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Neurotoxicology

Knowing early nutritional status have been shown to be an important factor in determining the act... more Knowing early nutritional status have been shown to be an important factor in determining the activity level of rats later in life, we studied offspring of dams which had received 50, 70 or 700 mg/kg of 2,4-Dichlorophenoxyacetic acid (2,4-D) during nursing. Neonatal tissues and the stomach content (milk) were examined up to 16 post natal days to detect body and organs weight alterations and 2,4-D residues after 2,4-D maternal dosing every-other-day, from post natal day 1. We detected 2,4-D residues in stomach content, blood, brain and kidney of 4-day-old neonates breast-fed by 2,4-D exposed mothers and onward. 2,4-D residues were dose- and exposure-time-dependent. The highest dose impaired body growth, as well as low tissue weights and diminished stomach contents. Levels of 2,4-D residues in stomach content, blood, kidney and brain of post natal rats (age PD 4-PD 16) fed through lactation from dams treated with 2,4-D demonstrated that 2,4-D was transferred to the neonates and the di...

PubMed, Dec 1, 1998

As reported in our previous studies, "Serotonin Syndrome", rearing and circling behaviors, were t... more As reported in our previous studies, "Serotonin Syndrome", rearing and circling behaviors, were the responses of rats treated with the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and challenged with amphetamine. An altered serotonergic and dopaminergic system may be responsible for these behaviors. In this work, endogenous levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), and 5-hydroxyindolacetic acid (5-HIAA) were measured in the areas of the mesocortico-limbico and nigrostriatal systems of rats treated with 50 or 100 mg/kg of 2,4-D, but also challenged with amphetamine (5 or 10 mg/kg), in order to determine regional brain contents of biogenic amines and their metabolites and to find a correlation with the behaviors described. The prefrontal cortex (PFc), striatum, nucleus accumbens (NA), midbrain, ventral tegmental area (VTA), substantia nigra (SN) and cerebellum were assayed. The herbicide 2,4-D increased the 5-HT and DA basal levels and these increments were dependent on sex, brain area and 2,4-D doses. The challenge with 5 or 10 mg/kg amphetamine to 2,4-D (50 or 100 mg/kg) treated rats also resulted in an area-, sex- and dose-dependent alterations of the 2,4-D effect on dopaminergic and serotonergic systems. We are demonstrating a correlation between rat behavior altered by the herbicide's treatment and the contents of 5-HT and DA in brain areas, such as PFc, VTA, SN, striatum, NA, midbrain and cerebellum. In order for 2,4-D to produce the neurobehavioral alterations, not only are high levels of 5-HT and DA necessary, but these neurotransmitters must be released.

Fems Immunology and Medical Microbiology, Dec 1, 2006

Clofibric acid (CL) is a compound used to control hypertriglyceridemia, and ethacrynic acid (ET) ... more Clofibric acid (CL) is a compound used to control hypertriglyceridemia, and ethacrynic acid (ET) is administered to enhance diuresis. These compounds are structurally analogous to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), as they have a chlorinated phenoxy moiety. As these agents are mainly excreted by the renal route, they could potentially coexist with Escherichia coli in the urinary tract of infected patients. Induction of the in vitro resistance of E. coli to hydrophilic antibiotics was determined by increasing the values of the minimum inhibitory concentration (2-40-fold). These results correlated with drastically inhibited expression of the hydrophilic bacterial channel OmpF. In vivo assays were performed in ascending urinary tract infection in female BALB/c mice. Treatment with the hydrophilic antibiotic cephalexin 25 mg kg À1 day À1 by the oral route diminished renal infection. The CFU mean values in the kidneys were between 75% and 89% lower than those in animals without treatment. Simultaneous exposure to CL (at a therapeutic dose, 28.6 mg kg À1 day À1) did not change the effect of the treatment. In contrast, ET at 2.9 mg kg À1 day À1 or 2,4-D at 70 mg kg À1 day À1 inhibited the antibiotic therapeutic effect. Moreover, 2,4-D dramatically increased bacterial infection after 9 days of exposure.

Neurotoxicology and Teratology, Sep 1, 2003

The effects of 2,4-dichlorophenoxyacetic acid (2,4-D, 70 or 100 mg/kg dam's body weight) on iron ... more The effects of 2,4-dichlorophenoxyacetic acid (2,4-D, 70 or 100 mg/kg dam's body weight) on iron (Fe), zinc (Zn) and copper (Cu) in brain, liver and serum of well-nourished and undernourished pups exposed through dam's milk were determined. Undernourishment produced a high Fe decrease (serum and brain) and a delay in weight gain similar to that produced by the highest dose of 2,4-D on well-fed pups. In the latter animals, copper was found to be the most altered ion, increasing its level in serum, liver and some brain areas and decreasing in whole brain. Zinc was the most affected ion in brain areas. Well-nourished pups lactationally exposed to 70 mg 2,4-D/kg dam's body weight altered neither their metal levels nor their body weight in any of the tissues studied. Undernourished pups were more vulnerable to the 2,4-D effect than well-nourished pups. Undernourished pups exposed to a lower 2,4-D dose showed a decrease in their body, brain and liver weight similar to well-fed animals exposed to 100 mg 2,4-D/kg. A noticeable decrease in liver L-tryptophan peroxidase activity by 2,4-D was also registered. This effect was higher in undernourished and 2,4-D-exposed pups. These results suggest that brain areas have a different susceptibility to the herbicide and that undernourishment produces a higher vulnerability to the herbicide and exacerbates the 2,4-D effect.

