Cytotoxic, acute oral toxicity, genotoxic and mutagenic assessment of the essential oil from fresh leaves of Croton argyrophyllus (Kunth.).

ETHNOPHARMACOLOGICAL RELEVANCE: Croton argyrophyllus Kunth., commonly known as "marmeleiro" or "cassetinga," is widely distributed in the Brazilian Northeast region. Its leaves and flowers are used in traditional medicine as tranquilizers to treat flu and headaches. AIM OF THE STUDY: This study was conducted to determine the chemical composition and toxicological safety of essential oil from C. argyrophyllus leaves using in vitro and in vivo models. MATERIALS AND METHODS: The chemical composition of the essential oil was determined using a gas chromatograph coupled to a mass spectrometer. Cytotoxicity was tested in the HeLa, HT-29, and MCF-7 cell lines derived from human cells (Homo sapiens) and Vero cell lines derived from monkeys (Cercopithecus aethiops) using the MTT method. Acute toxicity, genotoxicity. Mutagenicity tests were performed in Swiss mice (Mus musculus), which were administered essential oil orally in a single dose of 2000 mg/kg by gavage. RESULTS: The main components of the essential oil were p-mentha-2-en-1-ol, α-terpineol, ß-caryophyllene, and ß-elemene. The essential oil exhibited more than 90% cytotoxicity in all cell lines tested. No deaths or behavioral, hematological, or biochemical changes were observed in mice, revealing no acute toxicity. In genotoxic and mutagenic analyses, there was no increase in micronuclei in polychromatic erythrocytes or in the damage and index in the comet assay. CONCLUSIONS: The essential oil was cytotoxic towards the tested cell lines but did not exert toxic effects or promote DNA damage when administered orally at a single dose of 2000 mg/kg in mice.

Biological evaluation of 1,3-benzodioxole acids points to 3,4-(methylenedioxy) cinnamic acid as a potential larvicide against Aedes aegypti (Diptera: Culicidae).

Aedes aegypti serves as the primary vector for viruses like dengue, Chikungunya, Zika, and yellow fever, posing a significant public health challenge in Brazil. Given the absence of approved vaccines for these diseases, effective mosquito control becomes paramount in preventing outbreaks. However, currently available chemical insecticides face issues related to toxicity and the emergence of resistance, necessitating the exploration of new active compounds. Drawing inspiration from natural products, we identified the 1,3-benzodioxole group as a key pharmacophore associated with insecticidal activity. Therefore, this study aimed to synthesize and assess the larvicidal activity of 1,3-benzodioxole acids against Ae. aegypti, as well as their toxicity in mammals. Among the compounds evaluated, 3,4-(methylenedioxy) cinnamic acid (compound 4) demonstrated larvicidal activity. It exhibited LC50 and LC90 values of 28.9 ± 5.6 and 162.7 ± 26.2 µM, respectively, after 24 h of exposure. For reference, the positive control, temephos, displayed both LC50 and LC90 values below 10.94 µM. These findings underline the significance of the 3,4-methylenedioxy substituent on the aromatic ring and the presence of a double bond in the aliphatic chain for biological activity. Furthermore, compound 4 exhibited no cytotoxicity towards human peripheral blood mononuclear cells, even at concentrations up to 5200 µM. Lastly, in mice treated with 2000 mg kg-1, compound 4 showed mild behavioral effects and displayed no structural signs of toxicity in vital organs such as the kidney, liver, spleen, and lungs.

Insecticidal activity of essential oil from leaves of Eugenia stipitata McVaugh against Aedes aegypti.

Aedes aegypti, a mosquito, is responsible for the spread of many diseases, including dengue, zika, and chikungunya. However, due to this mosquito's developed resistance to conventional pesticides, effectively controlling it has proven to be challenging. This study aimed to evaluate the insecticidal potential of the essential oil from the leaves of Eugenia stipitata against Ae. aegypti, offering a natural and sustainable alternative for mosquito control. Tests were conducted using third-stage larvae to evaluate larvicidal activity and pupae collected up to 14 h after transformation to investigate pupicidal activity. Throughout the bioassays, the organisms were exposed to various essential oil concentrations. The findings demonstrated that the essential oil of E. stipitata exhibited larvicidal action, resulting in 100% larval mortality after 24 h and an LC50 value of 0.34 mg/mL. The effectiveness of essential oil as a pupicidal agent was also demonstrated by its LC50 value of 2.33 mg/mL and 100% larval mortality in 24 h. It can be concluded that the essential oil of E. stipitata holds promise as a natural pest control agent. Its use may reduce the reliance on conventional chemical pesticides, providing a more sustainable and effective strategy to combat diseases spread by mosquitoes.

Pectin-like polysaccharide extracted from leaves Crataeva tapia promotes antioxidant, immunomodulatory and emulsifiers applied in therapeutic formulations.

The objective of this work was to isolate a polysaccharide similar to pectin from Crataeva tapia leaves, not yet reported in the literature, and to evaluate its antioxidant, cytotoxic and immunomodulatory profile. Pectin was extracted from the leaves in three stages, organic solvent followed by acidified water and ethanol precipitation. With the pectin obtained, the physicochemical characterization of the molecule was carried out using high-performance liquid chromatography, Fourier-transform infrared spectroscopy, nuclear magnetic resonance (13C and 1H) and different thermal and elemental analysis. Furthermore, the antioxidant activities were evaluated in vitro, and using human peripheral blood mononuclear cell culture, cytotoxicity and immunostimulatory actions were investigated. Physical and chemical analyses showed characteristic signs of pectin. Antioxidant activity tests showed that pectin had moderate to low antioxidant activity. Furthermore, pectin did not affect the viability of erythrocytes and PBMC and induced an immunostimulatory state when it promoted the production of cytokines IL-6, IL-10 and TNF-α and increased the activation of CD8 + T lymphocytes. This study showed that pectin from Crataeva tapia is not cytotoxic and promoted a pro-inflammatory profile in peripheral blood mononuclear cell with application as an immunostimulating and emulsifying compound.

