Isis M. Hueza

Zearalenone, an Estrogenic Mycotoxin, Is an Immunotoxic Compound

The aim of this study was to assess the toxic effects of zearalenone (ZEA) on the immune function. Ovariectomised rats were treated daily by gavage with 3.0 mg/kg of ZEA for 28 days. Body weight gain, food consumption, haemotological parameters, lymphoid organs, and their cellularities were evaluated. Moreover, acquired immune responses and macrophage activity were also assessed. ZEA promoted reduction in body weight gain, which is not fully explained by diminished food consumption. Despite no effect on haematological parameters, ZEA caused thymic atrophy with histological and thymocyte phenotype changes and decrease in the B cell percentage in the spleen. With respect to acquired and innate immune responses, no statistically significant differences in delayed-type hypersensitivity were noticed; however, in the ZEA-treated rats, antibody production and peroxide release by macrophages were impaired. The observed results could be related to ZEA activity on ERs; thus, ZEA is an immunotoxic compound similar to estrogen and some endocrine disruptors.

Immunomodulatory effects of Pteridium aquilinum on natural killer cell activity and select aspects of the cellular immune response of mice

Pteridium aquilinum (bracken fern) is one of the most common plants. Epidemiological studies have revealed a higher risk of certain types of cancers (i.e., esophageal, gastric) in people who consume bracken fern directly (as crosiers or rhizomes) or indirectly through the consumption of milk from livestock that fed on the plant. In animals, evidence exists regarding the associations between chronic bracken fern intoxication, papilloma virus infection, and the development of carcinomas. While it is possible that some carcinogens in bracken fern could be responsible for these cancers in both humans and animals, it is equally plausible that the observed increases in cancers could be related to induction of an overall immunosuppression by the plant/its various constituents. Under the latter scenario, normal tumor surveillance responses against nascent (non-bracken-induced) cancers or responses against viral infections (specifically those linked to induction of cancers) might be adversely impacted by continuous dietary exposure to this plant. Therefore, the overall objective of this study was to evaluate the immunomodulatory effects of bracken fern following daily ingestion of its extract by a murine host over a period of 14 (or up to 30) days. In C57BL/6 mice administered (by gavage) the extract, histological analyses revealed a significant reduction in splenic white pulp area. Among a variety of immune response parameters/functions assessed in these hosts and isolated cells, both delayed-type hypersensitivity (DTH) analysis and evaluation of IFNγ production by NK cells during TH1 priming were also reduced. Lastly, the innate response in these hosts—assessed by analysis of NK cell cytotoxic functionality—was also diminished. The results here clearly showed the immunosuppressive effects of P. aquilinum and that many of the functions that were modulated could contribute to the increased risk of cancer formation in exposed hosts.

Evaluation of immunomodulatory activity of Ipomoea carnea on peritoneal cells of rats.

In the present study, animals of the experimental groups were treated with an aqueous fraction (AF) of Ipomoea carnea diluted in drinking water in order to obtain daily doses of 3gdryleaves/kg/body weight (bw) and 15g/kg/bw for 14 and 21 days, or by gavage 15g/kg/bw administered for 14 days, respectively. Peritoneal macrophages were collected and submitted to the spreading, phagocytosis, and hydrogen peroxide release tests. AF administration in drinking water for 14 and 21 days promoted increased macrophage phagocytosis activity and hydrogen peroxide release. However, the administration of 15g/kg/bw of AF by gavage for 14 days resulted in no alteration in macrophage activity. These results suggest that low dosages of Ipomoea carnea induced enhanced phagocytosis activity and hydrogen peroxide production by macrophages.

Identificação de princípios ativos presentes na Ipomoea carnea brasileira

In the Convolvulaceae family, the Ipomoeas species are cultivated and found in all regions of the world because of their ornamental bright coloured flowers. It is well known that some Ipomoeas species are toxic. Ipomoea carnea, species of this study, causes depression, general weakness, loss of body weight, stagering gait and death of animals after prolonged periods of plant intake. These toxic effects are attributed to the alkaloids swainsonine and calystegines present in the plant, wich promotes inhibition of galactosidases and manosidases, important enzymes for an adequate metabolism of carbohydrates in the organism. The objective of the present study was to detect and characterize the chemical components of the Brazillian plant. For that, thin layer chromatography, high pressure liquid chromatography coupled to mass spectrometry detector and nuclear ressonance of protons and carbon were used. The aqueous extract of I. carnea presented 0.09% swainsonine, 0.11% calystegine B2, 0.14% of calystegine B1 , 0.06% calystegine C1 and the no proteic imino acid N-methyl-trans-4-hydroxy-L-proline.

