Helenice de Souza Spinosa

Perinatal fenvalerate exposure: behavioral and endocrinology changes in male rats.

The effects of maternal exposure to fenvalerate during the prenatal and postnatal periods of sexual brain differentiation were studied in adult male offspring. Behavioral (open field, stereotyped, and sexual behaviors), physical (sexual maturation, body and organ weights), endocrine (testosterone levels), and neurochemical (striatal and hypothalamic monoamine and respective metabolite levels) data were assessed. The results showed that there was no change in the age of testis descent or testis weight, nor were there changes in monoamine levels or stereotyped behavior. However, there were significant reductions in ductus deferens and seminal vesicle weights and plasma testosterone concentrations. In addition, treated offspring showed decreased male sexual behavior and increased immobility in the open field. These results indicate that perinatal exposure to fenvalerate during the critical periods of male brain sexual differentiation has long-term effects on the reproductive physiology and behavior of male rats.

Pesticide residues in cow milk consumed in São Paulo City (Brazil).

Residues of pesticides were surveyed in 132 samples of cow milk collected from bulk transports (38 samples of raw milk) and market (94 samples of pasteurised milk). These samples were analysed by the multiresidue analytical method DFG S19 for pesticide contamination. More than 70 active substances were studied and the identification and quantification were made by gas chromatographic technique. The results showed that 0.76% of samples were contaminated with HCH (alpha isomer) and 10.60% with endosulfan (alpha and beta isomers). Both pesticides, endosulfan and HCH, found in milk samples, indicated their use in agriculture practices, although legislation in Brazil does not permit the use of HCH since 1985 and endosulfan can be used only in a few crops. These compounds should not be present in milk because there are implications on human health. Organophosphorus, carbamates, pyrethroids, herbicides, and fungicides were not detected in cows milk samples.

Effects of Ipomoea carnea aqueous fraction intake by dams during pregnancy on the physical and neurobehavioral development of rat offspring

The effects of daily prenatal exposure to 0.0, 0.7, 3.0 and 15.0 mg/kg of the aqueous extract (AQE) of Ipomoea carnea dried leaves on gestational days 5-21 were studied in rat pups and adult offspring. The physical and reflex developmental parameters, open-field, plus-maze, social interaction, forced swimming, catalepsy and stereotyped behaviors, as well as striatal, cortical and hypothalamic monoamine levels (at 140 days of age) were measured. Maternal and offspring body weights were unaffected by exposure to the different doses of the AQE. High postnatal mortality, smaller size at Day 1 of life, reversible hyperflexion of the carpal joints and delay in the opening of both ears and in negative geotaxis were observed in the offspring exposed to the higher dose of AQE. At 60 and 90 days of age, open-field locomotion frequency was quite different between 0.0 and animals treated with 0.7 and 3.0 mg/kg AQE. No changes were observed in the plus-maze, social interaction, forced swimming, catalepsy, stereotyped behavior and central nervous system monoamines concentrations. Dams treated with the higher AQE dose showed severe cytoplasmic vacuolation in liver, kidney, pancreas and thyroid tissues, in contrast to the mild vacuolation observed in the other experimental groups. No alterations were observed in the histopathological study of the offspring of all experimental groups at 140 days of age. During adulthood, behavior was not modified in offspring exposed to the higher dose of AQE as well as no changes occurred in central nervous system neurotransmitters. The present data show that the offspring development alterations were not severe enough to produce behavioral and central monoamine level changes.

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.

Possible anxiogenic effects of fenvalerate, a type II pyrethroid pesticide, in rats

Pyrethroids are insecticides extensively used to control pests around houses as well as in agriculture. It has been suggested that type II pyrethroids may act on GABA receptors as benzodiazepine antagonists. Because benzodiazepines are used in anxiety, the present study was undertaken to investigate the possible anxiogenic effects of fenvalerate, a type II pyrethroid, in rats. Behavior in the open-field, social interaction, plus-maze behavior, and one-way passive avoidance were studied in rats orally treated with 1, 10, or 30 mg/kg fenvalerate. This pyrethroid reduced locomotion and rearing frequencies and increased immobility duration. Ten and 30 mg/kg of fenvalerate reduced social interaction, whereas the 1 mg/kg dose had no effect on this behavior. Fenvalerate administration did not change the plus-maze behavior of rats. Pretraining administration (1, 10, and 30 mg/kg) did not modify the behavior of rats during the training session of a passive avoidance task, while in the test session 10 mg/kg fenvalerate caused an increase in the crossing latency, and the 30 mg/kg dose reduced this parameter and increased the percent of animals crossing to the shock compartment. The behavioral alterations observed in this study suggest that fenvalerate has an anxiolytic effect on rats.

