Human immunodeficiency virus (HIV) infection is in growing incidence throughout the world. Due to the increasing proportion of affected women in reproductive years, the association of pregnancy with HIV infection becomes a matter of major Public Health concern. Antiretroviral drug administration turned out to be imperative during pregnancy in order to prevent the vertical transmission; accordingly, new antiretroviral drugs and anti-HIV drug associations have been tested in experimental pregnancy models before they are approved to be included in protocols for use during human pregnancy. Lamivudine is a nucleoside reverse transcriptase inhibitor currently used in association with other antiretrovirals. Since no data exist on the perinatal safety of lamivudine alone, as it is used in combination with other antiretroviral agents, and, until now, only preliminary data on the lamivudine-zidovudine combination were available, we decided to examine the gross maternal and fetal effects of lamivudine administered alone during the entire period of rat pregnancy. Forty pregnant animals were assigned at random to 4 groups (G1, G2, G3 and G4). G1 received drug vehicle; G2, G3 and G4 received daily oral doses of 5, 15 or 45 mg/kg of lamivudine, respectively. Rats were weighed on days 0, 7, 14 and 20 of pregnancy. On day 20 they were killed, their fetuses and placentas counted and weighed. The body weight gain of the rats was that normally expected for the gestation progression; no differences were noticed among the groups. In addition, no effects were observed regarding the fetal or placental number and weight, nor in the number of implantations, reabsortions, fetal or maternal deaths. In conclusion, the adverse effects reported for the lamivudine-zidovudine combination therapy may well be not due to lamivudine; further research involving a variety of strategies is needed to definitively ascertain the safety of that combination for preventing maternal-infant HIV transmission

La infección por el virus de la inmunodeficiencia humana (HIV) presenta incidencia creciente en todo el mundo. Debido al aumento en la proporción de mujeres afectadas en sus años reproductivos, el binomio embarazo/infección con HIV constituyen un tema preocupante en Salud Pública. Por esto que, la administración de fármacos antirretrovirales ha sido considerada obligatoria durante la gestación para prevenir la transmisión vertical del HIV; de este modo, nuevos fármacos y combinaciones de fármacos con actividad anti-HIV han sido desarollados y testeados en modelos de preñez experimental, previo a su empleo en estrategias de terapia antirretroviral durante la gestación humana. Lamivudina es un inhibidor nucleosídico de la transcriptasa reversa usada en combinación con otros antirretrovirales, pero no hay datos sobre la seguridad de su uso aislado. En el presente trabajo son estudiados los posibles efectos de la lamivudine cuando es administrada durante toda la preñez de la rata albina. Cuarenta ratas preñadas fueron tratadas durante toda la preñez (desde el día 0 hasta el día 20 de la gestación) con 5, 15 o 45 mg/kg de lamivudina, una vez al día. Los controles recibieron el vehículo de la droga. La evolución del peso corporal de los animales fue lo esperado para la progresión normal del peso durante la preñez, sin diferencias significativas entre los grupos. Igualmente no hubo diferencias en cuanto al número de fetos y de placentas y tampoco en cuanto a sus pesos. Ningún efecto fue notado con respecto al número de implantaciones o de reabsorciones. Se concluye que los efectos adversos reportados para la combinación zidovudina-lamivudina no deben, en principio, ser atribuidos a la presencia de la lamivudina

Misuse and abuse of the non-steroidal anti-inflammatory and analgesic mefenamic acid among pregnant women in developing coutries constitute a matter of medical concern, mainly as a function of the potentially serious side effects of that drug, notably at the digestive system level. Female rats were treated during the entire pregnancy period (from day 0 up to day 20) with 5, 15, or 45 mg/kg of mefenamic acid (MA) once daily, by gavage. Controls received the drug vehicle. We observed that there was a slight yet significant impairment of maternal body weight gain of the animals treated with the two highest doses of MA. Although the drug was proven to exert deleterious effects on kidney and liver metabolic functions, no gross signs of renal or hepatic toxicity were detected in our animals and in their concepts. The digestive effects would be presumably caused by the inhibitory actions of MA on the luminal fluid movement and are accounted for by the observed body weight loss during pregnancy.

En los países del tercer mundo, el uso indiscriminado durante el embarazo del fármaco antiinflamatorio no-esteroide, ácido mefenámico, es un tema de preocupación, fundamentalmente, porque este fármaco posee efectos colaterales potencialmente graves, principalmente, a nivel del aparato digestivo. En este trabajo, ratas hembras fueron tratadas durante toda la preñez (desde el día 0 hasta el día 20 de la gestación) con 5, 15 o 45 mg/kg de ácido mefenámico (AM), una vez al día. Los controles recibieron el vehículo de la droga. Se observó una discreta, aunque significativa, disminución del ritmo de aumento del peso de las madres tratadas con las dos dosis más altas (15 y 45 mg/kg AM). Si bien hay relatos de que el fármaco puede producir efectos adversos importantes sobre funciones metabólicas hepáticas y renales, no hemos observado señales de toxicidad sobre el hígado o los riñones, tanto de las madres como de sus crías. Los efectos digestivos del AM son inhibición del movimiento del fluído luminal para fuera de la luz del tubo digestivo y por ende, aumento del tránsito intestinal, lo que podría responder por la pérdida de peso corporal materno observada, principalmente, durante el último tercio de la preñez

