Lethal and teratogenic effects of naringenin evaluated by means of an amphibian embryo toxicity test (AMPHITOX)

• Published in: Food and chemical toxicology 2004-02, Vol.42 (2), p.299-306
• Main Authors: Pérez-Coll, C.S., Herkovits, J.
• Format: Article
• Language: English
• Subjects: abnormal development; adverse effects; amphibians; AMPHITOX; Animals; antioxidants; Biological and medical sciences; Bufo arenarum; Bufo arenarum - embryology; Developmental toxicity; dosage; dose response; Dose-Response Relationship, Drug; embryo (animal); Embryo, Nonmammalian - drug effects; Embryology: invertebrates and vertebrates. Teratology; embryotoxicity; Female; Flavanones - administration & dosage; Flavanones - toxicity; Flavonoids - administration & dosage; Flavonoids - toxicity; Fundamental and applied biological sciences. Psychology; Gills - drug effects; Gills - embryology; health effects assessments; lethal dose; naringenin; Naringenin toxicity; neurotoxicity; organogenesis; pathophysiology; phytochemicals; Pregnancy; safety testing; Teratogenesis; teratogenicity; Teratology. Teratogens; toxicity testing
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2003.09.004

The effect of naringenin on the survival and morphogenesis of amphibian embryos was evaluated by means of the AMPHITOX test reporting early life stage and chronic toxicity effects. Lethality, malformation incidence and the degree of adverse effects were concentration-dependent. The Teratogenic Index (TI) for naringenin was 2 pointing out the high developmental hazard of this substance. For instance, 10 mg/l naringenin exerted 100% malformations while only 30% of the abnormal embryos died. Main abnormalities were reduced body size, axial curves, microcephaly, abdominal edema, underdeveloped gills and delayed development. Scanning electronic microscopy (SEM) showed alterations in epithelial cell shapes related to malformations. The results obtained by means of treatment of Bufo arenarum embryos with naringenin from complete operculum stage onwards show that at this final stage of development, the susceptibility of the embryos to this flavonoid is slightly lower for lethal effects but exerted sublethal adverse effects such as transient narcosis, abnormal contortions, loss of equilibrium, reduced motility and edema. Overall, amphibian early life stages appeared more susceptible to the embryotoxicity associated with exposure to naringenin, especially at concentrations greater than 5 mg/l. This increased susceptibility may result from the relatively high rates of cellular differentiation and morphogenesis that occur at this early stage of development.