2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most widely used herbicides due to its relatively moderate toxicity and to its biodegradability in the soil. In toxic concentrations, 2,4-D displays strong neurotoxicity, partly due to generation of free radicals. Since melatonin has remarkable antioxidant properties, the objective of this study was to assess to what extent it was effective in preventing the 2,4-D effect on redox balance of rat cerebellar granule cells (CGC) in vitro. Cellular viability, generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), reduced glutathione (GSH) levels, and the activities of the antioxidant enzymes Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-SOD, selenium-glutathione peroxidase (Se-GPx) and catalase (CAT) were measured in CGC exposed to 2,4-D and/or melatonin for 48 h. In CGC cultures exposed to 2,4-D, cell viability, GSH levels and CAT activity decreased significantly whereas ROS generation and Se-GPx activities were augmented. Except for Se-GPx activity, all these changes were counteracted by the concomitant addition of 0.1 or 0.5 mM melatonin. In addition, incubation of CGC with melatonin alone resulted in augmentation of cell viability, GSH levels and Se-GPx activity. RNS generation and SOD activity remained unaffected by either treatment. Since melatonin was able to counteract most of redox changes produced by 2,4-D in CGC in culture, the experimental evidence reported further support the efficacy of melatonin to act as a neuroprotector.

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.

Dopamine-beta-hydroxylase (DbetaH), the enzyme that synthesizes noradrenaline from dopamine, was studied in the locus coeruleus (LC) of neonate rats exposed to 2,4-dichlorophenoxyacetic acid (2,4-D) through lactation for 14 days (from PND 9 to 22). Pups (22 days old) were anesthetized and fixed by transcardiac perfusion. Control and treated serial sections from brain stem--which correspond with the LC according to the Paxinos and Watson atlas--were simultaneously processed by an immunohistochemistry method for the DbetaH detection. Using an image analysis system, the immunostaining optical density (OD) was measured as an estimation of the enzyme content, and an OD significant decrease in the LC of 2,4-D-exposed animals was observed. As tyrosine hydroxylase levels in the LC are regulated by serotonin and in a previous study we demonstrated that this neurotransmitter was increased in 2,4-D-exposed pups, an indirect effect through serotonergic inhibition could be involved in the decreased DbetaH synthesis in the LC of these pups.

properties-synthesis-and-control-ofweeds/oxidative-stress-as-a-possible-mechanism-of-toxicity-of-the-herbicide-2-4-dichlorophenoxyacetic-acid

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is used on a wide variety of terrestrial and aquatic broadleaf weeds. 2,4-D has been shown to produce a wide range of adverse effects on animal and human health. The aim of the current study was to evaluate the effects of pre- and postnatal exposure to 2,4-D on rat ventral prostate (VP). Pregnant rats were exposed daily to oral doses of 70 mg/kg/day of 2,4-D from 16 days of gestation up to 23 days after delivery. Then, the treated groups (n = 8) were fed with a 2,4-D added diet until sacrificed by decapitation on postnatal day (PND) 45, 60, or 90. Morphometric studies were performed and androgen receptor (AR) protein levels in the VP were determined. AR, insulin-like growth factor-I (IGF-1) and insulin-like growth factor-I receptor (IGF-1R) mRNA expression in the VP along with testosterone (T), dihydroxytestosterone (DHT), growth hormone (GH) and IGF-1 serum levels were also determined to ascertain whether these parameters were differentially affected. Results of this study showed that 2,4-D exposure during gestation and until adulthood altered development of the prostate gland in male rats, delaying it at early ages while increasing its size in adults, indicate that 2,4-D could behave as endocrine disruptors (EDs).