https://tedebc.ufma.br/jspui/handle/tede/1456 2026-08-10T23:27:17Z https://tedebc.ufma.br/jspui/handle/tede/7133 Título: Avaliação do efeito analgésico e anti inflamatório do ambroxol em modelo experimental de osteoartrite em rato Autor: MESQUITA, Micheline Joana Tenório Albuquerque Madruga Primeiro orientador: GARCIA, João Batista Santos 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. Instituição: Universidade Federal do Maranhão Tipo do documento: Tese 2026-07-08T00:00:00Z https://tedebc.ufma.br/jspui/handle/tede/6994 Título: Análise genômica e caracterização funcional de Limosilactobacillus fermentum JAC 231 como candidato a probiótico Autor: CAMPOS, Carmem Duarte Lima Primeiro orientador: MONTEIRO-NETO, Valerio Abstract: The genus Lactobacillus is composed of Gram-positive, catalase-negative, acid-tolerant, non- spore-forming, carbohydrate-fermenting bacteria. A recent reclassification of this genus led to a change in nomenclature, generating 23 new genera. The species Lactobacillus fermentum was renamed Limosilactobacillus fermentum. L. fermentum strains of occupy various niches, and in humans it is considered an indicator of a normal and healthy microbiota. Many strains have been investigated for their role in maintaining the epithelial barrier function, competitive exclusion, immunomodulatory activity and synthesis of antimicrobial substances (lactic acid, H2O2 and bacteriocins) with broad activity against pathogenic microorganisms, motivating their use as probiotics. In this sense, the characterization of probiotic activity and genome sequencing technologies have been important tools to obtain information about the metabolic and safety aspects of each strain, directing research towards its biotechnological and therapeutic use. This study aimed to sequence the complete genome of the vaginal isolate, L. fermentum JAC 231, analyzing general and safety aspects of the strain, investigating the genotypic and phenotypic bases for its probiotic potential, such as tolerance to diverse gastrointestinal conditions (bile salts, adhesion to mucin, adhesion to eukaryotic cells and pH), presence of resistance and virulence genes. Here we expand the characterization of the antimicrobial and anti-adhesion activity of this strain, evaluating its effect on Klebisiella pneumoneae ATCC 700603, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Salmonella enteritidis ATCC 13076, Enterococcus faecalis ATCC 29212 and enteropathogenic Escherichia coli O127:H6 E2348/69-EPEC. From the bioinformatics analysis, we identified that the genome contained 2.064.918 bp, with a GC content of 51.4%, presenting 1.993 protein-coding sequences related mainly to the metabolism of proteins, carbohydrates and amino acids. Comparative analysis revealed that L. fermentum JAC 231 shares 2.204 orthologous clusters with the other five probiotic strains of L. fermentum (MCC 2760, AGR 1485, ATCC 23271, CECT 5716, e IFO 3956). Genome investigation demonstrated that L. fermentum JAC 231 has genes encoding a bacteriocin (Enterolysin A), stress tolerance genes, vitamin synthesis, and survival under gastrointestinal conditions. Furthermore, we observed the absence of genes for virulence factors and the presence of genes for intrinsic resistance to vancomycin. Phenotypically, L. fermentum JAC 231, was susceptibility to most of the antibiotics tested, except vancomycin, as already visualized in the genome analysis. It was able to tolerate acid pH (with growth of 107.7% at pH 2 and 75.29% at pH 4), as well as bile salts at concentrations of 0.5% (87.34) and 1% (84.76%). It also demonstrated adhesion capacity to mucin and HeLa cells, presenting logarithmic growth of 5.9 and 5.7, respectively. Additionally, it presented antagonistic activity in the overlay test, inhibiting the growth of all bacteria used, with inhibition zones ranging from 16.6 ± 2.08 to 28.3 ± 2.88 mm, in addition to the anti-adhesion potential observed, mainly, in the displacement and exclusion tests. In this way, our study confirms the characteristics and safety profile of L. fermentum JAC 231 as a probiotic strain. Genome analysis proved to be effective in evaluating the beneficial properties of this strain, showing correlation with the data obtained in vitro. In addition, we verified the antagonistic and anti-adhesive activity displayed by L. fermentum JAC 231. Further studies are needed to elucidate the mechanisms by which this promising strain exerts its broad-spectrum antimicrobial effects. Instituição: Universidade Federal do Maranhão Tipo do documento: Tese 2025-12-02T00:00:00Z https://tedebc.ufma.br/jspui/handle/tede/6951 Título: Alterações funcionais cocleovestibulares em pacientes com doença renal crônica em hemodiálise Autor: CALDAS, Érica Alessandra Primeiro orientador: SALGADO FILHO, Natalino Abstract: Introduction: Chronic kidney disease is characterized by progressive and irreversible reduction of renal function and can be classified according to glomerular filtration rate. When this rate reaches very low values, we find what is called renal functional failure, when it is necessary some kind of renal replacement therapy. Hemodialysis, one kind of these therapy can induce electrolyte, biochemical, immunological, osmotic