Phytochemical Analysis and Antiplasmodial (curative) Activities of Methanolic Leaf Extract of Morinda lucida (Ewe Oruwo) in Male Swiss Mice Infected with Plasmodium berghei NK65

Aim:Medicinal plants have been used for the treatment of many infections and diseases including malaria. The study was conducted to determine the effect of in vivoanti-plasmodialand antioxidant properties of the methanolic leaf extract of Morinda lucidain male Swiss albino mice infected with Plasmodium Berghei NK65. Study Design and Methodology:Phytochemical, GC-MS and AAS analyses were determined in the plant. Swiss albino mice were inoculated intraperitoneally with Plasmodium bergheiNK65. Thirty-five (35) mice were grouped into seven groups, five per group. Group A were not infected with P.bergheiNK65.Group B, C and D served as the negative and positive control groups while Group E, F and G mice were treated with 400, 600 and 800 mg/kg body weight of methanolic leaf extract of M. lucida. Haematological parameters were determined in the whole blood using BC-3200 Auto Hematology Analyzer. TP, MDA, CAT, SOD % inhibition, SOD unit and vitamin A were all determined in the liver homogenateusing standard procedures.Results:The GC-MS result of the M. lucidashows the presence of five bioactive compounds. It was also observed that the plant contains the following minerals: iron, magnesium, potassium, phosphorus and copper. Acute toxicity shows that the LD50>000mg/Kg b.wt. The extract caused 30.96%, 32.93% and 67.23% reduction in parasitemia at 400, 600 and 800 mg/kg body weight respectively while chloroquine exerted 96.53% and artesunate exerted 92.03% reduction at 10 mg/kg body weight respectively. The Haematological parameters showed that the plant extractis nothaematotoxic since it significantly (P<0.05) reduced WBC count, and increase RBC, HGB, and HCT values in the treated mice compared to the infected untreated mice. This study shows that the mean lipid peroxidation (MDA) level was significantly decreased in the malaria treated mice (group C, D, E, F and G) compared to the untreated mice (group B). There was also a significant increase in the total protein, catalase, SOD % inhibition, SOD unit and Vitamin A levels in the liver homogenate of animals treated with chloroquine, artesunate and extract of M. lucidacompared to the untreated mice. Conclusions: The study shows that Morinda lucidapossess antiplasmodial activity in male Swiss mice infected with Plasmodium berghei NK 65.

Estudo da alteração do esvaziamento gástrico em roedores

Fatores que alteram os níveis plasmáticos de substâncias químicas e, por conseguinte, modificam a sua cinética, como por exemplo, a gravidez, podem ter impactos sobre a segurança e eficácia de medicamentos. Em estudo recente, realizado por Carmo (2015), no Laboratório de Toxicologia Ambiental do Departamento de Biologia da Escola Nacional de Saúde Pública da Fundação Oswaldo Cruz (ENSP/FIOCRUZ), foi observado que a concentração plasmática do antimalárico difosfato de primaquina em camundongos fêmeas grávidas DBA/2 era menor do que a concentração do fármaco registrada em igual intervalo de tempo pós-adminstração em camundongos fêmeas não grávidas. Vários estudos sugerem que a diminuição da concentração plasmática de fármacos na gestante pode se dever a um retardo no esvaziamento gástrico e/ou um aumento no volume de distribuição. Alterações do trânsito no trato gastrintestinal podem influenciar diretamente a absorção de fármacos, resultando em absorção mais rápida ou mais lenta. O fármaco analgésico e antipirético paracetamol é absorvido quase que exclusivamente no intestino. Assim a velocidade da sua absorção depende do tempo de esvaziamento gástrico. Fatores tais como alimentação, idade, gravidez e/ou o uso de fármacos que promovem aceleração (metoclopramida) ou o retardo (morfina) da motilidade gastrointestinal, podem influenciar em sua absorção. O objetivo desse trabalho foi desenvolver e padronizar uma metodologia de análise do paracetamol que permitisse investigar o efeito da gravidez sobre o esvaziamento gástrico sobre a cinética de fármacos administrados em pequenos roedores. O método empregado para determinar as concentrações plasmáticas de paracetamol foi a cromatografia em fase líquida de alta eficiência com detector por arranjo de diodos e visualização no ultravioleta (CLAE-DAD-UV), em equipamento Shimadzu Class-VP...