Food and Chemical Toxicology, 2006

2,4-Dichlorophenoxyacetic acid (2,4-D) and its derivatives are herbicides widely used to control ... more 2,4-Dichlorophenoxyacetic acid (2,4-D) and its derivatives are herbicides widely used to control the growth of broadleaf and woody plant. Human and animal exposure to 2,4-D through agriculture use, food products, or use in lawn and garden care has been well documented, but little information is available on the transfer from serum to milk in exposed dams. In this study, we measured the content of 2,4-D in rat milk from mother exposed to 15, 25, 50 or 7 0mg 2,4-D/kg bw through the diet (4 treated groups, 8 dam each; 1 control group with 8 dams) over a period of 16 days starting on the post-natal day 1 (PND 1). The effect of 2,4-D on milk components was also evaluated. All doses tested caused a decrease in the body weight gain of the pups (4 groups, 64 pups each). It also produce a 30% in the content of total lipids and a changed the content of minor proteins in milk of the treated groups. 2,4-D produces an important decrease in some fatty acids content, being the polyunsaturated fatty acids the most affected. Further analysis showed that 2,4-D concentrations chromatographically detected both serum of dams and pups and milk were dose-dependent.

PubMed, May 4, 2000

Knowing early nutritional status have been shown to be an important factor in determining the act... more Knowing early nutritional status have been shown to be an important factor in determining the activity level of rats later in life, we studied offspring of dams which had received 50, 70 or 700 mg/kg of 2,4-Dichlorophenoxyacetic acid (2,4-D) during nursing. Neonatal tissues and the stomach content (milk) were examined up to 16 post natal days to detect body and organs weight alterations and 2,4-D residues after 2,4-D maternal dosing every-other-day, from post natal day 1. We detected 2,4-D residues in stomach content, blood, brain and kidney of 4-day-old neonates breast-fed by 2,4-D exposed mothers and onward. 2,4-D residues were dose- and exposure-time-dependent. The highest dose impaired body growth, as well as low tissue weights and diminished stomach contents. Levels of 2,4-D residues in stomach content, blood, kidney and brain of post natal rats (age PD 4-PD 16) fed through lactation from dams treated with 2,4-D demonstrated that 2,4-D was transferred to the neonates and the diminished body and tissues weight during this developmental period could be due to a diminished milk intake or/and to the direct 2,4-D toxic effect. Besides, when the herbicide treatment (100 mg 2,4-D/kg) was withdrawn from the dams, 2,4-D residues remained in the stomach content of neonates for at least one week. This fact indicated that dams continued depurating the herbicide through their milk.

El Texto ha sido pensado como un libro introductorio al análisis de lípidos de biomembranas para ... more El Texto ha sido pensado como un libro introductorio al análisis de lípidos de biomembranas para estudiantes de posgrado de Biología, Bioquímica, Biología Molecular y otros carreras afines. En el mismo se ha priorizado el desarrollo experimental de la metodología analítica de lípidos de biomembranas En cada etapa del análisis se presenta una breve introducción para luego desarrollar un método seleccionado por los autores, en cada capítulo se incluye un experimento con sus resultados esperados obtenidos de experimentos realizados por estudiantes del curso. Se agregaron además notas adicionales con algunas técnicas y datos útiles para el analista. Se han seleccionado técnicas simples y económicas que bastan para obtener información suficiente sobre la membrana del eritrocito y otros tejidos y membranas de origen natural. Se ha seleccionado como técnica separativa la cromatografía en capa fina que permite visualizar resultados con una inversión en equipamiento muy económica.

Clofibric acid (CL) is a compound used to control hypertriglyceridemia, and ethacrynic acid (ET) ... more Clofibric acid (CL) is a compound used to control hypertriglyceridemia, and ethacrynic acid (ET) is administered to enhance diuresis. These compounds are structurally analogous to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), as they have a chlorinated phenoxy moiety. As these agents are mainly excreted by the renal route, they could potentially coexist with Escherichia coli in the urinary tract of infected patients. Induction of the in vitro resistance of E. coli to hydrophilic antibiotics was determined by increasing the values of the minimum inhibitory concentration (2-40-fold). These results correlated with drastically inhibited expression of the hydrophilic bacterial channel OmpF. In vivo assays were performed in ascending urinary tract infection in female BALB/c mice. Treatment with the hydrophilic antibiotic cephalexin 25 mg kg À1 day À1 by the oral route diminished renal infection. The CFU mean values in the kidneys were between 75% and 89% lower than those in animals without treatment. Simultaneous exposure to CL (at a therapeutic dose, 28.6 mg kg À1 day À1) did not change the effect of the treatment. In contrast, ET at 2.9 mg kg À1 day À1 or 2,4-D at 70 mg kg À1 day À1 inhibited the antibiotic therapeutic effect. Moreover, 2,4-D dramatically increased bacterial infection after 9 days of exposure.

