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An increase in peripheral blood eosinophils in helminth infections is expected, and these cells are known to promote immunity against these parasites. However, studies have suggested that in some specific helminths, eosinophils may promote the needs and longevity of these parasites, and their role in these infections remains undefined, including in Toxocara canis infection. Thus, this study aimed to investigate the role of eosinophils in the context of larval migration of T. canis and the immunopathological aspects of infection. For this, we used wild-type mice and mice genetically deficient for the transcription factor GATA-binding factor 1 (GATA1−/−), infected with 1000 eggs of T. canis. At 0, 3, 14 and 63 days post-infection, parasite load, tissue cytokine production, leucocyte profile, bronchoalveolar lavage cells and histopathological analyses were carried out. Collectively, our results demonstrate that the presence of eosinophils mediates susceptibility to T. canis, inducing leucocytosis and the formation of granulomas, increasing the pulmonary and cerebral parasite load, and reducing the number of neutrophils, which may be necessary to control the infection.

Curatella americana L. is employed in popular medicine for treating diabetes. However, the understanding around its outcomes during pregnancy is unclear.To evaluate the phytochemical and hypoglycemic analysis of the C. americana extract and its maternal-fetal effect on diabetic rats.Diabetes was chemically induced 24 h after birth in Wistar female newborn rats. At adulthood, after diabetes status confirmation, the rats were mated and randomized into four experimental groups: Nondiabetic (Control): given water; Treated: given C. americana extract; Diabetic, and Treated Diabetic rats. The aqueous extract of C. americana leaves (300 mg/kg) was administered daily through oral route during pregnancy. Maternal toxicity and biochemical profile, reproductive outcomes, fetal development, and phenolic composition and biogenic amines in aqueous extract were analyzed.Phytochemical analysis revealed that the main phenolic components are 3-hydroxytyrosol, kaempferol, and quercetin, while tryptophan and putrescine derivatives were identified as the dominant amines. C. americana extract treatment improved the lipid profile, although no effect on hyperglycemic control in diabetic rats was observed. Maternal diabetes or C. americana extract caused embryo losses confirmed by the lower number of pre-embryos in early pregnancy and higher percentage of abnormal morphologically pre-embryos. C. americana extract previously caused premature pre-embryo fixation before implantation window in nondiabetic and diabetic mothers and intrauterine growth restriction in the fetuses of treated nondiabetic dams, complicating the embryo fetal development. These findings reinforce the caution of indiscriminate use of medicinal plants, especially during pregnancy.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico A toxocarose é uma zoonose, que tem como principal agente etiológico o Toxocara canis. É uma doença negligenciada, cosmopolita e que possui soroprevalência de 19% em todo o mundo. Os humanos são infectados pela ingestão acidental de ovos contendo larvas infectantes de T. canis, que, ao chegarem ao intestino, eclodem, penetram na mucosa e migram para vários tecidos, como fígado, pulmões e cérebro. De forma geral a resposta contra helmintos segue o padrão Th2, mas são poucos os estudos que esclarecem o padrão de resposta imunológica e fisiopatológica desencadeada pelo hospedeiro na toxocarose. O presente trabalho teve como objetivo avaliar os mecanismos imunológicos e fisiopatológicos envolvidos na infecção por Toxocara canis em modelo experimental murino, investigando a via IL-33/ST2, a presença de eosinófilos e a via IL-17/IL-17RA. Para isso, foram utilizados camundongos geneticamente deficientes para ST2, GATA1, IL-17RA e os respectivos selvagens (BALB/c e C57BL/6) infectados por gavagem com 1000 ovos embrionados de T. canis sendo realizada a avaliação parasitológica, imunológica e fisiopatológica com 0 dias pós-infecção (dpi) (controle), 3dpi, 14dpi e 63dpi. Os resultados demonstraram que os camundongos ST2-/- e GATA1-/- durante a infecção por T. canis reduziram a carga parasitária hepática, pulmonar e cerebral e diminuíram a formação de granulomas associado a menores danos teciduais. Por outro lado, os camundongos IL-17RA-/- apresentaram aumento na carga parasitária pulmonar, reduziram a frequência de neutrófilos produtores de IL-17 no lavado broncoalveolar e diminuíram o número de granulomas nos pulmões. Assim, observamos que as vias IL-33/ST2 e a presença de eosinófilos induzem susceptibilidade à infecção por T. canis e aumentam o número de granulomas, enquanto a via IL-17/IL-17RA está associada a resistência à migração larval, porém induzem maior formação de granulomas que podem resultar em dano tecidual. Toxocariasis is a zoonosis, whose main etiological agent is Toxocara canis. It is a neglected, cosmopolitan disease that has a 19% seroprevalence worldwide. Humans become infected by accidental ingestion of eggs containing T. canis infective larvae, which upon reaching the intestine, hatch, penetrate the mucosa and migrate to various tissues such as liver, lungs and brain. In general, the response against helminths follows the Th2 pattern, but there are few studies that clarify the pattern of immune and pathophysiological response triggered by the host in toxocarosis. This study aimed to evaluate the immunological and pathophysiological mechanisms involved in T. canis infection in a murine experimental model, investigating the IL-33/ST2, IL-17/IL-17RA pathway and the presence of eosinophils. For this purpose, mice genetically deficient for ST2, GATA1, IL-17RA and the respective wild ones (BALB/c and C57BL/6) infected by gavage with 1000 embryonated eggs of T. canis were used, and the parasitological, immunological and pathophysiological evaluation was performed with 0 days post-infection (dpi) (control), 3dpi, 14dpi and 63dpi. The results demonstrated that ST2-/- and GATA1-/- mice during T. canis infection reduced the hepatic, pulmonary and cerebral parasite load and decreased the formation of granulomas associated with less tissue damage. On the other hand, IL-17RA-/- mice showed an increase in the pulmonary parasite load, reduced the frequency of IL-17-producing neutrophils in the bronchoalveolar lavage, and decreased the number of granulomas in the lungs. Thus, we observed that the IL-33/ST2 pathways and the presence of eosinophils induce susceptibility to infection by T. canis and increase the number of granulomas, while the IL-17/IL-17RA pathway is associated with resistance to larval migration, however induce greater formation of granulomas that can result in tissue damage.

