Neurogenic Disorders and the Lower Urinary Tract Dysfunction: Proposed Approach for the Gynecologist.

BACKGROUND: The scenario of the patient with neuropathies, which are related to urinary disorders, impacts the quality of life. Symptoms can lead to social isolation, impair activities of daily living, and shorten life expectancy. This study aims to make a practical and integrative review of current recommendations for the urogynecological approach of patients with neuropathy and urinary dysfunction. METHODS: The authors searched for data on combinations of the terms "lower urinary tract symptoms" AND "neurogenic voiding dysfunction" from January 2012 to January 2022 in the following scientific databases: PUBMED, MEDLINE, EMBASE, and The Cochrane Library. INCLUSION CRITERIA: randomized clinical trials, protocols from specialized societies and articles before that period, and according to clinical relevance. EXCLUSION CRITERIA: case series or reports, expert opinions not endorsed by medical societies in the area. RESULTS: From the 25 studies mentioned, 09 studies were selected according to pre-established criteria and qualitative analysis of relevance. The authors add 2 references for relevance in the area of ​​urogynecology and neurological diseases. According to the selected scientific references, the main neuropathies that can cause urinary dysfunction are CNS injuries such as stroke, spinal cord injury, meningomyelocele, and amyotrophic lateral sclerosis. Ten steps below were compiled to facilitate the gynecological approach, according to the researched literature. CONCLUSION: It is important for the medical assistant to pay close attention to careful anamnesis and post-emptying urinary residual volume. The treatment in general addresses greater fluid intake, maneuvers to favor bladder emptying, medications, and/or intermittent self-catheterization. The approach of a multidisciplinary team can make a difference in the patient's prognosis and quality of life.

Sida tuberculata: In vitro cytotoxicity and in vivo anti-inflammatory effect.

ETHNOPHARMACOLOGICAL RELEVANCE: Sida tuberculata R. E. Fries (Malvaceae) is a pioneer species considered a weed in farm fields in Southern Brazil. Widely distributed in South Brazil, S. tuberculata is popularly used to treat inflammatory conditions. AIMS OF THE STUDY: The current study aimed to assess the in vitro cytotoxic and in vivo anti-inflammatory properties of S. tuberculata. MATERIALS AND METHODS: Initially, extracts obtained from leaves (STLE) and roots (STRE) were submitted to cytotoxicity tests using human leukocytes (non-malignant cell line) and HepG2 and MCF-7 (tumor cell lines). In sequence, anti-inflammatory properties were investigated against carrageenan-induced peritonitis model. RESULTS: In vitro analyses displayed a significant decrease in human leukocytes viability without genotoxic damage. IC50 results from tumor cells presented significant decrease in cell viability, slightly more pronounced for STRE. In addition, STLE significantly inhibited the inflammatory and oxidative parameters (TBARS, NPSH, SOD, MPO activity, cell influx, and cytokines release). CONCLUSION: Our findings indicate S. tuberculata extracts have cytotoxic potential more pronounced on tumor cell lines, as well as leaves extract shows a significant reduction in acute inflammation process, as already reported for Sida genus and specifically for this species.

Evaluation In Vitro of Toxicity of Hydroalcoholic Extract of Leaves and Roots from Yacon (Smallanthus sonchifolius).

Yacon is an Andean plant that has been used in folk medicine for its medicinal properties. The beneficial effects of this plant are possibly due to the high content of phenolic compounds present in its leaves and roots. This study evaluated the in vitro toxicity of the hydroalcoholic extract of leaves and roots from yacon (1, 10, 50, and 100 µg/mL) through cell viability tests, genotoxic and mutagenic activity in leukocytes culture cells; and cytotoxicity and apoptosis cell death (1, 10, 50, 100, and 500 µg/mL) in cell line originally established from the primary mouse embryonic fibroblast cells that were cultured by the designated protocol, so-called 3T3 protocol "3-day transfer, inoculum 3 × 105 cells" (3T3 cell line). No mutagenic and cytotoxic activities were observed in leukocyte cultures. Cytotoxic activity was evidenced in the highest concentrations of yacon leaf extract (50 and 100 µg/mL), whereas all concentrations tested with yacon leaf extract there was induction for apoptosis in the 3T3 cells. Genotoxic potential was observed only at higher doses of leaf (50 and 100 µg/mL) and root (100 µg/mL) extract. These results suggest that yacon leaf at high concentrations may present toxic potential showing concentration-dependent behavior; however, in vivo studies should be performed to validate these results.