Neurotoxicology, 1998

As reported in our previous studies, "Serotonin Syndrome", rearing and circling behavio... more As reported in our previous studies, "Serotonin Syndrome", rearing and circling behaviors, were the responses of rats treated with the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and challenged with amphetamine. An altered serotonergic and dopaminergic system may be responsible for these behaviors. In this work, endogenous levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), and 5-hydroxyindolacetic acid (5-HIAA) were measured in the areas of the mesocortico-limbico and nigrostriatal systems of rats treated with 50 or 100 mg/kg of 2,4-D, but also challenged with amphetamine (5 or 10 mg/kg), in order to determine regional brain contents of biogenic amines and their metabolites and to find a correlation with the behaviors described. The prefrontal cortex (PFc), striatum, nucleus accumbens (NA), midbrain, ventral tegmental area (VTA), substantia nigra (SN) and cerebellum were assayed. The herbicide 2,4-D increased the 5-HT and DA basal level...

Toxicology, 2008

Exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) has several deleterious effects on the nervous... more Exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) has several deleterious effects on the nervous system such as alterations in the concentrations of neurotransmitters in the brain and/or behavioral changes, myelination rate, ganglioside pattern . Increased sensitivity in dopamine D(2)-like brain receptors from 2,4-dichlorophenoxyacetic acid (2,4-D)exposed and amphetamine-challenged rats. Ann. N.Y. Acad. Sci. 965, 314-323; Duffard, R., García, G., Rosso, S., Bortolozzi, A., Madariaga, M., DiPaolo, O., Evangelista de Duffard, A.M., 1996. Central nervous system myelin deficit in rats exposed to 2,4-dichlorophenoxyacetic acid throughout lactation. Neurotoxicol. Teratol. 18, 691-696; Evangelista de Duffard, A.M., Orta, C., Duffard, R., 1990. Behavioral changes in rats fed a diet containing 2,4-dichlorophenoxyacetic butyl ester. Neurotoxicology 11, 563-572; Evangelista de Duffard, A.M., Bortolozzi, A., Duffard, R.O., 1995. Altered behavioral responses in 2,4-dichlorophenoxyacetic acid treated and amphetamine challenged rats. Neurotoxicology 16, 479-488; Munro, I.C., Carlo, G.L., Orr, J.C., Sund, K., Wilson, R.M. Kennepohl, E. Lynch, B., Jablinske, M., Lee, N., 1992. A comprehensive, integrated review and evaluation of the scientific evidence relating to the safety of the herbicide 2,4-D. J. Am. Coll. Toxicol. 11, 559-664;, and its administration to pregnant and lactating rats adversely affects litter growth and milk quality. Since normal growth of the offspring depends on adequate maternal nursing and care, we evaluated the effect of 2,4-D on rat maternal behavior as well as the dam's monoamine levels in arcuate nucleus (AcN) and serum prolactin (PRL) levels. Wistar dams were exposed to the herbicide through the food from post partum day (PPD) 1 to PPD 7. Dams were fed either with a 2,4-D treated diet (15, 25 or 50 mg 2,4-D/kg/day bw) or with a control diet. We observed that maternal nesting behavior was not modified by 2,4-D treatment. However, mother-pup interactions, specially the nursing behavior, were altered. Retrieval, crouching and licking of pups were reduced or suspended after 2,4-D treatment. We also observed an increase in the latency of retrieval and crouching in the dams treated with the herbicide. Dams showed movement along cage peripheries, food consumption during the light phase and high self-grooming. In addition of the deficits observed in maternal behavior parameters, increased catecholamine levels and a drastic decrease in indolamine levels in the AcN of treated dams were determined. Serum PRL levels were also diminished by 62%, 68% and 70% with respect to control dams in the 15, 25 and 50 mg 2,4-D/kg bw treated dams, respectively. In conclusion, exposure to 2,4-D during the first post partum days produced changes in maternal behavior, serum prolactin and monoamine levels in the AcN of treated dams.

Toxicology, 2010

The effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on brain monoamines and the serum level of ... more The effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on brain monoamines and the serum level of hormones involved in milk synthesis and on the milk ejection reflex in rats were evaluated. Dams were treated with 2.5, 5, 15, 25, 50 or 70mg 2,4-D/kg bw according to two experimental designs: (a) through food from post partum day 1 (PPD 1) to PPD 16 and the respective control groups or (b) an unique i.p. injection on PPD 11. To measure milk ejection, the litter was separated from the mother at the 11th day of lactation during 8h, returned to their mothers and allowed to suckle for a period of 15min. The procedure was repeated on 3 consecutive days until the end of treatment. The change in litter weight during the suckling period was taken as a measure of the amount of milk ejected during this period. The dams' serum prolactin (PRL), oxytocin (OT) and growth hormone levels were determined by radioimmunoassay. Both treatment regimens produced a dose-dependent decrease in the amount of milk ejected and circulating PRL and OT secreted in response to the suckling stimulus. Administration of OT before returning the pups restored the milk ejection, indicating no impairment in the capacity of the mammary gland to produce and secrete milk. In addition, dopamine levels were increased by the 2,4-D treatments in arcuate nucleus (ArN) and anterior lobe of pituitary gland (AL), while serotonin level was drastically decreased in ArN. 2,4-D treatment increased both calcium-dependent and calcium-independent nitric oxide synthase (NOS) activities in ArN. These results suggest that 2,4-D inhibits the suckling-induced hormone release, milk transfer to the litter at the central level, through a stimulation of hypothalamic NOS and dopamine and by an inhibition of hypothalamic serotonin transmission.

