Fluoxetine alters rat's milk properties causing impact on offspring's development.

Fluoxetine is an antidepressant used to treat several conditions including postpartum depression. This disease causes cognitive, emotional, behavioral and physical changes, negatively affecting the mother, child and family life. However, fluoxetine is excreted in breast milk, causing short and long-term effects on children who were exposed to the drug during lactation, so studies that seek to uncover the consequences of these effects are needed. Thus, the aim of this study was to evaluate the effects of fluoxetine on the nutritional characteristics of milk and on growth and neurobehavioral development of the offspring on a rat model. Lactating rats were divided into 4 groups: control group and three experimental groups, which were treated with different doses of fluoxetine (1, 10 and 20 mg/kg) during the lactation. Dams body weight and milk properties were measured, as well as offspring's growth and physical and neurobehavioral development. Results showed that the use of fluoxetine during lactation decreased dam's body weight and alters milk's properties, leading to a decrease in offspring's growth until adulthood. Therefore, the use of fluoxetine during lactation needs to be cautiously evaluated, with the benefits to the mothers and the associated risk to the offspring carefully balance.

Peripubertal exposure of atrazine cause decrease in exploratory activity, deficits in sociability and few alterations on brain monoaminergic systems of rats.

Atrazine is a pesticide used to control weeds in both in pre- and post-emergence crops. The chronic exposure to atrazine can lead to severe damage in animals, especially in the endocrine and reproduction systems, leading to the inclusion of this pesticide into the endocrine disrupting chemicals group. Studies with rats showed that atrazine exposure during lactation in dams caused changes in the juvenile offspring, however; there is still limited information regarding the effects of atrazine during puberty. Thus, the aim of this study is to evaluate the effects of peripubertal exposure of atrazine in rats, assessing motor activity, social behavior and neurochemical alterations. Juvenile rats were treated with different doses of atrazine (0, 10, 30 or 100 mg/kg) by gavage from postnatal day 22 to 41. Behavioral tests were conducted for the evaluation of motor activity and social behavior, and neurochemical evaluation was done in order to assess monoamine levels. Atrazine caused behavioral alterations, evidenced by decrease in the exploratory activity (p values variation between 0.05 and 0.0001) and deficits in the social behavior of both male and females as adults (p values variation between 0.01 and 0.0001). As for the monoaminergic neurotransmission, atrazine led to very few alterations on the dopamine and serotonin systems that were limited to the females (p < 0.05). Altogether, the results suggests that peripubertal exposure of atrazine cause behavioral and neurochemical alterations. More studies need to be conducted to fully understand the differences in atrazine's effects and its use should be considered carefully.

Ketamine causes poor maternal care in rats with postpartum depression and leads to few behavioral and neurochemical alterations on male offspring.

Ketamine is an anesthetic drug that also has antidepressant properties, with quick action. Despite the great number of studies showing its effectiveness as a treatment for major depression, there is little information about its effects on postpartum depression, as pharmacological treatments bring risks to the health of both mother and child. Thus, this study aimed to evaluate the effects of prolonged treatment with subanesthetic doses of ketamine in a rat model of postpartum depression. Female dams were induced to postpartum depression by the maternal separation model from lactating day (LD) 2-12. They were divided into four groups: one control and three experimental groups, which were treated with different doses of ketamine (5, 10 or 20 mg/kg) from LD 2-21 i.p. Maternal studies were conducted from LD5 to LD21 and the offspring studies from postnatal day 2 through 90. Ketamine causes poor maternal care, with few neurochemical alterations. However, the highest dose used in this study had an antidepressant effect. Regarding the male offspring, indirect exposure to ketamine through breast milk caused few behavioral changes during infancy, but they were not permanent, as they faded in adulthood. Nevertheless, this exposure was able to cause alterations in their monoaminergic neurotransmission systems that were found in both infancy and adulthood periods.

Postpartum depression in rats causes poor maternal care and neurochemical alterations on dams and long-lasting impairment in sociability on the offspring.

Postpartum depression is a mentally disabling disease with multifactorial etiology that affects women worldwide. It can also influence child development and lead to behavioral and cognitive alterations. Despite the high prevalence, the disease is underdiagnosed and poorly studied. To study the postpartum depression caused by maternal separation model in rats, dams were separated from their litter for 3 h daily starting from lactating day (LD) 2 through LD12. Maternal studies were conducted from LD5 to LD21 and the offspring studies from postnatal day (PND) 2 through PND90. The stress caused by the dam-offspring separation led to poor maternal care and a transient increase in anxiety in the offspring detected during infancy. The female offspring also exhibited a permanent impairment in sociability during adult life. These changes were associated with neurochemical alterations in the prefrontal cortex and hippocampus, and low TSH concentrations in the dams, and in the hypothalamus, hippocampus and striatum of the offspring. These results indicate that the postpartum depression resulted in a depressive phenotype, changes in the brain neurochemistry and in thyroid economy that remained until the end of lactation. Changes observed in the offspring were long-lasting and resemble what is observed in children of depressant mothers.