As a less potent opioid analgesic and CNS depressant than morphine, propoxyphene abuse constitutes a potential risk among pregnant women. Since literature data indicate the possibility of serious side effects on liver compartment, in this work we examined the effects the chronic administration of this drug on both pregnant rats and their concepts. Female rats were treated during the entire pregnancy (from day 0 up to day 20) with 5, 15 or 45 mg/kg of propoxyphene napsylate once daily, by gavage. Controls received the drug vehicle. At term, samples from both maternal and foetal kidneys and livers were taken and prepared for optical and electron microscopy examination. Upon optical microscopy or electron microscopy examination, no morphological alterations were seen on either maternal or foetal livers of propoxyphene-treated pregnant rats. However, maternal and foetal kidneys showed signs of toxicity mainly in the group of rats treated with the highest dose of the drug, especially at the proximal convoluted tubules. Our results suggest that, in the rat, the physiological modifications inherent to pregnancy shifted the main focus of toxicity of propoxyphene from the liver to the kidney. The mechanisms involved in such phenomenon are at present unresolved

El uso del napsilato de propoxifeno (NP), fármaco analgésico opioide y depresor del SNC, involucra riesgo potencial de abuso y sus consecuencias, particularmente durante el embarazo. Como en la literatura hay datos indicando la posibilidad de serios efectos colaterales del NP sobre el hígado, el objetivo de este trabajo fue examinar los efectos del NP en ratas preñadas y sus fetos. Ratas hembras fueron tratadas durante toda la preñez (desde el día 0 hasta el día 20) con 5, 15 ó 45 mg/kg de NP, una vez al día, por gavage. Grupos controles recibieron el líquido usado como vehículo (aceite de acacia). Al término, muestras de hígado y riñón de las ratas preñadas y sus fetos fueron extraídos. Las muestras fueron procesadas para microscopías óptica y electrónica. No se detectaron alteraciones morfológicas en hígados de ratas preñadas o fetos con ninguna dosis de NP empleada. Los rinõnes de estos animales mostraron signos de toxicidad, particularmente, con la dosis más alta del fármaco y, especialmente, en las células de los túbulos contorneados proximales. Nuestros resultados sugieren que, en la rata, las alteraciones fisiológicas propias de la gravidez parecen cambiar el órgano-blanco de la toxicidad del NP, es decir, los efectos se manifiestan en el riñón y no en el hígado. Los mecanismos involucrados en este cambio no son aún conocidos.

O objetivo deste trabalho é avaliar os efeitos do napsilato de propoxifeno sobre a prenhez da rata albina. Para tanto utilizamos 50 ratas prenhes divididas ao acaso em cinco grupos iguais. Todas receberam diariamente, por gavagem, o volume de 1 ml, desde os dias 0 (zero) até o 20 de prenhez, com as seguintes características: grupo I - somente água destilada (controle); grupo II - solução aquosa de acácia 2% (veículo); grupos III, IV e V - respectivamente, 5, 15 e 45 mg/kg de peso de napsilato de propoxifeno dissolvido em solução de acácia a 2%. Os pesos maternos foram anotados nos dias 0 (zero), 7, 14 e 20 de prenhez; no 20º dia as matrizes foram sacrificadas. Nossos resultados mostraram que os animais tratados com 45 mg/kg do fármaco apresentaram redução dos pesos individuais dos fetos como também dos pesos das ninhadas e das placentas. Quanto às outras variáveis apreciadas: número de reabsorções, de implantações e de placentas não houve diferença significante entre os grupos tratados em relação ao grupo controle.

The purpose of this study is to evaluate the effects of propoxyphene napsylate on the pregnancy of the rat. We used fifty pregnant rats divided into five groups. All the animals received daily 1 ml of the solution by gavage from day 0 to the 20th day of pregnancy. Group I - only distilled water (control); group II - aqueous solution of acacia 2% (vehicle); groups III, IV and V - respectively, 5, 15 and 45 mg/kg of weight of propoxyphene napsylate diluted in 2% acacia solution. The animals were weighed on days 0, 7, 14 and 20 of pregnancy. All animals were sacrificed on the 20th day of pregnancy. Our results showed that the animals treated with 45 mg/kg of propoxyphene napsylate presented reduction of the individual weights of the fetuses, as well as of the weights of the newborns and placentas. The difference betewwn number of resorptions, implantations and placentas of the treated groups was shown to be non significant cohen compered with the control groups.