Neurotoxicology and Teratology, 2003

The effects of 2,4-dichlorophenoxyacetic acid (2,4-D, 70 or 100 mg/kg dam's body weight) on iron ... more The effects of 2,4-dichlorophenoxyacetic acid (2,4-D, 70 or 100 mg/kg dam's body weight) on iron (Fe), zinc (Zn) and copper (Cu) in brain, liver and serum of well-nourished and undernourished pups exposed through dam's milk were determined. Undernourishment produced a high Fe decrease (serum and brain) and a delay in weight gain similar to that produced by the highest dose of 2,4-D on well-fed pups. In the latter animals, copper was found to be the most altered ion, increasing its level in serum, liver and some brain areas and decreasing in whole brain. Zinc was the most affected ion in brain areas. Well-nourished pups lactationally exposed to 70 mg 2,4-D/kg dam's body weight altered neither their metal levels nor their body weight in any of the tissues studied. Undernourished pups were more vulnerable to the 2,4-D effect than well-nourished pups. Undernourished pups exposed to a lower 2,4-D dose showed a decrease in their body, brain and liver weight similar to well-fed animals exposed to 100 mg 2,4-D/kg. A noticeable decrease in liver L-tryptophan peroxidase activity by 2,4-D was also registered. This effect was higher in undernourished and 2,4-D-exposed pups. These results suggest that brain areas have a different susceptibility to the herbicide and that undernourishment produces a higher vulnerability to the herbicide and exacerbates the 2,4-D effect. D

Environmental Toxicology, 2001

2,4-Dichlorophenoxyacetic acid (2,4-D) is a herbicide widely used in the world and mainly excrete... more 2,4-Dichlorophenoxyacetic acid (2,4-D) is a herbicide widely used in the world and mainly excreted by the renal route in exposed humans and animals. Herbicides can affect other nontarget organisms, such as Escherichia coli. We observed that a single exposure to 1 mM 2,4-D diminished growth and total protein content in all E. coli strains tested in vitro. In addition, successive exposures to 0.01 mM 2,4-D had a toxic effect decreasing growth up to early stationary phase. Uropathogenic E. coli adhere to epithelial cells mediated by fimbriae, adhesins, and hydrophobic properties. 2,4-D exposure of uropathogenic E. coli demonstrated altered hydrophobicity and fimbriation. Hydrophobicity index values obtained by partition in p-xylene/water were 300-420% higher in exposed cells than in control ones. Furthermore, values of hemagglutination titer, protein contents in fimbrial crude extract, and electron microscopy demonstrated a significant diminution of fimbriation in treated cells. Other envelope alterations could be detected, such as lipoperoxidation, evidenced by decreased polyunsaturated fatty acids and increased lipid degradation products (malonaldehyde), and motility diminution. These alterations decreased cell adherence to erythrocytes, indicating a diminished pathogenic capacity of the 2,4-D-exposed E. coli.

Drug and Chemical Toxicology, 2004

In the present work we show morphological data of the in vivo susceptibility of CNS myelin to sod... more In the present work we show morphological data of the in vivo susceptibility of CNS myelin to sodium metavanadate [V(+5)] in adult rats. The possible role of vanadium in behavioral alterations and in brain lipid peroxidation was also investigated. Animals were injected intraperitoneally (i.p.) with 3 mg/kg body weight (bw) of sodium metavanadate [1.25 V/kg bw/day] for 5 consecutive days. Open field and rotarod tests were performed the day after the last dose had been administered and then animals were sacrificed by different methods for histological and lipid peroxidation studies. The present results show that intraperitoneal administration of V(+5) to adult rats resulted in changes in locomotor activity, specific myelin stainings and lipid peroxidation in some brain areas. They support the notion that CNS myelin could be a preferential target of V(+5)-mediated lipid peroxidation in adult rats. The mechanisms underlying this action could affect the myelin sheath leading to behavioral perturbations.

El Texto ha sido pensado como un libro introductorio al análisis de lípidos de biomembranas para ... more El Texto ha sido pensado como un libro introductorio al análisis de lípidos de biomembranas para estudiantes de posgrado de Biología, Bioquímica, Biología Molecular y otros carreras afines. En el mismo se ha priorizado el desarrollo experimental de la metodología analítica de lípidos de biomembranas En cada etapa del análisis se presenta una breve introducción para luego desarrollar un método seleccionado por los autores, en cada capítulo se incluye un experimento con sus resultados esperados obtenidos de experimentos realizados por estudiantes del curso. Se agregaron además notas adicionales con algunas técnicas y datos útiles para el analista. Se han seleccionado técnicas simples y económicas que bastan para obtener información suficiente sobre la membrana del eritrocito y otros tejidos y membranas de origen natural. Se ha seleccionado como técnica separativa la cromatografía en capa fina que permite visualizar resultados con una inversión en equipamiento muy económica.