Prenatal exposure to fipronil disturbs maternal aggressive behavior in rats.

Fipronil is a second-generation phenilpirazol insecticide that is used in agriculture and veterinary medicine for protection against fleas, ticks, ants, cockroaches and other pests. The insecticide blocks the chloride channels associated with the gamma-amino butyric acid (GABA) receptors in mammals and the chloride channels associated with the GABA and glutamate (Glu) receptors in insects. In this study, a commercial product that contain fipronil was administered orally to pregnant Wistar rats at dosages of 0.1, 1.0, or 10.0 mg/kg/day from the 6th to the 20th day of gestation (n=10 pregnant rats/group) to assess the maternal aggressive behavior (on the 6th day of lactation) and the histopathology of the ovaries and the thyroid gland of the dams. The fipronil caused a disturbance of the maternal aggressive behavior; the aggression against a male intruder decreased at the lowest dose, but increased at the highest dose, without interfering with the general activity of the dams in the open field test at either dose. The histopathological analysis revealed no abnormalities. The differential effects of fipronil behavior appeared to be a consequence of actions on central nervous system areas that control these behaviors. We suggest that fipronil acts on maternal aggressive behavior through GABA(A) receptors.

Prenatal exposure to a low fipronil dose disturbs maternal behavior and reflex development in rats.

Fipronil (FPN) is a phenylpyrazole insecticide used in veterinary services and agriculture, and it is of considerable concern to public health. It inhibits the chloride channels associated with gamma-amino butyric acid (GABA) receptors in mammals and also inhibits the chloride channels associated with GABA and glutamate (Glu) receptors in insects. In this study, a commercial product containing fipronil was orally administered to pregnant Wistar rats at dose levels of 0.1, 1.0, or 10.0mg/kg/day from the sixth to twentieth day of gestation (n=10 pregnant rats/group). Its toxicity was evaluated based on maternal toxicity, reproductive quality, maternal behavior, and offspring physical as well as reflex development. All parameters observed in the observed offspring were assigned to one ink-marked couple in each litter (n=20 animals/group - 10 males and 10 females). The offspring couple represented the litter. Slight maternal toxicity presented during the second week of gestation for each fipronil dose and during the third gestational week at the highest dose due to lower chow intake. However, no effects were observed for gestational weight gain or gestation time, and the reproductive quality was not impaired, which suggests no adverse maternal effects from the doses during pregnancy. Moreover, the lowest fipronil dose compromised the active and reflexive maternal responses, but the highest dose induced a stereotyped active response without interfering in the reflexive reaction. For offspring development, no differences in physical growth parameters were observed between the groups. However, considering reflex development, our results showed that negative geotaxis reflex development was delayed in the offspring at the lowest fipronil dose, and palmar grasp was lost earlier at the lowest and intermediate fipronil doses. These results suggest that the alterations observed herein may be due to either the GABAergic system or endocrine disruption, considering that fipronil also acts as an endocrine disruptor.

The use of ultrasonography to study teratogenicity in ruminants: evaluation of Ipomoea carnea in goats.

BACKGROUND: Ipomoea carnea (I. carnea) is a poisonous plant found in Brazil and other tropical countries that often poison livestock. The plant contains the alkaloids calystegines and mainly swainsonine, which inhibit cellular enzymes and cause systematic cell death. The objective of this study was to evaluate the perinatal effects of I. carnea in goats. METHODS: Forty-seven pregnant goats were randomly allocated into 5 treatment groups and given the following doses (g/kg BW) of I. carnea: 0 (IC0), 1.0 (IC1), 3.0 (IC3), 5.0 (IC5) and 7.5 (IC7). The treatment animals were given fresh I. carnea from day 27 of gestation to parturition. Weight gains and serum biochemistry were evaluated. Fetuses were evaluated using ultrasonographic measurements. RESULTS: Goats from the IC7 group showed clinical signs of poisoning. Ultrasound examination revealed that I. carnea feeding in all treatment groups reduced fetal movement compared to the controls. There was an increase in the total number of birth defects (retrognathia and arthrogyposis) in the IC7 and IC5 groups compared to the controls. CONCLUSION: The results show that I. carnea has teratogenic potential in goats. In addition, ultrasounds were useful in evaluating fetotoxicity and teratogenicity.

Increased antitumor efficacy by the combined administration of swainsonine and cisplatin in vivo.