Background Ascariasis and malaria are highly prevalent parasitic diseases in tropical regions and often have overlapping endemic areas, contributing to high morbidity and mortality rates in areas with poor sanitary conditions. Several studies have previously aimed to correlate the effects of Ascaris-Plasmodium coinfections but have obtained contradictory and inconclusive results. Therefore, the present study aimed to investigate parasitological and immunopathological aspects of the lung during murine experimental concomitant coinfection by Plasmodium berghei and Ascaris suum during larvae ascariasis. Methods C57BL/6J mice were inoculated with 1 × 104P. berghei strain NK65-NY-infected red blood cells (iRBCs) intraperitoneally and/or 2500 embryonated eggs of A. suum by oral gavage. P. berghei parasitaemia, morbidity and the survival rate were assessed. On the seventh day postinfection (dpi), A. suum lung burden analysis; bronchoalveolar lavage (BAL); histopathology; NAG, MPO and EPO activity measurements; haematological analysis; and respiratory mechanics analysis were performed. The concentrations of interleukin (IL)-1β, IL-12/IL-23p40, IL-6, IL-4, IL-33, IL-13, IL-5, IL-10, IL-17A, IFN-γ, TNF and TGF-β were assayed by sandwich ELISA. Results Animals coinfected with P. berghei and A. suum show decreased production of type 1, 2, and 17 and regulatory cytokines; low leukocyte recruitment in the tissue; increased cellularity in the circulation; and low levels of NAG, MPO and EPO activity that lead to an increase in larvae migration, as shown by the decrease in larvae recovered in the lung parenchyma and increase in larvae recovered in the airway. This situation leads to severe airway haemorrhage and, consequently, an impairment respiratory function that leads to high morbidity and early mortality. Conclusions This study demonstrates that the Ascaris-Plasmodium interaction is harmful to the host and suggests that this coinfection may potentiate Ascaris-associated pathology by dampening the Ascaris-specific immune response, resulting in the early death of affected animals.