Neurotoxicology

Knowing early nutritional status have been shown to be an important factor in determining the act... more Knowing early nutritional status have been shown to be an important factor in determining the activity level of rats later in life, we studied offspring of dams which had received 50, 70 or 700 mg/kg of 2,4-Dichlorophenoxyacetic acid (2,4-D) during nursing. Neonatal tissues and the stomach content (milk) were examined up to 16 post natal days to detect body and organs weight alterations and 2,4-D residues after 2,4-D maternal dosing every-other-day, from post natal day 1. We detected 2,4-D residues in stomach content, blood, brain and kidney of 4-day-old neonates breast-fed by 2,4-D exposed mothers and onward. 2,4-D residues were dose- and exposure-time-dependent. The highest dose impaired body growth, as well as low tissue weights and diminished stomach contents. Levels of 2,4-D residues in stomach content, blood, kidney and brain of post natal rats (age PD 4-PD 16) fed through lactation from dams treated with 2,4-D demonstrated that 2,4-D was transferred to the neonates and the di...

PubMed, Dec 1, 1998

As reported in our previous studies, "Serotonin Syndrome", rearing and circling behaviors, were t... more As reported in our previous studies, "Serotonin Syndrome", rearing and circling behaviors, were the responses of rats treated with the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and challenged with amphetamine. An altered serotonergic and dopaminergic system may be responsible for these behaviors. In this work, endogenous levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), and 5-hydroxyindolacetic acid (5-HIAA) were measured in the areas of the mesocortico-limbico and nigrostriatal systems of rats treated with 50 or 100 mg/kg of 2,4-D, but also challenged with amphetamine (5 or 10 mg/kg), in order to determine regional brain contents of biogenic amines and their metabolites and to find a correlation with the behaviors described. The prefrontal cortex (PFc), striatum, nucleus accumbens (NA), midbrain, ventral tegmental area (VTA), substantia nigra (SN) and cerebellum were assayed. The herbicide 2,4-D increased the 5-HT and DA basal levels and these increments were dependent on sex, brain area and 2,4-D doses. The challenge with 5 or 10 mg/kg amphetamine to 2,4-D (50 or 100 mg/kg) treated rats also resulted in an area-, sex- and dose-dependent alterations of the 2,4-D effect on dopaminergic and serotonergic systems. We are demonstrating a correlation between rat behavior altered by the herbicide's treatment and the contents of 5-HT and DA in brain areas, such as PFc, VTA, SN, striatum, NA, midbrain and cerebellum. In order for 2,4-D to produce the neurobehavioral alterations, not only are high levels of 5-HT and DA necessary, but these neurotransmitters must be released.

Fems Immunology and Medical Microbiology, Dec 1, 2006

Clofibric acid (CL) is a compound used to control hypertriglyceridemia, and ethacrynic acid (ET) ... more Clofibric acid (CL) is a compound used to control hypertriglyceridemia, and ethacrynic acid (ET) is administered to enhance diuresis. These compounds are structurally analogous to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), as they have a chlorinated phenoxy moiety. As these agents are mainly excreted by the renal route, they could potentially coexist with Escherichia coli in the urinary tract of infected patients. Induction of the in vitro resistance of E. coli to hydrophilic antibiotics was determined by increasing the values of the minimum inhibitory concentration (2-40-fold). These results correlated with drastically inhibited expression of the hydrophilic bacterial channel OmpF. In vivo assays were performed in ascending urinary tract infection in female BALB/c mice. Treatment with the hydrophilic antibiotic cephalexin 25 mg kg À1 day À1 by the oral route diminished renal infection. The CFU mean values in the kidneys were between 75% and 89% lower than those in animals without treatment. Simultaneous exposure to CL (at a therapeutic dose, 28.6 mg kg À1 day À1) did not change the effect of the treatment. In contrast, ET at 2.9 mg kg À1 day À1 or 2,4-D at 70 mg kg À1 day À1 inhibited the antibiotic therapeutic effect. Moreover, 2,4-D dramatically increased bacterial infection after 9 days of exposure.

Neurotoxicology and Teratology, Sep 1, 2003

The effects of 2,4-dichlorophenoxyacetic acid (2,4-D, 70 or 100 mg/kg dam's body weight) on iron ... more The effects of 2,4-dichlorophenoxyacetic acid (2,4-D, 70 or 100 mg/kg dam's body weight) on iron (Fe), zinc (Zn) and copper (Cu) in brain, liver and serum of well-nourished and undernourished pups exposed through dam's milk were determined. Undernourishment produced a high Fe decrease (serum and brain) and a delay in weight gain similar to that produced by the highest dose of 2,4-D on well-fed pups. In the latter animals, copper was found to be the most altered ion, increasing its level in serum, liver and some brain areas and decreasing in whole brain. Zinc was the most affected ion in brain areas. Well-nourished pups lactationally exposed to 70 mg 2,4-D/kg dam's body weight altered neither their metal levels nor their body weight in any of the tissues studied. Undernourished pups were more vulnerable to the 2,4-D effect than well-nourished pups. Undernourished pups exposed to a lower 2,4-D dose showed a decrease in their body, brain and liver weight similar to well-fed animals exposed to 100 mg 2,4-D/kg. A noticeable decrease in liver L-tryptophan peroxidase activity by 2,4-D was also registered. This effect was higher in undernourished and 2,4-D-exposed pups. These results suggest that brain areas have a different susceptibility to the herbicide and that undernourishment produces a higher vulnerability to the herbicide and exacerbates the 2,4-D effect.

