Protección de la Spirulina maxima sobre la citotoxicidad de la hidroxiurea en células embrionarias de ratón / Protection of Spirulina maxima on cytotoxicity of hydroxyurea in mouse embryonic cells / Proteção de Spirulina maxima em citotoxicidade de hidroxiureia em células embrionárias de camundongo

La Spirulina maxima (SP) tiene efectos farmacológicos protectores por su contenido de ficobiliproteínas que están relacionados con su actividad antioxidante. La hidroxiurea (HU) es un fármaco antineoplásico, citotóxico y teratógeno que implica la inducción del estrés oxidativo. El objetivo de este trabajo fue determinar si la SP y su extracto acuoso de proteína (SPE) protegen contra el efecto citotóxico de HU en cultivos celulares primarios a partir de embriones de ratón de once días. Los efectos de SP, SPE e HU sobre la viabilidad celular se determinaron por el ensayo de fluorescencia de resazurina en cultivos celulares de embriones completos de ratones de once días, de encéfalo y de brotes de extremidades anteriores. Se demostró que ni SP ni su extracto provocaron efectos citotóxicos en ninguna concentración ensayada, por lo que se aumentaba la viabilidad celular. Se encontró que las células expuestas a HU de embriones completos y encéfalo mostraron mayor toxicidad que las células de los miembros anteriores. La SP y el SPE protegieron contra la citotoxicidad de HU de una manera dependiente de la concentración hasta 48 h después de la exposición al fármaco. Este efecto podría ser adecuado para prevenir la muerte celular que deriva en un proceso teratogénico, atribuido a sus propiedades antioxidantes.

Spirulina maxima (SP) has protective pharmacological effects that are related to the antioxidant activity due to its phycobiliprotein content. Hydroxyurea (HU) is an antineoplastic, cytotoxic and teratogenic drug, which involves the induction of oxidative stress. The aim of this study was to determine whether SP and its aqueous protein extract (SPE) protect against the cytotoxic effect of HU in primary cell cultures from mouse embryos. The effects of SP, SPE, and HU on cell viability were determined by resazurin fluorescence assay in whole embryo cell cultures, encephalon, and eleven-day-old forehead bud outbreaks. It was shown that neither SP nor its extract caused cytotoxic effects at any concentration tested, increasing cell viability. It was found that cells exposed to HU of whole embryos and encephalon showed higher toxicity than cells of the previous limbs. SP and SPE protected HU cytotoxicity in a concentration-dependent manner up to 48 hours after exposure to the drug. This effect could be adequate to prevent cell death resulting in a teratogenic process attributed to its antioxidant properties.

Spirulina maxima (SP) tem efeitos farmacológicos protetores devido a seu conteúdo de ficobiliproteínas, que estão relacionadas com sua atividade antioxidante. A hidroxiureia (HU) é uma droga antineoplásica, citotóxica e teratogênica, que envolve a indução do estresse oxidativo. O objetivo deste estudo foi determinar se a SP e seu extrato aquoso de proteína (SPE) protegem contra o efeito citotóxico da HU em culturas celulares primárias a partir de embriões de camundongo de onze dias. Os efeitos de SP, SPE e HU na viabilidade celular foram determinados pelo ensaio de fluorescência de resazurina em culturas celulares de embriões inteiros de camundongos de onze dias, de encéfalo e de surtos de extremidades anteriores. Demonstrou-se que nem a SP nem seu extrato causaram efeitos citotóxicos em qualquer concentração testada, aumentando a viabilidade celular. Verificou-se que as células expostas à HU de embriões completos e encéfalo mostraram maior toxicidade do que as células dos membros anteriores. SP e SPE protegem contra a citotoxicidade de HU de forma dependente da concentração até 48 h após a exposição ao medicamento. Esse efeito poderia ser adequado para prevenir a morte celular, que resulta em um processo teratogênico atribuído a suas propriedades antioxidantes.

Micro hardness of dental tissues influenced by administration of aspirin during pregnancy / Microdureza de los tejidos dentales influenciada por la administración de aspirina durante el embarazo

The study is associated with the effect of aspirin (Acetyl Salicylic Acid) on the microhardness of mineralized tissues of the offspring's teeth, in response to the ingestion of the drug during pregnancy. Aspirin is a widely used analgesic and antipyretic medicine, for symptomatic treatment. Misuse of this drug during pregnancy may instigate developmental defects in offspring. An experimental control study was designed, in which female rabbits were taken as representative mammalian models and treated with aspirin during pregnancy. Their offspring's teeth were used to assess the microhardness of dental tissues. The rabbits were alienated into two groups, treated and control, consisting of seven rabbits in each set (n= 7). Microhardness was evaluated in three types of the sample teeth. The total number of teeth examined were, 2x7x12= 168 samples. Vicker's Hardness degree values were measured and recorded vis-à-vis (50 g for 15 s with 3 indentations per specimen on enamel and dentine separately). The range of hardness obtained was statistically analyzed and the Student's t-tests was applied, with the aid of SPSS version 20. The P-values for both enamel and dentine from maxillary incisors and molars were less than 0.05. The same trend was observed in the mandibular teeth. However, a teratogenicity of Acetyl Salicylic Acid was pragmatic in the recent in vivo studies. Based on the analysis, it was evident that the aspirin administration could produce negative effects leading to reduction in the microhardness of dental tissues of the offsprings.

