title: Interactions in sheep between tall fescue ergot alkaloids and hepatotoxic carbon tetrachloride and Senecio pyrrolizidine alkaloids.
abstract: 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.
authors.affiliation: Department of Physiology/Pharmacology, Oregon Health Sciences University, Portland 97201-3098, USA.
authors.forename: W T
authors.initials: WT
authors.lastname: Debessai
authors.forename: J
authors.initials: J
authors.lastname: Huan
authors.forename: P R
authors.initials: PR
authors.lastname: Cheeke
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000821:Animal Feed / Q000009:adverse effects / Q000382:microbiology; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004347:Drug Interactions; D004876:Ergot Alkaloids / Q000494:pharmacology*; D005260:Female; D005506:Food Contamination; D005658:Fungi / Q000502:physiology; D008297:Male; D010944:Plants / Q000382:microbiology / Q000633:toxicity; D010947:Plants, Toxic; D011388:Prolactin / Q000097:blood; D011763:Pyrrolizidine Alkaloids / Q000494:pharmacology*; D011897:Random Allocation; D012674:Senecio / Q000737:chemistry*; D012756:Sheep / Q000378:metabolism*; D013448:Sulfobromophthalein / Q000493:pharmacokinetics; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D000470:Alkaloids; D004876:Ergot Alkaloids; D011763:Pyrrolizidine Alkaloids; D013448:Sulfobromophthalein; D011388:Prolactin; D002251:Carbon Tetrachloride; D005723:gamma-Glutamyltransferase