PLGA-5-氟尿嘧啶缓释微球治疗结直肠癌裸鼠的探讨

目的研究PLGA-5-氟尿嘧啶缓释微球瘤周给药对结直肠癌移植瘤的治疗效果。方法将60只结直肠癌荷瘤鼠随机分为6组,每组10只。A、B组瘤周注射PLGA-5-氟尿嘧啶缓释微球,5-氟尿嘧啶剂量分别为200mg/kg和100 mg/kg;C、D组瘤周注射5-氟尿嘧啶注射液,5-氟尿嘧啶剂量分别为200 mg/kg和100 mg/kg;E组瘤周注射PLGA微球,800 mg/kg;F组不给予任何治疗。于0、3、6、9、12、15d观察裸鼠生存状况、称体重、测量肿瘤大小。15d时处死动物,称瘤重,计算抑瘤率,绘制肿瘤生长曲线;取血行白细胞计数、肝肾功能检查。结果A、B组肿瘤生长曲线平缓,15 d时A、B组肿瘤体积与C、D、E、F组比较,结果差异有显著性,C、D组肿瘤体积与E、F组比较差异无显著性;A、B组抑瘤率分别为75%和62%,与C、D组比较,结果差异有显著性;A、B、C、D、E组体重在0 d及15 d与F组比较,差异无显著性,15 d时各组白细胞计数及肝肾功能检查值均在正常范围。结论PLGA-5-氟尿嘧啶缓释微球瘤周给药能有效抑制结直肠癌移植瘤的生长,且无明显的毒副作用。     

桑色素对小鼠的急性毒性研究

桑色素是一种天然的黄酮类化合物,具有抗炎、抗肿瘤及抗氧化等作用,本实验中使用上下法主试验,腹腔注射给予ICR雌雄小鼠不同剂量的桑色素(230、280、330、390、450、530、630 mg/kg),观察动物的毒性反应,存活动物观察14 d,计算半数致死量LD50。观察期结束后,通过体重、外周血指标、血清生化指标和病理组织学检查来衡量桑色素对小鼠的急性毒性。研究发现,高剂量桑色素对小鼠有一定的急性毒性,腹腔注射半数致死量LD50为463.24 mg/kg,并且毒性强弱与给药剂量密切相关。     

苦豆碱对小鼠的急性毒性研究

本文拟探讨苦豆碱对小鼠的急性毒性,并明确其半数致死量(LD_(50))以及毒性靶器官。采用腹腔注射给药方式,给予600.00、480.00、384.00、307.20、245.76 mg/kg的苦豆碱,实验后观察7 d,记录体重变化及自主活动情况,检测苦豆碱对小鼠的急性毒性作用,用加权回归几率法(Bliss)计算LD_(50),并对死亡小鼠进行主要脏器的病理学检查。结果显示,苦豆碱的小鼠LD_(50)为395.62 mg/kg,95%可信限为305.23~535.04 mg/kg,LD_5为143.00 mg/kg,LD95为1094.47 mg/kg。7 d内小鼠体重有增长趋势。病理结果显示,苦豆碱对小鼠的主要毒性靶器官为肝脏。     

归辛胶囊急性毒性实验研究

目的：进行归辛胶囊急性毒性实验,对小鼠和大鼠可能产生的毒性反应及严重程度,确定无毒反应剂量,为拟定人用安全剂量提供参考。方法：依据《中药、天然药物急性毒性研究技术指导原则》进行急性毒性实验。取小鼠、大鼠各40只,随机分为空白、归辛胶囊低、中、高剂量4个组,每组10只,分别对小鼠、大鼠灌胃给药,给药后连续地观察14天,于给药第1、7、14天称量动物体重,并观察动物饮食、外观、行为、分泌物、排泄物、死亡情况及中毒情况,测定半数致死量（LD50）;在药物毒性较低无法测出LD50时测定小鼠、大鼠的最大耐受量（MTD）。取小鼠、大鼠各40只,随机分为空白组和归辛胶囊高剂量组,每组20只,给药后连续观察14天测定最大耐受量（MTD）,观察指标同测定LD50结果：实验动物未出现死亡无法测出LD50,继而测定MTD,小鼠为24．0g／kg,大鼠为16．0g／kg,各组动物主要脏器均未发现明显病理学改变。结论：归辛胶囊推荐临床日用剂量为0．09g／kg,按此剂量用药具有安全性。     