Quinolines derivatives as promising new antifungal candidates for the treatment of candidiasis and dermatophytosis.

Fungal infections have emerged as a current serious global public health problem. The main problem involving these infections is the expansion of multidrug resistance. Therefore, the prospection of new compounds with efficacy antifungal becomes necessary. Thus, this study evaluated the antifungal profile and toxicological parameters of quinolines derivatives against Candida spp. and dermatophyte strains. As a result, a selective anti-dermatophytic action was demonstrated by compound 5 (geometric means (GM = 19.14 µg ml-1)). However, compounds 2 (GM = 50 µg ml-1) and 3 (GM = 47.19 µg ml-1) have presented only anti-Candida action. Compounds 3 and 5 did not present cytotoxic action. Compound 5 did not produce dermal and mucosal toxicity. In addition, this compound showed the absence of genotoxic potential, suggesting safety for topical and systemic use. Quinolines demonstrated a potent anti-dermatophytic and anti-yeast action. Moreover, compound 5 presented an excellent toxicological profile, acting as a strong candidate for the development of a new effective and safe compound against dermatophytosis of difficult treatment.

Sucralose causes non-selective CD4 and CD8 lymphotoxicity via probable regulation of the MAPK8/APTX/EID1 genes: An in vitro/in silico study.

One of the most widely used sweeteners in the world is sucralose. With sweetening power 600 times greater than sucrose, its use grows among those who seek to cut calories. Research shows that when heated, sucralose generates toxic products that attack the organism and interact with DNA. Our objective was to test this sweetener under unheated conditions and at average concentrations of consumption, evaluating parameters of cytotoxicity, genotoxicity, and immunotoxicity. For this purpose, we made use of lymphocyte cultures and the analysis of their CD3+ , CD4+ , and CD8+ subpopulations. In a complementary way, the mechanism of action is proposed here by computational methods. Our results showed that sucralose reduces non-selectively the total lymphocytes due to falls in the levels of the CD4+ , CD8+ , and CD4+ CD8+ subpopulations. We observed an increase in the level of DNA damage and a gradual incidence of structural changes in the lymphocyte chromosomal sets. It was possible to propose that sucralose modulates the gene expression, interfering especially with the MAPK8, APTX, and EID1 genes. This article presents the results of an evidence-based approach to the safety of human health in the use of sucralose. Finally, this study points out that sucralose has cytotoxic, genotoxic, and mutagenic effects in the concentrations and conditions tested in human lymphocyte cell culture.

Fumonisin B1 induces toxicity in human leukocytes at low concentrations: Are computational studies effective to determine biosafety?

Fumonisin B1 is a mycotoxin produced by Fusarium verticillioides and Fusarium proliferatum found in various crops, particularly maize. Besides carcinogenicity, other manifestations have been registered in different animals and in humans. In the case of humans, epidemiological studies have reported high prevalence of esophageal cancer in populations exposed to fumonisins. This study aimed to evaluate the minimum concentration of FB1 capable of inducing cytotoxicity (cell viability test), genotoxicity (comet assay) and mutagenicity (micronucleus) in cultured human leukocytes and to evaluate the effectiveness of in silico tests to predict FB1 toxicity. All concentrations analyzed (200; 100; 50; 5; 0.5; 0.05; 0.005 µg/mL and 300; 30; 3; 1; 0.1; 0.01 fg/mL) except the lowest demonstrated dose-dependent toxicity in all parameters analyzed (p < 0.05 to p < 0.0001). As for predictions, only the Lazar software showed carcinogenicity of FB1 for rats. Thus, it is evident that FB1 is able to induce dose-dependent damage at low concentrations, and that computational tests, although desirable for prediction, are not effective as biological tests to determine toxicity, at least of FB 1 and within the experimental conditions tested.

Design, synthesis, and evaluation of novel 2-substituted 1,4-benzenediol library as antimicrobial agents against clinically relevant pathogens.

