Toxic effects of cyclopiazonic acid in the early phase of pregnancy in mice.
The reproductive toxicity of a single oral dose/mouse (15-50 mg/kg) of cyclopiazonic acid (CPA) in the early phase of pregnancy (day 2-8) was investigated. Male mice used in this study were untreated. A limited number of pregnant mice were treated with 66 mg/kg ergonovine maleate (po, sc) to compare its effect with that of an equivalent dose of CPA (50 mg/kg). Among control sperm-positive mice treated with po NaHCO3 solution, 97.5% were gravid on necropsy day (pregnancy day 12). A single dose of CPA (15-50 mg/kg, po) given on days 2 to 8, decreased the pregnancy rates significantly. In groups treated with a single dose of CPA on pregnancy day 4 to 8, vaginal hemorrhage was observed 1 to 7 days after treatment, and it usually resulted in termination of pregnancy (abortion). Fetal resorption rates were higher than the control rate only in the groups treated with 30 mg/kg CPA po on day 4 or 8. CPA decreased body weight gains and the weights of uteri with fetuses. The ovary weights were generally not changed. Ergonovine maleate (66 mg/kg, sc, po) had no significant effect on all of the parameters examined. The estrous cycle returned without any delay in sperm-positive mice in which nidation of fertilized eggs had been inhibited by CPA, and also in nonpregnant mice (used for the LD50 determination) surviving near lethal doses of CPA (50-70 mg/kg, po). The oral LD50 value for CPA in nonpregnant mice was 64 +/- 4.4 mg/kg, and the toxicity signs were ptosis, hypokinesia, hypothermia, action tremor, cessation of food and water intake and resulting cachexia. The duration and intensity of these toxic signs were dose dependent.
D000375:Aging / Q000502:physiology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D007211:Indoles / Q000633:toxicity*; D007928:Lethal Dose 50; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009183:Mycotoxins / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D012098:Reproduction / Q000187:drug effects
D007211:Indoles; D009183:Mycotoxins; C000543:cyclopiazonic acid