Mimosine in goat diet

• Effects of mimosine administered to a perfused area of skin in Angora goats
• Influence of mineral supplementation on 2,3-dihydroxypyridine toxicity in Angora goats
• Effect of mimosine on portal-drained visceral net flux and concentrations of amino acids and minerals in plasma of Alpine goats
• Tissue residues of mimosine and 2,3-dihydroxypyridine after intravenous infusion in goats
• Blood metabolite and regulatory hormone concentrations and response to metabolic challenges during the infusion of mimosine and 2,3-dihydroxypyridine in Alpine goats
• Determination of mimosine and 3,4-dihydroxypyridine in milk and plasma of goats

Effects of mimosine administered to a perfused area of skin in Angora goats

British Journal of Nutrition 75:69-79. 1996.
R. Puchala, S.G. Pierzynowski, T. Sahlu and S.P. Hart

The effect of mimosine on a perfused area of skin tissue was studied using an isolated perfusion technique. Four mature Angora wethers (body weight 35 kg, SE 2.3) were cannulated bilaterally with indwelling silicon catheters in the superficial branches of the deep circumflex iliac artery and vein. Mimosine (40 mg/kg BW^0.75/d) was infused intraarterially into one iliac artery of each goat for 3 d and saline was infused in the contralateral (control) iliac artery. Iliac venous blood samples were taken from both sides along with arterial samples from the carotid artery. Mimosine infusion elevated plasma mimosine in the carotid artery (52.6, SEM 19.21) and iliac vein on the saline treated side to 54.1 M (SEM 16.31) and in the iliac vein on the mimosine treated side to 191.3 M (SEM 19.14; P<0.01). Mimosine decreased feed intake (2.3 vs 0.6 kg/d, SEM 0.29; P<0.001) and water consumption (5.2 vs 1.3 L/d, SEM 0.67; P<0.001). Mimosine did not cause defleecing in the area of infusion and was cleared from the bloodstream within 12 h of cessation of infusion. The following effects were also observed during mimosine infusion: decrease in plasma amino acids to half pre-infusion values (methionine 22.7 vs 13.1 M, SEM 1.41; lysine 95.9 v. 37.4 M, SEM 4.28; P<0.001), decrease in plasma T₃ (149.5 vs 69.5 ng/dL, SEM 4.31; P<0.001), T₄ (6.15 vs 1.95 g/dL, SEM 0.18; P<0.001) and insulin 28.7 vs 17.3 IU/ml, SEM 1.89; P<0.01), increase in plasma cortisol (1.4 vs 6.2 g/dL, SEM 0.35; P<0.001); decrease in plasma zinc and magnesium (0.97 vs 0.49 mg/L, SEM 0.063; P<0.001 and 21.4 vs 14.6 mg/L, SEM 1.74; P<0.001, respectively). All reported parameters returned to their normal values 24 h after cessation of mimosine infusion except feed intake which was affected for a longer period. Mohair length and diameter were not affected by mimosine infusion. The toxicity of mimosine may be due to the drastic depletion of zinc and magnesium in the blood as mimosine possesses very strong chelating properties and is excreted in the urine as a chelate.

Influence of mineral supplementation on 2,3-dihydroxypyridine toxicity in Angora goats

Animal Feed Science and Technology 55:253-262. 1995.
R. Puchala, T. Sahlu, Jennifer J. Davis and S.P. Hart

To study the effect of mineral supplementation on 2,3-DHP toxicity, 16 mature Angora wethers were randomly allocated to four treatment groups (M, DM, D and C). Two hours after the morning feeding; group M received a mineral mixture of 2 g of Fe₂(SO₄)₃ • 7H₂0, 2 g of MgSO₄ • 7H₂0 and 2 g of ZnSO₄ • 7H₂0 intraruminally in 80 mL of water; group DM received a similar mineral mixture plus 6 g of 2,3-DHP (DHP chelated with metal ions), group D received 6 g of 2,3-DHP in 80 mL of water and group C received 80 mL of water. In group D, two animals died within 24 h of receiving DHP and the other two animals were sacrificed to prevent suffering. Ruminal concentration of DHP was approximately 18 times higher in group D than in group DM (2.8 vs 0.16 mmol L^-1; P<0.05) 4 h following treatment. Plasma DHP concentration, 6 h post treatment, was lower in group DM than in group D ( 15.2 vs 85.9 nmol mL^-1, P<0.05). Urinary excretion of 2,3-DHP was much faster in group DM than in group D (P<0.05). Plasma triiodothyronine in group D was lower (110 vs 211 ng dL^-1; P<0.05) than in group DM. It appears that mineral supplementation prevented 2,3-DHP toxicity. Faster urinary excretion of chelated 2,3-DHP suggests that 2,3-DHP must be chelated to be efficiently transported and cleared by the kidney.

Effect of mimosine on portal-drained visceral net flux and concentrations of amino acids and minerals in plasma of Alpine goats

Small Ruminant Research 18:43-49. 1995.
M. Smuts, S. G. Pierzynowski, R. Puchala, A. Al-Dehneh, T. Sahlu, J. M. Fernandez, and R. N. Heitmann

This experiment was designed to investigate whether circulating mimosine imposes limitations on absorption of amino acids and minerals from the gastrointestinal tract of Alpine goats. Circulating mimosine, portal blood and plasma flow rate, and concentrations and net absorption of amino acids and minerals were measured 60 h before (PRE) and 24 h after (POST) the femoral vein infusion of mimosine (12.5 mg kg^-1 BW^0.75 h^-1). Mimosine infusion did not affect portal plasma flow rate. Venous and arterial plasma amino acid and mineral concentrations were depressed and the absorption of alanine (P < 0.09), serine (P < 0.04), and methionine (P < 0.03) from the gastrointestinal tract were reduced for up to 24 h after the cessation of mimosine infusion, even when normal feeding was resumed. This disruption was possibly caused by the circulating mimosine (4.88 µm L^-1 during POST) directly, via chelation or competition for absorption, or, indirectly, by gastrointestinal lesions resulting from circulating mimosine. Pivotal to this experiment was the observation that mimosine was eliminated from the goat circulatory system approximately 40 times more rapidly in a 24 h period than when similar concentrations were infused in sheep.

