Debessai W T, Huan J, Cheeke P R
Department of Physiology/Pharmacology, Oregon Health Sciences University, Portland 97201-3098, USA.
Vet Hum Toxicol. 1999 Jun;41(3):129-33.
The interaction between ergot alkaloids in endophyte-infected (E+) tall fescue (Festuca arundinacea) seed and pyrrolizidine alkaloids (PA) in tansy ragwort (TR; Senecio jacobaea) when simultaneously fed to sheep was investigated. Because of the hepatogenic effects of prolactin (PRL), it was hypothesized that low serum PRL induced by ergot alkaloids would increase the susceptibility of sheep to hepatotoxicity induced by PA. Sheep are normally resistant to PA-induced hepatotoxicity. Twenty-four wether lambs weighing 34.1 +/- 2.3 kg were used after being randomly assigned to 1 of 6 treatments of 4 wethers each. The diets offered were a control basal diet containing endophyte-free (E-) tall fescue seed, control + carbon tetrachloride (CCL4), E+ tall fescue basal diet, E+2CCl4, E(-)+TR, or E+2TR. The diets were composed of 50% alfalfa meal, 34.5% rolled barley, 5% soybean meal, 4% cane molasses, 0.5% trace mineralized salt and 6% tall fescue (E- or E+) seed. In the 2 TR treatments 25% of the alfalfa was replaced by TR. Interaction between ergot alkaloids in E+ tall fescue and PA in TR was assessed by gamma glutamyl transferase (GGTP) activity and/or sulfobromophthalein (BSP) clearance rate, both of which measure liver function. Serum GGTP activity was measured on days 14 and 28; plasma BSP clearance was monitored on days 28 and 70 by collection of blood at 4, 8 and 16 min after i.v. BSP injection. Serum PRL assays were performed on days 14, 70 and 84. Serum GGTP activity was elevated by CCl4 drenching on days 14 and 28. On day 28 TR feeding reduced GGTP activity, but there was no difference between the 2 TR treatments. There was no difference in the mean BSP half-times (t1/2) and % BSP retentions on day 28 among any of the 6 treatments. On day 70, there was no difference in the t1/2 or % BSP retention 4 min after BSP injection among any of the treatments. At 8 min after BSP injection, however, % BSP retention was significantly higher for the control +CCl4 than for the E+2CCl4 treatment. At 16 min after BSP injection, the E+ treatment had a higher mean % BSP retention value than the E+2CCl4 treatment; there were no differences among the other treatments. Serum PRL levels were reduced by E+ or CCl4 on all 3 dates of PRL evaluation. The lack of interaction between ergot alkaloids in E+ tall fescue seed and PA in TR as assessed by GGTP activity and/or BSP clearance in sheep may imply that the target sites o the 2 alkaloids are metabolically different. The low serum PRL with E+ did not increase susceptibility of sheep to CCl4 or PA.
研究了将内生真菌感染（E+）的高羊茅（Festuca arundinacea）种子中的麦角生物碱与同时喂给绵羊的千里光（TR；Senecio jacobaea）中的吡咯里西啶生物碱（PA）之间的相互作用。由于催乳素（PRL）的致肝效应，推测麦角生物碱诱导的低血清PRL会增加绵羊对PA诱导的肝毒性的易感性。绵羊通常对PA诱导的肝毒性具有抗性。24只体重为34.1±2.3 kg的阉公羊在随机分配到6种处理中的1种后使用，每种处理4只阉公羊。提供的日粮为含无内生真菌（E-）高羊茅种子的对照基础日粮、对照+四氯化碳（CCL4）、E+高羊茅基础日粮、E+2CCl4、E（-）+TR或E+2TR。日粮由50%苜蓿粉、34.5%轧制大麦、5%豆粕、4%甘蔗糖蜜、0.5%微量矿化盐和6%高羊茅（E-或E+）种子组成。在2种TR处理中，25%的苜蓿被TR取代。通过γ-谷氨酰转移酶（GGTP）活性和/或磺溴酞钠（BSP）清除率评估E+高羊茅中的麦角生物碱与TR中的PA之间的相互作用，这两者均用于衡量肝功能。在第14天和第28天测量血清GGTP活性；在静脉注射BSP后4、8和16分钟采血，在第28天和第70天监测血浆BSP清除率。在第14、70和84天进行血清PRL检测。在第14天和第28天，CCL4灌胃使血清GGTP活性升高。在第28天，TR喂养降低了GGTP活性，但2种TR处理之间没有差异。在6种处理中的任何一种中，第28天的平均BSP半衰期（t1/2）和%BSP保留率均无差异。在第70天，任何处理在BSP注射后4分钟的t1/2或%BSP保留率均无差异。然而，在BSP注射后8分钟，对照+CCl4的%BSP保留率显著高于E+2CCl4处理。在BSP注射后16分钟，E+处理的平均%BSP保留值高于E+2CCl4处理；其他处理之间没有差异。在PRL评估的所有3个日期，E+或CCl4均降低了血清PRL水平。通过GGTP活性和/或绵羊中的BSP清除率评估，E+高羊茅种子中的麦角生物碱与TR中的PA之间缺乏相互作用，这可能意味着这两种生物碱的靶位点在代谢上是不同的。E+导致的低血清PRL并未增加绵羊对CCl4或PA的易感性。
