Developmental toxicology of solamargine and solasonine glycoalkaloids in frog embryos.

As part of an effort to improve the safety of plant foods, a need exists to define the relative toxicities of structurally different glycoalkaloids and metabolites which may be present in Solanum plant species such as potatoes, tomatoes and eggplants. The objectives of this study were to determine the relative toxicities and the modes of action of the eggplant (Solanum melongena) glycoalkaloids solamargine and solasonine in Xenopus laevis frog embryos, using membrane potential and embryo growth and teratogenicity assays. In the cell membrane assays, adverse effects on embryos were evaluated by measuring membrane potentials using an electrochromic dye, di-4-ANEPPS, as a fluorescence probe for the integrity of the membranes. In the embryo growth and teratogenesis assays, the survival of the embryos and organ malformations was used as an index of embryo toxicity. The relative potencies of glycoalkaloids are similar for frog embryo effects (survival and teratogenicities) and for membrane effects (membrane potential). Experiments with solasonine at pH 6 and 8 suggest that the unprotonated form of the glycoalkaloids appears to be involved in the membrane effects. The nature of the carbohydrate side-chains of the steroidal glycosides governs relative potencies. The possible significance of the findings to food safety and plant physiology and possible application of the membrane assays to bacterial toxins are discussed.

Developmental toxicology of potato alkaloids in the frog embryo teratogenesis assay--Xenopus (FETAX).

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.