DSpace Coleção:

Avaliação citotóxica de derivados glicosídicos da lausona em linhagens tumorais

2026-03-09T13:11:27Z

Título: Avaliação citotóxica de derivados glicosídicos da lausona em linhagens tumorais Autor(es): Sousa, Rauan Cruz de Abstract: Cancer is a disease characterized by the abnormal growth of cells that can invade other tissues and spread to other organs, representing a major public health issue. One of the main challenges in cancer treatment is the low selectivity of the chemotherapeutic agents currently used, highlighting the need to investigate new compounds. Lawsone, a plant-derived product, has shown cytotoxic effects in different tumor cell lines, and chemical modifications to its structure can lead to more potent derivatives. Additionally, anomeric isomer derivatives exhibit similar chemical structures, differing only in the orientation of the anomeric carbon, which may influence their biological properties. Therefore, the aim of this study was to evaluate the cytotoxic activity of two anomeric derivatives of lawsone, APSO-5 and APSO-19, in lung carcinoma (A549), melanoma (B16-F10), and glioma (C6) cell lines. The cytotoxicity of the lawsone derivatives, as well as of lawsone itself, was assessed using the Sulforhodamine B assay in the tumor cell lines to determine the IC50 and select the most responsive cell line for subsequent experiments. The results showed that both compounds exhibited cytotoxic effects in all tested cell lines, with IC50 values below 12 μM. The A549 cell line was selected for further experiments, as lung carcinoma is the most prevalent and deadly type of cancer, making the identification of promising therapeutic compounds particularly relevant. The clonogenic assay demonstrated that both compounds reduced colony formation in A549 cells. Furthermore, APSO-19 was found to inhibit cell migration after 24 hours of treatment. Fluorescence assays using DAPI and Phalloidin/FITC revealed morphological changes in A549 cells treated with the derivatives, such as cytoplasmic shrinkage, cell rounding, and the presence of apoptotic bodies. It was also observed that higher concentrations of APSO-19 induced ROS production in A549 cells. Finally, none of the studied compounds showed toxicity toward human erythrocytes. In conclusion, the anomeric glycosidic derivatives of lawsone demonstrated strong cytotoxic effects in the tested cell lines and exhibited distinct biological activities, with APSO-19 showing greater ROS induction and inhibition of migration capacity in A549 cells.

Estudo da interferência do álcool perílico na atividade antitumoral da doxorrubicina em camundongos com sarcoma 180

2026-03-04T13:19:16Z

Título: Estudo da interferência do álcool perílico na atividade antitumoral da doxorrubicina em camundongos com sarcoma 180 Autor(es): Lima, Lorrane Nere de Abstract: The therapeutic management of sarcomas remains a clinical challenge due to the high heterogeneity and complexity of these neoplasms. Therefore, the combination of antineoplastic agents is fundamental to increase antitumor efficacy and mitigate toxic effects. Doxorubicin, the drug of choice in the treatment of sarcomas, has broad clinical efficacy; however, it can cause a risk of cardiotoxicity, as well as hepatotoxicity and hematological toxicity mediated by oxidative stress and inflammation. Perillyl alcohol, a monoterpene with anticancer, antioxidant, and anti-inflammatory properties, could potentiate the antitumor effect of doxorubicin and attenuate its toxic effects. Therefore, the aim of this study was to evaluate the interference of perillyl alcohol on the antitumor activity of doxorubicin in mice with sarcoma 180. For this, 56 male Swiss mice, transplanted with Sarcoma 180 cells, were distributed into 8 groups (n=7), namely: Saline [tween 80 0.2%, orally, on consecutive days + sodium chloride 0.9%, on alternate days, intraperitoneally (ip.)]; DOX (doxorubicin 2 mg/kg, on alternate days, i.p.); POH 50 (perillyl alcohol 50 mg/kg/day, orally), POH 100 (perillyl alcohol 100 mg/kg/day, orally), POH 200 (perillyl alcohol 200 mg/kg/day, orally), POH 50 + DOX (perillyl alcohol 50 mg/kg/day, orally + doxorubicin 2 mg/kg, every other day, intraperitoneally), POH 100 + DOX (perillyl alcohol 100 mg/kg/day, orally + doxorubicin 2 mg/kg, every other day, intraperitoneally), and POH 200 + DOX (perillyl alcohol 200 mg/kg/day, orally + doxorubicin 2 mg/kg, every other day, intraperitoneally). These treatments were administered for 9 days. Following the experiment, parameters of tumor inhibition, body and organ mass, biochemical markers of cardiac and hepatic injury, oxidative stress in cardiac and hepatic tissue – through levels of malondialdehyde (MDA), total sulfhydryls, and activity of glutathione peroxidase (GPX) and superoxide dismutase (SOD) – and hematological analysis were evaluated. Data were processed using the Shapiro-Wilk test, analysis of variance (one-way or two-way), and Tukey's post-hoc test. The results showed that the combined treatment did not present a significant antitumor effect. In toxicological parameters, the combined treatment led to loss of body mass and heart and liver mass, as well as elevation of levels of biochemical markers of cardiac and hepatic injury, especially in the POH 50 + DOX and POH 100 + DOX groups. In oxidative stress of cardiac tissue, the POH 100 + DOX and POH 200 + DOX groups showed elevated MDA levels, with increased SOD activity in the latter group. In liver tissue, MDA levels decreased in both combined treatment groups, and GPX activity increased. Hematological analysis showed that the alterations induced by doxorubicin persisted in the combined treatment. Therefore, perillyl alcohol combined with doxorubicin did not show promise in the treatment of sarcoma 180.

