alpha-chaconine and Abnormalities--Drug-Induced

As one of the major agricultural crops, the cultivated potato is consumed each day by millions of people from diverse cultural backgrounds. A product of global importance, the potato tuber contains toxic glycoalkaloids (GAs) that cause sporadic outbreaks of poisoning in humans, as well as many livestock deaths. This article will discuss some aspects of the potato GAs, including their toxic effects and risk factors, methods of detection of GAs and biotechnological aspects of potato breeding. An attempt has been made to answer a question of vital importance - are potato GAs dangerous to humans and animals and, if so, to what extent?

Topics: Abnormalities, Drug-Induced; Animals; Cell Division; Cell Line, Tumor; Cell Physiological Phenomena; DNA Damage; Humans; Plant Poisoning; Solanaceous Alkaloids; Solanine; Solanum tuberosum; Viruses

The embryo toxicities of two major potato glycoalkaloids, alpha-chaconine and alpha-solanine, were examined individually and in mixtures using the frog embryo teratogenesis assay-Xenopus. Calculations of toxic units (TUs) were used to assess possible antagonism, synergism or response addition of several mixtures ranging from approximately 3:1 to 1:20 TUs of alpha-chaconine to alpha-solanine. Some combinations exhibited strong synergism in the following measures of developmental toxicity: (a) 96-hr LC50, defined as the median concentration causing 50% embryo lethality; (b) 96-hr EC50 (malformation), defined as the concentration causing 50% malformation of the surviving embryos; and (c) teratogenic index which is equal to LC50/EC50 (malformation). The results indicated that each of the mixtures caused synergistic mortality or malformation. Furthermore, these studies suggested that the synergism observed for a specific mixture cannot be used to predict possible synergism of other mixtures with different ratios of the two glycoalkaloids; toxicities observed for individual glycoalkaloids may not be able to predict toxicities of mixtures; and specific combinations found in different potato varieties need to be tested to assess the safety of a particular cultivar.

Topics: Abnormalities, Drug-Induced; Animals; Drug Synergism; Embryo, Nonmammalian; Embryonic Development; Solanine; Survival Rate; Teratogens; Toxicity Tests; Xenopus

Potato glycoalkaloids were extracted from potato sprout and then analyzed to determine their purity by using TLC and HPLC methods and compare with pure alpha-Solanine and alpha-Chaconine of Sigma. The result indicated that the purity of potato glycoalkaloids is 78. 31%, which contains 73.64% alpha-Solanine and 4.67% alpha-Chaconine. The LD50 of mice was 44.721 +/- 5.860 4 mg/kg. In order to determine the toxicity and teratogenicity of potato glycoalkaloids, the effect of potato glycoalkaloids on Kunming pregnant mice were studied. The results showed that: (1) potato glycoalkaloids have teratogenic effects on embryos of mice. It could induce neural tube defects (NTDs), and may be an important teratogen of NTDs. (2) potato glycoalkaloids have embryo toxicity. It could cause the death of embryos and result in absorbed and dead fetuses. (3) potato glycoalkaloids could evidently affect the development of embryos and lead to intrauterine growth retardation (IUGR). An interesting phenomena which just like the clinical manifestation of miscarriage in human being was noticed. If potato glycoalkaloids were given to the pregnant mice on the 5th or 6th day of gestation intraabdominally, vaginal bleeding and abortion would occur, and this has not been reported yet. The animal model of NTDs in this experiments supported our hypothesis that sprouted potato could be a teratogen of NTDs.

Topics: Abnormalities, Drug-Induced; Animals; Female; Fetal Death; Fetal Growth Retardation; Lethal Dose 50; Mice; Neural Tube Defects; Pregnancy; Solanine; Solanum tuberosum

Potatoes frequently contain growth inhibitors and toxic compounds including digestive enzyme inhibitors, lectins and glycoalkaloids. The literature suggests that Solanum alkaloids have the ability to induce neurological damage such as spina bifida and other malformations. As part of a programme of improvement in the safety of potatoes using molecular plant genetics and parallel food safety evaluation, we evaluated the effect of several potato glycoalkaloids and aglycones in the frog embryo teratogenesis assay--Xenopus (FETAX) with and without metabolic activation by Aroclor 1254-induced rat liver microsomes. The data suggest that the glycoalkaloid alpha-chaconine is teratogenic and more embryotoxic than alpha-solanine, in terms of the median lethal concentration (LC50) after 96 hr of exposure, the concentration inducing gross terata in 50% of the surviving frog embryos (96-hr EC50, malformation), and the minimum concentration needed to inhibit the growth of the embryos. Since these two compounds differ only in the nature of the carbohydrate side chain attached to the 3-OH group of solanidine, the side chain appears to be an important factor in governing teratogenicity. The aglycones demissidine, solanidine and solasodine were less toxic than the glycosides alpha-chaconine and alpha-solanine. The in vitro teratogenesis assay should be useful for: (a) predicting the teratogenic potential of solanaceae alkaloids, glycoalkaloids and related natural products; and (b) facilitating experimental approaches to suppress plant genes and enzymes that control the biosynthesis of the most toxic compounds.

Topics: Abnormalities, Drug-Induced; Animals; Diosgenin; Embryo, Nonmammalian; Lethal Dose 50; Microsomes, Liver; Rats; Solanaceous Alkaloids; Solanine; Solanum tuberosum; Teratogens; Xenopus

Keeler et al. (78) showed that potato sprouts could be teratogens for the central nervous system in the Syrian hamster. We demonstrate here the same teratogenic effect from a British cultivar, Arran Pilot. Most of the activity was traced to the two solanidine triglycosides, alpha-chaconine and, at a higher dose level, alpha-solanine. Some possible implications for the study of human neural-tube defects are considered.

Topics: Abnormalities, Drug-Induced; Animals; Cricetinae; Dose-Response Relationship, Drug; Female; Humans; Male; Mesocricetus; Neural Tube Defects; Pregnancy; Sex Factors; Solanine; Vegetables

The pharmacological responses produced by alpha chaconine and tomatine on guinea pig ileum, on the isolated electrically stimulated frog ventricle, and recordings of EEG, ECG, respiration and blood pressure in the rabbit showed no essential differences from those produced by alpha solanine. The LD50 values of chaconine and solanine in the mouse and rabbit are also similar and suggest that compounds other than these are probably responsible for the predominant toxic effects of certain hybrid potatoes in man and animals. The failure of the three glycoalkaloids to produce a significant teratological effect in the chick embryo lends no support to the hypothesis that they may be the teratogens responsible for certain congenital malformations in man.

Topics: Abnormalities, Drug-Induced; Alkaloids; Animals; Anura; Birth Weight; Blood Pressure; Chick Embryo; Chickens; Electroencephalography; Glycosides; Guinea Pigs; Heart Rate; Ileum; In Vitro Techniques; Lethal Dose 50; Male; Mice; Muscle Contraction; Muscle, Smooth; Rabbits; Solanine; Species Specificity; Teratogens; Time Factors; Tomatine