title: Acute hemolytic anemia after oral administration of L-tryptophan in ponies.
abstract: The hematologic and pathologic effects of orally administered L-tryptophan and indoleactic acid and of L-tryptophan administered IV were studied in ponies. Sixteen adult Shetland ponies were allotted into 4 experimental groups. Group 1 consisted of 5 ponies (1-5) given 0.6 g of tryptophan/kg of body weight in a water slurry via stomach tube. Group 2 included 4 ponies (6-9) given 0.35 g of tryptophan/kg orally. Group-3 ponies (10-13) were given 0.35 g of indoleacetic acid/kg orally. Group 4 consisted of 3 ponies (14-16) given a single 4-hour IV infusion of 0.1 g of tryptophan/kg. Restlessness, increased respiratory rate, hemolysis, and hemoglobinuria were detected in 4 of the 5 group-1 ponies. Only pony 7 in group 2 developed hemolysis, hemoglobinuria, and a significant increase in respiratory rate. Renal pathologic lesions, consistent with hemoglobinuric nephrosis, were seen in ponies 2, 4, 5, and 7. Bronchiolar degeneration was evident in 4 of 9 ponies given tryptophan orally. The importance of these respiratory lesions was unknown. Clinical or pathologic abnormalities were not noticed in the ponies of groups 3 and 4. Mean plasma tryptophan values increased significantly in groups 1 and 2 at 6 hours after dosing. A second peak of tryptophan was detected in both groups at 12 hours. Values returned to predose values by 48 hours. Plasma indole and 3-methylindole concentrations were detectable in only 2 ponies (4 and 7). In vitro incubations of cecal fluid from ponies 6, 8, and 9 yielded a percentage conversion of tryptophan to indole of 16.75%, 5.84%, and 7.96%, respectively. 3-Methylindole was not produced. These results suggested that indole was the major metabolite of orally administered tryptophan in these ponies.
authors.affiliation: Department of Medicine, Tufts University School of Veterinary Medicine, North Grafton, MA 01536.
authors.forename: M R
authors.initials: MR
authors.lastname: Paradis
authors.forename: R G
authors.initials: RG
authors.lastname: Breeze
authors.forename: W M
authors.initials: WM
authors.lastname: Bayly
authors.forename: D F
authors.initials: DF
authors.lastname: Counts
authors.forename: W W
authors.initials: WW
authors.lastname: Laegreid
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000743:Anemia, Hemolytic / Q000139:chemically induced / Q000662:veterinary*; D000818:Animals; D005260:Female; D006400:Hematocrit / Q000662:veterinary; D006456:Hemoglobinuria / Q000139:chemically induced / Q000662:veterinary; D006461:Hemolysis / Q000187:drug effects; D006734:Horse Diseases / Q000139:chemically induced*; D006736:Horses; D007210:Indoleacetic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D007211:Indoles / Q000378:metabolism; D007668:Kidney / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D012862:Skatole / Q000378:metabolism; D014364:Tryptophan / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*
chemical_list: D007210:Indoleacetic Acids; D007211:Indoles; C030737:indoleacetic acid; C030374:indole; D014364:Tryptophan; D012862:Skatole