Role of synthetical amynoquinone ethyl 2-(1,4-dioxo-1,4-dihydronaphthalen-2-ylamino) acetate in inhibition of Ehrlich's tumor.

Quinones are naturally or synthetically occurring secondary metabolites that have various bio-dynamics, highlighting their antitumor potential. This has been explored through their selective cytotoxicity, and studies in medicinal chemistry about the relation between biological activity versus chemical structure may lead to the solution of the toxicity problems associated with quinones. In this context, the antitumor effect of a synthetic naphthoquinone, named Ethyl 2-(1,4-Dioxo-1,4-Dihydronaphthalen-2-Ylamino) Acetate, was tested using mice transplanted with Ehrlich ascitic tumor as an experimental model. The acute toxicity test was performed using 30 mice that received the aminoquinone at doses of 100, 200, 300, and 600 mg/kg. After evaluation of the clinical findings in the spontaneous activity tests, the LD50 calculation for the test substance showed low levels of toxicity at doses lower than 244.11 ± 23.29 mg/kg. Thus, three experimental groups were established, where animals transplanted with tumor cells received NaCl vehicle solution (control, n = 6), and the others were treated with 71.7 mg/kg of Methotrexate (n = 6) or 20 mg/kg of Aminoquinone (n = 6). All administrations were intraperitoneal, in a single dose. Three days after the implantation of the tumor cells the animals were weighed daily and evaluated for tumor biometry and development. The treatments occurred five days after the implantation of the tumor cells and were extended for 7 more days. At the end of the 12-day experimental period, all animals were euthanized for biochemical and histopathological analyses of the tumors and vital organs. The spontaneous activity test showed that the amount of responses associated with the nervous system tends to increase with the increase in dosage, highlighting the excitatory effect on the central nervous system in almost all dosages employed, followed by depressant activities on this system. There was a significant tumor reduction, both in animals treated with methotrexate (71.7 %) and in those treated with aminoquinone (91.6 %) in the control group. There was no significant difference in tumor volume between the animals treated with aminoquinone or methotrexate. The histopathological analysis revealed that in both treatments there were fewer mitoses in the tumor mass compared to the control group. However, there was apparent toxicity to the liver, heart, and left kidney in the treatment with methotrexate compared to aminoquinone. The significant capacity for tumor reduction presented by aminoquinone allows pointing it as a promising alternative for the development of a more efficient drug to control tumor development, being necessary for the development of new studies to deepen the knowledge about its mechanisms of action.

Drimys (cataia, canelo, quiebra-muelas): uma revisão literária sobre sua fitoquímica, atividades biológicas, farmacológicas e toxicológicas / Drimys (cataia, canelo, quiebra-muelas): a literature review on its phytochemistry, biological, pharmacological and toxicological activities / Drimys (cataia, canelo, quiebra-muelas): una revisión bibliográfica sobre sus actividades fitoquímicas, biológicas, farmacológicas y toxicológicas

Drimys é um dos gêneros mais conhecidos da família botânica Winteraceae. As espécies que compõe este gênero têm sido amplamente utilizadas na medicina popular latino americana para o tratamento de malária, dores gástricas, dor de dente, anemia, entre outros. Além do mais, em algumas localidades, as folhas secas e as bagas dos frutos são utilizadas na culinária como condimento pois possuem sabor apimentado. O objetivo deste trabalho foi realizar uma revisão sistemática sobre a fitoquímica, atividades biológicas, farmacológicas e toxicologicas das espécies do gênero Drimys. Para isso, foram realizadas buscas em diferentes plataformas, no período de 1987 e 2022, utilizando-se a palavra "Drimys", indicativa do gênero botânico, acompanhado dos descritores: "Winteraceae", "pharmacology", "neoplasm", "inflammation", "insecticides", "clinical trial", "pain", "food", "ulcer", "malaria" e "toxicity". Incluiu-se trabalhos sobre o perfil fitoquímico, atividades biológicas e potencial farmacológico. Foram selecionados 77 artigos científicos sobre as espécies D. winteri, D. brasiliensis, D. angustifolia, D. granadensis e D. piperita com informações de estudos in vivo e in vitro que possibilitam o conhecimento medicinal, a conservação e o uso sustentável destas espécies.

Drimys is one of the best known genera of the botanical family Winteraceae. The species that make up this genus have been widely used in Latin American popular medicine for the treatment of malaria, gastric pain, toothache, anemia, among others. Moreover, in some places, the dried leaves and berries of the fruits are used in cooking as a condiment because they have a spicy flavor. The objective of this work was to perform a systematic review on the phytochemical, biological, pharmacological and toxicological activities of the species of the genus Drimys. For this, searches were made in different platforms, between 1987 and 2022, using the word "Drimys", indicative of the botanical genus, accompanied by the descriptors: "Winteraceae", "pharmacology", "neoplasm", "inflammation", "insecticides", "clinical trial", "pain", "food", "ulcer", "malaria" and "toxicity". Papers on phytochemical profile, biological activities, and pharmacological potential were included. A total of 77 scientific articles on the species D. winteri, D. brasiliensis, D. angustifolia, D. granadensis and D. piperita were selected, with information from in vivo and in vitro studies that enable medicinal knowledge, conservation and sustainable use of these species.

Drimys es uno de los géneros más conocidos de la familia botánica Winteraceae. Las especies que componen este género han sido ampliamente utilizadas en la medicina popular latinoamericana para el tratamiento de la malaria, dolor gástrico, dolor de muelas, anemia, entre otros. Además, en algunos lugares, las hojas secas y las bayas de los frutos se utilizan en la cocina como condimento porque tienen un sabor picante. El objetivo de este trabajo fue realizar una revisión sistemática sobre las actividades fitoquímicas, biológicas, farmacológicas y toxicológicas de las especies del género Drimys. Para ello, se realizaron búsquedas en diferentes plataformas, entre 1987 y 2022, utilizando la palabra "Drimys", indicativa del género botánico, acompañada de los descriptores: "Winteraceae", "farmacología", "neoplasia", "inflamación", "insecticidas", "ensayo clínico", "dolor", "alimentación", "úlcera", "malaria" y "toxicidad". Se incluyeron artículos sobre perfil fitoquímico, actividades biológicas y potencial farmacológico. Se seleccionaron 77 artículos científicos sobre las especies D. winteri, D. brasiliensis, D. angustifolia, D. granadensis y D. piperita, con información de estudios in vivo e in vitro que permiten el conocimiento medicinal, la conservación y el uso sostenible de estas especies.

Avaliação da atividade antimicrobiana e antitumoral, frente ao sarcoma 180, do extrato bruto de luffa operculata cogn. (cucurbitaceae) / Assessment of antimicrobial and anti-tumor activity, against sarcoma 180, of the crude extract of luffa operculata cogn. (cucurbitaceae) / Evaluación de la actividad antimicrobiana y antitumoral frente a sarcoma 180 del extracto crudo de luffa operculata cogn. (cucurbitaceae)

Luffa operculata Cogn. pertence à família Cucurbitaceae, sendo popularmente denominada como buchinha, cabaçinha e purga-dos-paulistas. Sua análise fitoquímica demonstrou a presença de glicosídeos, saponina e resina, esteróis livres, ácidos orgânicos, fenóis e, com ausência de taninos. Além disso, essa família é produtora de triterpenos com esqueletos modificados denominados de cucurbitacinas, substâncias de alto valor farmacológico. Este trabalho teve como objetivo avaliar a atividade antimicrobiana e antitumoral, frente ao Sarcoma 180, do extrato bruto da Luffa operculata Cogn.. No ensaio antimicrobiano foram utilizadas espécimes bacterianas e fúngicas da origem clínica e de coleção. Para analisar a atividade antitumoral, células tumorais foram implantadas na região axilar de camundongos albinos Swiss (Mus musculus). O grupo controle recebeu solução salina 0,9% e no grupo padrão administrou-se metotrexato (10 mg/kg de peso corpóreo). Os grupos tratados receberam por via intraperitoneal doses nas concentrações de 0,3, 0,6 ou 1,0 mg/kg de peso corpóreo do extrato bruto etanólico de Luffa operculata Cogn.. Os resultados demonstraram que o extrato do Luffa operculata Cogn. apresenta atividade antimicrobiana contra Staphylococcus aureus, Staphylococcus epidermidis, Candida albicans e Candida tropicalis. No que diz respeito a atividade antitumoral, os animais tratados com o extrato nas doses 0,3 e 0,6 mg/kg não apresentaram redução relevante dos tumores de Sarcoma 180, quando comparado com o grupo controle. Entretanto, os animais tratados com a dose 1,0 mg/kg obtiveram índice de inibição de 61,7%. Dessa forma, concluímos que o extrato bruto de Luffa operculata Cogn. apresenta atividade antimicrobiana e, na dose de 1 mg/kg, apresenta atividade antitumoral reduzindo significativamente os tumores de Sarcoma 180.

Luffa operculata Cogn. belongs to the Cucurbitaceae family, popularly known as buchinha, cabaçinha and purga-dos-paulistas. Its phytochemical analysis demonstrated the presence of glycosides, saponin and resin, free sterols, organic acids, phenols and the absence of tannins. In addition, this family produces triterpenes with modified skeletons called cucurbitacins, substances of high pharmacological value. This work aimed to evaluate the antimicrobial and antitumor activity, against Sarcoma 180, of the crude extract of Luffa operculata Cogn.. In the antimicrobial assay, bacterial and fun- gal specimens of clinical and collection origin were used. To analyze the antitumor activ- ity tumor cells were implanted in the axillary region in albino Swiss mice (Mus musculus). The control group received 0.9% saline solution; and the standard group received meth- otrexate (10 mg/kg per body weight). The treated groups received intraperitoneal doses at concentrations of 0.3, 0.6; and 1.0 mg/kg per body weight of crude ethanolic extract of Luffa operculata Cogn., respectively. The results demonstrated that the extract of Luffa operculata Cogn. has antimicrobial activity against Staphylococcus aureus, Staphylococ- cus epidermidis, Candida albicans, and Candida tropicalis. Concerning antitumor activ- ity, the animals treated with the extract at doses of 0.3 and 0.6 mg/kg did not show a relevant reduction in Sarcoma 180 tumors, when compared to the control group. How- ever, animals treated with a dose of 1mg/kg had an inhibition rate of 61.7%. Thus, we concluded that the crude extract of Luffa operculata Cogn. it has antimicrobial activity; and only at the highest dose (1 mg/kg) did it significantly reduce Sarcoma 180 tumors. KEYWORDS: Luffa Operculata Cogn.; Antimicrobian Activity; Sarcoma 180.

Luffa operculata Cog. pertenece a la familia de las Cucurbitáceas, siendo popularmente conocida como buchinha, cabaçinha y purga-dos-paulistas. Su análisis fi- toquímico demostró la presencia de glucósidos, saponina y resina, esteroles libres, ácidos orgánicos, fenoles y ausencia de taninos. Además, esta familia es produtora de triterpenos con esqueletos modificados llamados cucurbitacinas, sustancias de alto valor farmacoló- gico. Este trabajo tuvo como objetivo evaluar la actividad antimicrobiana y antitumoral, contra el Sarcoma 180, del extracto crudo de Luffa operculata Cogn.. En el ensayo anti- microbiano se utilizaron especímenes bacterianos y fúngicos de origen clínico y de co- lección. Para analizar la actividad antitumoral, se implantaron células tumorales en la región axilar de ratones albinos suizos (Mus musculus). El grupo control recibió solución salina al 0,9% y el grupo estándar recibió metotrexato (10 mg/kg por peso corporal). Los grupos tratados recibieron dosis intraperitoneales a concentraciones de 0,3, 0,6 y 1,0 mg/kg por peso corporal de extracto etanólico crudo de Luffa operculata Cogn., respec- tivamente. Los resultados demostraron que el extracto de Luffa operculata Cogn. tiene actividad antimicrobiana contra Staphylococcus aureus, Staphylococcus epidermidis, Candida albicans y Candida tropicalis. En cuanto a la actividad antitumoral, los animales tratados con el extracto a dosis de 0,3 y 0,6 mg/kg no mostraron una reducción relevante de tumores Sarcoma 180, al compararlos con el grupo control. Sin embargo, los animales tratados con una dosis de 1 mg/kg tuvieron una tasa de inhibición del 61,7 %. Por lo tanto, concluimos que el extracto crudo de Luffa operculata Cogn. tiene actividad antimicro- biana y solo en la dosis más alta (1 mg/kg) redujo significativamente los tumores Sarcoma 180.

