BACKGROUND: The purpose of this study was to evaluate the in vivo efficacy of 13 compounds and to further characterize the load limiting and potential toxicity of the most efficacious compound. The cascade of biochemical and molecular events that results in the formation of postsurgical adhesions provides numerous theoretical opportunities for prophylactic intervention. METHODS: Candidate agents were loaded into sodium hyaluronate (HA) films and administered to male Sprague-Dawley rats using a cecal-sidewall model of surgical adhesions. An adhesion score was obtained for each rat based on the strength and extent of the adhesions. The most efficacious agent, fucoidan, was further evaluated in a load-limiting study with a concentration range of 0.0033 to 33% w/w per film. The potential toxicity of fucoidan was evaluated in a separate study by comparison of hematology findings, blood chemistry, urinalysis, and incision thickness from rats administered control films or 33% w/w fucoidan films 1 to 4 d prior to sacrifice. RESULTS: Fucoidan loaded films reduced adhesion scores by approximately 90% compared with control films (P<0.05). A total of 50% to 100% of animals were adhesion free at fucoidan film loadings of 0.33% to 33% w/w compared with all control film animals having adhesions. No adverse effects were observed from 33% w/w fucoidan films equivalent to approximately 30 mg fucoidan/kg body weight. CONCLUSIONS: Local administration of fucoidan film during rat cecal-sidewall surgery safely reduced adhesion scores by approximately 90% and resulted in 50% to 100% of animals being adhesion free.
BACKGROUND: The purpose of this study was to evaluate the in vivo efficacy of 13 compounds and to further characterize the load limiting and potential toxicity of the most efficacious compound. The cascade of biochemical and molecular events that results in the formation of postsurgical adhesions provides numerous theoretical opportunities for prophylactic intervention. METHODS: Candidate agents were loaded into sodium hyaluronate (HA) films and administered to male Sprague-Dawley rats using a cecal-sidewall model of surgical adhesions. An adhesion score was obtained for each rat based on the strength and extent of the adhesions. The most efficacious agent, fucoidan, was further evaluated in a load-limiting study with a concentration range of 0.0033 to 33% w/w per film. The potential toxicity of fucoidan was evaluated in a separate study by comparison of hematology findings, blood chemistry, urinalysis, and incision thickness from rats administered control films or 33% w/w fucoidan films 1 to 4 d prior to sacrifice. RESULTS:Fucoidan loaded films reduced adhesion scores by approximately 90% compared with control films (P<0.05). A total of 50% to 100% of animals were adhesion free at fucoidan film loadings of 0.33% to 33% w/w compared with all control film animals having adhesions. No adverse effects were observed from 33% w/w fucoidan films equivalent to approximately 30 mg fucoidan/kg body weight. CONCLUSIONS: Local administration of fucoidan film during rat cecal-sidewall surgery safely reduced adhesion scores by approximately 90% and resulted in 50% to 100% of animals being adhesion free.
Authors: Juliana de Moura Alonso; Ana Liz Garcia Alves; Marcos Jun Watanabe; Celso Antonio Rodrigues; Carlos Alberto Hussni Journal: Vet Med Int Date: 2014-01-20