Combined Treatment with Hyaluronic Acid and Mesalamine Protects Rats from Inflammatory Bowel Disease Induced by Intracolonic Administration of Trinitrobenzenesulfonic Acid

Abstract

Drugs such as mesalamine (5-ASA) are currently recommended for the treatment of inflammatory bowel disease (IBD). To reduce the frequency of their administration and improve their therapeutic effect, this study investigated the adhesion efficacy, wound healing promotion, and decrease in inflammation in ulcers in the colonic tissue of rats with colitis after combined treatment with hyaluronic acid (HA) and 5-ASA (IBD98-M). HA-fluoresceinamine (FL) conjugates successfully adhered to the mucosal layer and were conjugated in the vascular tissue. In addition, macroscopic and microscopic observations indicated that colonic injuries reduced significantly after treatment with IBD98-M. Compared with PBS and 5-ASA treatment alone, treatment with IBD98-M more effectively reduced bowel inflammation and promoted colonic mucosal healing in TNBS-induced colitis. IBD98-M treatment also reduced myeloperoxidase activity and the expression levels of cyclooxygenase 2 and tumor necrosis factor-αin the colitis tissue. In conclusion, IBD98-M treatment strongly promoted wound healing in colonic injuries and significantly inhibited MPO activity in the inflamed colon tissue of rats. Combined treatment with HA and 5-ASA can accelerate wound healing and reduce inflammatory reaction in rat colitis.

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

“…It is known that A2A is not only present on the surface of fibroblast and epithelial cells, but also on T cells and monocytes suppressing the production of specific inflammatory cytokines as IL-12, TNF-α, and IFN-γ [ 7 ]. Moreover, our results confirmed the protective effect of HA in IBD in agreement with preclinical and clinical studies previously published [ 11 , 39 , 40 ]. Additionally, the data obtained in this study support the hypothesis that this combination might be considered as a new approach since the administration of Poly + HA promoted both intestinal re-epithelization and mucosa healing during ulcerative colitis.…”

“…Moreover, HA has an important role in reducing inflammatory responses through activation of CD44 pathways that promote the Rac-signaling cascade with improvements in DNA repair and survival function [ 47 ]. Furthermore, CD44 plays a role in cell migration and modulation of CD44–HA binding and may have profound effects on immune cell recruitment and aid in wound repair [ 11 ]. All this evidence corroborates the present findings and supports the usefulness of the Poly + HA combination.…”

“…HA has numerous wound-healing properties; in particular, it stimulates cell motility through two cell surface receptors: cluster of differentiation 44 (CD44) and hyaluronan-mediated motility receptors (RHAMM). Currently, the binding to CD44 appears to be the one that most likely directly activates intracellular signals required to stimulate processes relevant to angiogenesis [ 11 ]. Moreover, during IBD, endothelial cells display an activated phenotype and are known to express high levels of CD44 that appear to have a pivotal role for immune cell (such as monocytes, macrophages, neutrophils and lymphocytes) recruitment into inflamed tissues [ 12 ].…”

Evaluation of a Methylcellulose and Hyaluronic Acid Hydrogel as a Vehicle for Rectal Delivery of Biologics

“…Therefore, this property has the advantages of liquid enema enabling more proximal delivery, but addresses retention issues associated with liquids [6]. Additional potential advantages of the MCHA hydrogel for rectal administration in IBD include the wound-healing properties of HA [30], as demonstrated by a recent study where it promoted colonic mucosal healing in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis when administered rectally in a combination with 5-ASA (HA and 5-ASA combination was more effective than 5-ASA alone) [31]. Furthermore, HA has mucoadhesive properties [24], particularly to the injured mucosa; fluorescently-labeled HA conjugates were shown to adhere on injured colon more strongly than to normal tissue [31].…”

“…Additional potential advantages of the MCHA hydrogel for rectal administration in IBD include the wound-healing properties of HA [30], as demonstrated by a recent study where it promoted colonic mucosal healing in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis when administered rectally in a combination with 5-ASA (HA and 5-ASA combination was more effective than 5-ASA alone) [31]. Furthermore, HA has mucoadhesive properties [24], particularly to the injured mucosa; fluorescently-labeled HA conjugates were shown to adhere on injured colon more strongly than to normal tissue [31]. Although the mucoadhesive and inflammation-targeting properties of MCHA hydrogel were not studied in the present work, the MCHA hydrogel could show these beneficial properties which would facilitate its function as a vehicle for local delivery of biologics.…”