Alterações comportamentais e fisiológicas após exposição crônica de cletodim em ratos

2026-02-26T19:28:40Z

Título: Alterações comportamentais e fisiológicas após exposição crônica de cletodim em ratos Autor(es): Barbosa, Abraão de Jesus Abstract: Clethodim (CL) is a selective herbicide belonging to the oxime-cyclohexanedione chemical group, whose mechanism of action involves the inhibition of acetyl coenzyme A. It is widely used to combat plants that are resistant to glyphosate. Due to the scarcity of studies in the literature on the impacts of this compound on human or animal health, studies seeking to assess its toxicity in non-target organisms are necessary. The objective of this study was to evaluate behavioral and physiological changes after repeated exposure to CL in rats. As materials and methods, after obtaining approval from the Animal Use Ethics Committee of the Federal University of Sergipe (CEUA/UFS) under protocol no. 5228100323, 30 adult male rats aged 6- 8 months (350-500 g) of the Wistar strain were used. The animals were divided into four groups with seven to eight animals per group, according to the concentration of the compound: control (CTL-0.9% saline solution), CL at concentrations of 0.06% (CL-0.06), 0.3% (CL-0.3), and 0.6% (CL-0.6). Twenty-five nebulization exposures were performed (one every 48 hours, lasting 10 minutes each) with saline solution or CL according to the experimental group. Throughout the experiment, behavioral tests were performed, namely: catalepsy (every 48 hours), open field (OF - days 0 and 38), novel object recognition (NOR - day 12), spontaneous alternation (SA - day 16), and forced swim test (FST - day 25). In addition, assessments of body mass (every 4 days), food intake (day 44), glycemic tolerance (day 48), and organ mass measurement and brain removal after perfusion (day 50) were performed. The brains were then processed to assess the immunoreactivity of Brain-Derived Neurotrophic Factor (BDNF), cFos, and Choline-O-Acetyl-Transferase (ChAT) proteins. Our results showed that the CL-0.06 group had a shorter time in the catalepsy test and lower spleen mass; in the CL-0.6 group, we observed a shorter time in the center in the CA and impairment in working memory in the AE, but not in the RO, increased body variation, and lower glycemic peak in the glucose tolerance test; in all concentrations, we observed lower food consumption and a higher number of immobility events with longer immobility time in the TNF. Regarding neurochemical assessments, lower immunoreactivity for BDNF and c-Fos was identified in hippocampal regions in the CL-0.06 and CL-0.3 groups, with no changes in ChAT expression in cholinergic areas. In conclusion, our study demonstrated that exposure to CL according to concentration was capable of promoting anxiety- and depression-like behavior, memory deficits, increased body mass, and decreased hippocampal activity.

Efeito anti-inflamatório e antioxidante da gliciteína em modelo de edema de orelha em camundongos

2025-10-31T10:19:30Z

Título: Efeito anti-inflamatório e antioxidante da gliciteína em modelo de edema de orelha em camundongos Autor(es): Sales, Marciel Rosa de Abstract: Inflammation is a protective factor for the body, but it can cause tissue damage when excessive. Considering inflammatory skin diseases and the limitations of their conventional treatments, it is interesting to develop therapies that can be administered topically. In this sense, glycitein, a soy isoflavone, may be a promising alternative. The present study investigated the anti-inflammatory and antioxidant effects of glycitein in a mouse model of acute skin inflammation. The study was approved by the Animal Use Ethics Committee (CEUA) of the Federal University of Sergipe under protocol number 8947220923. The animals received a topical administration of TPA (12-O tetradecanoylphorbol 13-acetate; 1 μg/ear) in the right ear to induce inflammation. 5 min later, they were treated with glycitein (0.3, 1.0, and 3.0 mg/ear), vehicle (acetone), or dexamethasone (0.05 mg/ear). Euthanasia and removal of the ears occurred 6 h later. Ear analyses showed that glycitein reduced ear edema (24.2% p=0.036; 36.8% p=0.0002 and 33.2% p=0.001), myeloperoxidase activity (90.1, 87.2 and 72.1%, p<0.0001 each) and tissue concentrations of IL-6 (58.5% p=0.0007; 56.5% p=0.0006; 66.8% p<0.0001), IL-1β (57.3% p=0.0002; 54.8% p=0.0002; 59.3% p<0.0001) and TNF-α (54.9% p=0.011; 61.2% p=0.002; 61.6% p=0.002), for 0.3, 1.0 and 3.0 mg/ear respectively compared to the vehicle group. In the histological evaluation, less intense edema and dermo-epidermal thickness were observed in the treatment with doses of 1.0 and 3.0 mg/ear (p<0.0001, each), but not for 0.3 mg/ear, in relation to the control. In addition, treatment with glycitein decreased the concentrations of total hydroperoxides by 60.1% (p=0.014) and 81.4% (p=0.0004) for 1.0 and 3.0 mg/ear, respectively. Furthermore, the dose of 1.0 mg/ear was tested for antioxidant activity and promoted a increase of 55.8% (p=0.009) for catalase (CAT) activity and 76.3% (p=0.001) for superoxide dismutase (SOD). These results demonstrate that glycitein has anti-inflammatory and antioxidant effects in the TPA-induced ear edema model in mice and has the potential to contribute to the development of new topical treatments for inflammatory skin diseases.