Avaliação toxicológica e determinação da dl 50 do extrato bruto de luffa operculata cogn. (cucurbitaceae) / Toxicological evaluation and determination of ld 50 of the crude extract of luffa operculata cogn. (cucurbitaceae) / Evaluación toxicológica y determinación de la dl 50 del extracto crudo de luffa operculata cogn. (cucurbitáceas)

As plantas medicinais têm sido bastante utilizadas para o tratamento de várias enfermidades pelo homem. Numerosos compostos bioativos obtidos de plantas medicinais apresentam atividades antimicrobianas, antivirais, anticancerígenas, anti- inflamatórias, antioxidantes e neuromoduladoras. Entretanto, existe um número crescente de estudos científicos que comprovam a toxicidade de plantas medicinais. O fruto da Luffa operculata Cogn. é utilizado popularmente como purgante, emenogogo, expectorante e rinossinusite. Este trabalho teve como objetivo avaliar a toxicidade aguda e determinar a dose letal 50% (LD50) do extrato bruto etanólico de Luffa operculata Cogn., por via intraperitoneal em camundongos. No experimento foi utilizado camundongos albinos fêmeas Swiss (Mus Muscullus). Os animais foram divididos em grupos (n=6/grupo), e a toxicidade foi avaliada em duas etapas: preliminar e definitiva. As reações comportamentais relacionadas às doses administradas do extrato de Luffa operculata Cogn. foram taquicardia, taquipneia, movimentos estereotipados e circulares e piloereção. Após essa fase, os animais apresentaram reações depressoras envolvendo apneia e prostração. Além disso, os animais apresentaram outros comportamentos como: contorções abdominais, tônus da musculatura abdominal, espasmos e irritação da conjuntiva. O extrato de Luffa operculata Cogn. apresentou uma DL50 de 3,3 mg/Kg de peso corpóreo, sendo considerada muito tóxica. Como essa planta é largamente usada pela população para fins terapêuticos, alertamos quanto a utilização indiscriminada devido ao alto potencial tóxico.

Medicinal plants have been sed for the treatment of various diseases by man. Numerous bioactive compounds obtained from medicinal plants exhibit antimicrobial, antiviral, anticancer, anti-inflammatory, antioxidant, and neuromodulatory activities. However, the number of scientific studies proving the toxicity of medicinal plants is increasing. The fruit of Luffa operculata Cogn. it is popularly used as a purgative, emmenagogue, expectorant, and rhinosinusitis. This work aimed to evaluate the acute toxicity and determine the lethal dose of 50% (LD50) of the crude ethanolic extract of Luffa operculata Cogn., intraperitoneally. In the experiment, Swiss female albino mice (Mus Muscullus) were used. The animals were divided into groups (n=6/group), and toxicity was evaluated in two steps: preliminary and definitive. Behavioral reactions related to administered doses of Luffa operculata Cogn. were tachycardia, tachypnea, stereotyped, and circular movements and piloerection. After this phase, the animals presented depressive reactions involving apnea and prostration. In addition, the animals showed other behaviors such as abdominal contortions, abdominal muscle tone, spasms, and irritation of the conjunctiva. The extract of Luffa operculata Cogn. presented an LD50 of 3.3 mg/Kg of body weight, being considered very toxic. As this plant is widely used by the population for therapeutic purposes, we warn about its use due to its high toxic potential.

Las plantas medicinales han sido ampliamente utilizadas para el tratamiento de diversas enfermedades por parte del hombre. Numerosos compuestos bioactivos obte- nidos de plantas medicinales exhiben actividades antimicrobianas, antivirales, anticance- rígenas, antiinflamatorias, antioxidantes y neuromoduladoras. Sin embargo, hay un nú- mero creciente de estudios científicos que prueban la toxicidad de las plantas medicinales. El fruto de Luffa operculata Cogn. se utiliza popularmente como purgante, emenogogo, expectorante y rinosinusitis. Este trabajo tuvo como objetivo evaluar la toxicidad aguda y determinar la dosis letal al 50% (DL50) del extracto etanólico crudo de Luffa operculata Cogn., por vía intraperitoneal. En el experimento se utilizaron ratones albinos hembra suizos (Mus Muscullus). Los animales se dividieron en grupos (n=6/grupo) y la toxicidad se evaluó en dos etapas: preliminar y definitiva. Reacciones conductuales relacionadas con las dosis administradas de Luffa operculata Cogn. fueron taquicardia, taquipnea, mo- vimientos estereotipados y circulares y piloerección. Después de esta fase, los animales presentaron reacciones depresivas involucrando apnea y postración. Además, los anima- les mostraron otros comportamientos como: contorsiones abdominales, tono muscular abdominal, espasmos e irritación de la conjuntiva. El extracto de Luffa operculata Cogn. presentó una DL50 de 3,3 mg/Kg de peso corporal, considerándose muy tóxico. Como esta planta es muy utilizada por la población con fines terapéuticos, advertimos contra su uso indiscriminado por su alto potencial tóxico.

