常山总碱的亚急性毒性试验

为评价常山总碱的安全性和今后系统研究其药理作用以及为临床安全用药提供试验依据,在小鼠急性毒性试验的基础上,进行亚急性毒性试验。80只大鼠随机分成常山总碱高、中、低剂量组和空白对照组,药物组按照大鼠体质量6.50,3.25,1.63g/kg的剂量灌胃给药,连续给药14d,所有大鼠于给药后分2次（7,14d）扑杀。结果表明,常山总碱低、中剂量组大鼠的体质量、脏器系数、血液学指标、血液生化指标、组织病理学变化等各项指标与对照组比较均无显著性差异（P〉0.05）;高剂量组对上述部分指标有一定影响,需要进一步研究。本试验结果提示,常山总碱的毒性很低,临床用药较为安全。     

Tryptamine alkaloid toxicosis in feedlot sheep

Tryptamine alkaloid toxicosis (Phalaris staggers) was diagnosed in feedlot sheep. Clinical signs of toxicosis, which were exacerbated by excitement, included gait abnormalities, muscular tremors, nystagmus, and convulsions. An estimated 8% of the most severely affected lambs had clinical signs of toxicosis. Gross lesions detected in the brain of affected lambs consisted of focal gray-green discoloration in the brain stem and thalamus; these areas had microscopic evidence of intraneuronal pigment accumulation. Brain specimens obtained at slaughter indicated that 60% of the lambs had lesions consistent with tryptamine alkaloid toxicosis. Tryptamine alkaloids were found in low concentrations in the feed. Lambs exposed to these feeds had higher death losses than those that were not exposed to the feeds. Cobalt concentration in the feed was higher than that previously reported to be associated with Phalaris staggers.     

紫外分光光度法测定盐穗木生物碱含量

探讨盐穗木中有效成分生物碱含量测定方法,用紫外分光光度法测定盐穗木中生物碱的含量,选定波长为280 nm。结果显示,测定在0.079-0.573 mg/mL范围内线性关系良好,回归方程为A=69.20 C＋0.019,R=0.999（n=5）。采用紫外分光光度法测定盐穗木中生物碱含量具有精度高、稳定性好、操作简便的特点,是提取盐穗木全草生物碱的有效测定方法。     

Ergot alkaloid transport across ruminant gastric tissues

Ergot alkaloids cause fescue toxicosis when livestock graze endophyte-infected tall fescue. It is generally accepted that ergovaline is the toxic component of endophyte-infected tall fescue, but there is no direct evidence to support this hypothesis. The objective of this study was to examine relative and potential transport of ergoline and ergopeptine alkaloids across isolated gastric tissues in vitro. Sheep ruminal and omasal tissues were surgically removed and placed in parabiotic chambers. Equimolar concentrations of lysergic acid, lysergol, ergonovine, ergotamine, and ergocryptine were added to a Kreb's Ringer phosphate (KRP) solution on the mucosal side of the tissue. Tissue was incubated in near-physiological conditions for 240 min. Samples were taken from KRP on the serosal side of the chambers at times 0, 30, 60, 120, 180, and 240 min and analyzed for ergot alkaloids by competitive ELISA. The serosal KRP remaining after incubation was freeze-dried and the alkaloid species quantified by HPLC. The area of ruminal and omasal tissues was measured and the potential transportable alkaloids calculated by multiplying the moles of transported alkaloids per square centimeter of each tissue type by the surface area of the tissue. Studies were conducted to compare alkaloid transport in reticular, ruminal, and omasal tissues and to determine whether transport was active or passive. Ruminal tissue had greater ergot alkaloid transport potential than omasal tissue (85 vs 60 mmol) because of a larger surface area. The ruminal posterior dorsal sac had the greatest potential for alkaloid transport, but the other ruminal tissues were not different from one another. Alkaloid transport was less among reticular tissues than among ruminal tissues. Transport of alkaloids seemed to be an active process. The alkaloids with greatest transport potential were lysergic acid and lysergol. Ergopeptine alkaloids tended to pass across omasal tissues in greater quantities than across ruminal tissues, but their transport was minimal compared to lysergic acid and lysergol.     