Food and Chemical Toxicology, 2006

2,4-Dichlorophenoxyacetic acid (2,4-D) and its derivatives are herbicides widely used to control ... more 2,4-Dichlorophenoxyacetic acid (2,4-D) and its derivatives are herbicides widely used to control the growth of broadleaf and woody plant. Human and animal exposure to 2,4-D through agriculture use, food products, or use in lawn and garden care has been well documented, but little information is available on the transfer from serum to milk in exposed dams. In this study, we measured the content of 2,4-D in rat milk from mother exposed to 15, 25, 50 or 7 0mg 2,4-D/kg bw through the diet (4 treated groups, 8 dam each; 1 control group with 8 dams) over a period of 16 days starting on the post-natal day 1 (PND 1). The effect of 2,4-D on milk components was also evaluated. All doses tested caused a decrease in the body weight gain of the pups (4 groups, 64 pups each). It also produce a 30% in the content of total lipids and a changed the content of minor proteins in milk of the treated groups. 2,4-D produces an important decrease in some fatty acids content, being the polyunsaturated fatty acids the most affected. Further analysis showed that 2,4-D concentrations chromatographically detected both serum of dams and pups and milk were dose-dependent.

PubMed, May 4, 2000

Knowing early nutritional status have been shown to be an important factor in determining the act... more Knowing early nutritional status have been shown to be an important factor in determining the activity level of rats later in life, we studied offspring of dams which had received 50, 70 or 700 mg/kg of 2,4-Dichlorophenoxyacetic acid (2,4-D) during nursing. Neonatal tissues and the stomach content (milk) were examined up to 16 post natal days to detect body and organs weight alterations and 2,4-D residues after 2,4-D maternal dosing every-other-day, from post natal day 1. We detected 2,4-D residues in stomach content, blood, brain and kidney of 4-day-old neonates breast-fed by 2,4-D exposed mothers and onward. 2,4-D residues were dose- and exposure-time-dependent. The highest dose impaired body growth, as well as low tissue weights and diminished stomach contents. Levels of 2,4-D residues in stomach content, blood, kidney and brain of post natal rats (age PD 4-PD 16) fed through lactation from dams treated with 2,4-D demonstrated that 2,4-D was transferred to the neonates and the diminished body and tissues weight during this developmental period could be due to a diminished milk intake or/and to the direct 2,4-D toxic effect. Besides, when the herbicide treatment (100 mg 2,4-D/kg) was withdrawn from the dams, 2,4-D residues remained in the stomach content of neonates for at least one week. This fact indicated that dams continued depurating the herbicide through their milk.

El Texto ha sido pensado como un libro introductorio al análisis de lípidos de biomembranas para ... more El Texto ha sido pensado como un libro introductorio al análisis de lípidos de biomembranas para estudiantes de posgrado de Biología, Bioquímica, Biología Molecular y otros carreras afines. En el mismo se ha priorizado el desarrollo experimental de la metodología analítica de lípidos de biomembranas En cada etapa del análisis se presenta una breve introducción para luego desarrollar un método seleccionado por los autores, en cada capítulo se incluye un experimento con sus resultados esperados obtenidos de experimentos realizados por estudiantes del curso. Se agregaron además notas adicionales con algunas técnicas y datos útiles para el analista. Se han seleccionado técnicas simples y económicas que bastan para obtener información suficiente sobre la membrana del eritrocito y otros tejidos y membranas de origen natural. Se ha seleccionado como técnica separativa la cromatografía en capa fina que permite visualizar resultados con una inversión en equipamiento muy económica.

Clofibric acid (CL) is a compound used to control hypertriglyceridemia, and ethacrynic acid (ET) ... more Clofibric acid (CL) is a compound used to control hypertriglyceridemia, and ethacrynic acid (ET) is administered to enhance diuresis. These compounds are structurally analogous to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), as they have a chlorinated phenoxy moiety. As these agents are mainly excreted by the renal route, they could potentially coexist with Escherichia coli in the urinary tract of infected patients. Induction of the in vitro resistance of E. coli to hydrophilic antibiotics was determined by increasing the values of the minimum inhibitory concentration (2-40-fold). These results correlated with drastically inhibited expression of the hydrophilic bacterial channel OmpF. In vivo assays were performed in ascending urinary tract infection in female BALB/c mice. Treatment with the hydrophilic antibiotic cephalexin 25 mg kg À1 day À1 by the oral route diminished renal infection. The CFU mean values in the kidneys were between 75% and 89% lower than those in animals without treatment. Simultaneous exposure to CL (at a therapeutic dose, 28.6 mg kg À1 day À1) did not change the effect of the treatment. In contrast, ET at 2.9 mg kg À1 day À1 or 2,4-D at 70 mg kg À1 day À1 inhibited the antibiotic therapeutic effect. Moreover, 2,4-D dramatically increased bacterial infection after 9 days of exposure.

