Richard F. Keeler

Effects of poisonous plants on livestock

Effects of poisonous plants on livestock , Effects of poisonous plants on livestock , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی

Cyclopamine and related steroidal alkaloid teratogens: their occurrence, structural relationship, and biologic effects.

A spontaneous congenital deformity is produced in lambs whose dams consumeVeratrum californicum on the 14th day of gestation. The deformity is generally expressed as cyclopia, cebocephaly, anophthalmia, or microphthalmia. This teratogenic effect is produced by certain steroidal alkaloid teratogens from the plant—most notably the compound cyclopamine. Cyclopamine is a C-nor-D-homo steroid with fused furanopiperidine rings E and F at right angles to the plane of the steroid because of spiro attachment at C-17 of the steroid. Among veratrum alkaloids, only those with an intact furan ring E were teratogenic in sheep, whereas those in which the piperidine ring is not rigidly positioned at right angles to the steroid were not. Many ruminants and laboratory animals are susceptible to the teratogen. It has wide species and tissue specificity and appears to have a direct effect on the embryo, not as a consequence of metabolic alteration of its structure nor as an indirect effect through a maternal influence. Other plant sources, notably potatoes, tomatoes, and eggplant contain related spirosolane steroidal alkaloids. Among naturally occurring spirosolanes, solasodine is teratogenic in hamsters, but neither tomatidine not diosgenin, the non-nitrogen containing analog of solasodine, is teratogenic. Results of these and other studies suggest that a basic nitrogen positioned α with respect to the steroidal plane and at appropriate distance beyond the D ring confers the teratogenicity on the molecule. Potato sprouts with high alkaloid content are teratogenic in hamsters, but tubers and peels are not.

Lupin alkaloids from teratogenic and nonteratogenic lupins. III. Identification of anagyrine as the probable teratogen by feeding trials

Alkaloidal extracts from teratogenic lupins produced congenital deformities in calves typical of crooked calf disease when the extracts were administered to pregnant cows during the susceptible gestational period. These data and previous epidemiologic studies suggest that one of the four alkaloids in the preparation, anagyrine, is the responsible teratogen. Severity of the malformations was directly related to the level of anagyrine present in the preparations administered.

Teratogenic effects of cyclopamine and jervine in rats, mice and hamsters.

Summary Golden hamster fetuses were extremely sensitive to the teratogenic action of jervine and cyclopamine, the steroidal alkaloid teratogens from Veratrum cali-fornicum. Cebocephaly, harelip/cleft palate, exencephaly, and a cranial bleb were the common deformities produced by dosing on the seventh day of gestation. Sprague-Dawley derived albino rats were susceptible to cyclopamine but not to jervine, and at an incidence very much lower than that of hamsters. Cebocephaly and microphthalmia were the common deformities. The terata were observed as a consequence of sixth-to ninth-day dosings. Single-day dosing produced no terata. Swiss Webster mice were apparently resistant to the teratogens.

Teratogenic Effects in Cattle of Conium maculatum and Conium Alkaloids and Analogs

The plant Conium maculatum produced congenital defects in calves born to cows gavaged the fresh green plant during days 50-75 of gestation. Both arthrogryposis and spinal curvature were produced and were similar to the defects produced by the piperidine alkaloid coniine. The arthrogrypotic manifestations of the condition markedly increased in severity as the animals aged. Animals gavaged dry plant had either normal or equivocally deformed offspring. A number of chain length and ring saturation analogs of coniine were not teratogenic. No congenital defects arose in offspring from maternal inhalation of either the teratogenic alkaloid coniine, or from the teratogenic green plant.

Teratogenic compounds of Veratrum californicum (Durand)

Abstract Alkaloid Q, one of three principal benzene extractable alkaloids from Veratrum californicum (Durand), was subjected to structural investigation by i.r., NMR, mass spectrometry and other means. The data allow a provisional, structural assignment as 5-veratranine-3β, 11α-diol 11 acetate, and the compound is now assigned the trivial name, muldamine.Alkaloid Q, one of three principal benzene extractable alkaloids from (Durand), was subjected to structural investigation by i.r., NMR, mass spectrometry and other means. The data allow a provisional, structural assignment as 5-veratranine-3β, 11α-diol 11 acetate, and the compound is now assigned the trivial name, muldamine.

Teratogenic compounds of Veratrum californicum (Durand) VII. The structure of the glycosidic alkaloid cycloposine

Abstract The structure was elucidated of a polar, glycosidic alkaloid, cycloposine, from Veratrum californicum , known to produce fetal cyclopia and related central nervous system malformations in sheep. Data from I.R., N.M.R., mass spectrometry and other means identified the structure as 3-glucosylcyclopamine. Thus, it is the glycoside of another teratogenic alkaloid, cyclopamine (11-deoxojervine) and hence 3-glucosyl-11-deoxojervine.

Steroidal Alkaloid Teratogens: Molecular Probes for Investigation of Craniofacial Malformations

AbstractHoloprosencephaly, a malformation sequence that results from impaired midline cleavage of the embryonic forebrain, is expressed as a spectrum of craniofacial anomalies of which cyclopia is the most severe. The Veratrum alkaloids are the most prominent of the teratogenic agents known to induce holoprosencephaly in mammals. Jervine and 11-deoxojervine (cyclopamine) are potent steroidal alkaloid teratogens from Veratrum californicum that are responsible for inducing cyclopic malformations in sheep.Extensive structure-terata investigations of jervanes, solanidanes, and spirosolanes have shown that teratogenicity induced upon oral administration of all three structural types is significantly higher if the C-5, C-6 bond is unsaturated. Research in progress on the pathogenesis of holoprosencephalic malformations in both hamsters and humans offers the potential to provide information on the receptors involved in the expressions of these craniofacial syndromes. A clearer understanding of steroidal alkaloid...

Lupine-Induced Crooked Calf Disease and a Management Method to Reduce Incidence

Highlight: Crooked calf disease is produced when pregnant cnws between the 40th and 70th days of gestation graze certain members of the genus Lupinus that contain the qninolizidine alkaloid anagyrine. Calves born to these cows may have twisted or bowed limbs (arthrogryposis), twisted or bowed spine (scoliosis or kyphosis), twisted neck (tortieollis), cleft palate, or a combination of any of these. The concentration of the teratogen anagyrine in these lupines is very high early in growth, decreases to a low level during flowering, rises abruptly in mature seeds, and decreases tn a very low level after seeds have dropped. Data collected from 6 ranches for 8to 25year periods showed no consistent correlation between incidence of the disease and the free-choice feeding of a variety of mineral supplements. Marked variation in incidence did occur, however, during these peridds. The variation was related to the period of gestation at which the cows grazed the lupine and to the stage of growth of the lupine-in other words, the amount 01 anagyrine ingested. Management programs that prevent pregnant cows from eating highly teratogenic early growth or seed-stage lupine plants between gestation days 40 and 70 will reduce crooked calf disease incidence.

Chemical Compounds of Veratrum calif ornicum Related to Congenital Ovine Cyclopian Malformations Extraction of Active Material.

Summary The teratogenic material from Veratrum californicum has been extracted from dried plant material by an ethanol extraction of the plant residue remaining after an initial benzene extraction in presence of ammonia, A 250-fold purified preparation from this extract also produced the malformations. It is theorized that the teratogenic material may be an alkaloid of the Veratrum series, likely a glycoside or parent alkamine.