Toxicological evaluations of long-term consumption of Solanum lycocarpum St. Hill fruits in male and female adult rats

Solanum lycocarpum St. Hill is a common plant in the Brazilian savanna. This plant contains an alkaloid with stereospecific configuration to the synthesis of steroid hormones. Because the plant may be consumed long-term, the present study was undertaken to determine the possible toxic effects of S. lycocarpum fruit ingestion (3% added to the diet) on male (60 days of administration) and female (37 days) adult rats. Few significant differences in body weight and consumption of food and water, no significant differences in male and female weight gain or estrous cycle were detected. Female treated rats showed a significant reduction in uterus and liver weights; however, no significant differences were observed in other organ (adrenal, liver, seminal vesicle, testicle and ovary) weights in either sex. Additionally blood enzymes and proteins evaluated were not affected by treatment with 3% S. lycocarpum added to the diet. The present data, however, show sex-related differences in S. lycocarpum toxicity. Thus, other studies have to be conducted to better investigate female toxicity and other toxic effects of higher levels of exposure to this plant.

The clinical, biochemical, haematological and pathological effects of long-term administration of Ipomoea carnea to growing goats.

Ipomoea carnea has been held responsible for several poisoning episodes, mainly in goats. This plant contains swainsonine, which inhibits acid or lysosomal α-mannosidase enzyme, causing cellular vacuolization. The objective of this study was to evaluate I. carnea toxicosis when four different doses of this plant were fed to growing goats. Twenty-five male goats were divided into five groups, one control group and four experimental groups that received 2.5, 5.0, 10.0 and 30.0 g of the plant per kg of live weight per day for 4 months. Blood samples were collected for haematological and biochemical determinations and fragments from some tissues were collected for histopathological study. All the experimental goats ingested the plant throughout the trial, presenting nystagmus, muscle tremors, weakness of the hind limbs and ataxia. They also had a significant increase in alanine aminotransferase (ALT) from the sixth week of the experiment compared to the goats in the control group. There was a significant reduction in haemoglobin concentration in the goats treated with I. carnea. Histopathology revealed degenerative vacuolar alterations in the liver, pancreas, thyroid and kidney cells, and in the neurons of the central nervous system in the animals that received the plant. All these alterations occurred in a dose-dependent manner.

Maternal and developmental toxicity of ayahuasca in Wistar rats

INTRODUCTION Ayahuasca is a psychotropic plant beverage initially used by shamans throughout the Amazon region during traditional religious cult. In recent years, ayahuasca has also been used in ceremonies of a number of modern syncretic religious groups, including pregnant women. However, no documented study has been performed to evaluate the risk of developmental toxicity of ayahuasca. METHODS In the present work, maternal and developmental toxicity was evaluated in Wistar rats. Ayahuasca was administered to pregnant rats in three different doses [the equivalent typical dose (TD) administered to humans, five-fold TD and 10-fold TD] during the gestational period (6-20 days). RESULTS Dams treated with the highest ayahuasca dose showed maternal toxicity with decrease of weight gain and food intake. Visceral fetal findings were observed in all treatment groups. Skeletal findings were observed in the intermediate- and high-dose groups. The fetuses deriving from the highest dose group also presented a decrease in body weight. CONCLUSIONS From these results, it is possible to conclude that there is a risk of maternal and developmental toxicity following ayahuasca exposure and that the level of toxicity appears to be dose-dependent.

Anxiolytic and anticonvulsant properties of doramectin in rats: behavioral and neurochemistric evaluations.

Doramecin is an antiparasitic drug that may interfere with gamma-aminobutyric acid (GABA) neurotransmission. Some behavioral manifestations are related with GABAergic neurotransmissions as anxiety and seizures. The objective of the present study was to examine the possible central nervous system (CNS) effects of doramectin (100, 300 and 1000 microg/kg, SC) in rats, using anxiety behavioral models, susceptibility to seizures and central neurotransmitter evaluations. The open-field results showed (i) few alterations in locomotion frequency; (ii) a biphasic effect on rearing frequency that may be the consequence of least habituation in open-field; (iii) the reduction of grooming durations might be attributed to a possible anxiolytic effect of doramectin since GABAergic agonists reduced this parameter in apparatus. Our data in the hole board showed no effects in locomotion and rearing frequencies but increased head dipping frequency of rats administered doramectin similarly to anxiolytic drugs. In plus-maze test, doramectin administration increased the number of entries and time into open arms, indicating also an anxiolytic effect. Doramectin protected animals from convulsant effects of picrotoxin, indicative of an anxiolytic pharmacological profile of a drug with GABAergic properties. The alterations observed in central dopaminergic, noradrenergic and serotoninergic neurotransmissions might be the consequence of reinforcement in central GABAergic neurotransmission induced by doramectin. The present results suggest that doramectin has the pharmacological profile of an anxiolytic/anticonvulsant drug with GABAergic properties.

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 β1,6-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.