https://tede.unioeste.br/handle/tede/504 2026-11-03T00:48:23Z https://tede.unioeste.br/handle/tede/8726 Title: Perda de força muscular do assoalho pélvico em portadoras de câncer de mama e mecanismos moleculares associados Autor: Silva, Cristiane Dallastra Candido da Primeiro orientador: Ribeiro, Lucinéia de Fátima Chasko Abstract: Breast cancer is the neoplasm that most affects women worldwide, in both developed and developing countries. Among the risk factors are hereditary, genetic, and environmental factors, with exposure to pesticides being correlated with an increased probability of disease development. Due to its inflammatory and systemic nature, survivors may develop new diseases or dysfunctions. Evidence demonstrates that breast cancer patients present loss of muscle strength, including that of the pelvic floor (PF). Pro-inflammatory mediators such as tumor necrosis factor alpha (TNF-α) and oxidative stress metabolites participate in the molecular mechanisms associated with this loss. Although there is no direct established correlation between elevated levels of pro-inflammatory cytokines and specific weakness of PF muscles, it is plausible that similar mechanisms affect this musculature given its composition and function. Thus, the objective of this study was to characterize pelvic floor muscle strength in breast cancer patients and investigate the clinical profile and associated molecular markers. The sample consisted of a total of 122 participants with infiltrating ductal carcinoma (IDC) treated at the 8th Regional Health Unit of Paraná – Brazil. After collecting sociodemographic data, clinical and gynecological data, and occupational pesticide exposure, pelvic floor muscle strength was measured through perineometry tests, with reference values between 0 and 46.4 mmHg, and bidigital palpation through pelvic floor assessment (PFA) with a scale between 0 and 5. Plasma levels of TNF-α and oxidative stress levels were quantified through lipoperoxide measurements by high sensitivity chemiluminescence, as well as levels of nitric oxide metabolites (NOx). Quantitative variables were evaluated with appropriate statistical tests, using GraphPad Prism 9.0, RStudio, and SPSS software, and p-values below 0.05 were considered statistically significant. Pelvic floor muscle strength of 73.8% of women was classified as mild to moderate through perineometry, and 61.5% of women had weak and non-resistant perineal function through PFA. A negative correlation was observed between perineometry values and TNF-α and NOx, indicating worse pelvic floor muscle conditions with increased levels of these inflammatory markers (p=2.06e-07 and p=1.700e-02). A significant correlation was also identified between PFA and the patients' pesticide exposure profile (p=0.0223), as well as a significant negative correlation with perineometry (p=0.0404). The group exposed to pesticides (n=66) presented lower perineometry values (95% CI: 0.007-0.409). Significant differences were also found between patients with unsatisfactory PFA and perineometry results with elevated TNF-α values, suggesting that this cytokine may be a mediator of pelvic floor strength loss in breast cancer (p=0.0001). Publisher: Universidade Estadual do Oeste do Paraná Tipo do documento: Tese 2026-06-23T00:00:00Z https://tede.unioeste.br/handle/tede/8706 Title: Efeito do Exercício Físico Resistido como Estratégia Profilática nas Lesões Funcionais e Morfológicas da Artrite Reumatoide no Músculo Sóleo de Ratos Autor: Kiekiss, Gabriella Canan Primeiro orientador: Torrejais, Marcia Miranda Abstract: Rheumatoid arthritis (RA) is a chronic, progressive inflammatory autoimmune disease that affects the joints and periarticular tissues, including skeletal muscle. Specific medications are used in therapeutic protocols for RA and may cause considerable adverse effects. However, other therapeutic approaches, such as physical exercise applied preventively, have emerged as promising strategies for modulating the inflammatory response and preserving joint and musculoskeletal integrity. Therefore, the present study aimed to analyze the morphofunctional effects of high-intensity resistance exercise (RE) on the soleus muscle of Wistar rats when applied preventively before the induction of RA. Thirty Wistar rats, approximately 12 weeks old and with a mean body weight of 320 g, were allocated into four experimental groups: control group (CG), arthritis group (AG), exercise group (EG), and exercise + arthritis group (EAG). Animals in the exercise groups underwent ladder-climbing resistance exercise, with progressive loading, a progressive number of sets, and a fixed number of repetitions, for nine weeks before RA induction. RA was induced using the Complete Freund's Adjuvant (CFA) model. During the experiment, the following assessments were performed: muscle strength, nociception, joint incapacitation, and motor function. Joint edema and the arthritic index were also evaluated. Euthanasia was performed on the eighth and ninth days following RA induction. The soleus muscle was collected and processed for morphological and morphometric analyses of muscle fibers using Hematoxylin and Eosin staining, as well as for analysis of connective tissue using Picrosirius Red staining. An increase in joint edema and arthritic index, as well as functional impairment, was observed in the AG and EAG, as evidenced by reduced muscle strength, nociception, and motor function, in addition to increased joint incapacitation. Morphological analyses indicated focal alterations in muscle fibers resulting from RA, including disorganization of muscle fascicles, muscle fibers with centrally located nuclei, nuclei surrounded by a basophilic halo, muscle fibers undergoing atrophy and necrosis, and inflammatory infiltrates. However, these alterations were less pronounced in the EAG. In the AG and EAG, muscle spindles with disorganized outer capsules and inflammatory cells within their structures were identified. Regarding the morphometric analyses, reductions in fiber area and major and minor diameters, along with increased muscle fiber density, were identified in the AG and EAG. However, these alterations were less evident in the EAG. An increase in connective tissue was observed in the group with RA, whereas no alteration was observed in the EAG. In conclusion, resistance exercise applied preventively in the context of RA demonstrated limited potential regarding functional parameters; however, it promoted partial attenuation of the muscle morphostructural alterations observed in the experimental model. Further studies using prolonged exercise protocols are required. Publisher: Universidade Estadual do Oeste do Paraná Tipo do documento: Dissertação 2026-02-27T00:00:00Z https://tede.unioeste.br/handle/tede/8686 Title: Mielotoxicidade e hepatotoxicidade da exposição crônica ao herbicida a base de glifosato em camundongos C57BL/6 Autor: Ferreira, Anderson Felipe Primeiro orientador: Bonfleur, Maria Lúcia Abstract: Introduction: The use of glyphosate-based herbicides (GBH) has intensified over the past decades, accompanying the expansion of agricultural production. This scenario has raised concerns regarding the potential health effects of chronic exposure to these compounds. Experimental studies have demonstrated alterations in various biological systems following exposure to glyphosate and commercial formulations containing this herbicide, including hepatic and hematological effects. However, the effects of chronic exposure on the bone marrow and the mechanisms involved in hematotoxicity remain incompletely understood. Objective: To evaluate the effects of chronic exposure to 5 and 50 mg/kg doses of a commercial GBH formulation on hematological parameters, bone marrow, and liver of male C57BL/6 mice. Methods: Male C57BL/6 mice, approximately 21 days old and with a mean body weight of 20 g, were distributed into three experimental groups: control (CTL), 5 mg/kg GBH (GBH-5), and 50 mg/kg GBH (GBH-50). The mice received the commercial formulation Xeque Mate HT® diluted in drinking water ad libitum for 20 weeks. At the end of the experimental period, following euthanasia, body profile assessment, hepatic histopathological analysis, complete blood count and reticulocyte count, cytological and histological evaluation of the bone marrow, and serum thrombopoietin (TPO) measurement were performed. Results: GBH exposure increased water and food consumption, without significantly affecting final body weight gain. Hepatic histopathological evaluation revealed hepatocellular hypertrophy, inflammatory infiltrate, and increased connective tissue. Regarding hematological evaluation, no relevant alterations in erythropoiesis were observed; however, alterations in the leukocyte profile were identified, with more pronounced leukocytosis, neutrophilia, and monocytosis in both GBH-exposed groups. In addition, platelet counts were reduced in the GBH-5 and GBH-50 groups compared with the CTL group, by 26.39% and 46.45%, respectively. Bone marrow evaluation revealed a significant increase in megakaryocyte numbers in the GBH-50 group compared with the CTL and GBH-5 groups, along with dysplastic alterations consistent with impaired megakaryopoiesis. Serum TPO concentrations remained unchanged among the experimental groups. Conclusions: Chronic exposure to 5 and 50 mg/kg doses of a commercial GBH formulation promoted hepatic and hematological alterations, as well as changes in the bone marrow of C57BL/6 mice. The main findings were thrombocytopenia