Development of new antimicrobial agents, capable of combating resistant and multidrug-resistant fungal and bacterial clinical strains, is necessary. This study presents the synthesis and antimicrobial screening of 42 2-substituted-1,4-benzenediols, being 10 novel compounds. In total, 23 compounds showed activity against fungi and/or bacteria. Benzenediol compounds 2, 5, 6, 8, 11, and 12 demonstrated broad spectrum antimicrobial actions, including resistant and multidrug-resistant species of dermatophytes (Trichophyton mentagrophytes), Candida spp. and the ESKAPE panel of bacteria. Minimum inhibitory concentrations of these compounds for fungi and bacterial strains ranged from 25 to 50 µg/ml and 8-128 µg/ml, respectively. The antifungal mechanism of action is related to the fungal cell wall of dermatophytes and membrane disruption to dermatophytes and yeasts, in the presence of compound 8. Specific structural changes, such as widespread thinning along the hyphae and yeast lysis, were observed by scanning electron microscopy. The effects of compound 8 on cell viability are dose-dependent; however they did not cause genotoxicity and mutagenicity in human leukocyte cells nor haemolysis. Moreover, the compounds were identified as nonirritant by the ex-vivo Hen's egg test-chorioallantoic membrane (HET-CAM). The furan-1,4-benzenediol compound 5 showed in vivo efficacy to combat S. aureus infection using embryonated chicken eggs. Therefore, the compounds 8, and 5 are promising as hits for the development of new antimicrobial drugs with reduced toxicity.

Novel Acaricidal Drug Fluazuron Causes Immunotoxicity via Selective Depletion of Lymphocytes T CD8.

Fluazuron is one of the newest veterinary antitick medicines. Belonging to the benzoylphenylureas group, its mechanism of action acts by the interference of the formation of the chitin of the tick, which is responsible for the hardening of its exoskeletons. In addition to taking care of the health of the animal so that it receives the medication in the doses and the correct form, it is important to analyze the safety of the operator. Reduced resistance to infectious disease was a well-documented consequence of primary and acquired immunodeficiencies, but a novel finding following xenobiotic exposure. The awareness of the consequences of altered immune function is the most likely outcome of inadvertent exposure. The human health implications of studies in which chemical exposure reduced resistance to infection drove an early focus on immunosuppression within the toxicology community. The main objective is to perform the evaluation by computational platforms and in cell culture, searching for data that can serve as a foundation for a better understanding of the toxic effects involved with the accidental contamination of Fluazuron and, thus, to assist the medical community and users to understand the risks inherent in its use. As far as we can determine in the literature, our work has unmistakably demonstrated that the Fluazuron can cause genotoxicity by probable chromatin rearrangement and immunodepleting by specific reduction of the CD8 T lymphocyte subpopulation, mediated by the decrease in gamma interferon production. Although the use of Fluazuron is a necessity for tick control and for cattle management, we must bear in mind that the imminent risks to its application exist. Careless use can damage the immune system which in turn carries a gigantic hazard by opening a door to diseases and pathogens and leaving us defenseless.

Biological Safety Studies and Simultaneous Determination of Linagliptin and Synthetic Impurities by LC-PDA.

A stability-indicating LC method was developed for quantification of linagliptin (LGT) and three synthetic impurities. The method utilizes a Thermo Scientific® RP-8 column (100 mm × 4.6 mm; 5 µm) with the PDA detector for quantitation of impurities. A mixture of 0.1% formic acid with pH 3.5 (A) and acetonitrile (B) was used as the mobile phase at a flow rate of 0.6 mL·min-1 with gradient elution. The percentage of mobile phase B increases from 30% to 70% over 5 min and decreases from 70% to 30% between 5 and 8 min. The method was validated according to International Council for Harmonization (ICH) guidelines. The LOD values obtained were 0.0171 µg·mL-1 and 0.015 µg·mL-1 for LGT and impurities, respectively. The LOQ values were 0.06 µg·mL-1 for LGT and impurities. In all cases, the correlation coefficients of LGT and impurities were >0.999, showing the linearity of the method. The % recovery of the LGT and added impurity were in the range of 92.92-99.79%. The precision of the method showed values less than 1.47% for LGT and less than 4.63% for impurities. The robustness was also demonstrated by small modifications in the chromatographic conditions. The selectivity was evidenced because the degradation products formed in stress conditions did not interfere in the determination of LGT and impurities. Toxicity prediction studies suggested toxicity potential of the impurities, which was confirmed using biological safety studies in vitro.

