RESUMEN
The safety of a refined arachidonic acid-rich oil (RAO) was evaluated for reverse mutation, chromosome aberration and gene mutation, and in a 90-day Wistar rat feeding study with in utero exposure. The results of the genotoxicity assays were all negative. The in utero phase of the 90-day study involved dietary exposure to 0.5%, 1.5% and 5% RAO and two controls diets, a standard feed low-fat diet and a high-fat diet supplemented with 5% corn oil. This exposure covered four-weeks prior to mating, through mating, gestation and lactation until offspring (F(1)) weaning. A subsequent 90-day feeding study in the F(1) rats evaluated the same test and control diets. Statistically significant effects were seen for selected histopathology, clinical chemistry and organ weight endpoints; however, other than increased absolute and relative monocytes seen in both sexes of high-dose rats, the observations were not attributed to treatment for one or more reasons. Based on these findings, no adverse treatment-related effects for RAO were seen at up to 5% in the diet, equivalent to an overall average RAO intake of 3170 mg/kg bwt/day. These and similar findings for other refined ARA-rich oils establish a strong body of evidence for the safety of this RAO.
Asunto(s)
Ácido Araquidónico/toxicidad , Grasas Insaturadas en la Dieta/toxicidad , Exposición Materna/efectos adversos , Monocitos/efectos de los fármacos , Mutágenos/toxicidad , Reproducción/efectos de los fármacos , Animales , Ácido Araquidónico/clasificación , Ácido Araquidónico/metabolismo , Células CHO , Línea Celular Tumoral , Aberraciones Cromosómicas/inducido químicamente , Cricetinae , Cricetulus , Grasas Insaturadas en la Dieta/clasificación , Grasas Insaturadas en la Dieta/metabolismo , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Femenino , Leucemia L5178/tratamiento farmacológico , Leucemia L5178/enzimología , Leucemia L5178/genética , Masculino , Monocitos/patología , Pruebas de Mutagenicidad , Mutágenos/clasificación , Mutágenos/metabolismo , Nivel sin Efectos Adversos Observados , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ratas , Ratas Wistar , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Timidina Quinasa/genética , Timidina Quinasa/metabolismoAsunto(s)
Humanos , Masculino , Femenino , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Inhibidores de la Ciclooxigenasa 2/análisis , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Medicina Basada en la Evidencia/métodos , Medicina Basada en la Evidencia/tendencias , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Ácido Araquidónico/clasificación , Ácido Araquidónico/uso terapéutico , Enfermedades Gastrointestinales/complicaciones , Prescripciones de Medicamentos/normas , Administración del Tratamiento Farmacológico/normas , Administración del Tratamiento Farmacológico/tendencias , Antiinflamatorios no Esteroideos/efectos adversos , España/epidemiologíaRESUMEN
In mammals, specific lipids and amino acids serve as crucial signaling molecules. In bacteria, conjugates of lipids and amino acids (referred to as lipoamino acids) have been identified and found to possess biological activity. Here, we report that mammals also produce lipoamino acids, specifically the arachidonyl amino acids. We show that the conjugate of arachidonic acid and glycine (N-arachidonylglycine (NAGly)) is present in bovine and rat brain as well as other tissues and that it suppresses tonic inflammatory pain. The biosynthesis of NAGly and its degradation by the enzyme fatty acid amide hydrolase can be observed in rat brain tissue. In addition to NAGly, bovine brain produces at least two other arachidonyl amino acids: N-arachidonyl gamma-aminobutyric acid (NAGABA) and N-arachidonylalanine. Like NAGly, NAGABA inhibits pain. These findings open the door to the identification of other members of this new class of biomolecules, which may be integral to pain regulation and a variety of functions in mammals.