Factors that affect plasma levels of chemicals, and consequently their kinetics, such as pregnancy, can impact on the safety and efficacy of medicines. In a recent study, conducted by Carmo (2015) at the laboratory of Environmental Toxicology (Department of Biological Sciences, National School Public Health, Oswaldo Cruz Foundation -ENSP / FIOCRUZ), it was shown that plasma concentrations of the anti-malarial drug primaquine diphosphate in pregnant female DBA/2 mice were lower than levels found in non pregnant female mice. During pregnancy a delayed gastric emptying and/or an increased volume of distribution may result in lower drug plasma concentrations. Pregnancy-produced changes in the gastrointestinal transit may influence drug absorption. Depending on whether gastric emptying is accelerated or slowed and on the place where drug absorption takes place (stomach or intestines) absorption can be accelerated or slowed. Paracetamol, an analgesic and antipyretic drug, is absorbed almost exclusively in the intestines and is used to investigate the effects of treatment on the gastric emptying rate. Factors such as diet, age, pregnancy or the administration of drugs which accelerate (metoclopramide) or delay (morphine) gastric emptying influence the absorption of paracetamol. The aim of this study was to develop and standardize a methodology to investigate the effect of gastric emptying on the kinetics of drugs administered in small rodents. The methodology used in the analysis of plasma concentrations of paracetamol was High Performance Liquid Chromatography coupled to diode-array detector and visualization on ultraviolet range (HPLC-DAD-UV), using a Shimadzu Class-VP equipment...

Central nervous system effects of Dioclea grandiflora pods on mice / Efectos en el sistema nervioso central de la vaina de Dioclea grandiflora en camundongos

Many plant substances are known for their interference with the central nervous system (CNS). Dioclea grandiflora Mart. Ex. Benth (Fabaceae) is a plant used in folk medicine to treat prostate disorders and kidney stones whose extracts from its seeds and root barks were reported to have a significant activity on the CNS and analgesic effect in rodents. In this study, the psychopharmacological activities of D. grandiflora were investigated, using the pods of this plant. Swiss mice were submitted to acute treatments with ethanol extract from the pods of D. grandiflora (EDgP) at doses of 75, 150 and 300 mg/kg by intraperitoneal administration followed by the evaluation of anxiety, depressant and anticonvulsant-related responses. The treatment with EDgP produced a depressant activity on the CNS and a sedative effect in mice. These findings suggest that EDgP has a central activity in mice, indicating an anxiogenic effect.

Varias sustancias de plantas son conocidas por su acción en el sistema nervioso central (SNC). La Dioclea grandiflora Mart. Ex. Benth (Fabaceae) es una planta utilizada en la medicina popular para tratar enfermedades en la próstata y piedras en los riñones, cuyos extractos de sus semillas y de las cáscaras de sus raíces presentan una actividad significativa sobre el SNC y efecto analgésico en roedores. En este estudio, las actividades psicofarmacológicas de D. grandiflora fueron investigadas, utilizando la vaina de la planta. Camudongos Swiss fueron sometidos a tratamientos agudos por la administración intraperitoneal del extracto etanólico de la vaina de D. grandiflora (EDgP) en dosis de 75, 150 y 300 mg/kg administrados intraperitonealmente seguida por la evaluación de respuestas relacionadas con la ansiedad, depresión y anticonvulsivo. El tratamiento con EDgP produjo una actividad depresora sobre el sistema nervioso central y un efecto sedante en camundongos. Estos resultados sugieren que EDgP tiene una actividad central en camundongos, indicando un efecto ansiogénico.