Neurotoxicology, 1998

As reported in our previous studies, "Serotonin Syndrome", rearing and circling behavio... more As reported in our previous studies, "Serotonin Syndrome", rearing and circling behaviors, were the responses of rats treated with the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and challenged with amphetamine. An altered serotonergic and dopaminergic system may be responsible for these behaviors. In this work, endogenous levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), and 5-hydroxyindolacetic acid (5-HIAA) were measured in the areas of the mesocortico-limbico and nigrostriatal systems of rats treated with 50 or 100 mg/kg of 2,4-D, but also challenged with amphetamine (5 or 10 mg/kg), in order to determine regional brain contents of biogenic amines and their metabolites and to find a correlation with the behaviors described. The prefrontal cortex (PFc), striatum, nucleus accumbens (NA), midbrain, ventral tegmental area (VTA), substantia nigra (SN) and cerebellum were assayed. The herbicide 2,4-D increased the 5-HT and DA basal level...

Toxicology, 2008

Exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) has several deleterious effects on the nervous... more Exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) has several deleterious effects on the nervous system such as alterations in the concentrations of neurotransmitters in the brain and/or behavioral changes, myelination rate, ganglioside pattern . Increased sensitivity in dopamine D(2)-like brain receptors from 2,4-dichlorophenoxyacetic acid (2,4-D)exposed and amphetamine-challenged rats. Ann. N.Y. Acad. Sci. 965, 314-323; Duffard, R., García, G., Rosso, S., Bortolozzi, A., Madariaga, M., DiPaolo, O., Evangelista de Duffard, A.M., 1996. Central nervous system myelin deficit in rats exposed to 2,4-dichlorophenoxyacetic acid throughout lactation. Neurotoxicol. Teratol. 18, 691-696; Evangelista de Duffard, A.M., Orta, C., Duffard, R., 1990. Behavioral changes in rats fed a diet containing 2,4-dichlorophenoxyacetic butyl ester. Neurotoxicology 11, 563-572; Evangelista de Duffard, A.M., Bortolozzi, A., Duffard, R.O., 1995. Altered behavioral responses in 2,4-dichlorophenoxyacetic acid treated and amphetamine challenged rats. Neurotoxicology 16, 479-488; Munro, I.C., Carlo, G.L., Orr, J.C., Sund, K., Wilson, R.M. Kennepohl, E. Lynch, B., Jablinske, M., Lee, N., 1992. A comprehensive, integrated review and evaluation of the scientific evidence relating to the safety of the herbicide 2,4-D. J. Am. Coll. Toxicol. 11, 559-664;, and its administration to pregnant and lactating rats adversely affects litter growth and milk quality. Since normal growth of the offspring depends on adequate maternal nursing and care, we evaluated the effect of 2,4-D on rat maternal behavior as well as the dam's monoamine levels in arcuate nucleus (AcN) and serum prolactin (PRL) levels. Wistar dams were exposed to the herbicide through the food from post partum day (PPD) 1 to PPD 7. Dams were fed either with a 2,4-D treated diet (15, 25 or 50 mg 2,4-D/kg/day bw) or with a control diet. We observed that maternal nesting behavior was not modified by 2,4-D treatment. However, mother-pup interactions, specially the nursing behavior, were altered. Retrieval, crouching and licking of pups were reduced or suspended after 2,4-D treatment. We also observed an increase in the latency of retrieval and crouching in the dams treated with the herbicide. Dams showed movement along cage peripheries, food consumption during the light phase and high self-grooming. In addition of the deficits observed in maternal behavior parameters, increased catecholamine levels and a drastic decrease in indolamine levels in the AcN of treated dams were determined. Serum PRL levels were also diminished by 62%, 68% and 70% with respect to control dams in the 15, 25 and 50 mg 2,4-D/kg bw treated dams, respectively. In conclusion, exposure to 2,4-D during the first post partum days produced changes in maternal behavior, serum prolactin and monoamine levels in the AcN of treated dams.

Toxicology, 2010

The effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on brain monoamines and the serum level of ... more The effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on brain monoamines and the serum level of hormones involved in milk synthesis and on the milk ejection reflex in rats were evaluated. Dams were treated with 2.5, 5, 15, 25, 50 or 70mg 2,4-D/kg bw according to two experimental designs: (a) through food from post partum day 1 (PPD 1) to PPD 16 and the respective control groups or (b) an unique i.p. injection on PPD 11. To measure milk ejection, the litter was separated from the mother at the 11th day of lactation during 8h, returned to their mothers and allowed to suckle for a period of 15min. The procedure was repeated on 3 consecutive days until the end of treatment. The change in litter weight during the suckling period was taken as a measure of the amount of milk ejected during this period. The dams' serum prolactin (PRL), oxytocin (OT) and growth hormone levels were determined by radioimmunoassay. Both treatment regimens produced a dose-dependent decrease in the amount of milk ejected and circulating PRL and OT secreted in response to the suckling stimulus. Administration of OT before returning the pups restored the milk ejection, indicating no impairment in the capacity of the mammary gland to produce and secrete milk. In addition, dopamine levels were increased by the 2,4-D treatments in arcuate nucleus (ArN) and anterior lobe of pituitary gland (AL), while serotonin level was drastically decreased in ArN. 2,4-D treatment increased both calcium-dependent and calcium-independent nitric oxide synthase (NOS) activities in ArN. These results suggest that 2,4-D inhibits the suckling-induced hormone release, milk transfer to the litter at the central level, through a stimulation of hypothalamic NOS and dopamine and by an inhibition of hypothalamic serotonin transmission.

