Pharmacodynamics And Acute Toxicology Of Angelica Sinensis Polysaccharide Iron Complex

1. Pharmacodynamics of APIC1.1 Effect of APIC on Iron Deficiency Anemia (IDA) in ratsThe therapeutic effect of APIC on rats with IDA was studied. Create animal model of rat with IDA by offering low-iron feed and periodic bloodletting. Rats were divided into a negative control group, a model group, three AIPC groups(of high, middle, and low dosage), an ASP group, a mixture group(ASP+FeCl3) and a positive control group(niferex) at random. Hemoglobin (Hb), red blood cell count (RBC), hematocrit (HCT) and iron in WB were determined. The results showed that there was significant difference before and after administration in the APIC groups and the positive control group, and all indexes were restored to about the normal level. There was significant difference before and after administration in the other two experimental groups (ASP and the mixture of ASP+ferric chloride), but the indexes were not restored to the normal level. There was significant difference between the changes of the indexes of all the APIC groups and those of the model group, but there was no significant difference between those of the APIC groups and those of the positive control group. However, the recuperation of APIC groups was superior to that of the positive control group.1.2 Effect of APIC on Mice with Hemolytic AnemiaThe therapeutic effect of APIC on mice with hemolytic anemia was studied. Create animal models of mice with hemolytic anemia by phenylhydrazine (PHZ) ip. Mice were divided into a negative control group, a model group, three experimental groups and a positive control group at random. The negative control group and the model gruop were given deionized water. The three experimental groups were given APIC (of high, middle, and low dosage), ferrous sulfate, and the mixture of Angelica sinensis polysaccharide and ferric chloride. The positive control group was given niferex. Changes of the index such as RBC, Hb and HCT were determined. There was significant difference between the index of experimental groups (except the APIC group of low dosage) and the positive control group and that of the model group. The index of Hb and HCT recuperated to the normal level. There was no significant difference between the index of APIC group of low dosage and that of the model group. However, the recuperation of APIC groups of low dosage was superior to that of the model group. APIC had therapeutic efficacy on hemolytic anemia. And the effects had certain dose-effect relationship; the APIC group of high dosage had the best recuperation.1.3 Effect of APIC on Bone Marrow Injured MiceThe therapeutic effect of APIC on Bone Marrow Injured mice. Bone marrow injured mice model was established by intraperitoneal injection of Cytoxan(CY) and Chloramphenicol(CH) and the therapeutic effect was observed. APIC can decrease adipose cell proliferation in bone marrow injured mice and hasten the recuperation. APIC has therapeutic efficacy on hemolytic anemia and bone marrow injury caused by chemicals, which is reported for the first time.2. Acute toxicology of APIC2.1 Acute toxicology of APIC by oral administration in miceAcute toxicology of APIC by oral administration in mice was observed. Mice were divided into 5 groups and give APIC at doses of 1250, 800, 512, 409.6mgFe.kg-1 and water. The activity, body weight, water and food consumption were observed for 14 days. Histopathology was examined on the 14th day. No obvious acute toxicology appeared in all groups, so maximum tolerable dose (MTD) was used to be the index of toxicology instead of LD50. MTD of APIC in mice was 4800 mgFe.kg-1 and it was 960 times of adult daily dose. APIC for oral use is safe and of little toxicology.2.2 Acute toxicology of APIC by intraperitoneal injection in miceAcute toxicology of APIC by intraperitoneal injection in mice was observed. Mice were divided into 5 groups and give APIC at doses of 400,300,225,168.75,126.5626 mgFe.kg-1. The negative control group was given NS. The activity, body weight, water and food consumption were observed for 14 days. Histopathology was examined on the 14th day. Half-lethal dose(LD50) was calculated by Bliss Method. Iron in WB were determined on the 0,1st,3rd ,5th h. Iron in tissues(spleen, lung, intestine and liver) were determined on the 0,1st,3rdh in the groups of 300 and 400 mgFe.kg-1. LD50 of APIC by intraperitoneal injection was 223.26 mgFe.kg-1, which was 4.65% of MTD by oral administration. It could arrived a high level of concentration in blood and accumulated in tissues which caused acute toxicity. It indicates that APIC for intraperitoneal injection is of high toxic and not suitable for routine administration.