Evaluation of the non-clinical toxicity of an antiparasitic agent: diminazene aceturate.

The diminazene aceturate (C14H15N7.2C4H7NO3) is a chemotherapeutic agent with more than six decades of use, however more studies regarding its toxicity still need to be performed. Thus, the present study determined the acute toxicity (14 days) of diminazene acetate (DIZE) in male and female swiss mice by changes in body mass, food consumption, biochemical and hematological parameters, locomotor activity and motor coordination. DIZE was administered at a single dose (1000 and 2000 mg/kg) orally. In addition, in vitro antioxidant capacity, hemolytic activity, toxicity in Artemia salina and in silico evaluation were also performed. The results obtained include several signs of toxicity (hypoactivity, loss of the straightening reflex and tachycardia), reduction of behavioral activity (locomotor activity and motor coordination) and significant changes (p < 0.05) in biochemical and hematological parameters. According to the in silico study, the DIZE can be classified based on the mean lethal dose (LD50) in category 4 (300 mg/kg < LD50 ≤ 2000 mg/kg, ProTox-II) or 3 (50 mg/kg < LD50 ≤ 300 mg/kg, AdmetSAR 1.0). Additionally, DIZE (30.3-969.9 nM) was not toxic to A. salina in the first 48 hours of treatment and was not cytotoxic to rat red blood cells after induced hemolysis. In vitro results indicated low antioxidant capacity against DPPH• and ABTS•+ radicals. Therefore, DIZE induces several adverse effects with influence on the central nervous system, changes in hematological and biochemical parameters and even mortality at the highest dose. However, absence of toxicity was observed in A. salina and rats red blood cells.

Absence of toxicity in Swiss mice following treatment with 7-acetoxy-4-aryl-3,4-dihydrocoumarin: Acute and repeated-dose toxicity study.

Neoflavonoids, which are classified as 4-arylcoumarin (neoflavone), 3,4-dihydro-4-arylcoumarin and neoflavene, have been the subject of a number of studies with respect to their therapeutic potential and, despite promising in vitro, ex vivo and in vivo pharmacological activities, there is a lack of studies demonstrating their toxicological properties. Therefore, this study aims to evaluate the acute (14 days) and repeated-dose (28 days) toxicity of synthetic neoflavonoid 7-acetoxy-4-aryl-3,4-dihydrocoumarin in Swiss mice through parameters related to changes in body weight, food and water intake, hematological and biochemical parameters. Toxicity studies using acute doses (300 and 2000 mg/kg) and repeated doses (250, 500 and 1000 mg/kg) orally were carried out as per Organization for Economic Co-operation and Development (OECD) guidelines 423 and 407, respectively. Based on the results of this study, treatment with 7-acetoxy-4-aryl-3,4-dihydrocoumarin was found to not cause clinical adverse symptoms and mortality in any animal used in the acute and repeated-dose toxicity study. In addition, no significant changes were observed in body weight and internal organs, food and water intake, hematological and biochemical parameters, compared to control group. Therefore, these results provide an initial understanding regarding the toxicity profile of 7-acetoxy-4-aryl-3,4-dihydrocoumarin, which can be considered a neoflavonoid with toxicity seen at doses higher than 2000 mg/kg in Swiss mice.

Non-clinical toxicity of ß-caryophyllene, a dietary cannabinoid: Absence of adverse effects in female Swiss mice.

ß-caryophyllene is a food additive that is found in food plants and has broad pharmacological potential. However, little toxicological information has been reported and its use is based on the fact that this bicyclic sesquiterpene is daily consumed as a plant food in much larger quantities than as a food additive. Thus, this study evaluated acute (14-day) and repeated-dose (28 days) oral ß-caryophyllene toxicity in female Swiss mice analyzing changes in body weight, food intake, water intake, hematological and biochemical parameters, organ weight after necropsy, oxidative stress markers and histopathology of various tissues. Acute (300 and 2000 mg/kg) and repeated-dose (300 and 2000 mg/kg) toxicity studies were performed according to the Organization for Economic Cooperation and Development (OECD) guideline 423 and 407, respectively. There was absence of adverse clinical signs and mortality in any animal subjected to acute and repeated-dose toxicity study. In addition, no significant changes in body weight, food and water intake, oxidative stress biomarkers, hematological and biochemical parameters were observed when compared to control group from single-dose and repeated-dose toxicity study. Therefore, the results of this study provide an understanding of the toxicity profile of ß-caryophyllene which can be considered a compound with toxicity at doses higher than 2000 mg/kg body weight.

Pre-clinical toxicology of garcinielliptone FC, a tautomeric pair of polyprenylated benzophenone, isolated from Platonia insignis Mart seeds.

