Atividade analgésica e anti-inflamatória do ambroxol no tratamento da endometriose: estudo experimental com ratas Wistar

Abstract

Endometriosis is a chronic inflammatory gynecological disease frequently associated with pelvic pain, infertility, and a significant impact on patients’ quality of life. Despite therapeutic advances, currently available treatments have limitations related to clinical response, symptom recurrence, and adverse effects, highlighting the need for new pharmacological approaches. Structured into two complementary chapters, this thesis aimed to investigate the therapeutic potential of ambroxol in endometriosis by integrating evidence from a bibliometric review and an original experimental study. Initially, a bibliometric analysis of the literature on the pharmacological activities of ambroxol in experimental models was conducted using the Web of Science and Scopus databases. Twenty-four studies published between 1994 and 2023 were included, with the main research areas comprising Medicine (33.3%), Pharmacology (30.6%), Biochemistry (16.7%), and Neuroscience (11.1%). Subsequently, an experimental study was conducted using an animal model of endometriosis, in which ambroxol was orally administered at doses of 10, 50, and 100 mg/kg/day for 21 days. Behavioral parameters of spontaneous pain, mechanical sensitivity, and motor performance were assessed using the Rat Grimace Scale, von Frey test, and rotarod test, respectively. Serum IL-1β levels, peritoneal inflammatory response, endometriotic implant volume, and epithelial integrity were also evaluated. Ambroxol reduced spontaneous pain manifestations and increased the mechanical withdrawal threshold during treatment, while motor performance was preserved. On day 21, serum IL-1β levels were 56.48, 5.01, and 47.65 pg/mL in the groups treated with ambroxol at 10, 50, and 100 mg/kg, respectively, compared with 178.96 pg/mL in the negative control group, with significant reductions in all treated groups. A reduction in the peritoneal inflammatory response was also observed. The 50 and 100 mg/kg doses reduced endometriotic implant volume and promoted histopathological changes characterized by decreased epithelial integrity. Taken together, the findings of this thesis demonstrate analgesic, anti-inflammatory, and structural effects of ambroxol in an experimental model of endometriosis and provide preclinical evidence supporting further investigation of its therapeutic potential in this condition.