The research aimed to investigate the acute toxicity and subchronic toxicity of polyinosinic injection on Kunming mice.Through intraperitoneal injection on Kunming mice with polyinosinic injection,its acute toxicity and subchronic toxicity were evaluated.Acute toxicity test showed that mice in each groups began to die after using polyinosinic for 4 h and death time were mainly 4～12 h after using polyinosinic,LD50 was 59.73 mg/kg.Subchronic toxicity test showed that in the 7th d after using polyinosinic,mice body weight in high-dosage group was significantly lower than that in low-dosage group,spleen coefficient in middle-dosage group was significantly higher than that in control group and high-dosage group,hematocrit in middle-dosage group and high-dosage group were significantly higher than that in control group.Total protein content in high-dosage group was significantly lower than that in low-dosage group and control group and albumin content in high-dosage group was significantly lower than that in control group.In pathology examination it was found that mice liver in high-dosage group had slight inflammation.Acute toxicity of polyinosinic was greater and long-term usage with high dose could lead to anaemia and slight liver damage,so its dosage and treatment period should be paid attention in clinical application.

BACKGROUND AIM: To study the embryonic and teratogenic toxicities of chitosan in rats during the period of organ formation. MATERIALS AND METHODS: Ninety pregnant SD rats were randomly divided into five groups with 18 rats in each, three chitosan dosage groups (50, 250, 1 000 mg/kg), one negative and one positive control group. Chitosan and normal saline was given by gavage to the treated groups and the negative control group for ten days during the period of organ formation (the 6th to 15th day of gestation),respectively. Rats in the positive control group received intraperitoneal cyclophosphamide (CP) on the 11th to 13th day of gestation at a daily dose of 7 mg/kg. The rats were sacrificed to examine the fetuses on the 20th day. RESULTS: The results showed that chitosan didn't produce significant effects on health, behavior, weight gain and reproductive parameters of pregnant rats and fetal growth, and didn't induce any teratogenic effect on the appearance, bones and bowels of the fetuses. CONCLUSION: Chitosan has no embryonic and teratogenic toxicity when used under 1 000 mg/kg.

A comparision of pharmacokinetics was investigated in 6 healthy pigs following intramuscular administration of two different doxycycline injections at a single dose of 10 mg/kg.Doxycycline concentration in plasma was determined by a high performance liquid chromatography with solid phase extraction method.The concentration-time data were analyzed with 3P97 computer program.The concentration-time data were both fitted a two-compartment open model with first-order absorption after single intramuscular administration of common doxycycline injection and long-acting injection.The main pharmacokinetic parameters were as follows,respectively: T1/2Ka(0.22±0.06) h and(0.51±0.17) h,T1/2β(5.21±1.78) hand(11.07±4.14) h,Tmax(0.62±0.27) hand(2.31±0.44) h,Cmax(2.61±0.58) μg/mL and(1.24±0.33) μg/mL,AUC(9.53±2.47)(μg·h/mL) and(19.85±5.62)(μg·h/mL).Doxycyline was absorbed fast and distributed extensively after intramuscular administration in healthy pigs.The long-acting formulationhad a sustained and long-acting charater.

Sixty 40-day-old cocks were randomly divided into control group,phenobarbital(PB)-treated group and dexamethasone(DEX)-treated group.Induction of phenobarbital and dexamethasone on hepatic cytochrome P450 in chickens was investigated by enzyme assays in vitro and antipyrsine clearance in vivo.The results showed that in comparison with control group the activities of hepatic microsomal enzymes and metabolic rate of antipyrine obviously increased in PB-group and DEX-group(P0.01).Microsomal cytochrome P450 enzymes in chickens could be obviously induced by phenobarbital and dexamethasone and the inducible model of cytochrome P450 in vivo was successfully established in this study.

The effect of ethanol(EtOH) on the activity of cytochrome P450 2E1 in Carassius auratus was investigated by pharmacokinetics with chlorzoxazone(CZX) as a specific substrate.130 fish were equally divided into two groups:EtOH-treated group and the control group.EtOH was administered orally to fish at the dose of 1 g/(kg·d) for 5 consecutive days.Fish in control group received an equal volume of normal saline only.On the 6th day,two groups of fish were given an intraperitoneal injection with 10 mg/kg CZX.The plasma concentrations of CZX were determined by HPLC,and the pharmacokinetic parameters were calculated.The results showed that the concentration-time data of CZX in two groups both fitted two compartment models.Compared with the saline-treated control group,elimination half life was increased by 0.9 fold(P0.01),area under the curve was increased by 0.8 fold(P0.01),and total clearance was shortened by 51.2%(P0.01) in the EtOH-treated group.The results indicated that the activity of CYP2E1 could be obviously inhibited by EtOH.