Saccharomyces uvarum mannoproteins stimulate a humoral immune response in mice

Yeasts discarded in industrial processes can be used as a nutritional supplement and to extract cellular components with biotechnological aims. In this study, the humoral immune response of Swiss mice treated with mannoproteins (MP) from the yeast Saccharomyces uvarum was evaluated. The mice were treated with MPs at different doses and times and inoculated with 2% sheep red blood cells. An increase in total Ig in mice treated with 100 μg of MP at the time of immunization or 24 h before was observed in the primary immune response; in the secondary immune response, an increase was observed in total Ig values for all groups, and an increase of IgG was observed in the mice treated with MPs (100 μg) at the time of immunization or 24 h before. These results show that S. uvarum MPs present an immunostimulatory action on the humoral immune response in mice.

Biological behavior of Trypanosoma cruzi stocks obtained from the state of Amazonas, Western Brazilian Amazon, in mice / Comportamento biológico de isolados de Trypanosoma cruzi obtidos no estado do Amazonas, Amazônia Ocidental Brasileira, em camundongos

INTRODUCTION: The biological diversity of circulating Trypanosoma cruzi stocks in the Amazon region most likely plays an important role in the peculiar clinic-epidemiological features of Chagas disease in this area. METHODS: Seven stocks of T. cruzi were recently isolated in the State of Amazonas, Brazil, from humans, wild mammals, and triatomines. They belonged to the TcI and Z3 genotypes and were biologically characterized in Swiss mice. Parasitological and histopathological parameters were determined. RESULTS: Four stocks did not promote patent parasitemia in mice. Three stocks produced low parasitemia, long pre-patent periods, and a patent period of 1 day or oscillating parasitemia. Maximum parasitemia ranged from 1,400 to 2,800 trypomastigotes/0.1mL blood. Mice inoculated with the T. cruzi stocks studied showed low positivity during fresh blood examinations, ranging from 0% to 28.6%. In hemoculture, positivity ranged from 0% to 100%. Heart tissue parasitism was observed in mice inoculated with stocks AM49 and AM61. Stock AM49 triggered a moderate inflammatory process in heart tissue. A mild inflammatory process was observed in heart tissue for stocks AM28, AM38, AM61, and AM69. An inflammatory process was frequently observed in skeletal muscle. Examinations of brain tissue revealed inflammatory foci and gliosis in mice inoculated with stock AM49. CONCLUSIONS: Biological and histopathological characterization allowed us to demonstrate the low infectivity and virulence of T. cruzi stocks isolated from the State of Amazonas.

INTRODUÇÃO: A diversidade biológica dos estoques Trypanosoma cruzi circulantes na Região Amazônica pode desempenhar importante papel nas características clínico-epidemiológicas peculiares da doença de Chagas nesta área. MÉTODOS: Sete isolados de T. cruzi do Estado do Amazonas provenientes de humanos, mamíferos silvestres e triatomíneos, pertencentes aos genótipos TcI e Z3, foram biologicamente caracterizados em camundongos Swiss. Foram avaliados parâmetros parasitológicos e histopatológicos. RESULTADOS: Quatro isolados não produziram parasitemia patente em camundongos. Três isolados promoveram baixa parasitemia com longos períodos pré-patentes, período patente de um dia ou parasitemia oscilante. A parasitemia máxima variou de 1.400 a 2.800 tripomastigotas/0,1mL de sangue. Os camundongos inoculados com os isolados estudados mostraram baixa positividade no exame a fresco, variando de 0 a 28,6%. Para a hemocultura, a positividade variou de 0 a 100%. Parasitismo cardíaco foi observado em camundongos inoculados com os isolados AM49 e AM61. O isolado AM49 produziu inflamação moderada no tecido cardíaco. Processo inflamatório discreto foi observado no tecido cardíaco de camundongos inoculados com os isolados AM28, AM38, AM61 e AM69. Processo inflamatório em músculo esquelético foi muito frequente. O exame do tecido cerebral revelou focos inflamatórios e gliose em camundongos inoculados com o isolado AM49. CONCLUSÕES: A caracterização biológica e histopatológica demonstrou baixa infecciosidade e virulência dos estoques de T. cruzi isolados no Estado do Amazonas.