A new exposure model to evaluate smoked illicit drugs in rodents: A study of crack cocaine.

The use of smoked illicit drugs has spread dramatically, but few studies use proper devices to expose animals to inhalational abused drugs despite the availability of numerous smoking devices that mimic tobacco exposure in rodents. Therefore, the present study developed an inexpensive device to easily expose laboratory animals to smoked drugs. We used crack cocaine as the drug of abuse, and the cocaine plasma levels and the behaviors of animals intoxicated with the crack cocaine were evaluated to prove inhaled drug absorption and systemic activity. We developed an acrylic device with two chambers that were interconnected and separated by a hatch. Three doses of crack (100, 250, or 500 mg), which contained 63.7% cocaine, were burned in a pipe, and the rats were exposed to the smoke for 5 or 10 min (n=5/amount/period). Exposure to the 250-mg dose for 10 min achieved cocaine plasma levels that were similar to those of users (170 ng/mL). Behavioral evaluations were also performed to validate the methodology. Rats (n=10/group) for these evaluations were exposed to 250 mg of crack cocaine or air for 10 min, twice daily, for 28 consecutive days. Open-field evaluations were performed at three different periods throughout the experimental design. Exposed animals exhibited transient anorexia, increased motor activity, and shorter stays in central areas of the open field, which suggests reduced anxiety. Therefore, the developed model effectively exposed animals to crack cocaine, and this model may be useful for the investigation of other inhalational abused drugs.

Low doses of monocrotaline in rats cause diminished bone marrow cellularity and compromised nitric oxide production by peritoneal macrophages

Monocrotaline (MCT) is a pyrrolizidine alkaloid found in a variety of plants. The main symptoms of MCT toxicosis in livestock are related to hepato- and nephrotoxicity; in rodents and humans, the induction of a pulmonary hypertensive state that progresses to cor pulmonale has received much attention. Although studies have shown that MCT can cause effects on cellular functions that would be critical to those of lymphocytes/macrophages during a normal immune response, no immunotoxicological study on MCT have yet to ever be performed. Thus, the aim of the present study was to evaluate the effect of MCT on different branches of the immune system using the rat – which is known to be sensitive to the effects of MCT - as the model. Rats were treated once a day by gavage with 0.0, 0.3, 1.0, 3.0, or 5.0 mg MCT/kg for 14 days, and then any effects of the alkaloid on lymphoid organs, acquired immune responses, and macrophage activity were evaluated. No alterations in the relative weight of lymphoid organs were observed; however, diminished bone marrow cellularity in rats treated with the alkaloid was observed. MCT did not affect humoral or cellular immune responses. When macrophages were evaluated, treatments with MCT caused no significant alterations in phagocytic function or in hydrogen peroxide (H2O2) production; however, the MCT did cause compromised nitric oxide (NO) release by these cells.

Intoxication by Cyanide in Pregnant Sows: Prenatal and Postnatal Evaluation

Cyanide is a ubiquitous chemical in the environment and has been associated with many intoxication episodes; however, little is known about its potentially toxic effects on development. The aim of this study was to evaluate the effects of maternal exposure to potassium cyanide (KCN) during pregnancy on both sows and their offspring. Twenty-four pregnant sows were allocated into four groups that orally received different doses of KCN (0.0, 2.0, 4.0, and 6.0 mg/kg of body weight) from day 21 of pregnancy to term. The KCN-treated sows showed histological lesions in the CNS, thyroid follicle enlargement, thyroid epithelial thickening, colloid reabsorption changes, and vacuolar degeneration of the renal tubular epithelium. Sows treated with 4.0 mg/kg KCN showed an increase in the number of dead piglets at birth. Weaned piglets from all KCN-treated groups showed histological lesions in the thyroid glands with features similar to those found in their mothers. The exposure of pregnant sows to cyanide thus caused toxic effects in both mothers and piglets. We suggest that swine can serve as a useful animal model to assess the neurological, goitrogenic, and reproductive effects of cyanide toxicosis.