Sepsis and septic shock: epidemiology, clinical parameters, and prognostic factors in a brazilian intensive care unit / Sepse e choque séptico: epidemiologia, parâmetros clínicos e fatores prognósticos em uma unidade de terapia intensiva brasileira / Sepsis y shock séptico: epidemiología, parámetros clínicos y factores pronósticos en una unidad de cuidados intensivos brasileña

Sepsis is an organ dysfunction caused by a dysregulated host response to infection and is associated with high morbidity and mortality. The identification of prognostic markers in this syndrome has been a strategy to increase treatment efficacy. The objectives of this study were: 1) to describe the epidemiological and microbiological profile of septic patients and 2) to investigate the association between laboratory/clinical parameters and mortality rate, identifying prognostic markers. Using a prospective observational protocol, epidemiological, clinical and laboratory data were collected from adult patients with sepsis or septic shock admitted to a Brazilian Intensive Care Unit. During the study period, 120 patients were diagnosed with sepsis and 71.67% (n = 86) were included in the protocol. The overall mortality was 69.76% and chronic diseases were identified in 79.07% of cases. The mortality rates for sepsis and septic shock were 51.06% and 92.31%, respectively. SOFA scores on the first, third, and seventh days of hospitalization gradually increased for patients who had clinical worsening. Hyperlactatemia and hyperglycemia were identified in 45.9% and 27% of patients, respectively, and were associated with mortality. INR values greater than 1.5 or thrombocytopenia were related to 92.9% and 88.6% mortality, respectively. In the study, gender, age, ICU stay, site of infection and microbiological agent were not associated with the risk of death. However, the presence of comorbidities, high SOFA scores, three or more organ dysfunctions, and sepsis severity correlated directly with mortality rate.

A sepse é uma disfunção orgânica causada por uma resposta desregulada do hospedeiro à infecção e está associada a alta morbidade e mortalidade. A identificação de marcadores prognósticos nessa síndrome tem sido uma estratégia para aumentar a eficácia do tratamento. Os objetivos deste estudo foram: 1) descrever o perfil epidemiológico e microbiológico de pacientes sépticos e 2) investigar a associação entre parâmetros laboratoriais/clínicos e a taxa de mortalidade, identificando marcadores prognósticos. Por meio de um protocolo observacional prospectivo foram coletados dados epidemiológicos, clínicos e laboratoriais de pacientes adultos com sepse ou choque séptico internados em uma Unidade de Terapia Intensiva brasileira. No período do estudo, 120 pacientes foram diagnosticados com sepse e 71,67% (n = 86) foram incluídos no protocolo. A mortalidade geral foi de 69,76% e doenças crônicas foram identificadas em 79,07% dos casos. As taxas de mortalidade por sepse e choque séptico foram de 51,06% e 92,31%, respectivamente. Os escores SOFA no primeiro, terceiro e sétimo dias de internação aumentaram gradativamente para os pacientes que apresentaram piora clínica. Hiperlactatemia e hiperglicemia foram identificadas em 45,9% e 27% dos pacientes, respectivamente, tendo sido associadas à mortalidade. Valores de INR maiores que 1,5 ou trombocitopenia foram relacionados a 92,9% e 88,6% de mortalidade, respectivamente. No estudo, sexo, idade, permanência na UTI, local da infecção e agente microbiológico não se associaram ao risco de óbito. No entanto, a presença de comorbidades, altos escores SOFA, três ou mais disfunções orgânicas e a gravidade da sepse correlacionaram-se diretamente com a taxa de mortalidade.

La sepsis es una disfunción orgánica causada por una respuesta desregulada del huésped a la infección y se asocia a una elevada morbilidad y mortalidad. La identificación de marcadores pronósticos en este síndrome ha sido una estrategia para aumentar la eficacia del tratamiento. Los objetivos de este estudio fueron: 1) describir el perfil epidemiológico y microbiológico de los pacientes sépticos y 2) investigar la asociación entre los parámetros de laboratorio/clínicos y la tasa de mortalidad, identificando marcadores pronósticos. Mediante un protocolo observacional prospectivo, se recogieron datos epidemiológicos, clínicos y de laboratorio de pacientes adultos con sepsis o shock séptico ingresados en una Unidad de Cuidados Intensivos brasileña. Durante el período de estudio, 120 pacientes fueron diagnosticados de sepsis y el 71,67% (n = 86) fueron incluidos en el protocolo. La mortalidad global fue del 69,76% y se identificaron enfermedades crónicas en el 79,07% de los casos. Las tasas de mortalidad por sepsis y shock séptico fueron del 51,06% y el 92,31%, respectivamente. Las puntuaciones SOFA en el primer, tercer y séptimo día de hospitalización aumentaron gradualmente en los pacientes que presentaron empeoramiento clínico. La hiperlactatemia y la hiperglucemia se identificaron en el 45,9% y el 27% de los pacientes, respectivamente, y se asociaron a mortalidad. Los valores de INR superiores a 1,5 o la trombocitopenia se relacionaron con un 92,9% y un 88,6% de mortalidad, respectivamente. En el estudio, el sexo, la edad, la estancia en la UCI, el lugar de la infección y el agente microbiológico no se asociaron con el riesgo de muerte. Sin embargo, la presencia de comorbilidades, las puntuaciones SOFA elevadas, tres o más disfunciones orgánicas y la gravedad de la sepsis se correlacionaron directamente con la tasa de mortalidad.

Naltrexone/bupropion modifies weight, food intake, and Drd2 gene expression in rats.

Obesogenic diets are known to induce obesity and changes in food intake in experimental animals. Obesity negatively affects the peripheral metabolism and neural aspects, such as changes in eating behavior. In obese animals, dopamine (DA) receptor levels are reduced. DA is one of the main peptides involved in the motivation and pleasure of eating. A combination of naltrexone/bupropion (NB) has shown promise in controlling metabolic alterations, but there are few studies on how they modulate dopaminergic expression. NB, in addition to reducing food intake and body weight, can modify tyrosine hydroxylase (Th) and DA receptor D2 (Drd2) levels in the mesolimbic areas of rats submitted to a high-fat diet (HF). The study evaluated the effect of NB on food intake, body weight, and expression levels of Th, Drd1a, and Drd2, in the nucleus accumbens and striatum of rats fed on HF diet. Wistar rats were grouped according to diet: standard (n = 20) and HF diet (n = 20). The food intake and body weight were analyzed. The gene expression of Th, Drd1a, and Drd2 was evaluated using real-time PCR. NB combination of 1 mg/kg and 20 mg/kg reduced food intake and body weight, increased Drd2 expression in rats on HF diet, and increased Th in rats on both experimental diets. The level of Drd1a was unchanged. We concluded that bodyweight reduction may be associated with decreased food intake in response to the increased Drd2 expression in the mesolimbic areas of rats that received an HF diet.

