Administração de naltrexona em alta dose apresenta efeito cicatrizante e anti-inflamatório em úlceras traumáticas orais na mucosa jugal de ratos wistar

Abstract

Naltrexone is studied for its effect on immune response modulation and cell proliferation, being able to improve the healing process, the therapeutic action of Naltrexone varies depending on the dose. This study aims to evaluate the influence of different doses (high, standard and low) of naltrexone administration on the time period of healing in traumatic ulcers oral mucosa of Wistar rats. One hundred and twelve animals were divided into a control group under distilled water by gavage administration, and three experimental groups under naltrexone 0.5, 10, and 50mg/kg/day administration. Ulcer was induced with a dermatological punch. On days 1, 3, 7 and 14 after induction, clinical ulcer diameter, weight variation, histological healing scores, histomorphometric analysis (polymorphonuclear count, mononuclear count, and fibroblasts/myofibroblasts count), assessment of collagen deposition (Picrosiruis Red stain), nociceptive animal response (Von Frey test), and adverse drug reactions (abdominal pain, stool evaluation, and feed intake) was evaluated. For all analysis, statistical software GraphPad Prism 5.0® was used, considering the significance level p<0.05. Animals had a significant smaller ulcer diameter than the control group on day 1 when treated with doses of 10 and 50mg/kg/day (p<0.001); and on day 3 (p<0.05) and 14 (p<0.01) when treated with 50mg/kg/day naltrexone. This dose also reduced the number of polymorphonuclear cells on the first day (p<0.05), mononuclear cells on the third day (p<0.05), and increased fibroblasts (p<0.001) and the percentage of total collagen (p<0.05) on seventh and fourteenth days, respectively. Furthermore, nociceptive response (ipsilateral and contralateral to the ulcer) was significantly lower in animals treated with naltrexone 50mg/kg/day (p<0.01) over the whole period of 14 days. At evaluated doses, no significant adverse reactions were observed. Naltrexone standard dose (50mg/kg/day) improves the time period of healing in traumatic oral ulcers by reducing the inflammatory response and promoting collagen synthesis. In addition, it decreases animals’ nociceptive response.