Golden mussel (Limnoperna fortunei) as a bioindicator in aquatic environments contaminated with mercury: Cytotoxic and genotoxic aspects.

This study evaluated the Limnoperna fortunei (golden mussel) as a bioindicator of cytotoxicity and genotoxicity in aquatic environments contaminated by heavy metals. Five groups of 50 subjects each were exposed to different concentration of mercuric chloride (HgCl2) (0.001 mg/L, group I; 0.005 mg/L, group II; 0.01 mg/L, group II; 0.02 mg/L, group IV; and 0.1 mg/L, group V). The control group for both chronic and acute treatment did not receive HgCl2. For chronic exposure, the respective groups were placed in aquaria with water contaminated with the above concentrations of HgCl2. For acute exposure, the different concentrations of HgCl2 were injected into the posterior adductor muscle of the individuals belonging to the aforementioned groups. The biological matrix used in the tests was the whole body muscle. Tests (cell viability assay, alkaline comet test; enumeration of micronuclei and necrotic cells, quantification of Hg content in tissues and water, and histopathological analysis of tissues), were carried out on the 7th, 15th, and 30th treatment days or 2 h after injection. Our results demonstrated that L. fortunei showed cell damage in both chronic and acute exposure groups. Significant DNA damage was observed at both the 15th (0.1 mg/L) and 30th (0.01-0.1 mg/L) days of chronic exposure. However, in acute treatment all concentrations induced DNA breaks. The presence of necrosis increased at all concentrations tested for both acute and chronic exposure. Tissue mercury retention on the 15th day was higher than on the 30th day of exposure, while in the same period, there was a decrease in the mercury content of aquarium water. Taking the data together, it is concluded that L. fortunei as a possible bioindicator of the quality of aquatic environments.

CdCl2 has zero-order kinetic cellular influx and induces cytotoxicity and genotoxicity at low concentrations in human leukocytes in vitro / El CdCl2 tiene un influjo celular cinético de orden cero e induce citotoxicidad y genotoxicidad a bajas concentraciones en leucocitos humanos in vitro

SUMMARY Cadmium (Cd2+) is a nonessential heavy metal that possesses a high capacity of bioaccumulation and exhibits toxic characteristics even at low concentrations. This study evaluated the genotoxicity and cytotoxicity in human leukocytes in vitro after exposure to a lower range of Cd2+concentration (1-25 (g/mL) using an unprecedented strategy by correlating between intracellular Cd2+ levels after exposure and cellular damage. Results demonstrated that Cd2+exposure from 5 to 25 fig/mL significantly increased the unviability of leukocytes, as well as the DNA damage, which was dose-dependent. The intracellular Cd2+ levels in leukocytes ranged from 9.85 to 94.38 pg/cell, and cytotoxicity and genotoxicity were induced at a concentration of24.22 pg/cell. The relationship between exposure concentration and intra-cellular Cd2+ levels suggests that its influx occurs in human leukocytes under zero-order kinetics.

RESUMEN El cadmio (Cd2+) es un metal pesado no esencial que posee una alta capacidad de bioacumulación y presenta características tóxicas incluso en bajas concentraciones. Este estudio evaluó la genotoxicidad y la citotoxicidad en leucocitos humanos in vitro después de la exposición a un rango inferior de concentración de Cd2+ (1-25 (g / mL) mediante una estrategia sin precedentes al correlacionar los niveles intracelulares de Cd2+ después de la exposición y el daño celular. Los resultados demostraron que la exposición a Cd2+ de 5 a 25 (g/mL aumentó significativamente la inviabilidad de los leucocitos, así como el daño en el ADN, que era dependiente de la dosis. Los niveles intracelulares de Cd2+ en leucocitos oscilaron entre 9,85 y 94,38 pg/célula, y se indujo la citotoxicidad y la genotoxicidad a una concentración de 24,22 pg/ célula. La relación entre la concentración de la exposición y los niveles intracelulares de Cd2+ sugiere que su influjo se produce en leucocitos humanos bajo una cinética de orden cero.

