Navegando por Assunto "Toxicity"

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Acesso aberto (Open Access)
Efeito de uma espécie do gênero Varronia sobre a viabilidade celular, atividade antimicrobiana, toxicidade dérmica aguda e o processo de cicatrização (in vitro e in vivo)
(Universidade Federal do Pará, 2019-09-09) RIBERA, Paula Cardoso; FONTES JÚNIOR, Enéas de Andrade; http://lattes.cnpq.br/7056265073849866; https://orcid.org/ 0000-0002-6186-9581
Tissue damage, particularly to the skin, results in damage to cell structures, layers, and lineages to the fullest extent. Under these conditions, wound healing is the physiological process responsible for tissue repair. Inflammation is an important stage in tissue repair and; therefore, a strong target for clinical studies. The species Varronia multispicata is popularly used for the treatment of bruises, with recently discovered anti-inflammatory and analgesic effects. The present work aimed to investigate the effect of aqueous extract of Varronia multispicata leaves (VAR01) on cell viability, antimicrobial analysis, dermal toxicity, and in vitro and in vivo healing. In the in vitro assays, there were evaluated the cell viability in BALB/c 3T3 murine fibroblasts, the antimicrobial action by the microdilution method for determination of minimum inhibitory concentration and petri dish culture technique for the minimum bactericidal concentration. Healing assays were performed in cultured fibroblast monolayers. For in vivo assays in the dermal toxicity test, female Wistar rats were used and divided into the following groups: saline, 100mg/ml, 200mg/ml, and 1000mg/ml of VAR01; as for healing evaluation, Mus musculus mice were used and divided into 4 groups: sham, negative control, treated (VAR01 10%), and positive control (Dersani®). V. multispicata kept the cells viable for 24h, with reduction of fibroblasts in the 48h period at a concentration of 500 µg/ml. It showed no antimicrobial activity, presented in vitro and in vivo injury contraction capacity, did not promote death or behavioral changes, did not cause changes in water and feed intake, weight gain, relative weight, and organ histological analysis, showed a reduction in alkaline phosphatase concentrations in the group treated with 100 mg/ml extract when compared as control group. It was also revealed a reduction in alanine aminotransferase levels in the 100 mg/ml extract-treated group when compared to the control group. However, a significant increase in TGP concentrations was found in the 200 mg/ml group when compared to the control group. While assessing the degree of irritation, VAR01 did not show an irritant profile when administered acutely topically. Therefore, the extract is safe and of low toxicity, promising in the process of tissue regeneration with possible modulation in the inflammatory pathway, being a stimulating result for the following steps of biological activity evaluation and elucidation of the healing process.
Acesso aberto (Open Access)
Estudos químico-farmacêuticos, atividade antitumoral e mutagênica de Eleutherine plicata. Herb.
(Universidade Federal do Pará, 2020-11-03) CASTRO, Ana Laura Gadelha; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/ 0000-0002-3328-5650; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649; https://orcid.org/ 0000-0003-0804-5804
Naphthoquinones have been linked to antitumor activity; however, they can cause DNA damage and be mutagenic. Some of these as the isoeleutherine and eleutherine, present in Eleutherine plicata Herb., do not have studies of mutagenicity and antitumor activity. This study evaluated the antitumor potential of the ethanolic extracts of E. plicata (EEEP), the fraction in which the quinones were found (Fraction dichloromethane-FDEP) and the genotoxic potential related to these substances. For understanding whether fractionation influences antitumor activity, EEEP was obtained by macerating the bulbs, it was fractionated under reflux and FDEP was obtained and fractionated in an open chromatographic column, resulting in the isolatation of eleutherine, isoeleutherine and eleutherol. Chemical-pharmaceutical studies were carried out: silica toxicity and pharmacokinetics (PreADMET), docking and dynamics. The antitumor activity was evaluated through the cytotoxicity in tumor cell line (oral cancer-SCC-9) and normal cell line (human keratinocytes-HaCaT), three-dimensional assay in spheroid model and cell migration in the same lines. Genotoxicity and mutagenicity were evaluated in Allium cepa model, the results of the isolated compounds were similar to those obtained in silico studies. In addition to the isoeleutherine and eleutherine, eleuterol was isolated from FDEP, the silica evaluation demonstrated similar pharmacokinetic profiles between these compounds. In the evaluation of anti-tumor activities, the EEEP fractionation contributed negatively to the activity, with EEEP (SCC09: IC50 = 12.87 ± 0.86 and HaCaT: 28.81 ± 1.82µg/mL) being the most promising with higher selectivity index for the tumor cell, interfering in the speed and directionality of tumor migration. Trying to understand this result, the capacity of naphthoquinones bind to Topoisomerase II (TOPII) was evaluated, confirming that they bind in its pouch, stabilizing the DNA-TOP II complex. In contrast, eleutherine proved to be more genotoxic, increasing the rate of mitosis, of aberrations, with micronucleus, bud and bridge being observed in the metaphase phase. However, it was not possible to differentiate the toxicity of eleutherine and isoleutherine in silico studies (Algae, Daphinia, fish and mutagenicity), obtaining similar results. In summary, EEEP is promising as a cytotoxic agent in tumor cells, and in the prevention of squamous cancer of the mouth. In relation to naphthoquinones, isoleutherine, due to its lower toxic potential and stabilization capacity of the DNA-TOP II complex, needs to be evaluated in other tumor strains.