披针叶黄华碱对小鼠半数致死量的测定

目的：以小鼠为试验动物,对披针叶黄华碱的毒性进行研究,测定其生物碱组分的半数致死量.方法：用体积分数为95％的乙醇结合超声波对披针叶黄华植物进行提取,以小鼠为试验动物,研究拨针叶黄华碱氯仿萃取组分的毒性.结果：通过试验测得披针叶黄华碱萃取组分的半数致死量为127.04 mg/kg,95％可信限为115.41-139.72 mg/kg.结论：试验结果与报道数据差异较大,可能与试验方法、萃取药液的实际浓度等因素有关.     

Treatment of pseudopregnancy with bromocriptin, an ergot alkaloid

One hundred and forty-two dogs with single or multiple pseudopregnancies were treated with bromocriptin at three different dose rates and once in combination with mobilerone. The treatments that scored best were 30 micrograms/kg bromocriptin for 16 days and 10 micrograms/kg bromocriptin for 10 days. Vomiting was a frequent side effect (about 20 per cent of cases) and was treated successfully with metoclopramide at a dosage of 0.5 mg/kg. Metoclopramide had no effect on the effectiveness of the bromocriptin.     

宽苞棘豆生物碱提取与毒性试验

采用醇类生物碱系统提取法,从宽苞棘豆中分离出A 、B、C、D四种组分,经薄层层析检测,并与苦马豆素标准品对照,结果表明B、C组分含有吲哚里西啶生物碱--苦马豆素,A、D组分不含有苦马豆素.将C组分按1 g/kg和2 g/kg分别家兔灌胃,结果家兔没有表现出明显的临床中毒症状和病理变化.     

Pyrrolizidine alkaloid poisoning of sheep in New South Wales

Pyrrolizidine alkaloid poisoning of sheep in New South Wales was reviewed, based on the records of the New South Wales Department of Agriculture's Regional Veterinary Laboratories. The plant species causing significant mortalities were Echium plantagineum and Heliotropium europaeum. The syndrome of hepatogenous chronic copper poisoning was more frequently diagnosed than primary pyrrolizidine alkaloid poisoning, particularly when grazing E. plantagineum. The data indicated that adult crossbred ewes were the most commonly affected class of sheep.     

醉马芨芨草生物碱薄层色谱分析及GC-MS检测

为了明确有毒植物醉马芨芨草所含生物碱成分种类,采用生物碱系统提取法、薄层色谱分析和GC-MS法检测技术,对采自内蒙古阿拉善的醉马芨芨草全草生物碱成分进行提取分离和检测。结果表明:醉马芨芨草酸性氯仿萃取部分、碱性氯仿萃取部分和碱性正丁醇萃取部分在薄层板上分别有3个、4个和2个生物碱显色斑点;经GC-MS分析鉴定出67种化合物,其中有5种生物碱,分别为甲基乙基马来酰亚胺、乙琥胺、三丙酮胺、芥酸酰胺和槐定碱,其中含量最高的为槐定碱,相对含量为6.447%。表明了本批醉马芨芨草中含有生物碱。     

牛心朴子总生物碱对小鼠的毒性试验

近年来 ,由于旱、风沙、鼠害、盐碱等自然条件的影响 ,以及草场管理不善 ,如载畜过重 ,过度采挖 ,过度放牧等 ,造成草场沙化、退化。使优良牧草大量减少 ,而有毒有害植物大量繁衍。毒草不仅与优良牧草竞争生存 ,降低优良牧草的产量 ,而且和优良牧草竞争养分、水分和阳光 ,以致使优良牧草逐年衰退 ,而毒草则愈加旺盛。据陈善科等 (1992 )报道 ,阿拉善盟荒漠草场牛心朴子又称老瓜头 ,属于萝摩纲萝摩科鹅绒藤属植物 Cynanchum komanovii,分布面积达 98万hm2 ,占可利用草场面积的 10 %。牛心朴子已成为内蒙与西部草场最具代表性植物 ,牛心朴子…     