El estudio asocia el efecto de la aspirina (ácido acetil salicílico) sobre la microdureza de los tejidos mineralizados de los dientes de crías, en respuesta a la ingesta del fármaco durante la preñez. La aspirina es un analgésico y antipirético ampliamente utilizado para el tratamiento sintomático. El mal uso de esta droga durante la preñez puede inducir defectos en el desarrollo de las crías. Se diseñó un estudio experimental de control, en el que se tomaron conejas como modelos de mamíferos representativos y fueron tratados con aspirina durante la preñez. Los dientes de sus crías fueron utilizados para evaluar la microdureza de los tejidos dentales. Los animales fueron distribuidos en dos grupos, tratados y control, con siete animales en cada grupo (n= 7). La microdureza se evaluó en tres tipos de dientes de la muestra. El número total de dientes examinados fueron 168 (2x7x12). Se midieron y registraron valores del grado de dureza Vickers vis-à-vis (50 g por 15 s con 3 indentaciones por especimen sobre el esmalte y la dentina por separado). Se analizó estadísticamente la gama de dureza obtenida y se aplicaron pruebas t de Student con la ayuda del programa SPSS versión 20. Los valores de p para el esmalte y la dentina de los incisivos maxilares y molares fueron menores a 0,05. Se observó la misma tendencia en los dientes mandibulares. Sin embargo, teratogenicidad producto del ácido acetil salicílico se encontró en recientes estudios in vivo. De acuerdo al análisis de los resultados, se evidenció que la administración de aspirina provocó efectos negativos que determinaron la reducción de la microdureza de los tejidos dentales de las crías.

Effect of aspirin on the developing teeth of neonates / Efecto de la aspirina en el desarrollo de los dientes de neonatos

The objective of the present study was to evaluate the effect of aspirin (Acetyl Salicylic Acid) on the developing teeth of the fetus while the mothers were treated through out the pregnancy. Aspirin is a widely used analgesic and antipyretic drug used for symptomatic treatment. However, recent animal studies have indicated a potent teratogenicity of Acetyl Salicylic Acid. Its easy availability without prescription has been associated with high possibility of misuse, especially in the developing world. An experimental control study was carried out where female rabbits being treated with aspirin were taken as mammalian model, and their offspring were used to evaluate the developmental defects in teeth. Quantitative analysis of minerals in three types of the sample teeth, was done using scanning electron microscope and energy dispersive X-ray spectroscopy (SEM-EDX). Calcium was the most affected mineral and incisors and mandibular molars were found to be the most affected teeth. Voluminous variations were observed in the mineral contents of samples from the treated and control group, however, significant results could not be achieved. A larger sample size could possibly be needed to produce more conclusive results.

El objetivo del estudio fue evaluar el efecto de la aspirina (ácido acetilsalicílico) sobre el desarrollo de los dientes en fetos de conejos, cuyas madres fueron tratadas durante toda la gestación. La aspirina es un fármaco ampliamente utilizado como analgésico y antipirético para el tratamiento sintomático. Sin embargo, estudios recientes en animales han indicado una teratogenicidad potente por parte del ácido acetilsalicílico. Su fácil disponibilidad, sin la necesidad de receta médica, se ha asociado con una alta posibilidad de su mal uso, especialmente en el mundo desarrollado. Se diseñó un estudio de control experimental, donde conejos hembras fueron tratadas con aspirina, tomándose como modelo de mamíferos, y sus crías fueron utilizadoa para evaluar los defectos en el desarrollo de los dientes. Se realizó el análisis cuantitativo de tres tipos de minerales en los dientes de la muestra mediante microscopio electrónico de barrido y espectroscopía de rayos X por dispersión de energía (SEM-EDX). El calcio fue el mineral más afectado y los incisivos y molares inferiores fueron como los dientes más afectados. Grandes variaciones se observaron en el contenido mineral de las muestras de los grupos tratado y control, sin embargo, no se lograron resultados significativos. Un tamaño de muestra más sería necesario para producir resultados más concluyentes.

