RESUMEN
Glycoalkaloids alpha-solanine and alpha-chaconine are naturally present toxicants in the potato plant (Solanumtuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of alpha-solanine to alpha-chaconine may determine the degree and nature of the glycoalkaloid toxicity in potatoes, as the toxicity of the two alkaloids act synergistically. The aim of the present study was to investigate whether an altered ratio of alpha-solanine and alpha-chaconine would reduce the toxicity of the glycoalkaloids. The Syrian Golden hamster was given daily doses of alpha-solanine and alpha-chaconine by gavage for 28 days. Doses of up to 33.3 mg total glycoalkaloids/kg body weight were applied in ratios of 1:3.7 and 1:70 (alpha-solanine:alpha-chaconine). Administration of the highest doses of both ratios resulted in distended and fluid filled small intestines and stomach. Animals receiving the ratio with the reduced content of alpha-solanine were less affected compared to those receiving the other ratio. Gene expression profiling experiments were conducted using RNA from epithelial scrapings from the small intestines of the hamsters administered the highest doses of the glycoalkaloid treatments. In general, more differential gene expression was observed in the epithelial scrapings of the hamsters fed the ratio of 1:3.7. Mostly, pathways involved in lipid and energy metabolism were affected by the ratio of 1:3.7.
Asunto(s)
Solanina/análogos & derivados , Acetilcolinesterasa/sangre , Acetilcolinesterasa/metabolismo , Animales , Disponibilidad Biológica , Recuento de Células Sanguíneas , Análisis Químico de la Sangre , Peso Corporal/efectos de los fármacos , Butirilcolinesterasa/sangre , Butirilcolinesterasa/metabolismo , Colinesterasas/sangre , Cricetinae , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Intubación Gastrointestinal , Mesocricetus , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN/biosíntesis , ARN/genética , Solanina/administración & dosificación , Solanina/farmacocinética , Solanina/toxicidad , Solanum tuberosum/químicaRESUMEN
Glycoalkaloids in potatoes may induce gastro-intestinal and systemic effects, by cell membrane disruption and acetylcholinesterase inhibition, respectively. The present single dose study was designed to evaluate the toxicity and pharmacokinetics of orally administered potato glycoalkaloids (alpha-chaconine and alpha-solanine). It is the first published human volunteer study were pharmacokinetic data were obtained for more than 24 h post-dose. Subjects (2-3 per treatment) received one of the following six treatments: (1-3) solutions with total glycoalkaloid (TGA) doses of 0.30, 0.50 or 0.70 mg/kg body weight (BW), or (4-6) mashed potatoes with TGA doses of 0.95, 1.10 or 1.25 mg/kg BW. The mashed potatoes had a TGA concentration of nearly 200 mg/kg fresh weight (the presently recognised upper limit of safety). None of these treatments induced acute systemic effects. One subject who received the highest dose of TGA (1.25 mg/kg BW) became nauseous and started vomiting about 4 h post-dose, possibly due to local glycoalkaloid toxicity (although the dosis is lower than generally reported in the literature to cause gastro-intestinal disturbances). Most relevant, the clearance of glycoalkaloids usually takes more than 24 h, which implicates that the toxicants may accumulate in case of daily consumption.
Asunto(s)
Solanina/análogos & derivados , Solanina/efectos adversos , Solanum tuberosum , Adulto , Área Bajo la Curva , Disponibilidad Biológica , Relación Dosis-Respuesta a Droga , Femenino , Semivida , Humanos , Masculino , Persona de Mediana Edad , Solanina/sangre , Solanina/farmacocinéticaRESUMEN
The development of a high-performance liquid chromatography (HPLC) method for the separation and quantification of potato glycoalkaloids and their aglycone solanidine in blood serum is reported. High selectivity was obtained by using solid-phase extraction followed by off-line dual-column HPLC. Injections were made via a sample enrichment column to achieve maximum sensitivity in the assay. The potato alkaloids in the HPLC effluents were detected by ultraviolet absorption at 200 nm. The detection limits were estimated to be 0.3 ng/ml of serum for each of the alkaloids. The method was used to study the pharmacokinetics of potato glycoalkaloids in humans. alpha-Solanine and alpha-chaconine were detected in all blood serum samples collected from seven volunteers 1-25 h after a meal of potatoes. Solanidine was detected in some samples, but there were no traces of the mono- or diglycosides. The average apparent biological half-lives for alpha-solanine and alpha-chaconine were 11 and 19 h, respectively.