Gooneratne S R, Patchett B J, Wellby M, Fletcher L R
Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln, New Zealand.
N Z Vet J. 2012 May;60(3):176-82. doi: 10.1080/00480169.2011.644189.
To determine the effect of oral dosing of sheep with loline alkaloids on their excretion in urine and faeces, and to monitor for any toxic effects.
In Experiment 1, six 9-month-old ewe lambs were given a single oral dose of loline alkaloids (52 mg/kg bodyweight (BW); acute exposure) as a suspension of ground meadow fescue (Festuca pratensis) seed in water. In Experiment 2, on six consecutive days, six ewe lambs were given three doses of loline (68 mg/kg BW/day; chronic exposure). Blood was collected at variable intervals up to 72 h in Experiment 1, and up to 8 days in Experiment 2, for haematology and measurement of alkaline phosphatase, aspartate aminotransaminase, creatine kinase and γ-glutamyl transferase in plasma. Urine and faecal samples were collected at similar times for measurement of creatinine in urine and loline alkaloid analysis. A post mortem with histopathology was carried out on two animals at the end of each experiment.
The loline alkaloids, N-acetyl norloline, N-formyl loline, N-acetyl loline, N-methyl loline and loline base were detected in urine within 15 minutes after the single dosing. N-formyl loline and loline base were the predominant metabolites in urine in both experiments. The total quantity of lolines excreted in both urine and faeces was 10% and 4% of the amount dosed in Experiments 1 and 2, respectively. In both experiments, the clinical chemistry parameters in blood and urine were within normal ranges. Post-mortem and histopathological examination did not show any abnormalities.
This is the first report of loline alkaloid profiles in both urine and faeces of sheep. The appearance of loline alkaloids and the loline base in urine within 15 minutes suggests rapid uptake, metabolism and excretion. Loline alkaloids were non-toxic to sheep at the concentrations they are exposed to under New Zealand grazing conditions. The low recovery of loline alkaloids in urine and faeces in the absence of toxicity signs suggests lolines are extensively metabolised; probably to forms other than N-formyl loline, N-methyl loline, N-acetyl loline, N-acetyl norloline, and loline base in the digestive tract of sheep prior to absorption, and/or in the liver or other tissues following absorption.
确定给绵羊口服洛林生物碱后其在尿液和粪便中的排泄情况，并监测是否有任何毒性作用。
在实验1中，给6只9月龄的母羊羔口服一剂洛林生物碱（52毫克/千克体重；急性暴露），以草地羊茅种子在水中的悬浮液形式给药。在实验2中，连续6天给6只母羊羔分三次给药洛林（68毫克/千克体重/天；慢性暴露）。在实验1中，直至72小时内的不同时间点采集血液，在实验2中直至8天内采集血液，用于血液学检查以及测定血浆中的碱性磷酸酶、天冬氨酸转氨酶、肌酸激酶和γ-谷氨酰转移酶。在相似时间采集尿液和粪便样本，用于测定尿液中的肌酐以及分析洛林生物碱。在每个实验结束时，对两只动物进行尸检和组织病理学检查。
单次给药后15分钟内，在尿液中检测到了洛林生物碱N-乙酰去甲洛林、N-甲酰基洛林、N-乙酰洛林、N-甲基洛林和洛林碱。在两个实验中，N-甲酰基洛林和洛林碱都是尿液中的主要代谢产物。在实验1和实验2中，尿液和粪便中排泄的洛林总量分别为给药量的10%和4%。在两个实验中，血液和尿液中的临床化学参数均在正常范围内。尸检和组织病理学检查未显示任何异常。
这是关于绵羊尿液和粪便中洛林生物碱谱的首次报告。15分钟内尿液中出现洛林生物碱和洛林碱表明其吸收、代谢和排泄迅速。在新西兰放牧条件下，绵羊接触的洛林生物碱浓度对其无毒。在没有毒性迹象的情况下，尿液和粪便中洛林生物碱回收率低表明洛林被广泛代谢；可能在绵羊消化道吸收前，和/或吸收后在肝脏或其他组织中代谢为除N-甲酰基洛林、N-甲基洛林、N-乙酰洛林、N-乙酰去甲洛林和洛林碱以外的形式。