Swainsonine is a natural α-mannosidase inhibitor found in numerous poisonous plants, such as Astragalus lentiginosus. Its mechanism of action is through the inhibition of Golgi α-mannosidase II activity in the N-glycan biosynthesis pathway. As a result, swainsonine inhibits the production of complex ß1,6-branched N-linked glycans, which are related to the malignant phenotype of tumor cells. In this study, we investigated whether treatment with swainsonine affects the sensitivity of Ehrlich ascites carcinoma (EAC) cells to cisplatin. To this end, male C57BL/6 mice were treated with swainsonine (SW--0.5 mg/kg, i.p., twice-daily for ten days) and/or cisplatin (Cis--0.25 mg/kg, i.p., every other day for a total of five applications) two days after transplantation with EAC cells. The results showed a greater reduction in the ascites volume in mice from the CisSW group (63.5%) than in mice from the Cis group (45.7%), an elevated induction of apoptosis by CisSW treatment when compared to Cis alone, as demonstrated by higher percentage of cells in the subG1 phase in that group (p<0.0001 Kruskal-Wallis, p<0.0001 control vs. CisSW, p<0.001 Co vs. Cis post-test Dunn), and an increase in the median survival from 12.5 days observed in the control group to 27 days in the CisSW group, which corresponds to a 116% survival increase (p=0.0022 Co vs. CisSW Log-rank test). In addition, the mice from the Cis group had a median survival of only 15 days, an increase of just 20% compared to controls. Our results indicate that swainsonine increases the sensitivity of EAC cells to cisplatin.

Cystic liver disease related to high Platynosomum fastosum infection in a domestic cat.

Platynosomum fastosum is a small fluke found in the biliary ducts and gallbladder of cats. Its lifecycle includes the snail Sublima octona as intermediate host, and lizards, toads and geckos as paratenic hosts. Affected cats are usually adult and acquire the parasite by feeding on infected lizards. This parasite occurs across the world but is more frequent in tropical areas. The clinical signs range from none to obstruction of the biliary tract, with hepatic failure and death, reinforcing the necessity of including the liver fluke Platynosomum fastosum in the differential diagnosis of hepatic diseases in cats. This report describes an unusual case of a cat with a polycystic hepatic disease and a severe infestation by Platynosomum fastosum and presents a review of the literature.

Impaired female sexual behavior of rat offspring exposed to Solanum lycocarpum unripe fruits during gestation and lactation: lack of hormonal and fertility alterations.

Solanum lycocarpum St. Hil (Solanaceae) is an invasive and native shrub very common in the Brazilian savanna. It is well known that this plant contain steroidal glycoalkaloids that can be transformed into an intermediate for steroidal drugs production, like oral contraceptives. In this way, it is very possible that these glycoalkaloids and its aglycone, once in the body by ingestion of S. lycocarpum fruits, may act disrupting to the endocrine system. Rat offspring were exposed to S. lycocarpum unripe fruits (10% in the diet) from gestational day (GD) 06 to post-natal day (PND) 07. The female exposed offspring showed, at adult age (PND 100), impaired sexual behavior. However, the fecal hormonal metabolite levels, measured at PND 30, PND 60 and PND 90, and the fertility (PND 120) of male and female experimental offspring were normal. We can assume that the steroidal glycoalkaloids, solamargine and solasodine, present in the fruit, are degradated, once inside the organism, to the steroidal alkaloid solasodine, which may penetrate, by simple diffusion, the placental and/or the hematoencephalical barriers and impact the fetuses. Finally, S. lycocarpum fruit may act as phytohormones, promoting perhaps some neural alterations that at adult age may impair the sexual behavior of the experimental female without impairing the fertility and sexual hormone synthesis. These changes observed can be the direct consequence of the toxic actions of the steroidal alkaloid on the female offspring during fetal development.

Determinaçäo de hidrocortisona em urina de cavalo de corrida empregando cromatografia a líquido de alta eficiência com detector de arranjo de diodos / Hydrocortisone determination in horseracing urine using high-performance liquid chromatography with diode arrangememt detection

A presença de hidrocortisona (cortisol) em amostras de urina de cavalos submetidas à análise de controle antidopagem pode ser decorrência não apenas da secreção endógena dessa substância pelo cortéx da adrenal, mas também da administração deste fármaco. Devido às suas propriedades antiinflamatórias, a hidrocortisona é enquadrada no Grupo II de substâncias proibidas pelo Código Nacional de Corridas. Este trabalho apresenta os resultados obtidos para um método de confirmação da presença de hidrocortisona em urina eqüina, o qual utiliza extração liquído-liquído, seguida de purificação por CCD e determinação por HPLC. Os resultados mostraram que o método empregado é adequado ao seu propósito.