| Background: Intraperitoneal chemotherapy is a regional selective chemotherapy.Because of its high effectiveness and simple operation,intraperitoneal chemotherapy is now widely used in colorectal,liver and ovarian cancer treatment of early gastric cancer or postoperative treatment.Traditional anticancer drugs increase patient 's survival,while its side effects are also seriously affect the patients' quality of life.Thus,it is of major significance to find intraperitoneal chemotherapy drugs who has significant anti-cancer effect and little side effectson for the clinical application of intraperitoneal chemotherapy.Resveratrol is a non-flavonoid polyphenolic compounds,also known as three stilbene phenols.In 1940,it is extracted from the root of Veratrum album first time.Now it has also been found in more than seventy kinds of plants,including peanuts,grapes,mulberry,veratridine,Polygonum cuspidatum,cassia,fleece-flower root,pineapple,cereal and so on.Resveratrol has been found many biological activities including antiviral,neuroprotective,anti-oxidation,cardiovascular protection,anti-inflammatory effects of plant estrogens and anti-tumor effect.About antitumor activity,resveratrol has now found a high incidence of multiple tumors inhibition,including lymphoid and myeloid tumors,multiple myeloma,breast cancer,prostate cancer,stomach cancer,colon cancer,pancreatic cancer,thyroid cancer,melanoma,head and neck squamous cell carcinoma,ovarian cancer and cervical cancer.However,many experimental results show that resveratrol pharmaceutically active in vivo and in vitro can not reach the same level,that means resveratrol has a low bioavailability,the drug concentration of plasma and organs is far below the effective concentration in v itro experiments,so it is not enough to play fairly pharmacological activity in vivo as in vitro experiments.Experimental methods provided by literature are resveratrol dissolved in a certain percentage of ethanol before injection,but our laboratory preliminary studies shows that resveratrol with 10% ethanol intraperitoneal injection of long-term,drug will accumulate in the abdominal cavity irregular white patches,and has poor treatment of ovarian cancer.This reminds us that the long-term in vivo by intraperitoneal injection of resveratrol,you mus t use a suitable solvent,to make it absorbed rapidly and completely in abdominal cavity,in order to improve the content of resveratrol in the organizations,to achieve therapeutic effect.Objective: Through sustained high doses of intraperitoneal administered Resveratrol to rat for analysis: 1)the influence of different solvents,10% ethanol and DMSO,to the distribution of resveratrol in rat major organs.2)whether 10% ethanol as solvent have the effect of delayed release at a certain extent,.3)by the method of HE staining,observing organization morphological changes of different solvent dose groups(10% ethanol and DMSO).Through these experiments,we explore the intraperitoneal injection of resveratrol suitable solvent and its safety.Methods: Isolate and enrich resveratrol from biological samples,and establish effective HPLC method for monitoring the content.C18 column: 5?m,4.6mm × 250mm;Nacalai Tesque,Japan.Mobile phase: A phase 20% acetonitrile(acetic acid adjusted to PH 3.5 Configuration of water),B phase 80% acetonitrile(acetic acid adjusted to PH 3.5 Configuration of water).Gradient: 0min0% B-12min40% B-20min100% B-28min100% B.Detection wavelength: 303 nm.Flow rate: 1ml / min.Column temperature: 30 ?.Sample volume: 15?l.12 rats were randomly divided into 3 groups: group of 10% ethanol solvent 1,group of DMSO solvent,group of 10% ethanol solvent 2.The rats were daily intraperitoneally(i.p.)injected with resveratrol(RVT: 20 mg/kg bw) after weighed for two weeks.Rats in group of 10% ethanol solvent 1 and group of 10% ethanol solvent 2 were injected resveratrol dissolved by 10% ethanol,the rats in group of DMSO solvent were injected resveratrol dissolved by DMSO,concentration of resveratrol were 10 mg/ml.After one hour of the last injection,10% ethanol solvent 1 and solvent DMSO group set the rats' neck to kill them,take heart,liver,spleen,lung,kidney,intestine,HPLC to detect the concentration of resveratrol,HE staining to observe the morphological changes.Rats in 10% ethanol solvent group 2 was observed at 1h after the last administration to see white spots formed and photographed to record.After suturing the abdominal cavity,intramuscular injection of penicillin-streptomycin 0.2ml.48 hours after the last dose abdominal cavity is opened again,photographed and take the heart,liver,spleen,lung,kidney,intestine,HPLC detected concentration of resveratrol.Results: 1)Rats in DMSO solvent group,the concentration of resveratrol in the heart,liver,spleen,lung,kidney,intestine are 4.17,2.54,5.93,4.23,2.10 and 1.91 times of those in 10% ethanol solvent group 1.2)The four rats in 10% ethanol solvent group 2,1h after the last dose,intraperitoneal irregular patches was observed,48 h after it disappears.3)tissue in 10% ethanol solvent group 1 and DMSO solvent group morphological changes did not happen.Conclusion: Resveratrol dissolved in DMSO,is completely absorbed by intraperitoneal injection.Resveratrol dissolved in 10% ethanol,has a poor solubility,i affect the absorption in the abdominal cavity.Long-term intraperitoneal injection of resveratrol dissolved in 10% ethanol,the drugs may accumulate in abdominal cavity,slow release after the drug was stopped,at a certain extent it played the role of sustained release.Long-term intraperitoneal injection with resveratrol dissolved in 10% ethanol or DMSO had no effects on tissues form of the organs. |
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