Sodium Salicylate as Feed Additive in Broilers: Absence of Toxicopathological Findings.

Antimicrobial growth promoters (AGPs) in animal production have been related to the increase in multidrug-resistant bacteria. The AGP ban in many countries has highlighted the growing need for alternatives for feed additives. Considering the non-antibiotic anti-inflammatory theory of AGPs, chicks received three different doses of sodium salicylate (SS) in feed (10, 30, 90 mg/kg), basal diet (BD) was used as a negative control, and zinc bacitracin (ZB) was used as a positive control. Chicks were individually housed to increase the accuracy of the dose of SS ingested. Performance parameters and footpad dermatitis were evaluated weekly, while haematology, serum biochemistry, histopathology, and tibial dyschondroplasia were determined on Days 21 and 42. A linear dose-dependent decrease in haemoglobin concentration was observed, but the values were within the normal reference range. Among all the other evaluated parameters, no relevant differences between treatments were observed; however, not even the AGP group performed better than the control group. It is possible that the conditions in which the birds were raised were not stressful enough to allow for anti-inflammatories to demonstrate their beneficial effects on performance. Studies should be conducted where the animals are exposed to commercial conditions, as the presence of natural stressors could allow a better evaluation of the efficacy of the anti-inflammatory agent as a growth promoter.

Potential immunomodulatory response associated with L-mimosine in male Wistar rats.

Leucaena leucocephala is a plant that is used as animal and human food worldwide. This plant contains the toxic compound namely L-mimosine. The main mechanism of action of this compound involves its ability to chelate metal ions, which may interfere with the proliferative activity of cells and being studied for the treatment of cancer. However, little is known about the effect of L-mimosine on immune responses. Thus, the aim of this study was to evaluate the effects of L-mimosine on immune responses in Wistar rats. Different doses of L-mimosine (25, 40 and 60 mg/kg body weight/day) were administered orally by gavage to adult rats for 28 days. No clinical signs of toxicity were observed in animals, but a decrease in the T-dependent response to sheep red blood cells (SRBC) in animals treated with 60 mg/kg L-mimosine and an increase in the intensity of S. aureus phagocytosis by macrophages in animals treated with 40 or 60 mg/kg L-mimosine were observed. Therefore, these findings suggest that L-mimosine did not compromise macrophage activity and inhibited T-dependent clonal expansion during the immune response.

Potential toxic effects produced by L-mimosine in the thyroid and reproductive systems. Evaluation in male rats.

Leucaena leucocephala is a worldwide plant used as forage; however, its use in animal production has been limited because of the presence of a toxic nonprotein amino acid, L-mimosine. L-mimosine exhibits negative effects not only in ruminants but also in monogastric animals; however, there is little information available on the effect of this amino acid in monogastric species. Thus, this study aimed to evaluate the general toxicity of L-mimosine in rats, as well as its effects on the endocrine and reproductive systems. L-mimosine was extracted from seeds of L. leucocephala that were administered orally by gavage to adult Wistar rats at different doses of 25, 40 and 60 mg/kg body weight/day for 28 days. The following parameters were evaluated: weight gain, feed intake, serum enzymes, histopathology (liver, kidney, thyroid, thymus, and spleen), serum hormones (testosterone, corticosterone, T3 and T4) and sexual behavior. No clinical signs of toxicity were observed in animals, but histopathology revealed consistent lesions in the thyroids. Additionally, rats exposed to L-mimosine presented low serum levels of testosterone, decreased mount numbers and increased mount intervals. Therefore, our study reinforces the assumption that L-mimosine has goitrogenic potential and causes impairment in male reproductive performance.

The effect of Ipomoea carnea on maternal reproductive outcomes and fetal and postnatal development in rats.

Ipomoea carnea is a toxic plant found in Brazil and other tropical countries. The plant contains the alkaloids calystegines and swainsonine, which inhibit key cellular enzymes and cause systematic cell death. It is known that swainsonine is excreted in the amniotic fluid of dams exposed to the plant. Thus, the aim of this study was to verify whether the toxic effect of I. carnea on fetuses is due to exclusively the passage of the active principle of the plant through the placenta, or if the placentotoxic effect of swainsonine could collaborate in the adverse effects observed in the fetus. The teratogenic effects of exposure to the toxic principles of I. carnea were evaluated not only using the conventional protocol but also at later stages in the postnatal developmental period. Females were treated, from gestation day (GD) 6 until GD19, with 0.0, 1.0, 3.0 or 7.0 g/kg body weight of I. carnea dry leaves. The plant did not induce changes in reproductive performance or biochemical profile of the dams. Dams that received the highest dose of I. carnea showed cytoplasmic vacuolization in the liver, kidney and placental tissue. I. carnea promoted different lectin binding patterns in different areas of placental tissue. No fetal skeletal or visceral malformations was observed. The postnatal evaluation revealed a lower litter weight and a lower pup body weight one day after birth in the group that received the highest dose of I. carnea. Physical milestones were unaffected by the treatments. Female pups from all experimental groups exhibited a delay in achieving a negative geotaxis response. The results show that the toxic principle of I. carnea produces injury in utero in mothers and fetuses, but these deleterious effects were better demonstrated using postnatal evaluation.

