Study Of Sepia Ink-Astragalus Preparation For Relieving Damage Caused By Chemotherapy

Objective:Cyclophosphamide (CP),a most commonly used immunosuppressive agent or anti-tumour drug in practice,could result in many side effects due to the cytotoxic activity originated from its metabolin, such as bone marrow suppression, hair loss and teratogenic effect,etc.,which restrict its clinical application. Squid ink is a natural multifunctional product, up to now, many reports have unveiled biological roles of proteoglycan complex and melanin from the dark ink. Our previous work discovered amelioratory effect of squid ink on injury induced by CP. Background researches have confirmed that traditional Chinese medicine was good for protecting normal tissues from chemotherapeutic damage through comprehensive synergistic action among various herbs. Therefore, based on Chinese crude drug compatibility theory,squid ink and astragalus were used to made into a preparation in different proportions to assess their effect on damage induced by CP in the paper. Mice were employed to construct damage model through intraperitoneal injection with cyclophosphamide,and /or treated with squid ink-astragalus preparation. Some biochemistry parameters in certain organs and blood were evaluated. This study aim to explore the amelioratory effect of squid ink-astragalus preparation on side effect of CP and its possible mechanism,and provide the scientific evidences to reasonable exploitation and application of sepia ink.Method: 40 healthy Kunming mice were divided into 5 groups at random including model group,squid ink group,astragalus membranaceus group,low and high dose of compatibility groups. Male and female share equal quantity in each group. After test cycle (15 days),detection was performed in peripheral blood profile,DNA contents in bone marrow,organ index,SOD activity as well as MDA content in liver and spleen.72 healthy Kunming mice were randomly divided into 9 groups: control group,model group,squid ink group,astragalus membranaceus group and 5 different proportion compatibility groups. Male and female share equal quantity in each group.After test cycle (15 days),body weight,peripheral blood profile,DNA contents in bone marrow and organ index(what organ),SOD activity and MDA content in liver and spleen were examined.70 healthy Kunming mice were allotted to 7 groups at random: control group,model group,and 5 different dosage compatibility groups. Male and female share equal quantity in each group. After test cycle (15 days),body weight,peripheral blood profile,DNA contents in bone marrow,the changes of index of liver and kidney,catalase (CAT) and lactate dehydrogenase (LDH) activities in blood were investigated. 84 healthy Kunming mice were allotted to 7 groups at random: control group,model group,squid ink group,astragalus membranaceus group and 3 different dosage compatib- ility groups. After test cycle (15 days),body weight,peripheral blood profile,DNA contents in bone marrow,organ index,activities of catalase, lactate dehydrogenase,creatine kinase(CK),Glutamic-pyruvic transaminase(GPT) and aspertate aminotransferase (AST)and blood urea nitrogen (BUN) icontent in serum were examined.Results:(1) Squid ink and astragalus could obviously alleviate bone marrow suppression cause by CP respectively. Meanwhile, squid ink and astragalus preparation showed synergistic effects,quantities of leukocytes,red blood cells and platelets and contents of DNA in bone marrow and hemoglobin (in where) were higher than those in the two single drug groups, the same results were also observed in oxidative damage degree.(2) Preparations in various proportions between squid ink and astragalus have different effects on the damage caused by CP, and the optimal proportion is 1:2. Compared with control group, quantities of red blood cells and platelets and hemoglobin content in the optimal proportion group were bounced significantly (P<0.05), increased by 50.4%, 40.3% and 35.9% respectively;bone marrow DNA content rised by 58.5% (P<0.01),SOD activity in liver and spleen increased by 26.3% and 62.2% (P<0.01),MDA content reduced by 25.2% and 22.1% (P<0.01) in the two organs.(3) The protective effect of preparation showed obviously dose-dependent, the optimal dose was 1 g/mL, namely each animal received 5mg/kg body weight. While the dosage exceeded the optimal 8mg/kg body weight,the catabatic effects reduced gradually(Paradox, please know about the meaning of dose-dependent).(4) squid ink-astragalus preparation alleviated severe chemotherapeutic damage caused by high-dose cyclophosphamide (450mg/kg),the surviving rate of mice was increased about 30%,body weight was elevated up to a maximum of 13.3%,the changes in some important enzymes in sera caused by cyclophosphamide were obviously inhibited by the natural mixture. Activities of catalase,lactate dehydrogenase, creatine kinase, glutamic-pyruvic transaminase and aspertate aminotransferase were down-regulated about 21.4%,31.8%,50.8% and 46.96%,blood urea nitrogen content was reduced 31.06% compared with model group which two groups.Conclusions:sepia ink- astragalus mixture could relieve cyclophosphamide-induced damage. Different proportion and dosage arised in different effects,the best proportion between squid ink and astragalus is 1:2 and the optimal dosage is 8 mg/kg body weight,superfluous drug may weaken the protective effects.