Maria Luísa Lima Barreto Do Nascimento

Organotellurium (OTe) compounds have pharmacological properties, including leishmanicidal, antimalarial, and antifungal activities. Herein, we assessed cytotoxicity effects of OTe RF07 in a panel of tumor cell lines, as well as its oxidative, toxicity, and hemolytic actions. The toxicity was evaluated on Allium cepa and Artemia salina larvae. Cell viability was also assessed by resazurin in murine cells (Sarcoma 180), human cells (HL-60, leukemia; AGP01, gastric adenocarcinoma; SKMEL-28, human melanoma; MRC-5, normal fibroblasts), and dog erythrocytes. The oxidative capacity of RF07 was evaluated by wild-type and antioxidant-mutated enzyme strains of Saccharomyces cerevisiae . RF07 presented cytotoxic action on all normal and tumor cells, whose IC ₅₀ ranged from 0.07 μg/mL (HL-60) to 73.45 μg/mL (Sarcoma 180) and toxicological activity on A. salina nauplii in a concentration-dependent manner after exposure for 24 h and 48 h (LC ₅₀ values of 15.02 and 5.43 μg/mL for 24 h and 48 h, respectively). Moreover, RF07 reduced mitotic index of meristematic A. cepa cells at 5, 10 and 20 μg/mL, caused arrest in interphase, and increased chromosomal changes, including micronucleus, c -metaphases, and chromosomal bridges, loss, and delays. In summary, RF07 exhibits antiproliferative action on animal cells, high toxicity on Artemia salina nauplii, as well as clastogenic effects on growing roots. This antimitotic action is not related to direct membrane damage, although it relies on chromosomal injuries and may be related to the induction of oxidative stress as observed in yeast cells.

This study aimed to synthesize a liposomal nanoformulation containing citrinin (LP-CIT) to improve its availability and to evaluate its toxicogenomic profile, focusing on cytotoxic and genotoxic effects in breast cancer (MDA-MB-231) and non-tumorigenic mammary epithelial (MCF-10A) cell lines. The formulation was characterized by macroscopic appearance, pH, particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and estability of nanoparticles. Citrinin content, encapsulation efficiency, and liposome stability were evaluated. Cytotoxicity was assessed using MTT, trypan blue exclusion, and flow cytometry. Cell death mechanisms were investigated by mitochondrial membrane potential analysis and expression of apoptotic markers (caspase-9 and BAX). Genotoxicity was evaluated using the comet assay. The liposomal nanosystem consisted of small unilamellar vesicles with a mean diameter of 143.3 nm, a PDI of 0.3, and a positive surface charge (+ 28.5 mV). The average was 63.69 ± 0.18% of citrinin encapsulated in liposomes with stability more than 21 days. Both free citrinin (CIT) and LP-CIT showed cytotoxic effects in MDA-MB-231 and MCF-10A cells, with lower LC₅₀ values observed for LP-CIT. Although LP-CIT induced more pronounced cytotoxic and genotoxic effects in the cancer cell line, toxic effects were also observed in non-tumorigenic cells, indicating limited selectivity. Cell death was associated with mitochondrial membrane depolarization and increased caspase-9 and BAX expression. Both formulations induced DNA damage as detected by the comet assay. Liposomal encapsulation enhanced citrinin biological activity but did not indicate tumor selectivity. Thus, this study represents a toxicogenomic assessment of citrinin and its liposomal formulation for potential therapeutic applicability.

