Avaliação do efeito analgésico e anti inflamatório do ambroxol em modelo experimental de osteoartrite em rato

Abstract

Ambroxol is a mucolytic agent widely used in the treatment of respiratory diseases; however, Ambroxol is a mucolytic agent widely used in the treatment of respiratory diseases. However, evidence from the literature has demonstrated its anti-inflammatory, analgesic, and immunomodulatory properties, suggesting its potential for drug repurposing. In this context, this thesis integrated a systematic review and an experimental study to investigate the mechanisms of action and therapeutic effects of ambroxol in experimental models of non pulmonary diseases, with an emphasis on osteoarthritis (OA). Initially, a systematic review was conducted, registered in the Open Science Framework (OSF), following the PICO strategy and PRISMA guidelines, with searches performed in the PubMed/MEDLINE, Embase, and Scopus databases. Of the 353 studies identified, eight met the eligibility criteria. The review demonstrated that ambroxol exerts anti-inflammatory, antioxidant, and antinociceptive effects in different non-pulmonary experimental models by reducing pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), increasing the activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione), decreasing oxidative stress, improving histopathological changes, and attenuating pain through mechanisms related, among others, to the blockade of voltage-gated sodium channels, thereby reinforcing its potential for drug repurposing. Subsequently, an experimental study was conducted to evaluate the antinociceptive and anti inflammatory effects of ambroxol in an experimental model of osteoarthritis. Adult male Wistar rats underwent OA induction on day zero (D0) by intra-articular injection of monosodium iodoacetate (MIA) and were allocated into the following groups: Healthy, Negative Control (CTRL−), Meloxicam (2 mg/kg), and Ambroxol (10, 50, and 100 mg/kg). Treatments were administered orally by gavage once daily for 28 days. Behavioral assessments included the Rotarod test, Gait Analysis, Weight Bearing test, Von Frey test, and Rat Grimace Scale, in addition to radiographic and histopathological evaluations and quantification of pro- and anti inflammatory cytokines (IL-1β, IL-6, and IL-10). Ambroxol treatment significantly improved nociceptive parameters and motor function, while reducing radiographic and histopathological scores, showing performance comparable to meloxicam in several outcomes. Marked reductions in IL-1β and IL-6 levels were observed, whereas IL-10 levels were lower in the ambroxol-treated groups, suggesting an earlier resolution of the inflammatory response. Taken together, the findings from the systematic review and the experimental study demonstrate that ambroxol exhibits consistent anti-inflammatory, antioxidant, and antinociceptive properties, in addition to attenuating structural joint damage associated with osteoarthritis. These findings reinforce the potential of ambroxol as a candidate for drug repurposing in osteoarthritis. Further studies are required to better elucidate its mechanisms of action, establish the optimal dosage regimen and treatment duration, and support the translation of these findings into clinical studies.