Is tartrazine really safe? In silico and ex vivo toxicological studies in human leukocytes: a question of dose.

The use of food colorings has a long-recorded history. Tartrazine (TRZ) is a dye that confers a lemon-yellow color to food and is widely used in the manufacture of numerous food products, as well as in pharmaceuticals and cosmetics. However, few studies have addressed the toxicology of TRZ in human cells or tissues. Considering the frequent consumption of the TRZ dye in food products and the lack of toxicological data, the present study aimed to evaluate the cytotoxicity and genotoxicity of the TRZ dye in human leukocyte cultures and perform theoretical studies to predict its toxicity in silico. Leukocyte cultures were treated with TRZ at concentrations of 5, 17.5, 35, 70, 100, 200, 300, 400, and 500 µg mL-1. All groups were assayed in triplicates. The mutagenicity was evaluated using the micronucleus test, the nuclear division index, and the nuclear division cytotoxicity index, and the chromosomal instability was quantitatively evaluated by band cytogenetics. Genotoxicity was evaluated using the alkaline comet test. Viability was assessed using the Trypan Blue method. Statistical analyses were performed using analysis of variance followed by Tukey's post hoc test, with a p value <0.05 reflecting statistical significance. No mutagenicity or cytotoxicity was found for the dye at the concentrations evaluated. However, DNA damage was induced by TRZ at a concentration of 70 µg mL-1. These results were confirmed by the predictive data from the in silico evaluations. Further studies are required to confirm our data, considering the frequency of the use of TRZ in the diet of the population, including that of children, as well as the exposure to TRZ through drugs, cosmetics, and other non-food products.

Immunotoxicological Evaluation of Schinus molle L. (Anacardiaceae) Essential Oil in Lymphocytes and Macrophages.

Schinus molle L. is used to treat various diseases; however, the literature lacks information regarding its possible immunotoxic effects. The aim of the study was to investigate the immunotoxic effects of essential oil from leaves of Schinus molle L. in cultures of human lymphocytes and macrophages. The cultures were treated with essential oil (EO) of Schinus molle L. and subsequently subjected to genotoxic analysis (comet assay), mutagenic analysis (micronucleus frequency and chromosomal aberration), and cytotoxic (cell viability) and functional parameters (interleukins secretions). Our analyses have determined that the essential oil from leaves of Schinus molle L. presents several compounds with α-pinene being the major compound; in addition, the compound verbenene was firstly identified; genotoxic effects were detected only in macrophages and only at the two highest concentrations tested. An important finding is that Schinus molle L. oil causes an activation of the immune system. This action has its mechanism centered by the cascade nitric oxide-interleukin-10-tumor necrosis factor alpha.

Cytotoxic and genotoxic effects of antihypertensives distributed in Brazil by social programs: Are they safe?

Hypertension, a chronic non-transmissible multifactorial condition, it is highly frequent in Brazil, affecting about 32.5% of the population over 25 years of age. It is characterized by the sustained increase in systolic and diastolic blood pressure levels above 140 mmHg and 90 mmHg, respectively. It is the major aggravating factor in cardiovascular complications and the appearance of other comorbidities. Aiming to promote greater adherence to treatment and improve the population's access to basic medicament, in 2004 the Federal Government created the Programa Farmácia Popular do Brasil (PFPB); partnership with private institutions that provides the population with medicament to control hypertension, free of charge or subsidized at up to 90% of the value. The PFPB distributes the anti-hypertensives atenolol, captopril, enalapril, hydrochlorothiazide, losartan and propranolol. In this way, this work aims to evaluate the genotoxic potential of antihypertensives in human lymphocytes and macrophages, since they are widely used drugs and with few studies about their genotoxicological safety. The tests were developed from cell cultures treated with five different antihypertensive concentrations, all based on plasma peaks, evaluating cell viability, DNA damage index and DNA double strand breakdown. The results show that, as the concentration of captopril and enalapril maleate increased, cell viability decreased. In addition, a DNA damage was observed with the use Captopril and Enalapril in the higher concentrations. Hydrochlorothiazide also caused DNA damage in the five doses tested. Regarding the breaking of double strands of DNA, all the compounds showed increased ruptures. This decrease in dsDNA is dose dependent for all compounds tested. The set of results shows that the use although frequent still requires care and greater knowledge. In general, the antihypertensive drugs that proved to be safer in relation to the genetic damage tested were Losartan and Propranolol.