and vascular changes that are capable of leading to changes in the functioning of the inner ear. Such changes can cause symptoms such as hearing loss and vestibular alterations. Objective: To determine which cochleovestibular alterations affect patients diagnosed with chronic kidney disease before and after hemodialysis. Method: Cross-sectional clinical study developed in the nephrology sector of the University Hospital of the Federal University of Maranhão. The sample consisted of 30 individuals aged between 18 and 59 years diagnosed with chronic kidney disease under hemodialysis treatment. The video head impulse test (vHIT) was performed for vestibular evaluation and the research of distortion product otoacoustic emissions (OAE-DP) and transient otoacoustic emissions (OAE-TE) for cochlear evaluation. All tests were performed before and after the hemodialysis session. Results: When analyzing the vestibulo-ocular reflex before and after hemodialysis through vHIT, no statistically significant changes were observed, regardless of gender, age group and treatment time on hemodialysis. Similarly, no alterations were observed in relation to asymmetry. Regarding the analysis of DPOAE, there was an increase in the number of patients who failed at the highest frequencies (4 and 5 KHz) in the post hemodialysis test, but no statistically significant change was observed after hemodialysis (p> 0.05). In relation to THEAE, when comfacing the pre and post HD tests there was an increase in patients who failed at frequencies of 2 and 4KHz, also without statistically significant alteration after hemodialysis (p> 0.05). Conclusion: There were no significant cochleovestibular alterations, assessed through vHIT and OAE, after a single hemodialysis session for the studied sample. Instituição: Universidade Federal do Maranhão Tipo do documento: Tese 2023-09-05T00:00:00Z https://tedebc.ufma.br/jspui/handle/tede/6950 Título: Espécies da flora da Amazônia oriental maranhense como alternativa e/ou complemento terapêutico para infertilidade feminina: a etnofarmacologia como ferramenta para a bioprospecção e a farmacovigilância em fitoterapia Autor: RODRIGUES, Silmara Ribeiro Batista Primeiro orientador: AMARAL, Flavia Maria Mendonça do Abstract: Infertility constitutes a significant global public health problem, affecting approximately 17.5% of the population and impacting physical, emotional, and social well-being. In Brazil, the prevalence of infertility among women of reproductive age is estimated at 10 to 15%, suggesting the importance of expanding access to specialized therapies and public policies for equitable care. Given the limitations and high costs of conventional treatments, especially assisted reproductive techniques, there is a growing popular interest in the use of plant species; a traditional practice recognized as a potential source for therapeutic purposes, but which can trigger adverse events due to irrational use. In this context, this research aims to conduct an ethnopharmacological study to identify plant species associated with female infertility in São Luís, Maranhão, followed by a systematic review of the most representative plant species in the ethnopharmacological research and to propose educational actions in Pharmacovigilance in Phytotherapy. The first chapter is an observational, cross-sectional analytical study with data collected through structured and semi structured interviews using a questionnaire containing 26 questions focused on characterizing the plant species used and/or known in popular culture for the treatment of female infertility. The study included 389 interviewees, of whom only 208 had knowledge of/used plants for infertility. Forty-one plant species used in popular culture were identified, with Himatanthus drasticus (janaúba) being the most frequently cited (34.2%), exhibiting high ethnobotanical indices (IVs=143, FRC=0.6875, UCs=1.375). Although 88.94% reported no adverse events, the documentary analysis revealed toxic risks in species such as Aloe vera (dermatitis) and Stryphnodendron adstringens (abortive effects), highlighting gaps in scientific validation for this purpose. The second chapter comprises a synthesized review of data from preclinical studies evaluating the efficacy and toxicity of extracts, fractions, and isolated substances from the latex of Himatanthus drasticus (Mart.) Plumel. The 10 preclinical (in vitro/in vivo) studies confirmed the promising profile of H. drasticus latex, with low toxicity at the tested doses (low risk of bias according to ROBINS-I), with anti-inflammatory, healing, and antidiabetic actions. The third chapter addresses pharmacovigilance actions represented by a comic strip of the plant species that were highlighted in response to the toxicity of the species inventoried in the ethnopharmacological research. It is concluded that the integration of traditional knowledge, scientific validation, and regulation is essential to ensure the rational and safe use of medicinal plants as a therapeutic resource in female infertility, especially among populations with greater social vulnerability. Instituição: Universidade Federal do Maranhão Tipo do documento: Tese 2026-02-27T00:00:00Z