Avaliação da mesalazina incorporada a polímero biodegradável no tratamento da retite actínica em ratos por meio de modelo alternativo de irradiação gama

Abstract

INTRODUCTION: Radiotherapy is essential for the treatment of pelvic tumors; nonetheless it can induce actinic proctitis, an irreversible damage to the rectum that can be acute or chronic. One of the options of treatment for such condition is mesalazine, although with doubtful results in the literature. A new formulation of mesalazine linked to chondroitin sulfate (what increases the release time of the drug and enables reduction of the dose) was recently published. OBJECTIVE: The present study aimed at testing this new drug and its components alone in the treatment of actinic proctitis in rats. METHODOLOGY: Forty-seven female Wistar rats were submitted to pelvic radiation and divided into eight groups: Control A: placebo gavage two weeks after irradiation and sacrifice three weeks after oral treatment; Mesalazine A: mesalazine gavage and sacrifice the same manner; Chondroitin A: chondroitin gavage and sacrifice the same manner; Conjugate A: mesalazine polymeric conjugate gavage and sacrifice the same manner; Control C, Mesalazine C, Chondroitin C and Conjugate C: gavage the same way as for the A groups but sacrifice six weeks after oral treatment. After sacrifice, the rectum was submitted to histological characterization for each of the findings: inflammatory infiltrate in the lamina propria, epithelial degeneration, mucosal necrosis and collagen deposition to the lamina propria.RESULTS: The inflammatory infiltrate was more intense in the Chondroitin A group (p=0,002) and Mesalazine A group (p=0,01) compared to the Control A group; and was also more intense in the Conjugate C group compared to the Control C group (p=0,002), the Chondroitin C group (p=0,002) and the Mesalazine C group (p=0,01). The collagen deposition was less intense in the Chondroitin A group (p=0,002) and Mesalazine A group (p=0,01) compared to the Control A group; and was more intense in the Control C group compared to the Chondroitin C group (p=0,01) and Mesalazine C group (p=0,002).CONCLUSION: Mesalazine was efficacious in inducing a delayed inflammatory response, hence reducing the late fibrosis. Chondroitin alone had the same result as mesalazine, what is a new unexpected finding. The conjugate was able to induce an ever more delayed inflammatory response.