Avaliação da mutagenicidade e antimutagenicidade de um biopolímero extraído do microorganismo Agrobacterium radiobacter em camundongos Swiss / Assessment of mutagenicity and antimutagenicity of a biopolymer extracted from the microorganism Agrobacterium radiobacter in mice

A presente pesquisa avaliou a ação mutagênica e antimutagênica de um biopolímero de glucose extraído da Agrobacterium radiobacter (Biopolímero de Agrobacterium radiobacter). O experimento foi realizado com camundongos Swiss machos divididos em oito grupos. O tratamento com o biopolímero foi realizado por gavage em dose única concomitante a uma dose de solução tampão fosfato nos grupos de avaliação da mutagenicidade, ou ao agente indutor de danos no DNA, ciclofosfamida, na concentração de 50 mg/kg (peso corpóreo - p.c.), nos grupos de avaliação da antimutagenicidade. Utilizou-se o teste de micronúcleo em sangue periférico e a coleta de sangue foi realizada 24 e 48 h após a aplicação das substâncias-teste. A análise estatística demonstrou que o biopolímero não possui atividade mutagênica e que é efetivo em prevenir danos no DNA. As porcentagens de redução de danos nos grupos de antimutagenicidade foram de 83,9 por cento, 89,1 por cento e 103,1 por cento em 24 h e 101,24 por cento, 98,14 por cento e 120,64 por cento em 48 h para as doses de 75, 150 e 300mg/kg (p.c.), respectivamente. A alta porcentagem de redução de danos associada à ausência de efeitos mutagênicos indica, além da atividade quimioprotetora, a possibilidade do biopolímero ser um alimento funcional candidato à utilização como co-adjuvante na quimioterapia para prevenir efeitos colaterais.

This study evaluated the mutagenic and ant mutagenic action of a biopolymer of glucose extracted from Agrobacterium radiobacter (Biopolymer of Agrobacterium radiobacter). The experiment was conducted with Swiss male mice divided into eight groups. Treatment with the biopolymer was performed in a single dose by gavage at a dose of concomitant phosphate buffer groups in the evaluation of mutagenicity, or the agent of inducing DNA damage, cyclophosphamide, the concentration of 50 mg/kg (body weight --b.w.), in groups of assessment ant mutagenic. We used the micronucleus test in peripheral blood. The blood sample was held 24 and 48 h after application of the test substances. Statistical analysis showed that the biopolymer has no mutagenic activity and it is effective in preventing damage to DNA. The percentages of damage reduction in groups of ant mutagenic were 83.9 percent, 89.1 percent and 103.1 percent in 24 h and 101.24 percent, 98.14 percent and 120.64 percent at doses of 48 to 75, 150 and 300 mg/kg (b.w.) respectively. The high percentage of damage reduction associated with the absence of mutagenic effects indicates the possibility of biopolymer chemoprotection action. It can also be considered a functional food candidate to be used as co-adjuvant chemotherapy to prevent side effects.

Estabelecimento de metodologia para alimentação de Aedes aegypti (Diptera-Culicidae) em camundongos swiss e avaliação da toxicidade e do efeito residual do óleo essencial de Tagetes minuta L (Asteraceae) em populações de Aedes aegypti / Establishment of the feeding methodology of Aedes aegypti (Diptera-Culicidae) in Swiss mice and evaluation of the toxicity and residual effect of essential oil from Tagetes minuta L (Asteraceae), in populations of Aedes aegypti