Tissue residues of mimosine and 2,3-dihydroxypyridine after intravenous infusion in goats

Journal of Animal Science 73:172-176. 1995.
T. Sahlu, R. Puchala, P. J. Reis, J. J. Davis, K. Tesfai, J. M. Fernandez, and A. A. Millamena

Sixteen growing Alpine wethers (average BW ± 2 kg) were assigned to one of four treatments to evaluate tissue retention of the leucaena toxins mimosine (MIM) and 2,3-dihydroxypyridine (2,3-DHP). Treatments were infused i.v. for 2 d and were 1) saline control, 2) MIM (200 mg · kg BW^-.75 · d^-1), 2,3-DHP (200 mg · kg BW^-.75 · d^-1), or 4) MIM (100 mg · kg BW^-.75 · d^-1) + 2,3-DHP (100 mg · kg BW^-.75 · d^-1). Immediately after the infusion, the goats were slaughtered and tissue concentrations of MIM and 2,3-DHP were determined via HPLC. No detectable levels of either toxin were found in spleen, heart, lung, or muscle; however, appreciable amounts of MIM and 2,3-DHP were found in plasma, kidney, and liver samples. Kidney MIM content was greater (P < 0.01) than that of liver, although liver tended to retain slightly more 2,3-DHP (P > 0.05). Infusion of MIM resulted in a plasma MIM content of 30 to 54 mol/L and reduced (P < 0.01) plasma PHE and LEU. Infusion of 2,3-DHP resulted in a plasma 2,3-DHP content of 9.4 mol/L and increased plasma THR, ARG, VAL, PHE, ILE, LEU, and LYS concentrations (P < 0.10). Humans consuming offals from ruminants consuming large amounts of the leguminous forage leucaena may be exposed to appreciable quantities of MIM and 2,3-DHP.

Blood metabolite and regulatory hormone concentrations and response to metabolic challenges during the infusion of mimosine and 2,3-dihydroxypyridine in Alpine goats

Journal of Animal Science 72:415-420. 1994.
A. Al-Dehneh, S. G. Pierzynowski, M. Smuts, T. Sahlu, and J. M. Fernandez

Sixteen Alpine wethers (average BW 35 ± kg) were used to evaluate the effect of continuous 48-h intravenous infusions of saline (CON), mimosine (MIM; 200 mg · kg^0.75·d^-1), 2-hydroxy-3(1H)-pyridine (2,3-DHP; 200 mg · kg^0.75·d^-1), or MIM + 2,3-DHP (100 mg of MIM plus 100 mg of 2,3-DHP · kg^0.75·d^-1) on hepatic function and selected blood metabolite and circulating hormone concentrations. Neither MIM nor 2,3-DHP affected plasma ammonia N, glucose, cortisol, or insulin concentrations over time (P > 0.10). Jugular plasma total protein concentration was greater in the MIM group (P < 0.07). Plasma triiodothyronine (P < 0.01) and thyroxine (P < 0.08) concentrations were higher in the goats receiving the MIM, 2,3-DHP, and MIM + 2,3-DHP infusions than in the goats receiving the CON infusion. Plasma urea N concentration was decreased by MIM (P < 0.10) and MIM + 2,3-DHP (P < 0.03) compared with the CON infusion. A Propionate Load Test was conducted at 24 to 28 h into the infusion to assess the toxins' effects on the liver's ability to increase circulating glucose concentrations in the presence of elevated propionate levels. The results indicated that neither 2,3-DHP nor MIM reduced the liver's ability to respond to a bolus dose of propionate (P > 0.10). Following a Urea Load Test, circulating ammonia N and glucose concentrations in the MIM, 2,3-DHP, and MIM + 2,3-DHP treatments had lower peak values than that in the CON treatment (P < 0.01). It is concluded that continuous short-term infusion of MIM and 2,3-DHP increased circulating thyroid hormone concentrations in goats and improved the goats' ability to detoxify a bolus dose of urea N without affecting its glucogenic capacity in response to elevated propionate levels.

Determination of mimosine and 3,4-dihydroxypyridine in milk and plasma of goats

Journal of Chromatography Biomedical Applications 685:375-378. 1996.
R. Puchala, J. J. Davis and T. Sahlu

A simple method for determination of mimosine and 3,4-dihydroxypyridine(3,4-DHP)in plasma and milk was developed. Milk and plasma, with tyrosine as internal standard, were deproteinized using 9% trichloracetic acid and extracted with diethyl ether. Metabolites were separated by isocratic high-performance liquid chromatography, with 0.02 M ortho phosphoric acid (pH 2.5) at 0.5 ml/min and a Hypersil ODS microbore column. Mimosine, 3,4-DHP and tyrosine were detected at 275 nm. The recovery of the mimosine added to the plasma samples was 101.6±2.3% and 103.3±1.0% for milk samples. 3,4-DHP recovery for plasma samples was 101.2±0.9% and for milk samples 100.8±1.4%. The analyses yielded relative standard deviation of 2.65 and 2.82%, respectively.