BACKGROUND: Garcinielliptone FC (GFC) is a tautomeric pair of polyprenylated benzophenone, which has proven to have antiepileptic, cytotoxic and antioxidant activity. PURPOSE: The aim of this study was to investigate the biochemical, hematological and pathological effects of the acute toxicity study as well as to assess the locomotor activity and motor coordination in mice treated with GFC. METHODS: Swiss mice of both sexes weighing 25-30 g divided into three separate groups of five animals matched by weight and size. GFC was aseptically suspended in 0.05% Tween 80, dissolved in 0.9% saline (vehicle) and administered orally (p.o.) and intraperitoneally (i.p.) (500, 1000 and 2000 mg/kg). The acute toxicity study was performed in compliance with the Anvisa regulations. RESULTS: Behavioral manifestations of toxicity, such as state of consciousness, coordination, muscle tone, reflexes, the activity on the central nervous system (shake, seizures, Straub tail reaction and anesthesia) and the activity of the autonomic nervous system (lacrimation, ptosis, urination, piloerection, hypothermia, breathing and hyperemia) were not seen in any of the animals treated with doses of 500, 1000 and 2000 mg/kg. Additionally, no significant difference in body weight, food and water intake, excreta production or macroscopic changes in the organs of treated animals were detected in comparison with control group. GFC did not affect the locomotor activity and motor coordination of the animals. CONCLUSION: The acute toxicity study indicated that GFC treatment, at selected doses given orally and intraperitoneally, showed relatively low risk of toxicity in all test animals, suggesting that it is safe for further investigation.

Use of calcareous algae and monensin in Nellore cattle subjected to an abrupt change in diet / Produto a base de algas calcárias e monensina na transição abrupta para dietas com elevada proporção de concentrado para bovinos Nelore

ABSTRACT: Additives are used in high concentrate diets to prevent metabolic disorders in cattle. This study was designed to evaluate the effect of calcium sources and monensin on the control of ruminal acidosis in Nellore cattle that were abruptly shifted to a high (92.3%) concentrate diet. Eight cannulated steers were randomly assigned to two contemporary 4x4 Latin square. Treatments involved the addition of a calcium source, either limestone (LI) or a product derived from calcareous algae (CA), to the basic diet with or without the presence of monensin. Calcareous alga (Lithothamnium calcareum) is a natural and renewable product and a source of calcium carbonate. The quantity of added limestone, calcareous algae and monensin was 7.1g kg-1, 7.4g kg-1 and 30mg kg-1 DM, respectively. There was no effect of calcium source (P=0.607) or monensin (P=0.294) on feed intake or on the concentration of short chain fatty acids. Treatments with calcareous algae resulted in a higher mean ruminal pH (P=0.039), a shorter amount of time with the ruminal pH under 5.2 (P<0.001) and a better control of blood pH (P=0.006). Treatments with monensin also resulted in a shorter amount of time with the ruminal pH below 5.2 (P=0.023). Calcareous algae were shown to be effective in controlling adverse changes in the rumen and in blood variables for Nellore cattle that were subjected to an abrupt change to a high concentrate diet.

RESUMO: Os aditivos são amplamente utilizados em dietas com elevada proporção de concentrado a fim de prevenir distúrbios metabólicos em bovinos. Este estudo foi desenvolvido para avaliar o efeito das diferentes fontes de cálcio, com ou sem monensina sódica na dieta, no controle da acidose ruminal de bovinos Nelore, recebendo, de forma abrupta, uma dieta com elevada proporção (92,3%) de concentrado. Oito bovinos portadores de cânulas ruminais foram distribuídos em um delineamento quadrado latino (4x4) duplo contemporâneo. Os tratamentos foram a adição de diferentes fontes de cálcio, calcário calcítico (LI) ou produto a base de alga calcária (CA), com (WIMO) ou sem (WOMO) a presença de monensina, à dieta base. A alga calcária, Lithothamnium calcareum, é um produto natural, renovável e fonte de carbonato de cálcio, podendo ser uma alternativa no controle desses distúrbios. A inclusão de LI, CA e monensina foi de 7,1g kg-1, 7,4g kg-1 e 30mg kg-1 MS, respectivamente. Não houve efeito das fontes de cálcio e da monensina sobre o consumo alimentar e concentração total dos ácidos graxos de cadeia curta. Os tratamentos com AC resultaram em maior pH ruminal médio (P=0,039), menor tempo com pH ruminal abaixo de 5,2 (P<0,001) e um maior pH sanguíneo (P=0,006). Os tratamentos com monensina apresentaram menor tempo com pH ruminal abaixo de 5,2 (P=0,023). O produto a base de alga calcária foi eficiente no controle das mudanças adversas das variáveis ruminais e sanguíneas em bovinos Nelore submetidos a mudanças abruptas para dietas com elevada proporção de concentrado.