蛇毒纤溶酶的毒理学研究

目的为保证临床用药安全,对蛇毒纤溶酶进行毒理学研究.方法急性毒性实验小鼠iv给药后,统计LD50及死亡率.亚慢性毒理学实验小鼠ip给药,家兔iv给药,观察动物的一般状态、死亡率、肝功能及血常规.结果LD50为19.30±1.77u/10g,急性毒性实验中,小鼠死亡时间在24～48h.亚慢性毒理学实验动物各项指标均正常.结论蛇毒纤溶酶的临床用量是安全的.     

沙棘籽渣水提物对正常和糖尿病小鼠血糖的影响

本文研究了沙棘籽渣水提物(Aqueous extract of seabuckthorn seed residues,ASSR)对正常及糖尿病小鼠血糖、血脂代谢的影响。首先采用ASSR灌胃昆明种小鼠的急性毒性试验评价了ASSR的安全性;继而以250mg/kg和500 mg/kg剂量的ASSR连续灌胃正常小鼠3周;以250、500和800 mg/kg剂量的ASSR连续灌胃Al-loxan诱导的糖尿病小鼠3周,监测血糖,测定体重、血清胰岛素、总胆固醇和甘油三酯水平。结果显示:ASSR的LD50大于9.8 g/kg体重;连续给药3周,ASSR对正常小鼠的血糖和血脂代谢没有明显影响,但能明显降低糖尿病小鼠的血清葡萄糖和甘油三酯水平。上述结果表明:ASSR的LD50大于5 g/kg体重,按WHO急性毒性分级标准属于实际无毒级,其在实验性1型糖尿病小鼠模型上具有降血糖和降甘油三酯活性。     

番茄叶水提物急性毒性及其对急性炎症的影响

本文观察了番茄叶水提物对小鼠的急性毒性及其对脂多糖诱导急性炎症模型大鼠的影响。采用经典的急性毒性试验方法,观察小鼠口服给予番茄叶水提物的死亡率,按寇氏法计算半数致死量(LD50)。50只SD大鼠随机分为正常组、模型组、阳性药泼尼松5 mg/kg组与番茄叶水提物3.19、1.59 g/kg组,连续给药10 d,每天一次。以腹腔注射脂多糖(LPS)建立急性炎症模型,ELISA法测定血清白细胞介素1(IL-1)、白细胞介素6(IL-6)、肿瘤坏死因子(TNF-α)。结果显示,番茄叶水提物单次灌胃给药的LD50为46.44g/kg,95%可信限为39.52～54.60 g/kg。3.19 g/kg番茄叶水提物可明显降低LPS诱导的急性炎症小鼠血清IL-1、IL-6和TNF-α水平。番茄叶水提物抑制LPS诱导急性炎症的作用机制可能与其降低血清炎症因子水平有关。     

合欢皮总皂苷急性毒理学研究

本文采用常规急性毒理学研究的方法探究合欢皮总皂苷对小鼠的毒性剂量。HE染色观察其主要器官形态学变化,玻璃毛细管法测定血液凝固时间,生化法测定超氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-PX)活性。合欢皮总皂苷的最小致毒量为7.5 mg/kg,近似致死量为1500 mg/kg,半数致死量(LD50)为2164 mg/kg。毒性表现为动物活动减少、1500 mg/kg以上剂量使小鼠食欲下降、2250 mg/kg剂量使小鼠体重明显下降;给药后1 d、7 d和14 d给药组血液凝固时间缩短;主要器官形态学明显改变,明显降低主要器官SOD和GSH-PX活性。结果表明合欢皮总皂苷对小鼠有一定的毒性作用。     