Toxic effects in rabbits after immunization against the pyrrolizidine alkaloid retrorsine]

Six rabbits were immunized against the pyrrolizidine alkaloid retrorsin, conjugated to bovine serum albumin. Seven i.v. inoculations were distributed over a period of half a year. The total antigen dose differed between animals. Towards the end of the experiment all animals (except 2 receiving the lowest antigen dose) suffered from apathy, anorexia and loss of body weight. Pathologically these symptoms correlated well with liver cirrhosis, gradually dependent on the total antigen dose. Blood-chemical parameters were disparate and contradictory.     

甘肃棘豆生物碱抑制小鼠肝癌H22的生长及机理试验

甘肃棘豆(Oxytropis Kansuensis Bunge)是豆科棘豆属植物,其研究已历经百年,在积极探讨其防除和综合利用的同时,大量研究结果表明,其生物碱部位具有明显的抗肿瘤活性[1-3].本试验以荷H22肝癌肿瘤小鼠为模型,进一步研究证实其抗肿瘤活性;并在细胞学水平观察甘肃棘豆生物碱阻止H22细胞恶性表型及直接杀伤肿瘤细胞的作用,在分子生物学水平观察与恶性肿瘤发生发展过程密切相关的增殖细胞核抗原(PCNA)、突变型p53蛋白表达及生物碱的干预作用,为研究甘肃棘豆生物碱抑制肿瘤活性机理提供科学依据.     

Comparison of hepatic in vitro metabolism of the pyrrolizidine alkaloid senecionine in sheep and cattle

OBJECTIVE: To compare hepatic metabolism of pyrrolizidine alkaloids (PAs) between sheep and cattle and elucidate the protective mechanism of sheep. SAMPLE POPULATION: Liver microsomes and cytosol from 8 sheep and 8 cattle. PROCEDURE: The PA senecionine, senecionine N-oxide (nontoxic metabolite) and 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP; toxic metabolite) were measured in microsomal incubations. The kcat (turnover number) was determined for DHP and N-oxide formation. Chemical and immunochemical inhibitors were used to assess the role of cytochrome P450s, flavin-containing monooxygenases (FMOs), and carboxylesterases in senecionine metabolism. The CYP3A, CYP2B, and FMO concentrations and activities were determined, in addition to the role of glutathione (GSH) in senecionine metabolism. RESULTS: DHP concentration did not differ between species. Sheep formed more N-oxide, had higher N-oxide kcat, and metabolized senecionine faster than cattle. The P450 concentrations and isoforms had a large influence on DHP formation, whereas FMOs had a large influence on N-oxide formation. In cattle, CYP3A played a larger role in DHP formation than in sheep. FMO activity was greater in sheep than in cattle. Addition of GSH to in vitro microsomal incubations decreased DHP formation; addition of cytosol decreased N-oxide formation. CONCLUSIONS AND CLINICAL RELEVANCE: Hepatic metabolism differences alone do not account for the variation in susceptibility seen between these species. Rather, increased ruminal metabolism in sheep appears to be an important protective mechanism, with hepatic enzymes providing a secondary means to degrade any PAs that are absorbed from the rumen.     

