Site of 3-methylindole and indole absorption in steers after ruminal administration of L-tryptophan.

To determine the site of 3-methylindole (3MI) and indole absorption in cattle after ruminal administration of L-tryptophan (TRP), 4 Holstein steers were given 0.4 g of TRP/kg of body weight directly into the rumen through ruminal cannulas. Chromium EDTA and ruthenium phenanthroline were added to feedings of orchard grass hay twice a day for measurement of fluid and particulate flow to the duodenum, respectively. Passage of 3MI and indole (products of ruminal fermentation of TRP) to the duodenum was determined by the products of digesta flow rate and concentration in duodenal contents. Ruminal fluid, duodenal contents, and jugular blood were sampled at postdosing hours (PDH) 0, 6, 12, 18, 24, 36, and 72 for analysis of 3MI, indole, and digesta flow markers. Ruminal, duodenal, and jugular plasma concentrations of 3MI and indole peaked at PDH 12 to 24 at 152.4 and 25.9; 15.5 and 1.0; and 8.7 and 2.2 mg/L, respectively. Most 3MI and indole reaching the duodenum were associated with the particulate phase of the digesta. On a molar basis, total passage of 3MI to the duodenum during 72 hours amounted to 1.0% of the TRP dose for 3MI and 0.1% of the TRP dose for indole. Absorption of 3MI and indole in these steers was almost entirely proximal to the duodenum.

Net absorption of 3-methylindole and indole in cattle after oral administration of L-tryptophan.

The time course and quantity of 3-methylindole (3MI) and indole absorbed after oral administration of L-tryptophan (TRP) was determined in 2 steers. The relationship between the appearance of 3MI and indole in the rumen and blood plasma to absorption of 3MI and indole was also studied. Two Hereford X Angus steers with portal vein, mesenteric vein, and femoral (steer 1) or iliac (steer 2) artery catheters were used. Absorption rates from the portal drained viscera (net absorption) of 3MI and indole were determined by the product of portal and arterial concentration difference and blood flow. Blood flow was determined by primed continuous infusion of p-aminohippuric acid into a mesenteric vein. Three absorption measurements 30 minutes apart were taken at midpoint times of 0, 12, 24, 36, and 48 hours after oral administration of 0.4 g of TRP/kg of body weight. Steer 1 was dosed twice resulting in a total of 45 absorption measurements. Net absorption of 3MI and indole peaked at an average of 1.05 and 0.81 g/hr, respectively. By 48 hours, 29.2% and 15.3% of the TRP dose were accounted for by 3MI and indole absorption, respectively. Closed system in vitro incubations of TRP with ruminal fluid from the same 2 steers resulted in a TRP to 3MI conversion of 23.2% and a TRP to indole conversion of 10.7%. Net absorption of 3MI and indole closely followed and was correlated with concentration of 3MI and indole in ruminal fluid and blood plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructural pathology of 3-methylindole-induced pneumotoxicity in cattle. I. Glycogen accumulation in the alveolar type II cells and tubular myelin accumulation in the alveoli.

3-Methylindole (3MI) was orally administered as a single dose of 0.1-0.2 gm/kgm which then produced acute pulmonary edema in cattle. Electronmicroscopic examination of lung tissue collected after 72 hours revealed vesiculation and desquamation of alveolar type I cells as well as hyperplasia of the alveolar type II cells. Hyaline membrane formation, along with massive accumulation of tubular myelin in the alveolar spaces, was observed. Pulmonary capillaries were occluded with microthrombi and leukocytes infiltrated the interstitium as well as the alveoli. Accumulation of large aggregates of glycogen in the alveolar type II cells were the most unusual changes seen in the experimental animals. It is suggested that accumulation of tubular myelin is a structural manifestation of surfactant inactivation by the plasma proteins. Furthermore, the disease process may be complicated by a compositional or quantitative defect in the surfactant produced by the alveolar type II cells, which are pathologically loaded with glycogen.

Prevention of tryptophan-induced acute bovine pulmonary oedema and emphysema (fog fever).

The pathogenesis of acute bovine pulmonary oedema and emphysema (ABPE) is related to the ruminal formation of 3-methylindole (3MI) from L-tryptophan (TRP), a naturally occurring amino acid and constituent of forage. The objectives of the present study were to determine whether monensin and lasalocid, both polyether antibiotics, were effective in reducing ruminal conversion of TRP to 3MI in vivo and to confirm that reduction in ruminal conversion of TRP to 3MI prevented tryptophan induced ABPE. Sixteen mature Hereford cows were assigned to one of four groups and given TRP to induce ABPE. Group 1 was given 100 mg monensin orally twice daily starting one day before and ending four days after TRP dosing. Group 2 was given 200 mg monensin once daily and group 3 was given 100 mg lasalocid twice daily. Group 4, the control, was given only TRP without further treatment. All control cows developed clinical signs of respiratory disease and lesions of ABPE; one control cow died of ABPE. Mean ruminal 3MI concentrations in control cows reached a peak of 36.4 micrograms per ml. Clinical signs of pulmonary disease appeared in two cows treated with lasalocid and one died. Mean ruminal 3MI in these animals peaked at 38.8 micrograms per ml. No clinical signs of respiratory disease were observed in any of the monensin treated cows and at necropsy there were no pulmonary lesions of ABPE. Mean ruminal 3MI concentrations in monensin treated cows did not exceed 8.9 micrograms per ml. In all groups plasma 3MI concentrations generally reflected ruminal 3MI concentrations but at lower concentrations. The results of this experiment demonstrate that reduction in ruminal 3MI formation by monensin prevents tryptophan induced ABPE.

Determination of indole and 3-methylindole in plasma and rumen fluid from cattle with fog fever or after L-tryptophan administration.

A modified gas liquid chromatography method has been developed to analyse the concentrations of indole and 3-methylindole in samples of plasma and rumen fluid from four cows with fog fever together with four control animals and from two cattle given L-tryptophan orally. Satisfactory recoveries of the metabolites were obtained in test samples examined by the gas liquid chromatography procedure and increased levels were found in rumen fluid after tryptophan administration. Absence of abnormal concentrations of the toxic metabolite 3-methylindole in samples from field cases of fog fever was not considered to rule out the metabolite as a possible cause of the disease in view of the rapid restoration of 3-methylindole to normal levels by the second day after loading with L-tryptophan.