益母草注射液小鼠急性毒性和Beagle犬重复给药毒性试验研究

通过小鼠单次给药急性毒性试验和Beagle犬重复给药毒性试验,评价益母草注射液(YMC)的安全性。用半数致死剂量法对小鼠进行急性毒性试验,观察小鼠的死亡情况和急性毒性症状,用Bills法计算半致死剂量(LD50)。将32只Beagle犬根据体质量、性别随机分为YMC 240.99 mg·kg~(-1)、120.50 mg·kg~(-1)、60.25 mg·kg~(-1)组和0.9%氯化钠注射液对照组,每组8只。静脉滴注给药,每周给药6 d,连续180 d,停药恢复30 d。对Beagle犬进行临床症状、体质量、心电图、血液学、血液生化学、血清电解质、尿液及组织病理学等检查。YMC小鼠静脉给药LD50为845.64 mg·kg~(-1),急性毒性症状主要表现为跳跃、烦躁、嗜睡、活动减少、阵挛性抽搐、眼球突出、尿失禁。重复给药毒性试验,Beagle犬出现呈剂量反应趋势的流涎、呕吐症状,未见肝、肾毒性,其余各项检测指标也均未见与药物毒性相关的明显异常。YMC小鼠静脉给药LD50相当于临床拟用剂量的394.6倍,YMC重复给药毒性试验对Beagle犬的安全剂量为120.50 mg·kg~(-1),相当于临床拟用剂量的56.2倍。提示YMC具有较高的安全性。     

紫茎泽兰醇提物的毒理学研究

为确保以紫茎泽兰提取物为主要原药的植物源农药的安全性,对紫茎泽兰醇提物进行了小鼠经口急性毒性试验、大白兔急性皮肤和眼刺激试验、小鼠骨髓嗜多染红细胞微核计数及小鼠精子畸形试验等急性毒性和遗传毒性试验。结果表明,受试物对两种性别的小鼠经口急性毒性试验,LD50大于5000mg／kg,对大白兔皮肤无刺激性;小鼠骨髓嗜多染红细胞微核试验及小鼠精子畸形试验结果均为阴牲,受试物未见遗传毒性。     

Tremorgenic Toxin from Penicillium verruculosum

A new mycotoxin that produces severe tremors and acute toxicity when administered orally or intraperitoneally (ip) to mice and 1-day-old cockerels was obtained from a strain of Penicillium verruculosum Peyronel isolated from peanuts. The ip 50% lethal dose (LD(50)) of this tremorgen was 2.4 mg/kg in mice and 15.2 mg/kg in chickens. Orally administered LD(50) values for the toxin were 126.7 mg/kg in mice and 365.5 mg/kg in chickens. The trivial name "verruculogen" is proposed for this tremorgenic mycotoxin. Physical and chemical characteristics of the mycotoxin are described.     

薏米黄酒的急性毒性研究

目的:研究薏米黄酒的急性毒性,评价该酒的食用安全性。方法:以ICR小鼠为受试对象,一次性给予最大剂量,观察薏米黄酒对小鼠的急性毒性反应,测定薏米黄酒的LD50和最大耐受剂量。结果:小鼠无一只死亡,无法测出LD50,最大耐受量大于20400 mg/kg。结论:实验检测表明,该黄酒无毒,为薏米黄酒的应用提供了毒理学依据。     

薏米黄酒的急性毒性研究

目的：研究薏米黄酒的急性毒性,评价该酒的食用安全性。方法：以ICR小鼠为受试对象,一次性给予最大剂量,观察薏米黄酒对小鼠的急性毒性反应,测定薏米黄酒的LD50和最大耐受剂量。结果：小鼠无一只死亡,无法测出LD50,最大耐受量大于20400 mg/kg。结论：实验检测表明,该黄酒无毒,为薏米黄酒的应用提供了毒理学依据。     

Antagonism of acute cocaine toxicity by buprenorphine.