Objetivou-se desenvolver um procedimento de alimentação de fêmeas de Aedes aegypti que não cause estresse em camundongo swiss e avaliar a toxicidade e o efeito residual do óleo essencial de Tagetes minuta L (Asteraceae) em populações de Aedes aegypti. Camundongos anestesiados: um observado tempo de sedação e outro colocado em gaiola para alimentação de fêmeas. Óleo essencial, diluído em acetona, foi utilizado em bioensaios para avaliação das concentrações letais em larvas de Bauru, SP e São José do Rio Preto, SP, respectivamente, sensíveis e resistentes ao temephos. Os dados obtidos foram comparados com a cepa Rockefeller-EUA. O procedimento com camundongos foi aprovado. Não houve diferença entre as populações quanto à susceptibilidade a Tagetes minuta e os ensaios demonstraram CL50 de 0,24, 0,25 e 0,21mL L-1 e CL99,9 em 0,35, 0,39 e 0,42mL L-1, respectivamente, para Rockfeller, Bauru e São José do Rio Preto. Não foi observado efeito residual da solução.

The objectives here were to develop a procedure for feeding females of Aedes aegypti that does not cause stress in Swiss mice and to evaluate the toxicity and residual effect of essential oil from Tagetes minuta L. (Asteraceae) in Aedes aegypti populations. Two mice were anesthetized: one was used to observe the duration of sedation and the other was placed in a cage to feed the female mosquitoes. Essential oil was diluted in acetone and used in bioassays to assess the lethal concentrations in larvae from the Cities of Bauru (SP) and São José do Rio Preto (SP) that were sensitive and resistant to temephos, respectively. The data obtained were compared with the American Rockefeller strain. The procedure with mice was approved. There was no difference between the populations regarding susceptibility to Tagetes minuta, and the assays showed LC50 of 0.24, 0.25 and 0.21 ml/l and LC99.9 of 0.35, 0.39 and 0.42 ml/l, for Rockefeller, Bauru and São José do Rio Preto, respectively. The solution did not show any residual effect.

Evaluation of Short-term Exposure to Rosmarinus officinalis on Male Swiss Mice's Organs and Reproductive System

Rosemary (Rosmarinus officinalis L. - Labiatae) is a plant in the treatment of urinary disorders, dysmenorhea and respiratory problems. Rosemary toxicity was evaluated in famale rats and an anti-implantation effect was reported after treatment with an aqueous extract of this plant. This works analyzes the effect of a short-term administration of R. officinalis aqueous extract on vital organs, on the organs of the reproductive system and sperm concentration of mature male Swiss mice. Treated animals received 260 mg/kg of body weight for five days. Body and organs weights, sperm production and food consumption were evaluated. This preliminary investigation reports that no body weight reduction and no toxic effect on the organd, gamete production or food intake were detected in any of the groups analyzed, given the experimental protocol used.

Jorge Lobo’s disease: experimental inoculation in Swiss mice

Sixty-four isogenic Swiss mice were intradermically inoculated in both hind foot pads. The inocula, consisting of fungal suspensions from biopsies obtained from Jorge Lobo’s Disease patients, had the total number of fungi and the viability index determined using a Neubauer chamber and the fluorescein diacetate-ethidium bromide technique (FD-EB), respectively. The animals were sacrificed at times ranging from ten days to eighteen months after inoculation. The cellular infiltrate, mainly consisting of macrophages containing fungi, increased progressively up to end of the study; however, no macroscopic alterations were observed in the inoculated feet. After nine months, small numbers of Langhans’ giant cells started to appear in the infiltrate. A considerable number of fungi was observed at the end of the experimental period, but only a few were viable when stained by the FD-EB technique. This fact suggests that there is a multiplication of fungal cells, which are destroyed by the macrophages but remain in the tissue for a long time due perhaps to the difficulties in their elimination. These findings led us to conclude that in spite of the maintenance of the infection in these animals, Swiss mice cannot be considered an ideal model to study Jorge Lobo’s Disease. However, the authors call attention to the possibility of other mouse strains being more susceptible to Paracoccidioides loboi