RESUMEN
This study aimed at verifying if the hypothesis that one day at 60°C is equivalent to one month at 20°C could be confirmed during linseed oil aging for 6months at 20°C and 6days at 60°C using the "Schaal oven stability test". Tests were conducted with linseed oil supplemented or not with myricetin or butyl-hydroxytoluene as antioxidants. Oxidation was evaluated with the peroxide and p-anisidine values, as well as the content in conjugated dienes and aldehydes. All four indicators of oxidation showed very different kinetic behaviors at 20 and 60°C. The hypothesis is thus not verified for linseed oil, supplemented or not with antioxidant. In the control oil, the conjugated dienes and the peroxide value observed were respectively of 41.8±0.8 Absorbance Unit (AU)/g oil and 254.3±5.8meq.O2/kg oil after 6months at 20°C. These values were of 18.2±1.3AU/g oil and 65.2±20.3meq.O2/kg after 6days at 60°C.
Asunto(s)
Compuestos de Anilina/análisis , Antioxidantes/farmacología , Aceite de Linaza/química , Peróxidos/análisis , Conservación de Alimentos , Oxidación-Reducción/efectos de los fármacos , TemperaturaRESUMEN
Imazalil (IMA) is a widely used imidazole-antifungal pesticide and, therefore, a food contaminant. This compound is also used as a drug (enilconazole). As intestine is the first site of exposure to ingested drugs and pollutants, we have investigated the effects of IMA, at realistic intestinal concentrations, on xenobiotic-metabolizing enzymes and efflux pumps by using Caco-2 cells, as a validated in vitro model of the human intestinal absorptive epithelium. For comparison, other conazole fungicides, i.e. ketoconazole, propiconazole and tebuconazole, were also studied. IMA induced cytochrome P450 (CYP) 1A1 activity to the same extent as benzo(a)pyrene (B(a)P) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in a dose- and time-dependent manner. Cell-free aryl hydrocarbon receptor (AhR) binding assay and reporter gene assay suggested that IMA is not an AhR-ligand, implying that IMA-mediated induction should involve an AhR-independent pathway. Moreover, IMA strongly inhibited the CYP3A4 activity in 1,25-vitamin D(3)-induced Caco-2 cells. The other fungicides had weak or nil effects on CYP activities. Study of the apical efflux pump activities revealed that ketoconazole inhibited both P-glycoprotein (Pgp) and multidrug resistance-associated protein 2 (MRP-2) or breast cancer resistance protein (BCRP), whereas IMA and other fungicides did not. Our results imply that coingestion of IMA-contaminated food and CYP3A4- or CYP1A1-metabolizable drugs or chemicals could lead to drug bioavailability modulation or toxicological interactions, with possible adverse effects for human health.
Asunto(s)
Citocromo P-450 CYP1A1/biosíntesis , Inhibidores del Citocromo P-450 CYP3A , Inhibidores Enzimáticos/farmacología , Contaminación de Alimentos , Fungicidas Industriales/farmacología , Imidazoles/farmacología , Mucosa Intestinal/efectos de los fármacos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/antagonistas & inhibidores , Transportadoras de Casetes de Unión a ATP/metabolismo , Antifúngicos/farmacología , Células CACO-2 , Calcitriol/farmacología , Cromatografía Líquida de Alta Presión , Citocromo P-450 CYP3A/metabolismo , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Inducción Enzimática , Inhibidores Enzimáticos/toxicidad , Fungicidas Industriales/toxicidad , Glutatión Transferasa/metabolismo , Humanos , Imidazoles/toxicidad , Mucosa Intestinal/enzimología , Cetoconazol/farmacología , Cinética , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/antagonistas & inhibidores , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Dibenzodioxinas Policloradas/farmacología , ARN Mensajero/biosíntesis , Receptores de Hidrocarburo de Aril/efectos de los fármacos , Espectrofotometría Ultravioleta , Triazoles/farmacologíaRESUMEN
The intestinal mucosa is not simply a barrier allowing entry of compounds such as nutrients or chemicals, and restricting that of others. Intestinal cells and activities perform selective absorption, biotransformations and efflux back to the lumen. Furthermore, food substances affect both bioavailability and intestinal function. Some are able to act as transcriptional regulators and enzyme modulators. This review points out plausible interactions between food contaminants and/or natural constituents at molecular and cellular levels and focuses on the effects of classical (pesticides and veterinary drugs), environmental (heavy metals, PCBs, dioxins, etc.) and food processing generated (PAHs, heterocyclic amines, etc.) contaminants on absorption, metabolism and efflux. Special attention is given to secondary metabolites of molds (mycotoxins) and plants (polyphenols). Molecular targets are briefly described as well as regulation mechanisms. Where possible, data referred to deal with human intestinal functions in vivo, and with in vitro studies on human intestinal Caco-2 cells; however, since data related to the intestine are rather scarce, effects on molecular targets in liver are also considered. This review also points out the urgent need for fully validated high throughput in vitro tools to screen combinations of substances, at realistic intestinal concentrations. A higher priority could then be given to combinations of nutrients, xenobiotics and food contaminants, with hazardous or beneficial impacts on human health.