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ToxSci Advance Access published online on May 5, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn085
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© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

C. Konjuh*, G. García*, LM. López{dagger}, AM. Evangelista de Duffard*, A. Brusco{dagger} and R. Duffard*

* LATOEX. Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario. Argentina {dagger} Instituto de Biología Celular y Neurociencia. LANAIS-MIE. Facultad de Medicina. Universidad de Buenos Aires. Argentina

Corresponding authors: Ricardo Duffard (RD) and Alicia Brusco (AB), Phone number (RD): #54 341 4804602 Fax number # 54 341 4804598 , E-mail: rduffard{at}fbioyf.unr.edu.ar rduffard{at}gmail.com, Laboratorio de Toxicología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR. Suipacha 531. (2000) Rosario. Prov. Santa Fe. Rep. Argentina. Phone number (AB): #54 11 5950-9500; ext. 2078 Fax number # 5411 5950-9626, E-mail: hbrusco{at}fmed.ub.ar, Instituto de Biología Celular y Neurociencia. Facultad de Medicina, UBA. Paraguay 2155, 3er piso. (1121) Buenos Aires. Argentina.

Received February 22, 2008; revision received April 22, 2008; accepted April 24, 2008


  Abstract

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.

Key Words: 2,4-Dichlorophenoxyacetic acid; herbicide; brain development; myelin proteins; myelin ultrastructure; neurotoxicity; neonate rat.


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