Polysaccharides are complex carbohydrates that play essential roles in several biological processes. The aim of this study was to isolate, characterize, and evaluate the cytotoxic, antitumor, and antiedematogenic potential in vitro and in vivo of red angico gum (RAG), a polysaccharide isolated from Anadenanthera colubrina var. cebil (Griseb.) Altschul. To confirm the chemical characteristics of RAG, nuclear magnetic resonance, size-exclusion chromatography, high-performance liquid chromatography analysis, and determination of uronic acid content by potentiometric titration were performed. RAG is composed mainly of arabinose and galactose with smaller proportions of rhamnose and glucuronic acid. In vitro cytotoxicity was determined by MTT and Alamar blue assays. For in vivo assays, mice bearing a sarcoma 180 tumor and the carrageenan-induced paw edema model were used to evaluate the antitumor and antiedematogenic effects. Hematological, biochemical, histopathological, and mutagenic analyses were performed to observe signs of toxicity after RAG administration. RAG did not show cytotoxicity in vitro; in contrast, it showed a significant tumor inhibition in vivo of up to 46.5%. Notably, such effects were observed without causing systemic and tissue toxicity in animals. Furthermore, RAG administration significantly reduced paw edema. These findings suggest that this polysaccharide exhibits antitumor and antiedematogenic potential in animal models, without showing signs of toxicity.

Stevia urticifolia Thunb. is an underexploited herb possessing bioactive flavonoids, saponins, and terpenoids. The aim of this study was to examine the antiproliferative and toxicogenetic properties of the ethyl acetate extract from Stevia urticifolia aerial parts (EtAcSur) upon Artemia salina, erythrocytes, Allium cepa and sarcoma 180 cells and fibroblasts, as well as in vivo studies on mice to determine systemic, macroscopic, and behavioral alterations and bone marrow chromosomal damage. The assessment using A. salina larvae and mouse blood cells revealed LC₅₀ and EC₅₀ values of 68.9 and 113.6 µg/ml, respectively. Root growth and mitosis were inhibited by EtAcSur, and chromosomal aberrations were detected only at 100 μg/ml. EtAcSur exhibited potent concentration-dependent viability reduction of S180 and L-929 cells and antioxidant capacity employing ABTS^• and DPPH^•. No previous in vivo studies were performed before with the EtAcSur. Signals of acute toxicity were not observed at 300 mg/kg. Physiological and toxicological investigations at 25 and 50 mg/mg/day i.p. for 8 days did not markedly change body or organ relative weights, nor patterns of spontaneous locomotor and exploratory activities. In contrast, clastogenic effects on bone marrow were found at 50 mg/mg/day. EtAcSur was found to (1) produce toxicity in microcrustaceans, (2) capacity as free radical scavenger, (3) antimitotic, cytotoxic and clastogenic activties upon vegetal and mammalian cells, and (4) lethality on both tumor and normal murine cells indistinctly. In vivo damage systemic effects were not remarkable and clinical signals of toxicity were not observed, suggesting the significant pharmacological potential of S. urticifolia for the development of antineoplastic agents. Abbreviations: ABTS: 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); DMSO: dimethylsulfoxide; DPPH: 1,1-diphenyl-2-picrylhydrazyl; EC₅₀: effective concentration 50%; EtAcSur: ethyl acetate extract from Stevia urticifolia aerial parts; Hb, hemoglobin; IC₅₀: inhibitory concentration 50%; LC₅₀,: lethal concentration 50%; MI: mitotic index; RBC, red blood cells; Trolox: 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid.

Healthcare-Related Infections (ARs) account for one third of infant mortality. IRAS are acquired infections that occur during hospitalization and are often caused by Gram Negative Bacteria (BGN). The objective of this integrative review work was to identify the main microorganisms responsible for causing healthcare-related infections in patients hospitalized in neonatal intensive care units, in addition to identifying the sites of infection. A search was carried out for scientific articles published in the last 5 years indexed in the databases BVS/LILACS, BVS/MEDLINE, Science Direct, PUBMED. The following descriptors were used: “neonatal intensive care unit”, “bacteremia “infection nosocomial”. With these search strategies, it was verified whether there was occurrence in the title, abstract or keywords of scientific articles published in Portuguese, English and Spanish. After screening, 1186 eligible articles were selected for the research, of these, only 24 articles were selected for the research. Klebsiella spp. was the most common pathogen found in nosocomial infections, followed by Acinetobacter baumanii, Coagulase negative Staphylococcus (CoNS), Escherichia coli, Pseudomonas aeruginosa, the other microorganisms identified were identified with less clinical importance. The infections that were most prevalent in the studies were: bloodstream infection, catheter use and ventilator-associated pneumonia, with Klebsiella pneumoniae, Acinetobacter baumanni and Staphylococcus Coagulase negative as the main causative microorganisms.