AIM: To investigate acute toxicity and accumulative toxicity of polyinosinic-polycytidylic acid (poly I:C) injection in Kunming mice. METHODS: The experiment was carried out in the Laboratory of Department of Pharmacology and Toxicity of Nanjing Agricultural University from April to May 2006. Experimental materials: The trial drugs was poly I:C injection (Nanjing Funa Biotechnology Co., Ltd.), lot number 060509-3, each 3 mg/mL. Kunming mice of clean grade were purchased from Animal Experiment Center, Nanjing University of Traditional Chinese Medicine (number of animal license SYXK 2005-0009). ①acute toxicity test: Totally 50 Kunming mice of 18-22 g body mass were randomly selected and equally divided into 5 groups, with 10 in each group, male and female (half and half). Mice were fasting but could drink water 6 hours before medication. Dosage of poly I:C was determined in each group on the basis of preliminary experiment. Ratior in consecutive two groups was 1.2. Drug dosage in the five groups was 36.17,43.40,52.08,62.50,75.00 mg/kg, respectively. Each group was administrated with 0.25 mL/10 g poly I:C and different dosages group received drug of different concentrations in the same volume. ②accumulative toxicity test: 60 Kunming mice of 15-18 g body mass were selected and randomly divided into 2 groups with 40 mice in test group and 20 mice in control group. The number of male and female mice was the same in each group. Accumulation coefficient method was used to evaluate the accumulative toxicity of poly I:C injection. Each mice was given poly I:C injection with the dose of 0.1 LD50 daily in the first 4 days and 1.5 fold dose in the next 4 days, totally 5 phases for 20 days. Saline was adjusted into the suitable concentration, and drug was given intraperitoneally every day. All the mice in test group were given 0.25 mL/10 g injection and the mice in control group were given saline with the same volume. The general status, mortality and the body mass changes were observed. Accumulation coefficient was calculated and tolerance of poly I:C in mice was observed. RESULTS: Totally 110 mice were involved in the analysis of results. ①acute toxicity test: Many toxic symptoms of the mice were observed after poly I:C including action retardation, gloomy spirit, chilly, clothing hair erection, and diarrhoea 3 hours after medication and death one by one 4 hours later. The mouse death was centralized from 4-12 hours after medication. 24 hours after medication, spirit and anorexia were recovered gradually in the survival mice, and no mice died in the next 6 days. It was tested out that the half death quantity (LD50) was 59.73 mg/kg and the 95% confidence interval was 29.49-120.97 mg/kg. ②accumulative toxicity test: No evidently toxic symptom was observed and no mouse was dead through the experiment. There was no significant difference in body mass of mice between the test group and control group (P > 0.05). ③tolerance test: The mortality of mice in test group was significantly lower than that in the control group(0,20%,P < 0.01). CONCLUSION: Though the acute toxicity is higher, the poly I:C is very safe compared to its dosage used in clinic. While no obvious cumulative toxicity, it can induce a certain obvious tolerance.

采用体外肝微粒体酶生化测定方法,研究地塞米松(DEX)和利福平(RFP)对鸡细胞色素P450酶系的影响。将36羽公鸡随机等分为对照组(生理盐水)、DEX处理组(5 mg.kg-1,腹腔注射7 d)和RFP处理组(15 mg.kg-1,口服7 d),第8天处死实验动物,提取肝微粒体,进行微粒体酶活性分析。结果显示:与对照组相比,DEX组相对肝重、肝微粒体蛋白浓度、细胞色素P450总含量和红霉素-N-脱甲基酶(ERND)的活性均显著升高(P<0.01),而RFP组各项指标没有统计学意义(P>0.05)。结果提示:腹腔注射地塞米松对鸡肝CYP450产生明显诱导作用,口服给予利福平对鸡肝CYP450无明显诱导作用。

评价新鱼腥草素钠对小鼠、肉鸡的急性毒性。采用常规方法染毒,改良寇氏法计算LD50。结果小鼠腹腔注射新鱼腥草素钠的LD50为119.14mg/kg;小鼠经口染毒,无法测定LD50,内服1日的最大耐受量为12g/kg;肉鸡按1g/kg、2g/kg、4g/kg经口染毒,无任何异常反应。说明新鱼腥草素钠口服无毒安全、腹腔注射有一定毒性。