Evaluation of potential embryo toxicity of albendazole sulphoxide in CF1 mice

Benzimidazole compounds are used in both humans and animals for controlling helminth parasites. Albendazole has teratogenic effects attributed to its active metabolite albendazole sulphoxide. The aim of this work was to evaluate the effect of the latter compound when administered to pregnant CF1 mice during the preimplantation period. Females were superovulated by intraperitoneal injection of 10 IU of eCG and 10 IU of hCG (48h later) and were paired with males of proven fertility. Albendazole sulphoxide (200 mg/kg) was orally administered by gavages at day 1, 2 or 3 of pregnancy; the control group received only the vehicle (carboxymethylcellulose). Females were killed by cervical dislocation at day 4 of pregnancy and embryos were flushed from uteri with Ham F10 media supplemented with bovine serum albumin (0.4%). Number of collected embryos per female, percentage of morphologically normal embryos, differentiation rate and number of cells per embryos were recorded. The variables were analyzed on a per litter basis by Kruskal-Wallis test. There was no effect of albendazole sulphoxide on parameters evaluated (P>0.05). We conclude that the preimplantation mouse embryo development was not significantly affected by albendazole sulphoxide.

Effects of albendazole sulphoxide on embryonic, foetal and placental parameters in Wistar rats / Efectos de albendazol sulfóxido sobre parámetros embrionarios, fetales y placentarios en ratas Wistar

The aim of this work was to evaluate the effect of albendazole sulphoxide (ABZSO), administered to Wistar rats during pregnancy on embryonic, foetal and placental parameters. A colpocytological control was performed daily and detection of spermatozoa in the vaginal smear was considered as day 0 of pregnancy. For the preimplantational study, ABZSO (10 mg/kg) was orally administered at day 2 of pregnancy; at day 4 the embryos were collected. For the postimplantational study, ABZSO (10 mg/kg) was orally administered by gavages at day 2, 6 or 10 of pregnancy (G2, G6 and G10 Groups respectively); the control group was administered the same volume of carboxymethylcellulose vehicle used to prepare the drug suspension. Fetuses were obtained from pregnant rats sacrificed on day 20 of gestation. Maternal body weight gains were analyzed using the one-way ANOVA test. Embryonic and foetal variables were analized on a per litter basis by the Kruskal-Wallis test. Skeletal anomalies were analyzed using an X² test. The significance level accepted was established at P<0.05. In the preimplantational analysis, the cleavage rate was lower in the experimental group (P<0.05). In the postimplantational analysis there were no differences in the net weight increase among females of the different groups (P>0.05). The number of fetuses and the foetal vesicles weight were lower in the G10 group (P<0.05). This group showed the highest percentage of resorptions (P<0.05) and fetuses morphologically abnormal. An increase in the number of bones affected in fetuses of G6 and G10 groups was observed. The most common malformations were at vertebral, costal and head level. Weights and placental diameters were lower in the G10 group (P<0.05). We conclude that ABZSO at the dose used in this study affects the cleavage rate in preimplantational embryo development, without interrupting pregnancy. Furthermore; the developmental toxicity is related to day of administration.

El objetivo de este trabajo fue caracterizar los efectos de albendazol sulfóxido (ABZSO) durante la gestación de ratas Wistar, sobre parámetros embrionarios, fetales y placentarios. Se efectuó colpocitología diaria de las hembras considerándose día 0 de gestación el día de aparición de espermatozoides en vagina. Estudio preimplantacional: ABZSO (10 mg/kg) fue dosificado oralmente el día 2 de gestación; el día 4 de gestación se realizó la recolección de embriones. Estudio post-implantacional: ABZSO (10 mg/kg) fue dosificado oralmente los días 2, 6 ó 10 de gestación (Grupos G2, G6 y G10, respectivamente). Hembras controles recibieron carboximetilcelulosa, vehículo usado para solubilizar la droga. Las hembras fueron sacrificadas al día 20 de gestación. Variables embrionarias y fetales fueron analizadas sobre la base de las camadas mediante test de Kruskal-Wallis; ganancia de peso de las madres por ANOVA y porcentaje de fetos con alteraciones esqueléticas mediante X2. Estudio preimplantacional: la tasa de recolección embrionaria, el número de embriones recolectados y el porcentaje de diferenciación fueron similares entre grupos (P>0,05). La velocidad de clivaje fue menor en el grupo experimental (P<0,05). Estudio post-implantacional: la ganancia de peso de las madres no difirió entre grupos (P>0,05), el número de fetos y el peso de las vesículas fetales fueron menores en el grupo G10 (P<0,05). Los porcentajes de reabsorciones y de fetos con características morfológicas anormales fueron mayores en el grupo G10 (P<0,05). Las alteraciones esqueléticas fueron mayores en los grupos G6 y G10 (P<0,05) observándose con mayor frecuencia en vértebras, costillas y cabeza. Pesos y diámetros placentarios fueron menores en el grupo G10 (P<0,05). Se concluye que, bajo las condiciones del presente estudio, el ABZSO administrado en la etapa preimplantacional afecta la velocidad de clivaje sin detener la gestación mientras que su efecto en el desarrollo post-implantacional...

Comparative assessment of the in vitro sensitivity of Brugia malayi infective larvae to albendazole, diethylcarbamazine and ivermectin alone and in combination.

The antifilaricidal drugs ivermectin (IVM), diethylcarbamazine (DEC), and albendazole (ALB), used alone or in combinations against infective third-stage larvae (L3) of nocturnally subperiodic (NSP) Brugia malayi (Narathiwat strain), were tested in vitro for sensitivity, for 7 days. IVM alone reduced larval motility at concentrations of 10(-7), 10(-6), and 10(-5) M on day 3. DEC alone also had this effect at concentrations of 10(-6). 10(-5), and 10(-4) M on day 2. ALB alone did not have this effect throughout the experiment, at various concentrations. However, it had greater effect when used in combination with either DEC or IVM. The result also indicated that DEC or IVM, when used in combination with ALB at concentrations of 10(-6) M/10(-6) M, and 10(-5) M/10(-5) M was effectively better than each drug used alone at those concentrations. When both drug combinations were compared, ALB/DEC seemed to be more effective than ALB/IVM at a concentration of 10(-6) M/10(-6) M on day 3. Although IVM and DEC can reduce larval motility when used alone or in combination with ALB, they cannot kill these larvae in an in vitro cultivation, even at a high concentration (10(-5) M).