Neonatal Hypomyelination by the Herbicide 2,4-Dichlorophenoxyacetic Acid. Chemical and Ultrastructural Studies in Rats

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 (UN) pups. Four experimental rat groups were used: well-nourished (WN) pups, litters with eight offsprings; UN pups, litters with fourteen offsprings; WN pups whose mother received 70 mg/kg/day of 2,4-D from postnatal day (PND) 9 to 21 (WN70 pups); and UN pups whose mother received 70 mg/kg/day of 2,4-D from PND 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 UN 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.

Environmental tobacco smoke in the early postnatal period induces impairment in brain myelination

“…exposure to herbicide 2,4-dichlorophenoxyacetic (2,4-D) during lactation induces a hypomyelination in the corpus callosum of rat pups (Konjuh et al 2008), while a single prenatal exposure to 2,3,7,8-tetrachlorodibenzop-dioxin (TcDD), a endocrine-disrupting chemical, causes persistent changes in myelination by altering the expression of myelin-specific proteins in different brain regions even in adulthood (Fernández et al 2010). Prenatal exposure to methamphetamine causes modifications on myelination process, by reducing the diameter of optic nerve, the myelin thickness, and MBP levels (Melo et al 2006), while prenatal exposure to nicotine interferes in protein levels and gene expression of myelin-specific proteins in brain of adolescent rats (cao et al 2013).…”

Prenatal exposure to multiple pesticides is associated with auditory brainstem response at 9months in a cohort study of Chinese infants

“…Treatment with DZN did not have an overall effect on myelin gene expression, but elicited a statistically significant reduction in individual myelin-related gene expression [65]. Similarly, neonatal exposure to 2,4-D resulted in myelin deficits in the rat pup brain, as measured by protein expression [66, 67] and electron microscopy [67, 68], and alterations in behavior [68]. …”

Investigação Dos Efeitos Do Ácido 2,4 Diclorofenoxiacético Sobre Diferentes Populações De Neurônios Mioentéricos Do Duodeno De Ratos

“…Resultados semelhantes foram observados em trabalhos nas doses de 2,5 e 5mg/Kg/peso em experimentos conduzidos por um período de 15 dias sobre o duodeno e o jejuno de ratos (PEREIRA; STABILLE, 2006;NANNI, 2010;CORREA et al, 2011, PEREIRA, et al, 2013. Doses superiores variando entre 15 e 70 mg/kg/dia também não interferiram no ganho de peso de ratos (STURTZ et al, 2006;KONJUH et al, 2008).…”

“…O 2,4-D parece ser inibidor moderado da fosforilação oxidativa e tem ação tóxica direta sobre os músculos estriados esqueléticos e uma possível, porém discutida, ação tóxica sobre os nervos (TSMAN, 1991). Contudo, o mecanismo da neurotoxicidade do 2,4-D ainda não está esclarecido (BONGIOVANNI et al, 2007;BJORLING-POULSEN;ANDERSON;GRAND-JEAN, 2008;KONJUH et al, 2008).…”