OBJECTIVETo observe the effect of Cinnabaris on mouse embryos after pregnant mice were treated by Cinnabaris in different periods of pregnancy.

METHODTwo separate experiments were performed: First, Cinnabaris was orally given into pregnant mice at the doses of 0.08, 0.4, 4.0 g x kg(-1) from D6 to D19 after pregnancy; Second, Cinnabaris was orally given into mice at the same doses mentioned above from D14 prior to pregnancy until D19 after pregnancy. All animals were sacrificed on D 20 of pregnancy by caesarean section. The numbers of survival, dead and absorbed fetuses were calculated and the survival fetus weight was measured. The survival fetuses were treated by two methods: One third survival fetuses were fixed and stained by Bouin solution for organ examination and the remaining two thirds fetuses were stained for skeleton examination.

RESULTNo obvious embryo toxicity was observed in the first experiment at Cinnabaris dose levels of 0.08, 0.4, or 4 g x kg(-1) x d(-1). There was no significant effect on embryonic development and the numbers of the survival, dead and absorbed fetus. No obvious malformations on appearance, organ, and skeleton examination of fetuses were found. The second experiment showed that the rates of abortion and absorbed fetus in 0.4, 4 g x kg(-1) x d(-1) Cinnabaris group were higher but without statistical significance compared with control group. Appearance and organ examination of Cinnabaris groups fetus showed no obvious malformation, but skeleton malformation was found in 0.4, 4 g x kg(-1) x d(-1) groups (the rates of skeleton malformation were 46.7% and 77.8%, respectively).

CONCLUSIONNo obvious embryonic development toxicity was observed when Cinnabaris was orally given in intermediate and late pregnant period, but the embryos in the early stage of pregnancy was more sensitive to Cinnabaris. When Cinnabaris was given prior to pregnancy until the whole period of pregnancy, it may be harmful for the fetuses at above the dose level 0.08 g x kg(-1) x d(-1) (equivalent to 5 times clinical intake dose), both in a dose-dependent manner.

Animals ; Drugs, Chinese Herbal ; toxicity ; Embryo, Mammalian ; Embryonic Development ; drug effects ; Female ; Fetal Development ; drug effects ; Mice ; Mice, Inbred ICR ; Models, Animal ; Pregnancy

OBJECTIVETo investigate the mercury cumulation following single dose or long-term use of Cinnabar to rats.

METHODThe Cinnabar which was used in the study contains 98% insoluble mercuric sulfide (HgS) and 21.5 mg x kg(-1) soluble mercuric compounds. Two separate experiments were performed: (1) Tweenty-eight fasting SD rats were orally given a single dose of Cinnabar at the dose of 0.8 g x kg(-1) and the other four rats were given ultra-filtrated water served as control group. Blood, livers, kidneys and brains of four rats were taken out at 0.5, 1, 2, 4, 8, 16, 36 h respectively after treatment. Mercury quantity of each organ or blood sample was measured. (2) Forty SD rats were randomly divided into four groups: control group and Cinnabar 0.1, 0.4, 0.8 g x kg(-1) groups, each group containing 5 females and 5 males. The rats were intra-gastrically treated with Cinnabar once a day for successively 90 days, while the control group was given ultra-filtrated water. Mercury contents in blood, livers, kidneys and brain of each rat were measured at 16 h of fasting after last dosing.

RESULTMercury contents of blood, liver, kidney and brain increased slightly after single dosing of Cinnabar at dose of 0.8 g x kg(-1), with the order from high to low liver > blood > brain > kidney. Whereas 90-day oral treatment of Cinnabar led to significant cumulation of mercury in organs but not in blood. Kidney' s cumulation of mercury was much higher than any other tested organs and blood. Brain's mercury cumulation was also very high. The contents of mercury in kidney and brain of 0.8 g x kg(-1) group (total intake of soluble mercury within 90 days was 1 548 microg x kg(-1)) were respectively 71.2 and 27.4 times higher than control group. Even though in the lowest dose 0.1 g x kg(-1) group (total intake of soluble mercury 194 microg? kg(-1)), the mercury cumulation folds in kidney and brain were 16.77 and 20.43 respectively. However, liver got lower mercury cumulation than kidney and brain, which led to only 2 folds mercury cumulation at dose of 0.8 g x kg(-1). Our previous study showed that 90-day administration of Cinnabar at the dose > or = 0.1 g x kg(-1) (total intake of soluble mercury 194 microg x kg(-1)) could cause pathological changes in kidney and liver, indicating both were the toxicity targets for Cinnabar. Those manifested that liver could be more sensitive than kidney to mercury. Though brain got 20 times mercury cumulation after 90 day treatment, the animals showed no abnormal signs in general behavior and brain histomorphology,which indicated that rat brain was not sensitive to mercury.

CONCLUSIONSoluble mercury in Cinnabar can be absorbed causing high cumulated in some organs, such as kidney and brain after long-term use of Cinnabar. Liver had also mercury cumulation, but was much lower than kidney. Total intake of soluble mercury for > or = 194 microg x kg(-1) within 90 days could cause toxicosis by mercury cumulation.

Administration, Oral ; Animals ; Brain ; metabolism ; Female ; Kidney ; metabolism ; Liver ; metabolism ; Male ; Mercury ; pharmacokinetics ; Mercury Compounds ; administration & dosage ; pharmacokinetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution