Showing papers on "Mimosine published in 1978"
TL;DR: Simplified extraction and colorimetric techniques have been developed for the determination of the toxic amino acid mimosine in Leucaena leucocephala and results were in agreement with a manual method based on electrophoretic separation.
Abstract: Simplified extraction and colorimetric techniques have been developed for the determination of the toxic amino acid mimosine in Leucaena leucocephala. Fresh leaf material is extracted with dilute hydrochloric acid containing activated carbon and the concentration of mimosine in the clarified extract determined with an Auto-Analyser. Satisfactory recoveries of added mimosine were obtained, and the results were in agreement with a manual method which was based on electrophoretic separation.
30 citations
01 Jan 1978
TL;DR: The chemical and physiological properties of some non-protein amino acids found in plants which have been shown to be toxic to man, livestock, and domestic animals are reviewed and most of these compounds have low general toxicities but prolonged administration of them can result in toxic effects in various mammalian tissues.
Abstract: I. ABSTRACT The chemical and physiological properties of some non-protein amino acids found in plants which have been shown to be toxic to man, livestock, and domestic animals are reviewed. Compounds discussed include hypoglycin A, the lathyrogenic amino acids, mimosine, indospicine, and canavanine. Most of these compounds have low general toxicities but prolonged administration of them can result in toxic effects in various mammalian tissues. Some features of the deleterious effects of these compounds are interference with the metabolism of the normal protein amino acids and involvement of specific tissues such as the skin and the thyroid (mimosine and its metabolite in ruminants), the liver (indospicine and canavanine), and the brain (some of the lathyrogenic amino acids).
29 citations
TL;DR: The mouse bone marrow system in which inhibition of incorporation of [3H]thymidine is used as an index of cytotoxicity was shown to be sensitive and reproducible, and could be useful for structure-activity investigations of other cytotoxic compounds.
Abstract: Mimosine, a plant amino acid which is toxic in mammals, was shown to be a potent inhibitor of incorporation of [3H]thymidine in mouse bone marrow cells in liquid culture (is greater than 70% inhibition at a concentration of 2 x 10(-4) M). To determine the parts of the molecule responsible for the inhibitory mechanism the effects of 13 chemically related compounds were examined in this system. The structural features necessary for inhibitory activity of the 4(1H)-pyridones were (1) the 3-hydroxyl-4-oxo function of the pyridone ring together with (2) an alpha-alanine or a 2-aminoethyl side chain. Compounds based on several other hydroxy heterocyclic functions were either weakly active or inactive. 3-Hydroxy-4(1H)-pyridone, the goitrogen to which mimosine is converted in ruminants, was only slightly inhibitory. These results are compared with published information on the effects of some of these compounds on other types of mammalian cells in vitro. The mouse bone marrow system in which inhibition of incorporation of [3H]thymidine is used as an index of cytotoxicity was shown to be sensitive and reproducible, and could be useful for structure-activity investigations of other cytotoxic compounds.
18 citations
TL;DR: Four Merino sheep were given intravenous infusions of mimosine for 2 days at a rate of 110–120 mg/kg/day, and the sheep were subsequently manually defleeced, and wool fibre growth stopped by about 1 day after the start of the infusions.
Abstract: Four Merino sheep were given intravenous infusions of mimosine for 2 days at a rate of 110–120 mg/kg/day. Wool fibre growth stopped by about 1 day after the start of the infusions, and the sheep were subsequently manually defleeced. It was estimated that, on average, fibre growth stopped for about 12 days. Wool growth rates were above the pre-infusion rates in the early regrowth (3–5 weeks after dosing), and the mean fibre diameter was still about 2 µm above pre-infusion values at 11 weeks after dosing. Groups of Merino sheep were given intravenous infusions of mimosine for 2 days at rates ranging over 40–320 mg/kg/day. The minimal rate of infusion required to produce consistent defleecing was 80 mg/kg/day; infusions at a rate of 60 mg/kg/day were sometimes effective for defleecing, but at 40 mg/kg/day produced no discernible effects on the strength of wool fibres. No adverse effects were observed at a mimosine infusion rate of 80 mg/kg/day, but one out of four sheep died when dosed at a rate of 160 mg/kg/day, and higher rates (240 and 320 mg/kg/day) were lethal. The concentration of mimosine in plasma was related to the rate of infusion of mimosine. Consistent defleecing was associated with a concentration of mimosine in plasma approaching 100 µmoles/l; lethal doses resulted in plasma mimosine concentrations above 300 µmoles/l. Abomasal infusions of mimosine at a rate of 80 mg/kg/day were equivalent to intravenous infusions. Single injections of mimosine into the abomasum did not influence the strength of wool fibres; pIasma concentrations foIlowing injections indicated rapid absorption of mimosine and rapid removal from the body.
