RESUMEN
2,4-dichlorophenoxyacetic acid (2,4-D) is a hormonal herbicide widely used in the world because of its efficacy in the control of broadleaf and woody plants. In this study we have demonstrated in vivo covalent binding of the phenoxyherbicide 2,4-D to a single protein of 52 kD (from rat liver mitochondrial preparation) detected through immunoblotting studies with the specific antiserum for 2,4-D. The direct involvement of 2,4-D in the formation of the adduct has also been demonstrated in vitro, using liver mitochondrial preparations exposed to 14C-UL-2,4-D. Radiolabeled protein separated by SDS-PAGE and afterwards electroeluted showed a single labeled protein of 52 kD. When mitochondria exposed to radiolabeled xenobiotic were devoid of their outer membrane, the specific activity observed suggest that protein involved in covalent interaction belongs to the inner mitochondrial membrane. We propose that covalent binding of the phenoxyherbicide 2,4-D to a very specific single protein of 52 kD observed in vitro and in vivo may be related to known alterations of the mitochondrial function.
Asunto(s)
Ácido 2,4-Diclorofenoxiacético/metabolismo , Herbicidas/metabolismo , Mitocondrias Hepáticas/metabolismo , Proteínas/metabolismo , Ácido 2,4-Diclorofenoxiacético/inmunología , Animales , Electroforesis en Gel de Poliacrilamida , Immunoblotting , Técnicas In Vitro , Masculino , Unión Proteica , Ratas , Ratas WistarRESUMEN
Neonate rats were treated with 2,4-dichlorophenoxyacetic acid (2,4-D) from the 7th or 12th until the 17th or 25th postnatal day. Two drug dosages were used: 70 and 100 mg/kg body weight of 2,4-D. At the 17th day of age, no changes were observed in body weight, protein and DNA content. However, 25-day-old treated pups showed diminutions in body and brain weight, protein and DNA levels, depending on doses and period of treatment. With respect to ganglioside levels, few changes were observed in treated animals until the 17th day of age. However, at the 25th day, with higher dose and longer treatment a diminution in all parameters analyzed was observed. These results suggest a delay in CNS development when pups were exposed to a very severe chemical injury with 2,4-D. On the other hand, when the chemical injury was not too severe, the brain would be capable to trigger biochemical mechanisms producing a plasticity response which is expressed as changes in ganglioside content and composition.
Asunto(s)
Ácido 2,4-Diclorofenoxiacético/envenenamiento , Envejecimiento/fisiología , Sistema Nervioso Central/efectos de los fármacos , Gangliósidos/metabolismo , Herbicidas/envenenamiento , Animales , Peso Corporal/efectos de los fármacos , Encéfalo/anatomía & histología , Femenino , Tamaño de los Órganos/efectos de los fármacos , RatasRESUMEN
Our results show that 2,4-dichlorophenoxyacetic acid (2,4-D) exposure through mother's milk during the period of rapid myelination (from the 15th to the 25th postnatal days) results in a myelin deficit in the pup's brain and demonstrates the vulnerability of the developing central nervous system (CNS) to 2,4-D. After 100 mg/kg 2,4-D administration to dams, brains of male and female rats show a significant diminution of myelin markers such as monohexosylceramide as well as phospholipids and free fatty acids (FFA) and an increase of cholesteryl esters. Histological studies revealed myelin deficit in some brain regions after 2,4-D treatment. These data indicate that 2,4-D, through the mother's milk, alters the myelination process during a specific postnatal period.