Characterization of a lignin from Crataeva tapia leaves and potential applications in medicinal and cosmetic formulations.

Lignins are phenolic macromolecules that have several applications. In this work, we examine some biological activities of a lignin-like macromolecule isolated from the Crataeva tapia leaves, not yet studied to evaluate its potential applications in medicinal and cosmetic formulations. Lignin was obtained by alkaline delignification and its physical-chemical characterization was made by means of FT-IR, UV-Vis, NMR spectroscopy, elementary analysis, molecular mass determination and thermal analysis. Lignin is of the GSH type, with levels of hydrogen (5.10%), oxygen (27.18%), carbon (67.60%), nitrogen (0.12%) and phenolic content of 189.6 ± 9.6 mg GAE/g. In addition, it is a thermally stable macromolecule with low antioxidant activity. Cytotoxicity and cytokine production were assessed by flow cytometry. The photoprotective activity was evaluated by adding different concentrations of lignin to a commercial cream. Lignin was not cytotoxic, it stimulated the production of TNF-α, IL-6 and IL-10 and did not promote a significant change in nitric oxide levels. In addition, this macromolecule was able to promote increased absorption of ultraviolet light from a commercial cream. These results reinforce the ethnopharmacological use of C. tapia leaves and suggest the need for further studies to determine the potential medicinal and cosmetic applications (sunscreen) of lignin from C. tapia leaves.

Toxicity assessment of saline extract and lectin-rich fraction from Microgramma vacciniifolia rhizome.

Microgramma vacciniifolia is broadly used in folk medicine but safety information is unavailable. Therefore, we evaluated the toxicity of a saline extract and a lectin-rich fraction of M. vacciniifolia rhizome. The extract showed hemolytic activity on mice erythrocytes at 1000 µg/mL, whereas the fraction promoted hemolysis (8.57-26.15%) at all tested concentrations (10-1000 µg/mL). Acute toxicity test in mice indicated an LD50 of >5000 mg/kg. Hematological alterations and increased serum alkaline phosphatase level were observed in the treated animals. Transaminases and urea levels increased in the groups treated with the extract or fraction at 5000 mg/kg. Leukocyte infiltration was observed in the liver of extract-treated animals and in the liver and lungs of mice treated with the fraction. The kidneys of animals treated with the fraction at 5000 mg/kg presented hydropic degeneration. The extract and fraction did not induce oxidative stress in the liver and did not show genotoxicity, as examined by micronucleus and comet assays. In conclusion, the preparations were not lethal to mice but caused some signs of toxicity, mainly the fraction. The results indicated the need to evaluate the toxicity of M. vacciniifolia rhizome in other models and in chronic assays.

Evaluation of the cytotoxicity, oral toxicity, genotoxicity, and mutagenicity of the latex extracted from Himatanthus drasticus (Mart.) Plumel (Apocynaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Himatanthus drasticus is a tree popularly known as janaguba. Endemic to Brazil, it is found in the Cerrado and Caatinga biomes, rock fields, and rainforests. Janaguba latex has been used in folk medicine for its antineoplastic, anti-inflammatory, analgesic, and antiallergic activities. However, studies investigating the safety of its use for medicinal purposes are limited. AIM OF THE STUDY: This study aimed to evaluate the toxicity of the latex extracted from H. drasticus. MATERIALS AND METHODS: The latex was extracted from H. drasticus specimens by removing a small area of bark (5 × 30 cm) and then dissolving the exudate in water and lyophilizing it. Phytochemical screening was performed by TLC and GC-MS, protein, and carbohydrate levels. Cell viability was performed by the MTT method. Acute oral toxicity, genotoxicity, and mutagenicity assays were performed in mice. RESULTS: TLC showed the presence of saponins and reducing sugars, as well as steroids and terpenes. The GC-MS analysis of the nonpolar fraction identified lupeol acetate, betulin, and α/ß-amyrin derivatives as the major compounds. The latex was toxic to S-180 cells at 50 and 100 µg/mL. No signals of toxicity or mutagenicity was found in mice treated with 2000 mg/kg of the latex, but genotoxicity was observed in the Comet assay. CONCLUSIONS: H. drasticus latex showed toxicity signals at high doses (2000 mg/kg). Although the latex was not mutagenic to mice, it was genotoxic in the Comet assay in our experimental conditions. Even testing a limit dose of 2000 mg/kg, which is between 10 to 35-fold the amount used in folk medicine, caution must be taken since there is no safe level for genotoxic compounds exposure. Further studies on the toxicological aspects of H. drasticus latex are necessary to elucidate its possible mechanisms of genotoxicity.