Human papillomavirus infection is the cause of several diseases in men and women. More than 100 types of HPV are known and about 30 are related to anogenital infection, with the most prevalent sexually transmitted viral infection worldwide. Given the proposal, the work aims to conduct a systematic review on the diagnosis of HPV in men. The study is a systematic review with the research question 'How is HPV diagnosed in men?' To answer this question, the descriptors “HPV OR papillomavirus” AND “diagnostic” and “man OR men” were used, in the PubMed, ScienceDirect and SciELO databases. After extracting the articles from the three databases and applying the inclusion and exclusion criteria, a total of 26 articles was reached at the end. Within the review, the most used methods for screening male HPV were seen, such as: peniscopy, cytological and histological evaluation, serological tests, p16 immunohistochemistry and molecular tests that are of great importance in the conclusive diagnosis, being reported in 14 articles. The genotype most found in the articles was HPV 16, a high-risk type of HPV, being mentioned in 11 studies. In addition, ten diseases were associated with HPV infection such as: cancer or anal dysplasia, head and neck cancer, penile cancer, co-infections with more than one HPV genotype and with HIV virus. This study was limited due to the lack of methodological standardization of the papers used. Although the prevalence of HPV infection in men is high, there is no consensus on which tests should be used to establish a diagnosis. The different methodologies have different sensitivity and specificity values, thus, the diagnosis of male HPV infection tends to associate the available methods.

Background: Alpha-terpineol is monoterpene alcohol with anti-tumor activity against different tumor cell lines (lung, breast, leukemias and colorectal) through blockage of NF-kB expression, which play an important role in tumor cells growth. Objective: Evaluate the antitumor activity of alpha-terpineol in murine Sarcoma 180 cell line Methods:: For the tests, different cytotoxic and genotoxic assays were used, including Trypan blue, cytokinesis- blocked micronucleus assay, comet assay, agarose gel DNA fragmentation, flow cytometry and cell viability using fluorescence. Ascitic fluid cells from sarcoma 180 were obtained from Mus musculus peritoneal cavity and Alpha-terpineol was tested at 100, 250 and 500 μg/mL. Doxorubicin and Cisplatin were used as positive controls. Results: Cytotoxic effects of alpha-terpineol were found in all concentrations tested, reducing cell viability in 50.9; 38.53; 30.82% at 100, 250 and 500 μg/mL, respectively. Alpha-terpineol induced genotoxic effects due to DNA fragmentation (increased frequency and index of damage), and was clastogenic by increased micronuclei formation, nucleoplasmic bridges and nuclear buds. DNA fragmentation and increased cell death indicated that alpha-terpineol can cause early, late, and necrotic apoptosis. Conclusion: Our data indicate that alpha-terpineol has antitumor activity revealed by cytogenetic mechanisms and / or loss of cell membrane integrity.

Background: The search for novel metallic chemical compounds with toxicogenic effects has been of great importance for more efficient cancer treatment. Objective: The study evaluated the cytotoxic, genotoxic and mutagenic activity of organoteluran RF07 in the S-180 cell line. Methods: The bioassays used were cell viability with 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, evaluation of apoptosis and necrosis using fluorescence and flow cytometry, cytokinesisblock micronucleus test and comet assay. The compound was tested at 1; 2.5 and 5μM. Results: The results showed the cytotoxicity of RF07 at concentrations of 2.5, 5, 10 and 20μM when compared to the negative control. For genotoxicity tests, RF07 showed effects in all concentrations assessed by increased index and frequencies of damage and mutagenic alterations. The compound was also cytotoxic due to the significant decrease in the nuclear division index, with significant values of apoptosis and necrosis. The results of fluorescence and flow cytometry showed apoptosis as the main type of cell death caused by RF07 at 5μM, which is thought to avoid an aggressive immune response of the organism. Conclusion: In addition to cytotoxic and genotoxic effects, RF07 creates good perspectives for future antitumor formulations.