The effect of buprenorphine pretreatment on the acute cocaine toxicity was assessed in male Swiss Webster mice. Buprenorphine pretreatment (0.15 or 0.30 mg/kg ip, 30 mins before) significantly attenuated the lethal effects of cocaine (60-140 mg/kg ip). The dose of cocaine which resulted in 50% mortality (LD50) in saline pretreated group was 100.61 mg/kg while the LD50 of cocaine in buprenorphine (0.15 and 0.3 mg/kg) pretreated groups were 113.57 and 118.16 mg/kg respectively. There was no significant change in the ratio of brain/plasma levels of cocaine in buprenorphine pretreated group when compared to the ratio from saline treated controls. Furthermore, neither naloxone (10 mg/kg ip, 15 mins before) nor naltrexone (3 mg/kg ip, 15 mins before) pretreatment affected the LD50 of cocaine. When tested 0.5, 1, 2, 4, 8 and 24 hrs after cocaine administration, sublethal dose of cocaine (80 mg/kg ip) injection resulted in significant increase in the plasma lactate dehydrogenase (LDH) levels. Buprenorphine pretreatment significantly attenuated cocaine-induced release of LDH. These results suggest that buprenorphine could be of potential advantage over naloxone in the management of cocaine and heroin ("speed ball") toxicity and in studies on the pharmacotherapy of cocaine-induced toxicity, LDH levels may be used as a biochemical marker to assess the protective effects of drugs.     

Chemoprotective effects of recombinant human IL-1 alpha in cyclophosphamide-treated normal and tumor-bearing mice. Protection from acute toxicity, hematologic effects, development of late mortality, and enhanced therapeutic efficacy

In this study, recombinant human IL-1 alpha (rhIL-1 alpha) was used to protect normal and tumor-bearing BALB/c mice from the acute toxicity caused by lethal doses of cyclophosphamide (Cy) and 5-fluorouracil. Pretreatment of mice for 7 days with 10,000 U/day of rhIL-1 alpha protected 70 to 100% of mice from the acute death induced by lethal doses of both Cy (380 mg/kg) and 5-fluorouracil (250 mg/kg). In contrast, post-treatment of mice with single or multiple doses of rhIL-1 alpha was not chemoprotective. Pretreatment of mice with rhIL-1 alpha increased the acute LD90 of Cy from 380 mg/kg to greater than 500 mg/kg in normal mice, an LD90 dose-modifying effect of at least 1.25, was accompanied by a more rapid recovery from neutropenia and a less severe reduction in the number of bone marrow single lineage monocyte, myeloid, or myelomonocytic colonies. Some of the mice (10 to 50%) that were successfully protected by pretreatment with rhIL-1 alpha died after day 50. These mice consistently presented with extensive pulmonary inflammation and fibrosis at death. Mice bearing murine renal cancer (Renca) were also protected from the acute toxic effects of Cy (450 mg/kg) by pretreatment with rhIL-1 alpha. Renca-bearing mice pretreated with rhIL-1 alpha and either sublethal (300 mg/kg) or lethal (450 mg/kg) doses of Cy exhibited enhanced survival times over those of untreated Renca-bearing mice. Interestingly, the cause of death in Renca-bearing mice that ultimately failed treatment with rhIL-1 alpha plus 300 mg/kg Cy was recurrent tumor, whereas most mice treated with rhIL-1 alpha plus 450 mg/kg Cy had no detectable tumor, although several died from late pulmonary inflammation and fibrosis. Thus, the dose escalation of Cy in rhIL-1 alpha-pretreated mice results in greater antitumor effects of Cy. However, the dose escalation of some cytotoxic agents allowed by the use of myelostimulatory agents can result in late fatal complications not detected in acute toxicity testing.     

A novel franchetine type norditerpenoid isolated from the roots of Aconitum carmichaeli Debx. with potential analgesic activity and less toxicity

Further investigation on the phytochemistry of the plant Aconitum carmichaeli Debx. led to isolate a new franchetine type C(19)-diterpenoid alkaloid, guiwuline 1. Its structure was established on the basis of the spectroscopic data (1D and 2D NMR, HRESIMS, UV, IR). In mouse hot-plate test and acute toxicity assay, compound 1 exhibited potential analgesic activity (ED(50), 15 mg/kg) and showed little toxicity to mice (LD(50), 500 mg/kg). The results indicate that compound 1 may be used as a lead molecule to develop novel analgesic agents.     

