A Combination of Chitosan, Cellulose, and Seaweed Polysaccharide Inhibits Postoperative Intra-abdominal Adhesion in Rats

Abstract

Intra-abdominal adhesion is a common complication after laparotomy. Conventional therapeutic strategies still cannot safely and effectively prevent this disorder. In this study, a combination of chitosan, cellulose, and seaweed polysaccharide (thereafter referred as CCS) was developed to significantly alleviate the formation of postoperative adhesion in rats with abdominal trauma. Transforming growth factor 1 (TGF-1, an important promoter of fibrosis) and its downstream factors-namely, alpha-smooth muscle actin and plasminogen activator inhibitor-1 (PAI-1)-were effectively suppressed by CCS in vivo, and as a result, the activation of tissue plasminogen activator (tPA, may generate plasmin that is a fibrinolytic factor capable of breaking down fibrin) was significantly promoted, presenting antifibrosis effects of CCS. In addition, the activity of kinases [e.g., transforming growth factor-activated kinase 1 (TAK1), c-Jun N-terminal kinase (JNK)/Stress-activated Protein Kinase (SAPK), and p38] in the mitogen-activated protein kinase (MAPK) inflammation signaling pathway was also significantly suppressed by CCS in vivo, demonstrating anti-inflammatory functions of CCS. The histologic studies further confirmed the role of CCS in the inhibition of fibrosis, collagen deposition, inflammation, and vascular proliferation. These results indicate the clinical potential of CCS in the treatment of postoperative intra-abdominal adhesion. CCS may induce both antifibrosis and anti-inflammatory effects, potentially inhibiting the postoperative intra-abdominal adhesion. For antifibrosis effects, the expression of PAI-1 (a key factor for the adhesion formation) can be regulated by different TGF-1-associated signaling pathways, such as the Smads/p53 pathway, metalloproteinase/tissue inhibitor of matrix metalloproteinases pathway, Mitogen-activated Extracellular signal-regulated Kinase (MEK)/extracellular regulated protein kinase (ERK) pathway, and Yes-associated protein/transcriptional coactivator with PDZ-binding motif pathway. Following the downregulation of PAI-1 achieved by CCS, the activation of tPA (which may generate plasmin that is a fibrinolytic factor capable of breaking down fibrin) is significantly promoted. For anti-inflammation effects, CCS may suppress the phosphorylation of classic kinases (e.g., TAK1, JNK, and p38) in the MAPK signaling pathway. In addition to the MAPK pathway, inflammatory pathways, such as Nuclear Factor-κ-gene Binding(NF-κB), MEK/ERK, and Ras homologue protein/Rho associated coiled coil forming protein, are associated with the formation of intra-abdominal adhesion. Therefore, the prevention mechanisms of CCS will be further investigated in the future, with a hope of fully understanding of antiadhesion effects.

Indomethacin Sustained-Release Anti-adhesion Membrane Composed of a Phospholipid and Polycaprolactone Blend

“…The anti-adhesion effect of sustained-release in-domethacin membrane composed of a phospholipid and PCL blend was investigated in vivo by creating defects in both the cecum and peritoneum of rats. At the early stage after tissue injury, various proinflammatory mediators (e.g., TNF-α, TGF-β, IL-1, and IL-6) are released at the damaged peritoneum, and inflammatory responses promote tissue fibrosis (37,38). Insufficient fibrinolysis in traumatized sites results in the deposition of extracellular matrix components and the formation of fibrinogen-rich adhesion tissue (1).…”

Subacute feeding toxicity of low‐sodium sausages manufactured with sodium substitutes and biopolymer‐encapsulated saltwort (Salicornia herbacea) in a mouse model

“…Additionally, biopolymers are shown to have antifibrotic and anti‐inflammatory effects. Tian et al . reported that chitosan, cellulose, and seaweed polysaccharide not only suppressed TGF‐B1 (an important promoter of fibrosis) and its downstream factors but also suppressed TAK1, JNK, SAPK, and MAPK inflammation signaling pathways.…”

“…[60][61][62][63][64][65][66][67][68][69][70][71][72][73] Additionally, biopolymers are shown to have antifibrotic and anti-inflammatory effects. Tian et al 74 reported that chitosan, cellulose, and seaweed polysaccharide not only suppressed TGF-B1 (an important promoter of fibrosis) and its downstream factors but also suppressed TAK1, JNK, SAPK, and MAPK inflammation signaling pathways. These studies prove that biopolymers are safe and can be applied in low-sodium sausage manufacturing.…”

Prevention of Post-Operative Adhesions: A Comprehensive Review of Present and Emerging Strategies

“…Chitosan-containing barriers are available as a film, gel, or combined with cellulose and seaweed polysaccharides. Several studies demonstrate that chitosan-based products decreased coverage and severity of adhesions in rabbit, porcine, and murine models in cardiac, abdominal, and gynecological surgeries [292][293][294][295][296][297][298][299]. To our knowledge, chitosan itself is yet to be employed in clinical use in humans.…”