Neonatal hypomyelination by the herbicide 2,4-dichlorophenoxyacetic acid. Chemical and ultrastructural studies in rats.
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.
Konjuh
Cintia
C
LATOEX, Facultad de Cs, Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina.
García
Graciela
G
López
Lidia
L
de Duffard
Ana María Evangelista
AM
Brusco
Alicia
A
Duffard
Ricardo
R
D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D000818:Animals; D000833:Animals, Suckling; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D007091:Image Processing, Computer-Assisted; D007274:Injections, Intraperitoneal; D007774:Lactation / Q000187:drug effects*; D008297:Male; D044342:Malnutrition / Q000378:metabolism / Q000503:physiopathology; D018811:Maternal Exposure; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D006540:Herbicides; D015084:2,4-Dichlorophenoxyacetic Acid