Effects Of Cortex Meliae And Toosendanin On Embryo Loss Of Early Pregnant Mice

Cortex Meliae has been used for decades in animals to repel parasites. Toosendaninis now widely used in agriculture as an insecticide for vegetables and fruits. Whether the herbal components will stay in the animal's body or on vegetables as residues and exert harmful effects to human beings remains unknown. The present study investigated the embryo toxicity of the herb Cortex Meliae and Toosendanin in animals by analyzing the immunity at the matemal-fatal interface, to provide references to clinical usage of the herb and drug.1 Abortion effect of Cortex MeliaeTen-week-old BALB/c mice were divided into 6 groups randomly. Group A as control, groups B, C, D, E, F were experimental groups. Distilled water was given to the mice in group A and water extract of Cortex Meliae to the groups B, C, D, E, F by oral administration for 0.4 mL per mouse on day 5 to 7 of gestation. The groups B, C, D, E, F were administrated 0.2g, 0.4g, 0.6g, 0.8g, 1.0g Cortex Meliae per mouse respectively. The bloods were obtained from the eyes of the day 8 of gestation mice, and then the mice were sacrificed by cervical dislocation. The serum and right uterine lysates were collected, the left uterus was fixed by Bouin's solution. The contents of cytokines IL-2, IL-4 in uterine lysate and serum were assayed by ELISA. The results showed that Cortex Meliae could produce "bell phenomenon" toxicity and the toxicity was related to the enhancement of Th1 responses and inhibition of Th2 responses at the maternal-fetal interface, with the increase of IL-2 and the decrease of IL-4 in the uterus and serum of the pregnant mice. The results of immunohistochemistry showed that the expression of F4/80⁺ macrophage, CD4⁺,CD8⁺ T lymophocytes and the ratio of CD4⁺/CD8⁺ were enhanced in Cortex Meliae treated mice, and indicated that enhancement of F4/80⁺ macrophage,CD4⁺,CD8⁺ T lymophocytes in the uterus was closely related with early embryo loss induced by Cortex Meliae.2 Abortion effect of ToosendaninTen-week-old BALB/c mice were divided into 5 groups randomly. Group A as control, groups B, C, D, E were experimental groups. 10% propylene glycol normal sodium was given to the mice in group A and 10% propylene glycol normal sodium toosendain solution was given to the group B, C, D by intraperitoneal injection for 0.4mL per mouse on day 5 to 7 of gestation. The groups B, C, D, E were admisnistrated toosendanin of 1/60 LD₅₀,1/30 LD₅₀,1/20 LD₅₀,1/15 LD₅₀ respectively. The bloods were obtained from the eyes of the day 8 of gestation mice, and then the mice were sacrificed by cervical dislocation. The serum and right uterine lysates were collected, the left uterus was fixed by Bouin's solution. The contents of cytokines TNF-α, INF-γ, in uterine lysate and serum were assayed by ELISA. The results showed that the toxicity was related to the dose of Toosendanin and the toxicity was related to the enhancement of Th1 responses at the maternal-fetal interface, with the increase of TNF-α, INF-γ, in the uterus and serum of pregnant mice. The results of immunohistochemistry showed that the expression of F4/80⁺ macrophage, CD₄⁺, CD₈⁺ T lymophocytes and the ratio of CD₄⁺/CD₈⁺ were enhanced Toosendanin treated mice, and indicated that enhancement of F4/80⁺ macrophage, CD₄⁺, CD₈⁺ T lympohocytes in the uterus was closely related with early embryo death induced by Toosendanin.