Nanoparticles in the Use of Natural Products for the Treatment of Lung Cancer / Nanopartículas en el empleo de productos naturales para el tratamiento del cáncer de pulmón

Objective: Carry out a bibliographical survey about the use of nanoparticles in the delivery of natural products for the treatment of lung cancer. Methods: A bibliographic review was made using the descriptors "Nanoparticles", "Biological Products" and "Lung Neoplasms", through the databases ScienceDirect, PubMed and SciELO, in the period from 2009 to 2018. Results: After analyzing the articles according to the inclusion criteria, we obtained 31 articles, of which 25.81% refer to natural products in the treatment of lung cancer, 29.03% to nanoparticles in the treatment of lung cancer and 45.16 % to nanoparticles as carriers of natural products for the treatment of lung cancer. Conclusion: The use of nanoparticles allows the delivery of natural products, increasing their therapeutic properties against lung cancer cells, and decreasing the side effects of these highly toxic agents

Objetivo: Realizar un estudio bibliográfico sobre el uso de nanopartículas en el transporte de productos naturales para el tratamiento del cáncer de pulmón. Métodos: Se realizó una revisión bibliográfica utilizando los descriptores "Nanoparticles", "Biological Products" y "Lung Neoplasms", a través de las bases de datos ScienceDirect, PubMed y SciELO, en el período comprendido entre 2009 y 2018. Resultados: Después del análisis de los artículos de acuerdo con los criterios de inclusión, obtuvimos 31 artículos, de los cuales 25.81% hacían referencia a productos naturales en el tratamiento del cáncer de pulmón, el 29.03% a nanopartículas en el tratamiento del cáncer de pulmón y un 45.16 % a nanopartículas como agentes transportadores de productos naturales para el tratamiento del cáncer de pulmón. Conclusión: El uso de nanopartículas permite el transporte de productos naturales, aumentando sus propiedades terapéuticas contra las células de cáncer de pulmón, además de disminuir los efectos secundarios de estos agentes altamente tóxicos

Correction: MOF@activated carbon: a new material for adsorption of aldicarb in biological systems.

Correction for 'MOF@activated carbon: a new material for adsorption of aldicarb in biological systems' by Carlos Alberto Fernandes de Oliveira et al., Chem. Commun., 2013, 49, 6486-6488.

Evaluation of acute toxicity of β-lapachone associated with chitosan as a cytoprotective agent / Avaliação da toxicidade aguda da β-lapachona associada à quitosana como agente citoprotetor

ABSTRACT INTRODUCTION: β-lapachone (β-LAP), a potent antitumor agent, has limited therapeutic use due to its low solubility and high toxicity. A possible strategy to overcome these drawbacks may be the use of adjuvants such as chitosan (CS), a cationic polysaccharide with biological properties of biocompatibility and biodegradability. OBJECTIVE: Evaluate the adjuvant action of CS as a cytoprotectant associated with β-LAP, through acute toxicity studies, evaluating histopathological changes in organs such as liver and kidneys. METHODS: The β-LAP-CS conjugate was prepared in a 1:1 ratio, administered orally, with a single dose of β-LAP of 80 mg/kg, in Swiss mice. Histomorphological and histomorphometric analyses of the kidneys and liver were performed. RESULTS: In the histomorphological studies of the tested groups, we observed that the hepatocytes of animals treated with the free drug presented morphological alterations, such as cytoplasmic vacuolization, cellular extravasation, atypical and pyknotic nuclei. In this same group, the kidneys presented granular aspects suggestive of glomerulonephritis. These changes were not found in the control group and in animals treated with CS-conjugated β-LAP. There was no statistical difference in the histomorphometric analyses of the distal tubules and the renal glomeruli between the three groups analyzed, even with evident histomorphological alterations. After histomorphometric studies, it was observed that the area of hepatocytes and their cell nuclei presented a statistically significant difference between the animals treated with free β-LAP and the β-LAP-CS. CONCLUSION: The decrease in β-LAP toxicity after conjugation may be related to the hepatoprotective property of CS.

RESUMO INTRODUÇÃO: A β-lapachona (β-LAP), um potente agente antitumoral, tem uso terapêutico limitado devido a sua baixa solubilidade e elevada toxicidade. Uma possível estratégia para contornar esses inconvenientes pode ser a utilização de adjuvantes como a quitosana (QS), um polissacarídeo catiônico com propriedades biológicas, como biocompatibilidade e biodegradabilidade. OBJETIVO: Avaliar a ação adjuvante da QS como citoprotetor associada à β-LAP por meio de estudos de toxicidade aguda, verificando as alterações histopatológicas em órgãos como fígado e rins. MÉTODOS: Um conjugado da β-LAP-QS foi preparado na proporção 1:1, administrado por via oral, com dose única da β-LAP de 80 mg/kg, em camundongos Swiss. Foram realizadas análises histomorfológicas e histomorfométricas dos rins e do fígado desses animais. RESULTADOS: Nos estudos histomorfológicos dos grupos testados, observamos que os hepatócitos dos animais tratados com a droga livre apresentaram alterações morfológicas, como vacuolização do citoplasma, extravasamento celular, núcleos atípicos e picnóticos. Nesse mesmo grupo, os rins apresentaram aspectos granulosos sugestivos de glomerulonefrite. Essas alterações não foram encontradas no grupo-controle e nos animais tratados com a β-LAP conjugada com QS. Não houve diferença estatística nas análises histomorfométricas dos túbulos distais e dos glomérulos renais entre os três grupos analisados, mesmo com alterações histomorfológicas evidentes. Após estudos histomorfométricos, foi observado que a área dos hepatócitos e seus núcleos celulares apresentaram diferença estatística significativa entre os animais tratados com a β-LAP livre e o conjugado β-LAP-QS. CONCLUSÃO: A diminuição da toxicidade da β-LAP, após ser conjugada, pode estar relacionada com a propriedade hepatoprotetora da QS.

Anacardic Acids from Cashew Nuts Prevent Behavioral Changes and Oxidative Stress Induced by Rotenone in a Rat Model of Parkinson's Disease.