Embryo Toxicity and Teratogenic Effects of Microula Seed Oil on Rat / 中国康复理论与实践

@#Objective To investigate toxicity and teratogenic effect of Microula seed oil on embryo of rat.Methods 150 mature Wistar rats (100 females, 50 males) were selected with female∶ male = 2∶1 cage match. During the daily morning examination the sperm was discovered in the vagina as the zero day for conception.100 pregnant rats were randomly divided into 5 groups (n=20 in each group): treatment group (included 3 groups: to give Microula seed oil 2.5 g /kg, 5.0 g /kg, 10.0 g /kg body weight, ig, respectively), cyclophosphamide group(7 mg/ kg body weight, sc) and the edible oil group (to give dose, such as volume as Microula seed oil, ig). From the 7th day of pregnancy, the treatment group, the edible oil group were given intervention once a day for 10 days. From the 11th day of pregnancy cyclophosphamide group was given cyclophosphamide as intervention once a day, for 3 days. On the 20th day the pregnant rats were killed.Results The body weight of pregnant rats and the rate of live births were significantly higher in the Microula seed oil dose group than in the cyclophosphamide group (P<0.01), stillbirth rate and birth rate of absorption was significantly lower in the Microula seed oil dose group than in the cyclophosphamide group (P<0.01), and no significant difference from the edible oil group (P> 0.05); the fetal rat, body weight, body length, tail length in all groups of Microula seed oil was no significant difference from the edible oil group (P> 0.05). There was no malformation in appearance, viscera, bones in the treatment group and the edible oil group while there were 112 fetal rats with deformity in 140 in the cyclophosphamide group.Conclusion Microula seed oil at doses of 2.5 g /kg, 5.0 g /kg, 10.0 g /kg body weight had no significant role in the toxicity and teratogenicity on embryos of pregnant rats.

Teratogenic Effect of Dopamine on the Embryonic Chick Heart

PURPOSE: To investigate the teratogenic potential of dopamine using a topical method of application to the developing Korean native chick embryo. METHODS: A 5 pg(0.05cc) of dopamine was applied to a 3-days-old chick embryo and the same amount of saline solution was applied as control. The embryo was then returned to the incubator and monitored. After 3 weeks the embryo was sacrificed and examined for cardiovascular malformation. RESULTS: The survival rate of the dopamine-administered group was not significantly lower than that of the control group(32.2% vs 41.5%). Cardiovascular malformation rates between the two groups were 14.3% and 2.6%, respectively. The dopamine-administered group had significant higher malformation rate(P=0.049). The type of malformation was ventricular septal defect and no aortic arch anomaly. In the control group, one trabecular type was observed. In the dopamineadministered group, malformations were 3 trabecular ventricular septal defects(VSDs), 2 infracrista VSDs, 1 inlet VSD and 1 large supracrista VSD. These results were quite different from each other. CONCLUSION: We proposed that low doses of dopamine influence the cardiovascular morphogenesis through -1 receptor weakly or through dopaminergic receptor.

TOXIC AND TERATOGENIC EFFECTS OF ALUMINIUM CHLORIDE ON CHICK EMBRYOS / 解剖学报

The toxic and teratogenic effect of AlCl_3 on leghorn chick embryos were studied. Different concentrations of AlCl_3 dissolved in redistilled water were injected into the air sac of the eggs (0.2 ml per egg) on the third day of incubation. It was identified that the maximal permissible dosage was 1.708 ?mol/egg, the minimal lethal dosage was 2.25 ?mol/egg, the absolute lethal dose was 35.34 ?mol/egg, and LD_(50) was 8.09 ?mol/egg. The mortality of the embryos raised with the increase of the dose of AlCl_3. AlCl_3 also retarded the development of chick embryos and showed apparent tetratogenic effects.

THE STUDY ON TERATOGENICITY OF CYCLOPHOSPHAMIDE AND MORPHOLOGICAL TERATOGENESIS MECHANISM OF NEURAL TUBE DEFECTS / 解剖学报

In this paper, further study was made on the teratogenicity and the morphological teratogenesis mechanism of neural tube defects (NTD) caused by cyclophosphamide(CP). Pregnant SD rats were given single intraperitoneal injection of CP 15 mg/kg on day 13 of gestation. The fetuses were removed on day 20 of gestation, weighed and examined for external malformations. Some embryos were removed respectively at 4, 8, 12, 24, 48 hr after administration of CP, and examined with light microscope and electron microscope. The results showed that CP has obvious embryotoxie and teratogenic effects. Of the survivings, 97.46％ showed external malformations including encephalocele, exencephaly, opened eyes, micrognathia, limb and digital defects etc. We considered that the possible way by which CP caused the malformation on developing embryos may involve the following aspects: (1) CP caused DNA-synthesising cells to degenerate and become necrosis. (2) The cellular organelle (mitochondria and endoplasmic reticulum, etc.) became irregular in shape and fragmented. (3) The mesenchyme surrounding the neural tube were also damaged by CP and therefore influenced the skull ossification.