The effect of breed, sex, and drug concentration on the pharmacokinetic profile of ivermectin in cattle.

Ivermectin (IVM) is one of the most widely used antiparasitic drugs worldwide and has become the drug of choice for anthelmintic and tick treatment in beef cattle production. It is known that pharmacokinetic parameters are fundamental to the rational use of a drug and food safety and these parameters are influenced by different factors. The aim of this study was to evaluate the pharmacokinetic profile of IVM in Bos indicus, Bos taurus, and crossbreed cattle (B. indicus × B. taurus) kept under same field conditions and the possible impacts of sex and IVM formulation (1% and 3.15%). It was observed that IVM concentration was significantly affected by breed. The plasma concentrations of IVM, AUC, Cmax , and t1/2ß were significantly higher in B. indicus compared to B. taurus. Crossbreed animals showed an intermediate profile between European and Indian cattle. No alteration in pharmacokinetics parameters was detected when comparing different gender. Concerning the pharmacokinetic data of IVM formulation, it was verified that Tmax , AUC, and t1/2ß were higher in 3.15% IVM animals than those from 1% IVM formulation. The results clearly indicated that the IVM plasma concentrations in B. indicus were higher than that in B. taurus.

The effect of Cynara scolymus (artichoke) on maternal reproductive outcomes and fetal development in rats.

Cynara scolymus (C.scolymus) is a plant employed worldwide as an herbal medicine. However, there is a paucity of data related to the evaluation of its toxicity in commercial preparations; thus, the aim of this study was to evaluate the possible teratogenic effect of the dry extract of C.scolymus leaves in Wistar rats. Females were treated, from gestation day (GD) 6 until GD19, with 0.0, 1.0, 2.0 or 4.0 g/kg body weight of C.scolymus extract. At GD20, a cesarean section was performed for evaluation of maternal and fetal parameters. C.scolymus did not induce changes in food consumption, preimplantation or postimplantation losses, placental weight or biochemical profile. An increase in water consumption was observed in pregnant females treated with the higher doses of C.scolymus. Experimental groups showed lower body weight gain during pregnancy and lower gravid uterus weight. Maternal body weight minus the gravid uterus weight did not result in significant differences. Reductions in fetal weight and length were observed in experimental groups. The number of live pups per litter was lower in the highest dose group. No fetal skeletal or visceral malformations were detected. The results showed that the consumption of artichoke during pregnancy clearly has a negative impact on fetuses.

Immunomodulatory effect of Cynara scolymus (artichoke) in rats.

Cynara scolymus is a plant used both as food as well as medicinal plant worldwide. Cynarin is one of the main active principles of the plant, and it is also present in species such as Echinacea purpurae, which is known to have immunomodulatory activity. Thus, the objective of this study is to evaluate the immune effects of C. scolymus in rats. Rats were treated with 1.0-, 2.0-, or 4.0-g/kg body weight of C. scolymus extract for 28 days. Haemogram, serum biochemistry, lymphoid organs weight, and their cell phenotypes were evaluated. Macrophages and neutrophils oxidative burst, specific humoral immune response, and the delayed-type hypersensitivity (DTH) were studied. No changes in the haemogram, biochemical profile, antibody titers, lymphoid organs, and in their cellularities were observed. An increase in the basal activity of reactive oxygen species from male's macrophage was observed. There was a suppression of the DTH response in both gender when treated with the highest dose of C. scolymus. This study is the first in the literature that revealed an immunosuppressive effect of C. scolymus. We also verified that the doses of artichoke extract here employed did not cause general toxicity.

Flow Cytometry to Evaluate Potential Developmental Toxicants in the Embryonic Stem Cell.

Embryonic stem cells (ESC) are widely used due to their unlimited capacity of differentiation into different cell lineages, which makes ESC a viable choice as a toxicology test model. Toxicological analysis using embryonic stem cells (ESC) has become an important tool in toxicology procedures. Regarding toxicological analysis methods, flow cytometry (FC) is one technique designed to detect and evaluate cells in suspension, for example, ESC suspension, thus making possible to study different biological, physical, and/or chemical characteristics of cells. Thus, FC can be very useful for cell toxicology and tumorigenic analyses.

Mimosine and cyclophosphamide: a potential new combination therapy used to prevent tumor development

The effects of mimosine (MI), which is an amino acid that is derived from Leucaena leucocephala, were evaluated on the growth of ascitic Ehrlich tumors, and the effects of the combination treatment of MI and cyclophosphamide (CY) on tumor growth were also assessed. Mice were divided into groups that received the following treatments over the course of 20 days: phosphate buffer solution (CO), MI, Ehrlich cells (E), E plus CY (EC), E plus MI (EM) and E plus MI and CY (EMC). No signs of toxicity were detected in the mice from the MI group. The mice from the EMC group showed reductions in body weights when compared with those from the E group. The animals from the EC, EM and EMC groups showed reductions in ascitic volume compared with those from the E group. The mice from the EMC group showed reductions in total cell numbers of ascitic fluid compared with those from the E, EC and EM groups. The combination of MI and CY was the most effective treatment for Ehrlich tumor ascites.