Mix-G200益生菌粉安全性毒理学评价

目的通过对Mix-G200益生菌粉的安全性毒理学进行研究,为以后的应用提供科学依据。方法采用雌雄小鼠急性毒性试验、小鼠骨髓细胞微核试验、小鼠精子畸形试验、Ames试验和大鼠30天喂养试验等对Mix-G200益生菌粉进行安全性试验研究。结果急性经口毒性试验表明,Mix-G200益生菌粉对雌雄小鼠的急性经口LD50均大于21500 mg/kg,以急性毒性半数致死量毒性分级,属无毒级物质。小鼠骨髓细胞微核试验、小鼠精子畸形试验、Ames试验结果均为阴性。30天喂养试验结果表明,大鼠生长情况良好,血液学检查、生化学检查、主要脏体以及组织学检查结果与对照组相比,差异均无统计学意义。结论 Mix-G200益生菌粉未见遗传毒性,使用Mix-G200益生菌粉是安全可靠的。     

Neurophysiological alterations following fluvalinate administration in mice.

Median lethal dose (LD50) of fluvalinate (Marvik 25EC) was 105 (94.6-116.5 mg/kg, ip) in albino mice. Gross observable signs were dose dependent and indicative of central and peripheral nervous system stimulation. Fluvalinate, at 10.5 and 21.0 mg/kg, ip doses in mice, facilitated maximal electroshock seizures, reduced reaction time in analgesic test and enhanced duration of ether anaesthesia. Acute and subacute (7 days) treatment at lower and higher doses enhanced pentobarbitone sleeping time. Acute and subacute treatment (7 days) with phenobarbitone (50 mg/kg, ip) prior to fluvalinate enhanced toxicity of fluvalinate.     

Administration-route-related differences in the micronucleus test with N-ethyl-N-nitrosourea

Administration-route-related differences in the micronucleus test were examined by giving N-ethyl-N-nitrosourea (ENU) to male mice of the MS/Ae and CD-1 strains by 2 different routes, intraperitoneally (i.p.) and orally (p.o.). The experiments consisted of 3 parts: (1) a simplified acute toxicity study, which gave LD50s of 490 (i.p.) and 840 mg/kg (p.o.) in MS/Ae and 640 (i.p.) and 960 mg/kg (p.o.) in CD-1 mice: (2) a pilot experiment for the full-scale micronucleus test to determine appropriate dosages and sampling time: and (3) the micronucleus test at doses of 12.5, 25, 50, and 100 mg/kg with a sampling time of 24 h. The results indicated that no route-related differences existed at the 2 lowest doses. At 50 mg/kg, markedly higher numbers of micronucleated polychromatic erythrocytes (MNPCEs) were induced in both mouse strains by the i.p. route. At 100 mg/kg, the difference between the routes decreased in strain CD-1 and even reversed in MS/Ae. Thus, route-related differences appeared to depend on the dose. Such differences became small, however, in both strains when the comparison was made on the basis of LD50 values.     

噻吩磺隆的毒性及致突变性

选用大鼠、豚鼠及家兔,采用经口及皮肤,粘膜染毒途径,研究其急性毒性。同时有Ames试验,小鼠骨髓嗜多染红细胞微核试验及小鼠睾丸初级精母细胞染色体畸变试验进行致突变性研究,了解噻吩磺隆的毒性及致突变性。大鼠急性经口LD50大于5000mg／kg,经皮LD50大于2000mg／kg。家兔皮肤刺激试验阴性,轻度眼刺激性和弱致敏性。Ames试验,微核试验及小鼠睾丸初级精母细胞染色体畸变试验结果均为阴性。结论 噻吩磺隆属低毒性农药,在本实验条件下无致突变作用。