Anacardic acids (AAs) are alkyl phenols mainly presenting in cashew nuts. The antioxidant effects of these compounds have been an area of interest in recent research, with findings suggesting potential therapeutic use for certain diseases. Nevertheless, none of these studies were performed in order to test the hypothesis of whether anacardic acids are capable of preventing behavioral changes and oxidative stress induced by the pesticide rotenone in experimental model of Parkinson's disease. In our research, adult male rats were treated orally with AAs (1, 3, 10, 25, 50, or 100 mg/kg/day) 1 h before rotenone (3 mg/kg; s.c.) for five consecutive days. The behavioral testing strategies, including tests for general locomotor activity (open field), motor coordination (rotarod), and spatial memory performance (elevated T-maze), were carried out. Lipoperoxidation levels and total superoxide dismutase (t-SOD) activity, as well as cytoplasmic and mitochondrial SOD gene expression, were assessed in the substantia nigra (SN), striatum, and cerebral cortex. The results showed that AAs dose-dependently prevented the rotenone-induced learning and motor impairment from 10 mg/kg/day. AAs also precluded rotenone-induced lipoperoxidation in all doses, acting directly on the mitochondria, and improved the t-SOD activity in the doses 25-100 mg/kg/day. AAs per se (100 mg/kg/day) increased SOD gene expression and t-SOD activity. Our findings indicate that the oral administration of AAs prevents rotenone-induced behavioral changes and oxidative stress, in part due to a modulatory action on the mitochondria and SOD gene expression. These data suggest that AAs have promising neuroprotective action against degenerative changes in Parkinson's disease.

Evaluation of acute toxicity, genotoxicity and inhibitory effect on acute inflammation of an ethanol extract of Morus alba L. (Moraceae) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus alba L. (white mulberry) is used in traditional medicine worldwide, including Brazil. The leaves of this plant are used to treat inflammatory disorders. Universal interest in this plant necessitates studies on the toxicological safety and scientific substantiation of the medicinal properties of M. alba. In previous work, we investigated the acute toxicity of orally administered M. alba ethanol extract in mice. AIM OF THE STUDY: This work was designed to investigate the ethanol extract obtained from M. alba leaves for acute toxicity when intraperitoneally administered, in vivo genotoxicity, and potential to reduce acute inflammation. In order to further investigate the constituents of the extract, we also obtained the high-performance liquid chromatography (HPLC) fingerprint of the extract. MATERIALS AND METHODS: Phytochemical analysis by thin layer chromatography (TLC) was performed and the results were used to obtain the HPLC fingerprint. Acute toxicity of 300 and 2000mg/kg b.w. i.p. doses administered to mice for 14 days was evaluated. Genotoxicity was evaluated by counting the number of micronucleated polychromatic erythrocytes in the blood of mice that either received or did not receive the extract at 75, 150 and 300mg/kg b.w. per os. The anti-inflammatory effect of the same doses administered per os was investigated using the carrageenan air pouch model. RESULTS: The TLC analysis of the extract revealed the presence of a remarkable amount of flavonoids and cinnamic acids. The HPLC fingerprint showed the presence of one major peak corresponding to chlorogenic acid and two smaller peaks corresponding to flavonoids. In the toxicity assays, there were no deaths or deviations in behavior of treated mice as compared to the control at any dose. However, biochemical, hematological, and histological analyses showed that intraperitoneal injection caused several forms of damage to the mice, which were not observed in case of oral administration, studied in our previous work. Oral administration of the extract did not result in genotoxicity and considerably reduced (58.6-65.6% inhibition) leukocyte migration in all doses evaluated, in comparison with the negative control. CONCLUSIONS: The ethanol extract from M. alba leaves administered intraperitoneally possesses a greater degree of toxicity in mice when compared to per os administration. The extract was not genotoxic when ingested by mice and exhibited a highly inhibitory effect against acute inflammation, which is probably linked to the presence of chlorogenic acid and flavonoids in the composition. This work contributes to the determination of safety of the medicinal use of M. alba leaves.

Toxicological evaluation of essential oil from the leaves of Croton tetradenius (Euphorbiaceae) on Aedes aegypti and Mus musculus.

For control of Aedes aegypti, the main vector of dengue, botanical insecticides can be a viable alternative. Herein, we evaluated the chemical composition and insecticidal activity of the essential oils of the leaves of Croton tetradenius on Ae. aegypti larvae and adults. We also evaluated the acute toxicity in Mus musculus. The essential oil chemical analysis was performed using chromatography coupled with mass spectrometry and flame ionization detection. Female mice were used for assessing toxicity according to the Organization for Economic Cooperation and Development's Test Guideline 423/2001. Doses administered to mice orally and intraperitoneally were 5, 50, 300, and 2000 mg kg(-1). There was a greater toxic effect on larvae (LC50 = 0.152 mg mL(-1) and LC90 = 0.297 mg mL(-1)) and on adults (LC50 = 1.842 mg mL(-1) and LC90 = 3.156 mg mL(-1)) of Ae. aegypti after 24 h of exposure, when compared to other periods of exposure. Chemical analysis revealed 26 components, with camphor (25.49 %) as the major component. The acute toxicity via the intraperitoneal route identified an LD50 = 200 mg kg(-1) and by the oral route an LD50 = 500 mg kg(-1). Thus, the essential oil of C. tetradenius presents insecticidal potential for Ae. aegypti and has high safety threshold at the concentrations evaluated in this study.

Evaluation of Toxicity and Antimicrobial Activity of an Ethanolic Extract from Leaves of Morus alba L. (Moraceae).

This work evaluated an ethanolic extract from Morus alba leaves for toxicity to Artemia salina, oral toxicity to mice, and antimicrobial activity. Phytochemical analysis revealed the presence of coumarins, flavonoids, tannins, and triterpenes in the extract, which did not show toxicity to A. salina nauplii. No mortality and behavioral alterations were detected for mice treated with the extract (300 and 2000 mg/kg b.w.) for 14 days. However, animals that received the highest dose showed reduced MCV and MCHC as well as increased serum alkaline phosphatase activity. In treatments with the extract at both 300 and 2000 mg/kg, there was a reduction in number of leukocytes, with decrease in percentage of lymphocytes and increase in proportion of segmented cells. Histopathological analysis of organs from mice treated with the extract at 2000 mg/kg revealed turgidity of contorted tubules in kidneys, presence of leukocyte infiltration around the liver centrilobular vein, and high dispersion of the spleen white pulp. The extract showed antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Candida krusei, Candida tropicalis, and Aspergillus flavus. In conclusion, the extract contains antimicrobial agents and was not lethal for mice when ingested; however, its use requires caution because it promoted biochemical, hematological, and histopathological alterations.