBS + Drug vehicle (B), DNBS + Poly (C), and DNBS + Poly + HA (D).
Figure 7
Figure 7
Representative Bcl-2 immunostaining (original magnification ×40) of tissues derived from control (A), DNBS + Drug vehicle (B), DNBS + Poly (C), and DNBS + Poly + HA (D).
Figure 8
Figure 8
The effects of treatments on malondialdehyde levels and myeloperoxidase activity in DNBS-treated animals are shown in (A,B). All values are expressed as means and SD based on observations made on 10 animals per group. * p < 0.0001 vs. control group; # p < 0.0001 vs. DNBS + Drug vehicle group; ° p < 0.001 vs. DNBS + HA; ^ p < 0.001 vs. DNBS + Poly.
Figure 9
Figure 9
(A) Representative H&E images (original magnification ×10) (B) CD3, (C) CD20, (D) CD44 immunostaining (original magnification ×20) of tissues derived from the DNBS + HA group. The arrow indicates the regenerated area.
See this image and copyright information in PMC

References

    1. Podolsky D.K. Inflammatory bowel disease. N. Engl. J. Med. 2002;347:417–429. doi: 10.1056/NEJMra020831. - DOI - PubMed
    1. Baumgart D.C., Sandborn W.J. Inflammatory bowel disease: Clinical aspects and established and evolving therapies. Lancet. 2007;369:1641–1657. doi: 10.1016/S0140-6736(07)60751-X. - DOI - PubMed
    1. Pavlick K.P., Laroux F.S., Fuseler J., Wolf R.E., Gray L., Hoffman J., Grisham M.B. Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease. Free Radic. Biol. Med. 2002;33:311–322. doi: 10.1016/S0891-5849(02)00853-5. - DOI - PubMed
    1. Rahimian R., Fakhfouri G., Daneshmand A., Mohammadi H., Bahremand A., Rasouli M.R., Mousavizadeh K., Dehpour A.R. Adenosine A2A receptors and uric acid mediate protective effects of inosine against TNBS-induced colitis in rats. Eur. J. Pharmacol. 2010;649:376–381. doi: 10.1016/j.ejphar.2010.09.044. - DOI - PubMed
    1. Shaulian E., Karin M. AP-1 as a regulator of cell life and death. Nat. Cell Biol. 2012;4:131–136. doi: 10.1038/ncb0502-e131. - DOI - PubMed