Genotoxicity and cytotoxicity of oxindole alkaloids from Uncaria tomentosa (cat's claw): Chemotype relevance.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria tomentosa (Willdenow ex Roemer & Schultes) DC. (Rubiaceae) or cat's claw is a climber vine from the South American rainforest used in folk medicine for cancer treatment. Its antitumor activity has been mostly ascribed to pentacyclic oxindole alkaloids (POA) from stem bark and leaves while the activity of tetracyclic oxindole alkaloids (TOA) remains unknown. In recent times, the occurrence of three chemotypes based on its oxindole alkaloid profile was noticed in U. tomentosa, namely, chemotype I (POA cis D/E ring junction); chemotype II (POA trans D/E ring junction) or chemotype III (TOA). Consequently, the relationship between the chemotype and cytotoxic and genotoxic activities deserves attention. AIM OF THE STUDY: To evaluate the influence of cat's claw chemotypes on genotoxicity and cytotoxicity against non malignant and malignant human cell line models. MATERIAL AND METHODS: Four authentic stem bark cat's claw samples (SI-SIV) and two leaf samples (LII and LIII) were analyzed by HPLC-PDA, properly extracted and fractioned by ion-exchange to obtain oxindole alkaloid purified fractions (OAPFs). The freeze-dried fractions were assayed for genotoxicity and cytotoxicity against human leukocytes (non malignant cell line) by the micronuclei frequency method and the alkaline comet DNA assay, and the trypan blue method, respectively. Moreover, the cytotoxicity of each OAPF was evaluated against a human bladder cancer cell line (T24) and human glioblastoma cell line (U-251-MG) by MTT method (malignant cell lines). Additionally, the isomerization of oxindole alkaloids throughout the course of cell incubation was monitored by HPLC-PDA. RESULTS: Based on HPLC-PDA analyses, sample SI was characterized as chemotype I, while samples SII and LII were characterized as chemotype II, and samples SIII, SIV and LIII as chemotype III. The chemotypes showed comparable cytotoxic activity toward malignant cell lines (T24 and U-251-MG) unlike human leukocytes (non malignant cell line), where this activity was clearly distinct. Chemotype II (POA trans D/E ring junction) showed a higher selectivity index (SI) against malignant cells (SI=1.11-3.04) than chemotype I (SI=0.10-0.19) and III (SI=0.21-0.57). No important genotoxic potential was found by micronuclei frequency and alkaline comet DNA assays. Despite the isomerization of oxindole alkaloids during the cell incubation, the chemotype of the cat's claw samples remained unchanged. CONCLUSION: Cat's claw chemotypes showed different selectivity against human malignant cells, so that the correct identification of each chemotype seems to be important to better understand its antitumor potential.

In vitro and in silico toxicity evaluation of bioactive 4'-aminochalcone derivatives.

The 4'-aminochalcones compounds are open-chain flavonoids structures which have shown a known array of pharmacological activities, such as antibacterial, antifungal, anti-inflammatory and antitumor effects. There is little toxicological information available about these compounds in the literature. Therefore, the investigation of toxic effects of three 4'-aminochalcone derivatives was performed using in silico and in vitro assays. In silico provided results that indicated the occurrence of mutagenic and genotoxic effects. In vitro tests, using Cellular Proliferation and Viability, Micronucleus, and DNA damage by Comet assay, showed that the compounds studied also present mutagenic and genotoxic effects, which confirm the result determined by the in silico analysis. The use of experimental and computational models is complementary to each other and the results determined for 4'-aminochalones suggest that the chalcones should also be carefully considered since they show some risks to cause toxic effects to human cells.

Synthesis and biological evaluation of hydrazone derivatives as antifungal agents.

Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were obtained and their antifungal activity was evaluated against Candida species (C. parapsilosis, C. tropicalis, C. krusei, C. albicans, C. glabrata and C. lusitaneae) and Trichosporon asahii, in an in vitro screening. The minimum inhibitory concentrations (MICs) of the active compounds in the screening was determined against 10 clinical isolates of C. parapsilosis and 10 of T. asahii. The compounds 4-pyridin-2-ylbenzaldehyde] (13a) and tert-butyl-(2Z)-2-(3,4,5-trihydroxybenzylidine)hydrazine carboxylate (7b) showed the most promising MIC values in the range of 16-32 µg/mL and 8-16 µg/mL, respectively. The compounds' action on the stability of the cell membrane and cell wall was evaluated, which suggested the action of the compounds on the fungal cell membrane. Cell viability of leukocytes and an alkaline comet assay were performed to evaluate the cytotoxicity. Compound 13a was not cytotoxic at the active concentrations. These results support the discovery of promising candidates for the development of new antifungal agents.

Antifungal activity against Cryptococcus neoformans strains and genotoxicity assessment in human leukocyte cells of Euphorbia tirucalli L.

In the last times, focus on plant research has increased all over the world. Euphorbia tirucalli L., a plant known popularly as Aveloz, and originally used in Africa, has been drawing attention for its use in the United States and Latin America, both for use as an ornamental plant and as a medicinal plant. E. tirucalli L. is a member of the family Euphorbiaceae and contains many diterpenoids and triterpenoids, in particular phorbol esters, apparently the main constituent of this plant, which are assumed to be responsible for their activities in vivo and in vitro. The in vitro antifungal activities of Euphorbia tirucalli (L.) against opportunistic yeasts were studied using microbroth dilution assay. The results showed that aqueous extract and latex preparation were effective against ten clinical strains of Cryptococcus neoformans in vitro (Latex and extract MIC range of 3.2 - > 411 µg/mL). Aiming the safe use in humans, the genotoxic effects of E. tirucalli were evaluated in human leukocytes cells. Our data show that both aqueous extract and latex preparation have no genotoxic effect in human leukocytes cells in vitro. Although the results cannot be extrapolated by itself for use in vivo, they suggest a good perspective for a therapeutic application in future. In conclusion, our results show that the aqueous extract and latex preparation from E. tirucalli L. are antifungal agents effectives against several strains of C. neoformans and do not provoke DNA damage in human leukocyte cells, considering the concentrations tested.

The 2',4',6'-trihydroxyacetophenone isolated from Myrcia multiflora has antiobesity and mixed hypolipidemic effects with the reduction of lipid intestinal absorption.

This study evaluated the hypolipidemic and antiobesity effects of phloroacetophenone (2',4',6'-trihydroxyacetophenone, THA) isolated from Myrcia multiflora and their relationship with triglyceride (TG) intestinal absorption and pancreatic lipase activity inhibition. The hypolipidemic effect of THA was evaluated by acute (Triton WR-1339 treatment) and chronic assay (high-fat diet treatment), the antiobesity effect was evaluated by chronic assay (high-fat diet treatment), while the inhibition of enzymatic activity of pancreatic lipase was measured in the intestinal tissue of mice treated with high olive oil concentration. In the acute assay, THA caused greater total cholesterol (37 %) and triglyceride (46 %) serum level reduction than lovastatin (32 and 1 %), a HMG-CoA reductase inhibitor or orlistat (26 and 34 %), a gastrointestinal lipase inhibitor. In addition, in the chronic assay with a high-fat diet, THA reduced cholesterol and triglyceride levels (32 and 61 %, respectively) while lovastatin showed a decrease of 35 and 49 %, respectively. THA also caused a reduction in weight gain very similar to orlistat (40 and 38 %, respectively) when the animals were submitted to a high-fat diet. Moreover, THA showed a stronger and continuous pancreatic lipase inhibitory activity when compared with orlistat, causing inhibition of this enzyme during 6 hours associated to a significant reduction of triglyceride serum levels. The IN VIVO antiobesity and hypolipidemic effects of THA may be partly mediated by delaying the intestinal absorption of dietary fat by inhibiting pancreatic lipase activity.