Neurotoxicology and Teratology, 2003

The effects of 2,4-dichlorophenoxyacetic acid (2,4-D, 70 or 100 mg/kg dam's body weight) on iron ... more The effects of 2,4-dichlorophenoxyacetic acid (2,4-D, 70 or 100 mg/kg dam's body weight) on iron (Fe), zinc (Zn) and copper (Cu) in brain, liver and serum of well-nourished and undernourished pups exposed through dam's milk were determined. Undernourishment produced a high Fe decrease (serum and brain) and a delay in weight gain similar to that produced by the highest dose of 2,4-D on well-fed pups. In the latter animals, copper was found to be the most altered ion, increasing its level in serum, liver and some brain areas and decreasing in whole brain. Zinc was the most affected ion in brain areas. Well-nourished pups lactationally exposed to 70 mg 2,4-D/kg dam's body weight altered neither their metal levels nor their body weight in any of the tissues studied. Undernourished pups were more vulnerable to the 2,4-D effect than well-nourished pups. Undernourished pups exposed to a lower 2,4-D dose showed a decrease in their body, brain and liver weight similar to well-fed animals exposed to 100 mg 2,4-D/kg. A noticeable decrease in liver L-tryptophan peroxidase activity by 2,4-D was also registered. This effect was higher in undernourished and 2,4-D-exposed pups. These results suggest that brain areas have a different susceptibility to the herbicide and that undernourishment produces a higher vulnerability to the herbicide and exacerbates the 2,4-D effect. D

Environmental Toxicology, 2001

2,4-Dichlorophenoxyacetic acid (2,4-D) is a herbicide widely used in the world and mainly excrete... more 2,4-Dichlorophenoxyacetic acid (2,4-D) is a herbicide widely used in the world and mainly excreted by the renal route in exposed humans and animals. Herbicides can affect other nontarget organisms, such as Escherichia coli. We observed that a single exposure to 1 mM 2,4-D diminished growth and total protein content in all E. coli strains tested in vitro. In addition, successive exposures to 0.01 mM 2,4-D had a toxic effect decreasing growth up to early stationary phase. Uropathogenic E. coli adhere to epithelial cells mediated by fimbriae, adhesins, and hydrophobic properties. 2,4-D exposure of uropathogenic E. coli demonstrated altered hydrophobicity and fimbriation. Hydrophobicity index values obtained by partition in p-xylene/water were 300-420% higher in exposed cells than in control ones. Furthermore, values of hemagglutination titer, protein contents in fimbrial crude extract, and electron microscopy demonstrated a significant diminution of fimbriation in treated cells. Other envelope alterations could be detected, such as lipoperoxidation, evidenced by decreased polyunsaturated fatty acids and increased lipid degradation products (malonaldehyde), and motility diminution. These alterations decreased cell adherence to erythrocytes, indicating a diminished pathogenic capacity of the 2,4-D-exposed E. coli.

Drug and Chemical Toxicology, 2004

In the present work we show morphological data of the in vivo susceptibility of CNS myelin to sod... more In the present work we show morphological data of the in vivo susceptibility of CNS myelin to sodium metavanadate [V(+5)] in adult rats. The possible role of vanadium in behavioral alterations and in brain lipid peroxidation was also investigated. Animals were injected intraperitoneally (i.p.) with 3 mg/kg body weight (bw) of sodium metavanadate [1.25 V/kg bw/day] for 5 consecutive days. Open field and rotarod tests were performed the day after the last dose had been administered and then animals were sacrificed by different methods for histological and lipid peroxidation studies. The present results show that intraperitoneal administration of V(+5) to adult rats resulted in changes in locomotor activity, specific myelin stainings and lipid peroxidation in some brain areas. They support the notion that CNS myelin could be a preferential target of V(+5)-mediated lipid peroxidation in adult rats. The mechanisms underlying this action could affect the myelin sheath leading to behavioral perturbations.

El Texto ha sido pensado como un libro introductorio al análisis de lípidos de biomembranas para ... more El Texto ha sido pensado como un libro introductorio al análisis de lípidos de biomembranas para estudiantes de posgrado de Biología, Bioquímica, Biología Molecular y otros carreras afines. En el mismo se ha priorizado el desarrollo experimental de la metodología analítica de lípidos de biomembranas En cada etapa del análisis se presenta una breve introducción para luego desarrollar un método seleccionado por los autores, en cada capítulo se incluye un experimento con sus resultados esperados obtenidos de experimentos realizados por estudiantes del curso. Se agregaron además notas adicionales con algunas técnicas y datos útiles para el analista. Se han seleccionado técnicas simples y económicas que bastan para obtener información suficiente sobre la membrana del eritrocito y otros tejidos y membranas de origen natural. Se ha seleccionado como técnica separativa la cromatografía en capa fina que permite visualizar resultados con una inversión en equipamiento muy económica.