Florescimento no Trabalho: Interfaces com Comportamentos de Carreira / Flourishing at work: Interfaces with career behaviors / Flourishing en el trabajo: interfaces con comportamientos de carrera profesional

O florescimento no trabalho se apresenta como um objetivo de muitos profissionais que investem em suas carreiras nos dias atuais. Porém, pouco ainda se sabe sobre quais fatores relativos à carreira ajudariam o profissional a florescer. Neste sentido, este estudo investigou de que forma comportamentos de carreira se relacionam com florescimento no trabalho. Foram testadas quatro hipóteses, que propuseram relações entre exploração de carreira, planejamento de carreira, comprometimento com a carreira e o florescimento no trabalho. Participaram deste estudo 149 profissionais, a maioria com até 45 anos de idade e, em média, sete anos de experiência profissional. Os resultados indicaram que o planejamento e exploração da carreira predizem maior florescimento, sendo esta relação mediada pelo comprometimento com a carreira. As evidências encontradas podem ser úteis para profissionais autônomos, orientadores profissionais, pesquisadores de carreira e organizações que buscam o florescimento no trabalho através do desenvolvimento de carreira.(AU)

Flourishing at work is a goal pursued by many professionals who put effort in their career nowadays. However, little is known about which career factors would help someone to flourish at work. Thus, this study investigated how career behaviors are related to flourishing at work. Four hypotheses were tested, proposing relations between career exploration, career planning and career commitment with flourishing at work. The study included 149 professionals, most were under 45 years old and had an average of seven years of professional experience. Results indicated that both career exploration and planning predict flourishing at work, being this relationship mediated by career commitment. These evidence may be useful for autonomous workers, professional advisors, career researchers and organizations which aim for flourishing at work through career development.(AU)

Flourishing en el trabajo es un objetivo perseguido por muchos profesionales que ponen esfuerzo en su carrera hoy en día. Sin embargo, poco se sabe sobre qué factores de carrera ayudarían a alguien a desarrollar en el trabajo. Por lo tanto, este estudio investigó cómo las conductas de carrera se relacionan con el flourishing en el trabajo. Cuatro hipótesis fueron probadas, que propusieron las relaciones entre la exploración de carreras, planes de carrera y el compromiso profesional con el flourishing en el trabajo. En el estudio participaron 149 profesionales, la mayoría eran menores de 45 años de edad y tenían un promedio de siete años de experiencia profesional. Los resultados indicaron que la planificación y exploración de carreras están directamente relacionadas con el flourishing en el trabajo y esta relación es mediada por el compromiso con la carrera profesional. Las evidencias pueden ser útiles para los trabajadores autónomos, asesores profesionales, investigadores profesionales y organizaciones que buscan prosperar en el trabajo a través del desarrollo de carrera.(AU)

Florescimento no Trabalho: Interfaces com Comportamentos de Carreira / Flourishing at work: Interfaces with career behaviors / Flourishing en el trabajo: interfaces con comportamientos de carrera profesional

O florescimento no trabalho se apresenta como um objetivo de muitos profissionais que investem em suas carreiras nos dias atuais. Porém, pouco ainda se sabe sobre quais fatores relativos à carreira ajudariam o profissional a florescer. Neste sentido, este estudo investigou de que forma comportamentos de carreira se relacionam com florescimento no trabalho. Foram testadas quatro hipóteses, que propuseram relações entre exploração de carreira, planejamento de carreira, comprometimento com a carreira e o florescimento no trabalho. Participaram deste estudo 149 profissionais, a maioria com até 45 anos de idade e, em média, sete anos de experiência profissional. Os resultados indicaram que o planejamento e exploração da carreira predizem maior florescimento, sendo esta relação mediada pelo comprometimento com a carreira. As evidências encontradas podem ser úteis para profissionais autônomos, orientadores profissionais, pesquisadores de carreira e organizações que buscam o florescimento no trabalho através do desenvolvimento de carreira.

Flourishing at work is a goal pursued by many professionals who put effort in their career nowadays. However, little is known about which career factors would help someone to flourish at work. Thus, this study investigated how career behaviors are related to flourishing at work. Four hypotheses were tested, proposing relations between career exploration, career planning and career commitment with flourishing at work. The study included 149 professionals, most were under 45 years old and had an average of seven years of professional experience. Results indicated that both career exploration and planning predict flourishing at work, being this relationship mediated by career commitment. These evidence may be useful for autonomous workers, professional advisors, career researchers and organizations which aim for flourishing at work through career development.

Flourishing en el trabajo es un objetivo perseguido por muchos profesionales que ponen esfuerzo en su carrera hoy en día. Sin embargo, poco se sabe sobre qué factores de carrera ayudarían a alguien a desarrollar en el trabajo. Por lo tanto, este estudio investigó cómo las conductas de carrera se relacionan con el flourishing en el trabajo. Cuatro hipótesis fueron probadas, que propusieron las relaciones entre la exploración de carreras, planes de carrera y el compromiso profesional con el flourishing en el trabajo. En el estudio participaron 149 profesionales, la mayoría eran menores de 45 años de edad y tenían un promedio de siete años de experiencia profesional. Los resultados indicaron que la planificación y exploración de carreras están directamente relacionadas con el flourishing en el trabajo y esta relación es mediada por el compromiso con la carrera profesional. Las evidencias pueden ser útiles para los trabajadores autónomos, asesores profesionales, investigadores profesionales y organizaciones que buscan prosperar en el trabajo a través del desarrollo de carrera.