ABSTRACT
BACKGROUND: The high consumption of medicines by the population and their storage at home might cause an increase in the number of pharmaceutical substances that may be inappropriately discarded in the sanitary sewage, reaching an environmental aquatic. Thus, the effects of these emerging contaminants need more studies. OBJECTIVES: To identify the profile of most medicines that are discarded by users of community pharmacy and evaluate the toxicity of the most disposed drugs. METHODS: This was a translational study. A descriptive observational study was carried out for convenience of community pharmacy users using a standardized questionnaire. Subsequently, the lethal concentration 50 (LC50) for medicine that is most frequently discarded was determined. After LC50, the embryos (n = 144) were exposed to sublethal concentrations for most discarded drug at 24, 48, and 72 h. Mortality, heartbeat, and embryo deformities were used as parameters of toxicity. RESULTS: Most respondents (96%) had a "home pharmacy." The primary forms of disposal were in the common household waste, kitchen sink, and/or bathroom. The medicines that were most incorrectly discarded by the interviewees were nimesulide (17.1%), dipyrone (10.7%), and paracetamol (5.2%). LC50 of nimesulide was calculated (0.92 µgmL-1). The toxicological test revealed that embryos exposed to nimesulide showed several abnormalities, such as defects in the spinal cord, tail, yolk sac, as well as pericardial edema. Furthermore, the heartbeat decreased by 30% at a concentration of 0.4 µgmL-1 as compared with control group. The yolk sac and pericardial areas increased to >100% in all treatment groups when compared with the control group. CONCLUSION: Respondents disposed medicines in an inappropriate manner primarily in household waste and in the toilet. Nimesulide was the most discarded drug according to study population. Moreover, teratogenic effects such as spinal cord defects, decreasing heartbeats, and increasing pericardial and yolk sac area in embryos were observed after exposure to nimesulide. These results show that nimesulide may promote risk to aquatic organisms and to human health if it is discarded in an unsafe manner.
Subject(s)
Sulfonamides/toxicity , Waste Management/methods , Water Pollutants, Chemical/toxicity , Adolescent , Adult , Aged , Animals , Embryo, Nonmammalian/abnormalities , Embryo, Nonmammalian/drug effects , Embryo, Nonmammalian/physiology , Female , Heart/drug effects , Heart/embryology , Heart/physiology , Heart Defects, Congenital/chemically induced , Heart Rate/drug effects , Humans , Male , Middle Aged , Pharmaceutical Preparations , Risk Assessment , Spinal Cord/abnormalities , Spinal Cord/drug effects , Tail/abnormalities , Tail/drug effects , Waste Products , Yolk Sac/drug effects , Young Adult , Zebrafish/abnormalities , Zebrafish/physiologyABSTRACT
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.
Subject(s)
Mice , Teratogens , Spirulina , Hydroxyurea , Toxicology , Brain , Oxidative Stress , Embryonic Structures , Phycobiliproteins , Primary Cell Culture , AntioxidantsABSTRACT
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.
Subject(s)
Animals , Female , Pregnancy , Rabbits , Analgesics/toxicity , Aspirin/toxicity , Dental Enamel/drug effects , Dentin/drug effects , Antipyretics/toxicity , Dentition , Hardness/drug effects , TeratogensABSTRACT
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.