Interactions in sheep between tall fescue ergot alkaloids and hepatotoxic carbon tetrachloride and senecio pyrrolizidine alkaloids

The interaction between ergot alkaloids in endophyte-infected (E+) tall fes cue (Festuca arundinacea) seed and pyrrolizidine alkaloids (PA) in tansy ra gwort (TR; Senecio jacobaea) when simultaneously fed to sheep was investiga ted. Because of the hepatogenic effects of prolactin (PRL), it was hypothes ized that low serum PRL induced by ergot alkaloids would increase the susce ptibility of sheep to hepatotoxicity induced by PA. Sheep are normally resi stant 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 endoph yte-free (E-) tall fescue seed, control+carbon tetrachloride (CCL4), E+ tal l fescue basal diet, E++CCl4, E-+TR, or E++TR. The diets were composed of 5 0% 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 t reatments 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 tra nsferase (GGTP) activity and/or sulfobromophthalein (BSP) clearance rate, b oth of which measure liver function. Serum GGTP activity was measured on da ys 14 and 28; plasma B$'P clearance was monitored on days 28 and 70 by coll ection of blood at 4, 8 and 16 min after iv BSP injection. Serum PRL assays were performed on days 14, 70 and 84. Serum CGTP activity was elevated by CCl4 drenching on days 14 and 28. On day 28 TR feeding reduced GGTP activit y, but there was no difference between the 2 TR treatments. There was no di fference in the mean BSP half-times (t1/2) and % BSP retentions on day 28 a mong 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 h igher for the control +CCl4 than for the E++CCl4 treatment. At 16 min after BSP injection, the E+ treatment had a higher mean % BSP retention value th an the E++CCl4 treatment; there were no differences among the other treatme nts. Serum PRL levels were reduced by E+ or CCl4 on all 3 dates of PRL eval uation. The lack of interaction between ergot alkaloids in E+ tall fescue s eed 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 differ ent. The low serum PRL with E+ did not increase susceptibility of sheep to CCl4 or PA.