The plant alkaloid sanguinarine is a potential inhibitor of follicular angiogenesis

Sanguinarine (SA), a phytobiotic from Sanguinaria Canadensis, has been demonstrated to inhibit vessel growth. Current restrictions on the use of antibiotic growth promoters have motivated addition of this alkaloid as a naturally appetizing feed additive for farm animals. However, concern may araise since angiogenesis is a fundamental event in ovarian follicle growth. Therefore, the aim of this study was to evaluate the potential negative role of SA in follicular angiogenesis. For this purpose, we studied the effect of 300 nM SA on the production of vascular endothelial growth factor (VEGF) by swine granulosa cells from follicles >5 mm and on the activation of Akt, the main effector of the VEGF signalling pathway. In addition, the potential interference of SA in vessel development was tested in an in vitro angiogenesis bioassay. SA inhibited both VEGF production and VEGF-induced Akt activation in swine granulosa cells. Moreover, it was able to block vessel growth induced by VEGF. Taken together, our results suggest that SA could be detrimental to follicular angiogenesis, and therefore supplementation of feed with this alkaloid should be carefully considered.     

The toxicity and kinetics of larkspur alkaloid,methyllycaconitine, in mice

Larkspur poisoning sporadically kills from 5 to 15% of the cattle on North American mountain rangelands. Of the 40 different diterpenoid larkspur alkaloids, the one that is thought to be responsible for much of the toxicity has been identified as methyllycaconitine (MLA). Little is known of MLA toxicokinetics or excretion. The purpose of this study was to further characterize the clinical effects of MLA toxicity in mice and determine the toxicokinetics of MLA excretion. Eight groups of mice were dosed intravenously with 2.0 mg/kg of BW of MLA, killed, and necropsied at 0, 1, 2, 5,10,15, 30, and 60 min after injection. Treated animals were reluctant to move, trembled, and developed dyspnea, muscular twitches, and convulsions. Within several minutes, the clinical signs abated and behavior slowly returned to normal over approximately 20 min. At necropsy serum, brain, liver, kidney, and skeletal muscle were collected and frozen. Blood and tissues were extracted and analyzed for MLA with HPLC and electron spray mass spectrometry. Blood MLA elimination followed a normal biphasic redistribution and excretion pattern (r = 0.99) with a K of elimination of 0.0376 and half-life of 18.4 min. Other tissues had similar clearance rates. These data indicate the MLA is rapidly distributed and excreted. In mice, the clinical effects of poisoning seem to affect the central nervous system, causing dyspnea and "explosive" muscular twitches and convulsions. Because livestock commonly eat larkspur at subclinical doses, they are likely to have larkspur alkaloids in many tissues. These results suggest that animals exposed to larkspur should rapidly excrete MLA (within several hours) and that the residues in animal tissues are not likely to be a problem if animals are given several days to allow toxin clearance.     

Clinicopathologic study of horses surviving pyrrolizidine alkaloid (Senecio vulgaris) toxicosis

Twenty horses of various ages had inadvertently ingested alfalfa hay contaminated with Senecio vulgaris. Among them, 4 died of liver disease. Blood was collected from affected horses at monthly intervals for 7 months and at the 9th and 14th months. The following serum enzymes and chemical items were assayed: aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, gamma-glutamyl transferase, sorbitol dehydrogenase, total bilirubin, BUN, glucose, cholesterol, inorganic phosphate, calcium, total protein, and albumin. Amino acid profiles, conjugated bile acids, sulfobromophthalein clearance times, and liver histopathologic changes via serial biopsies were also monitored. Liver histopathologic changes revealed lesions progressively increasing in severity. Aspartate aminotransferase and plasma amino acid ratios indicated chronic liver degeneration (0.05 level of significance). gamma-Glutamyl transferase and lactate dehydrogenase as well as BUN values fluctuated, but returned to within reference values. Horses appeared clinically normal 14 months after intoxication, but were unable to tolerate stress of exercise.     

Effect of total alkaloid ofPeganum harmala L. in the treatment of experimental haemosporidian infections in cattle

Cattle experimentally infected withBabesia bigemina orTheileria sergenti or mixed infestations of the two parasites were treated with Total Alkaloid ofPeganum harmala L. The results showed that treatment was effective againstB. bigemina infection, had a marked effect on the course of infection withT. sergenti and some effect on the course of the mixed infection.