Acute hemolytic anemia after oral administration of L-tryptophan in ponies

Mary Rose Paradis From the Department of Medicine, Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536 (Paradis); the USDA - ARS, Plum Island Animal Disease Center, Greenport, NY 11944 (Breeze, Laegreid); Department of Veterinary Clinical Medicine and Surgery, Washington State University, College of Veterinary Medicine, Pullman, WA 99164 (Bayly); and Marion Laboratories Inc, Park B, PO Box 9626, Kansas City, MO 64134 (Counts).

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R. G. Breeze From the Department of Medicine, Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536 (Paradis); the USDA - ARS, Plum Island Animal Disease Center, Greenport, NY 11944 (Breeze, Laegreid); Department of Veterinary Clinical Medicine and Surgery, Washington State University, College of Veterinary Medicine, Pullman, WA 99164 (Bayly); and Marion Laboratories Inc, Park B, PO Box 9626, Kansas City, MO 64134 (Counts).

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W. M. Bayly From the Department of Medicine, Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536 (Paradis); the USDA - ARS, Plum Island Animal Disease Center, Greenport, NY 11944 (Breeze, Laegreid); Department of Veterinary Clinical Medicine and Surgery, Washington State University, College of Veterinary Medicine, Pullman, WA 99164 (Bayly); and Marion Laboratories Inc, Park B, PO Box 9626, Kansas City, MO 64134 (Counts).

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D. F. Counts From the Department of Medicine, Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536 (Paradis); the USDA - ARS, Plum Island Animal Disease Center, Greenport, NY 11944 (Breeze, Laegreid); Department of Veterinary Clinical Medicine and Surgery, Washington State University, College of Veterinary Medicine, Pullman, WA 99164 (Bayly); and Marion Laboratories Inc, Park B, PO Box 9626, Kansas City, MO 64134 (Counts).

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W. W. Laegreid From the Department of Medicine, Tufts University School of Veterinary Medicine, 200 Westboro Rd, North Grafton, MA 01536 (Paradis); the USDA - ARS, Plum Island Animal Disease Center, Greenport, NY 11944 (Breeze, Laegreid); Department of Veterinary Clinical Medicine and Surgery, Washington State University, College of Veterinary Medicine, Pullman, WA 99164 (Bayly); and Marion Laboratories Inc, Park B, PO Box 9626, Kansas City, MO 64134 (Counts).

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SUMMARY

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 pomes. 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.

SUMMARY

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 pomes. 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.

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