associated with dysmegakaryocytopoiesis, with no change in serum TPO concentrations. These findings suggest ineffective thrombopoiesis as one of the mechanisms involved in herbicide-induced hematotoxicity. Publisher: Universidade Estadual do Oeste do Paraná Tipo do documento: Dissertação 2026-08-31T00:00:00Z https://tede.unioeste.br/handle/tede/8618 Title: Efeitos de uma Intervenção Profilática-Terapêutica com Exercício Resistido e Suplementação de Cúrcuma com Óleo de Peixe no Músculo Extensor Longo dos Dedos em Ratos Wistar Submetidos a um Modelo de Artrite Reumatoide Autor: Dressler, Vanessa Freitas Primeiro orientador: Bertolini, Gladson Ricardo Flor Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects the joints and can cause damage to muscle tissues. It is a disabling condition treated primarily with medication; however, the continuous, long-term use of these drugs can lead to unwanted side effects. Consequently, there is growing interest in low-cost, accessible integrative interventions, such as resistance exercise (RE) and supplementation with turmeric solubilized in fish oil. Therefore, this study aimed to evaluate the morphofunctional and immunological effects of prophylactic and therapeutic interventions involving resistance exercise and turmeric/fish oil supplementation—administered either alone or in combination—on the *extensor digitorum longus* muscle of Wistar rats subjected to an RA model. Sixty-eight male Wistar rats (15 weeks old) were used and divided into six groups: Control Group (GC, n=8), RA Group (GA, n=12), Exercise and Supplementation Group (GES, n=12), RA and Exercise Group (GAE, n=12), RA and Supplementation Group (GAS, n=12), and RA, Exercise, and Supplementation Group (GAES, n=12). A ladder-climbing resistance exercise protocol was employed, consisting of five days of unloaded training for adaptation followed by 16 training sessions on alternate days—eight interventions prior to RA induction and eight afterward. Load progression was set at 25%, 35%, and 50% of body weight, while the number of sets and repetitions remained fixed (three sets of eight repetitions with a two-minute rest interval). Supplementation was administered orally for 31 consecutive days using an adjustable volume pipette; the daily dose was 500 mg/kg of *Curcuma longa* L. dry extract diluted in 500 µL of fish oil to enhance bioavailability. Arthritis (RA) was induced using the Complete Freund's Adjuvant (CFA) model. A baseline assessment was performed on day 1, followed by six functional assessments throughout the study (days 8, 15, 22, 25, 28, and 31) to measure joint edema, grip strength, and nociception. Animals were euthanized on day 32. The extensor digitorum longus (EDL) muscle was harvested and divided into two portions: the proximal portion was processed for morphological analysis of muscle fibers and tissue. Arthritic groups exhibited significant increases in joint edema and higher levels of nociception compared to control groups (p < 0.01). The GES group maintained higher grip strength, whereas arthritic groups showed a reduction in this parameter. These results indicate functional impairment associated with RA that was not fully reversed by the tested interventions. Regarding body weight, the GES group showed a higher mean, with no significant differences in naso-anal length. The GA group exhibited greater EDL muscle weight, while the GES group showed greater muscle length. This finding suggests that inflammatory processes or edema may influence the increase in muscle weight in arthritic animals. Histometric analyses revealed no significant differences in fiber area and diameter, or in the number of capillaries and muscle fibers. However, the GA group showed a higher number of peripheral nuclei and—along with the GAS and GAES groups—a larger nuclear cross-sectional area. The IHP was higher in the GA group, whereas the GAE group displayed characteristics closer to those of the control group. Furthermore, an increase in fibroblasts and disorganization of the extracellular matrix were observed in the GA group, indicating greater structural muscle damage. It was concluded that moderate ladder-based resistance exercise, applied both preventively and therapeutically, was effective in improving the muscle microstructure of the EDL—particularly in the GAE group—but did not yield significant effects on muscle strength or nociception. Thus, the results suggest that the benefits of the interventions were predominantly structural, without a direct correlation to functional improvement during the analyzed period, indicating a need to adjust protocols or intervention durations in future studies. Publisher: Universidade Estadual do Oeste do Paraná Tipo do documento: Dissertação 2026-05-22T00:00:00Z