16 citations
TL;DR: 'Isomimosine' had a similar potency to mimosine for stopping fibre growth in sheep, whether given as an intravenous infusion or as a single oral dose, and was ineffective as a defleecing agent.
Abstract: Oral doses of mimosine (ranging from 400 to 800 mg/kg body weight) were given to 71 sheep, either as two successive daily doses (10 sheep) or as a single dose (61 sheep). The effectiveness of these treatments for defleecing was assessed and in some sheep measurements were made of the concentration of mimosine in plasma after dosing, and of the rate of wool growth before and after dosing. In addition, the effectiveness as defleecing agents of two related compounds (an analogue of mimosine, 'isomimosine', and a metabolite, 3,4-dihydroxypyridine (DHP)) was assessed. Two successive daily doses of mimosine (300 mg/kg/day) allowed all sheep to be defleeced. With sheep consuming a daily ration of 600 g, a single oral dose of mimosine (400 mg/kg) was sufficient to allow defleecing of most sheep; when the daily ration was 1200 g, a dose of 600 mg/kg was required to allow defleecing of most sheep. The effectiveness of oral doses for defleecing could be explained by the absorption of mimosine over a period in excess of 24 hr. Concentrations of mimosine in plasma were usually above 100 µmoles/l 24 hr after an effective dose. Failure to achieve complete cessation of fibre growth occurred occasionally, irrespective of dose level, and two sheep died after dosing. Fasting prior to dosing appeared to obviate the effects of previous high nutrition, but increased the risk of toxic effects. Fasting resulted in exceptionally high concentrations of mimosine in plasma (200–300 µmoles/l) 1 and 2 days after dosing. Both fibre diameter and mass of wool grown were increased in the early regrowth after dosing with mimosine. 'Isomimosine' had a similar potency to mimosine for stopping fibre growth in sheep, whether given as an intravenous infusion or as a single oral dose. DHP, given as an intravenous infusion, was ineffective as a defleecing agent.
9 citations
TL;DR: The provision of a high intake of energy, together with large amounts of amino acids available for absorption from the small intestines for at least 1 week prior to mimosine infusion, completely prevented defleecing with the standard infusion of Mimosine.
Abstract: The effectiveness of mimosine as a chemical defleecing agent was assessed in adult sheep that were subjected to a variety of nutritional treatments prior to administration of mimosine, and in lambs receiving relatively high feed intakes. Mimosine was given as a continuous intravenous infusion over a period of 2 days. Sheep receiving 600 g of a roughage-based diet per day were consistently defleeced following an infusion of mimosine at the rate of 80 mg/kg/day (designated the standard infusion). The prior feeding of a reduced intake of this diet (300 g/day) did not alter the amount of mimosine required to defleece sheep. Likewise, the prior abomasal infusion of an imbalanced mixture of amino acids, which depressed the wool growth rate, did not allow defleecing with a reduced amount of mimosine. A 4-day fast, commenced 3 days before the start of mimosine infusion, approximately halved the amount of mimosine required to defleece sheep. The provision of a high intake of energy, together with large amounts of amino acids available for absorption from the small intestines (supplied by casein), for at least 1 week prior to mimosine infusion, completely prevented defleecing with the standard infusion of mimosine. The effects of these nutritional treatments could be obviated by a 4-day fast as described above. Also, increasing the rate of infusion of mimosine to 120 mg/kg/day largely overcame the effects of previous high nutrition. Relatively greater amounts of mimosine were required to defleece lambs than adults. The concentration of mimosine in plasma was related to the rate of infusion of mimosine. However, fasting and a low dietary intake tended to enhance the concentration of mimosine in plasma for a given rate of infusion. Infusion of mimosine at the standard rate resulted in plasma mimosine concentrations of the order of 100 µmoles/l, but this concentration did not ensure that defleecing would be possible.
