Neronatal hypomyelination by the herbicide 2,4-dichlorophenoxyacetic acid. Chemical and ultrastructural studies in rats

KONJUH C, GARCIA G, LOPEZ L, EVANGELISTA DE DUFFARD AM, BRUSCO A, DUFFARD R

Toxicological Sciences

Oxford University Press

Año: 2008 vol. 104 p. 332 - 340

The purpose of this study was to determine whether 2,4-dichlorophenoxyacetic acid (2,4-D), which is an herbicide used to control the growth of broadleaf weeds, had a direct or an indirect (mediated by undernutrition) hypomyelinating effect. We also proposed to analyze the effect of 2,4-D on undernourished pups. Four experimental rat groups were used: well nourished (WN) pups -litters with eight offsprings- ; undernourished (UN) pups -litters with fourteen offsprings-; WN pups whose mother received 70 mg/kg/day of 2,4-D from post natal day 9 to 21 (WN70 pups) and UN pups whose mother received 70 mg/kg/day of 2,4-D from post natal day 9 to 21 (UN70 pups). In this work, we demonstrated that: 1) myelin proteins (analyzed by western-blot and/or immunohistochemical study) showed a significant decrease in WN70, UN and UN70 with respect to control group; 2) there is a good correlation between these myelin specific protein expression with the degree of myelin compaction detected by electron microscopy in groups exposed to 2,4-D; 3) a decreased and normal number of myelin sheets were detected in undernourished and 2,4-D exposed pups, respectively and 4) undernourishment sensitized pups to the hypomyelinating effect of 2,4-D. According to this and besides the fact that WN70 group have no body weight changes, these results are indicating that 2,4-D and undernourishment are two independent hypomyelinating factors