Acesso aberto (Open Access)
Investigação da toxicidade oral aguda e propriedades farmacológicas de uma espécie do gênero Cassytha
(Universidade Federal do Pará, 2019-05-15) BARROS, Mayra Arouck; FONTES JÚNIOR, Enéas de Andrade; http://lattes.cnpq.br/7056265073849866; https://orcid.org/ 0000-0002-6186-9581
Plants have been present in human culture since its inception, being used for several purposes, including for the treatment of diseases. This practice has been handed down from generation to generation. The evolution of knowledge, however, demands broader approaches on plant species with therapeutic potential, in order to ensure safety and validate its traditional use. Cassytha filiformis, a species of the genus Cassytha, is used in folk medicine to treat cancer, trypanosomiasis, kidney disease and gonorrhea. Among its proven activities, the antiplatelet, vascular relaxing, antioxidant, cytotoxic, antihypertensive, hepatoprotective, antiepileptic, diuretic and alpha-adrenergic receptor antagonist effects stand out. Among its secondary metabolites, alkaloids have been identified for therapeutic benefit. To date, however, there are no studies that support the safety of its therapeutic application or that explore possible anti-inflammatory properties as the basis for its therapeutic actions. Acute oral toxicity was assessed according to OECD 425. Starting from an administration of 2000 mg / kg (v.o) of extract in rats, the hippocratic signs of toxicity, spontaneous locomotor activity, weight gain, water and food consumption, as well as relative body weight and hematological patterns at the end of the period. The antinociceptive activity was evaluated in mice, using the acetic acid induced writhing test and the formalin test (CEUA nº 1050140817). The cutoff dose of the extract did not promote hipocratic signs of toxicity or death. There were also no changes in feed and water consumption or weight gain patterns. The evaluation of the relative weight of organs (liver, kidneys, stomach and heart) and hemogram showed equivalent standards between treated and control animals. Cas01 also did not impair the locomotor activity of the animals. Cas01 was shown to have no influence on the contortions induced by acetic acid, nor did it promote significant alterations on formalin-induced biphasic nociception. These findings demonstrate for the first time that Cas 01 is a xenobiotic of low acute oral toxicity. They also demonstrate that their therapeutic actions do not involve nociceptive or inflammatory mechanisms.
Acesso aberto (Open Access)
Planejamento, Síntese, Avaliação das Propriedades Teóricas de orto-Regioisômeros Substituídos do Paracetamol
(Universidade Federal do Pará, 2018-12-28) MORAIS, Roberto Barbosa de; BORGES, Rosivaldo dos Santos; http://lattes.cnpq.br/4783661132100859; https://orcid.org/0000-0003-4072-7573
Paracetamol is a clinically proven analgesic and antipyretic, which promotes analgesia by elevating the pain threshold and antipyretic through action in the hypothalamic center that regulates the temperature. Currently paracetamol is one of the medicines that is available in all the countries of the world in places related to health and can be acquired without prescription. Considered one of the most widely used drugs in the world as it is cheap and easy to access, it can also be used from birth to the elderly. Like non-steroidal anti-inflammatory drugs (NSAIDs) paracetamol is able to inhibit the synthesis of prostaglandins from arachidonic acid under specific conditions by inhibiting cyclooxygenase (COX). Although it is considered safe at therapeutic doses, Paracetamol has a toxicity attributed to one of its metabolic intermediates called N-acetyl-p-imine-benzoquinone (NAPQI), produced through enzymes present in cytochrome P450 (CYPE21). Thus, the objective of this present work is to plan, synthesize and evaluate possible antinociceptive and antipyretic activities of paracetamol analogues, ortacetamol and its derivatives in order to obtain a less toxic derivative. The calculations of electronic properties such as higher energy occupied molecular orbital (HOMO), lower energy unoccupied molecular orbital (LUMO), ionization potential (PI), phenolic bond dissociation energy (BDEOH) and spin densities were performed using the Gaussview and Gaussian 2009 packages. The values of the average values of BDENH, among others, are those that are observed with the quality of a heating cycle for the high speed with the possibility of a chelation defined by a hydrogen bond of the amide with the phenoxyl radical. Given the results it is possible that BDENH energy compounds may be less potent than hindering the action of CYP on oxidation to form toxic intermediates. A proposed chlorinated derivative was proposed and synthesized. It is in biological evaluation phase. Orthacetamol was more potent antioxidant than paracetamol. Experimental results are in aggrement with theoretical values. We conclude that ortcetamol may be a potentially safer bioactive candidate than paracetamol.