6 citations
TL;DR: Generally, the depilation produced in the mice by mimosine or cyclophosphamide differed from that produced by the steroid analogues tested, which was in good agreement with those reported to inhibit the growth of wool fibres in some sheep.
Abstract: Summary The chemicals were administered, subcutaneously, orally or topically. Generally, the depilation produced in the mice by mimosine or cyclophosphamide differed from that produced by the steroid analogues tested. In the first 2 cases almost completely naked mice were commonly seen, while in the steroid-treated groups the complete inhibition of all hair fibres was rare. This is discussed in relation to the effects of the same compounds on wool growth in sheep. When related to body weight, the doses of cyclophosphamide (62 mg/kgO.15) and dexamethasone (5-10 mg/kgO.7'), that depilated mice in our experiments were in good agreement with those reported to inhibit the growth of wool fibres in some sheep. An example of synergism in depilatory effect between dexamethasone and cyclophosphamide is also presented. The time of onset and the initial spread over the body of the 2nd hair cycle in depilated mice was observed. We are investigating chemicals that interrupt wool fibre growth in sheep, including mimosine (Reis, Tunks & Chapman, 1975) analogues of mimosine (Ward & Harris, 1976), adrenocortical steroid analogues (Panaretto & Wallace, 1978a, b), and alkylating agents such as cyclophosphamide (Reynolds, Dolnick, Sidwell & Terrill, 1972). A quick assessment of any inhibitory effects on hair growth is often wanted. Newly-synthesized analogues of molecules known to inhibit hair fibre growth are often produced in quantities too small for testing in large animals such as sheep, and a preliminary test is required to determine whether larger quantities should be made for further investigation. Another requirement is to determine whether 2 inhibitory substances can act synergistically. The tissue-culture system for screening depilatory agents (Ward & Harris, 1976) fulfils some of these requirements but could not be used, for example, for testing glucocorticoid hormones, which were inactive during the 4 h of their tests. The test system described here provided information not available from the in vitro system, for example, about toxicity or untoward side effects.
4 citations
TL;DR: Several pyrido[1,2-a]piperazines and their N-methyl derivatives have been prepared by condensation of carbonyl compounds with mimosine and mimosinamine in the absence of an acid catalyst as mentioned in this paper.
Abstract: Several pyrido[1,2-a]piperazines and their N-methyl derivatives have been prepared. These pyridine analogues of the 1,2,3,4-tetrahydroisoquinolines were formed by condensation of carbonyl compounds with mimosine and mimosinamine in the absence of an acid catalyst. A Mannich reaction converted one of these compounds, 1-(3,4-dimethoxybenzyl)-9-hydroxy-1,2,3,4-tetrahydro-8H-pyrido[1,2-a]- pyrazin-8-one, into a pyridone analogue of the tetrahydroprotoberberine caseadine.
4 citations
TL;DR: Several amino-substituted derivatives of the chemical defleecing agent L-mimosine have been synthesized, including the peptide glycyl-L- mimosine as discussed by the authors.
Abstract: Several amino-substituted derivatives of the chemical defleecing agent L-mimosine have been synthesized, including the peptide glycyl-L- mimosine. Preparative difficulties associated with the charge distribution in this basic amino acid are noted.
2 citations
01 Jan 1978
TL;DR: The presence of the toxic alkaloids mimosine in ipil-ipil could have caused the low survival rate, and mean weight gains for all groups were poor and not statistically significant.
Abstract: A study was carried out to determine the effect of 10 or 20% leaves or seeds in the diet of Penaeus monodon , and the extent to which local ipil-ipil (Leucaena leucocephala ) could replace head shrimp meal. A brief description is given of the experimental methodology, and details of composition of the diet, proximate chemical composition of the diets, mean weight gain and survival of Penaeus monodon larvae fed shrimp head meal and ipil-ipil as protein sources, are presented. Mean weight gains for all groups were poor and not statistically significant. Survival rates for those fed 10% ipil-ipil were significantly higher than those fed 20% diets. Wherever the survival rate was high, mean weight gain was low and vice versa. The presence of the toxic alkaloids mimosine in ipil-ipil could have caused the low survival rate.