Toxocariasis is a neglected disease that affects people around the world. Humans become infected by accidental ingestion of eggs containing Toxocara canis infective larvae, which upon reaching the intestine, hatch, penetrate the mucosa and migrate to various tissues such as liver, lungs and brain. Studies have indicated that Th2 response is the main immune defense mechanism against toxocariasis, however, there are still few studies related to this response, mainly the IL-33/ST2 pathway. Some studies have reported an increase in IL-33 during helminth infections, including T. canis. By binding to its ST2 receptor, IL-33 stimulating the Th2 polarized immune cell and cytokine responses. Thus, we aimed to investigate the role of the IL-33/ST2 pathway in the context of T. canis larval migration and the immunological and pathophysiological aspects of the infection in the liver, lungs and brain from Wild-Type (WT) BALB/c background and genetically deficient mice for the ST2 receptor (ST2-/-). The most important findings revealed that the IL-33/ST2 pathway is involved in eosinophilia, hepatic and cerebral parasitic burden, and induces the formation of granulomas related to tissue damage and pulmonary dysfunction. However, ST2-/- mice, the immune response was skewed to Th1/Th17 type than Th2, that enhanced the control of parasite burden related to IgG2a levels, tissue macrophages infiltration and reduced lung dysfunction. Collectively, our results demonstrate that the Th2 immune response triggered by IL-33/ST2 pathway mediates susceptibility to T. canis, related to parasitic burden, eosinophilia and granuloma formation in which consequently contributes to tissue inflammation and injury., Author summary Toxocariasis is a neglected disease caused by Toxocara canis, which has 19% worldwide seroprevalence, and is associated with socioeconomic, geographic and environmental factors. Humans become infected by accidental ingestion of T. canis eggs present in contaminated food, water or soil. After ingestion, the larvae hatch in the intestine and can reach various tissues such as liver, lung and brain. Helminth infections usually trigger a Th2 immune response in the host, by releasing cytokines such as IL-4, IL-5, IL-13 and IL-33. IL-33 is an alarmin that binds to the ST2 receptor, and some studies have observed an increase in this cytokine in toxocariasis, however there are no studies regarding the IL-33/ST2 role in this infection. Thus, we evaluated the influence of this pathway by analyzing immunological and pathophysiological aspects in T. canis-infected mice. Our results demonstrated that the IL-33/ST2 pathway is related to parasite burden on the liver and brain and also increases the number of eosinophils in the blood and tissues. In addition, it involved with the pulmonary immune response and granulomas with impact in lung function. In conclusion, the IL-33/ST2 pathway governs the host susceptibility to T. canis in mice.

Made available in DSpace on 2020-12-12T02:10:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-04-17 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Background: Hancornia speciosa is usually used in Brazilian folk medicine to treat diabetes. The hypothesis of the present study is that this medicinal plant exerts beneficial effects on hyperglycemia, preventing diabetic complications. Therefore, the aim of this study was to evaluate the treatment effect of the aqueous extract of H. speciosa leaves on metabolic parameters of diabetic rats. Methods: The H. speciosa extract (400 mg/Kg) was administered to both nondiabetic and severely diabetic female Wistar rats by gavage. The Oral Glucose Tolerance Test was performed and the area under the curve (AUC) was estimated on day 17 of pregnancy. After 21 days of treatment, the animals were anesthetized and killed to obtain organ weights. Blood samples were collected for an analysis of serum biochemical parameters. Results: After treatment with the H. speciosa extract, the parameters of nondiabetic rats remained unchanged. In treated diabetic rats, glycemia, AUC, dyslipidemia parameters, and relative organ weights were decreased compared with nontreated diabetic rats. Severely diabetic rats showed decompensated hyperglycemia, polydipsia, hyperphagia and dyslipidemia. However, the aqueous extract of H. speciosa leaves decreased diabetes complications (indicating a lack of toxicity), reduced blood glucose levels, and exerced lipid-lowering effects. Conclusion: Based on or findings, the H. speciosa leaf extract may be a safe and promising candidate treatment for diabetes and other diseases. Laboratory of System Physiology and Reproductive Toxicology Institute of Biological and Health Sciences Federal University of Mato Grosso (UFMT), Av. Valdon Varjão 6390 Laboratory of Experimental Research on Gynecology and Obstetrics Botucatu Medical School Univ Estadual Paulista_Unesp, Distrito de Rubião Júnior s/n Laboratory of Experimental Research on Gynecology and Obstetrics Botucatu Medical School Univ Estadual Paulista_Unesp, Distrito de Rubião Júnior s/n

Diabetes mellitus is a syndrome of great importance that affects an increasing number of people every day. In particular, diabetes is a common and important disease during pregnancy and is marked by complications, both fetal and maternal, that increase the risks of morbidity and mortality for diabetic pregnant women and their offspring. Drugs such as insulin and hypoglycemic drugs are given to treat diabetes, but regular exercise and adequate diet have also been indicated. Furthermore, coadjutant therapies such as medicinal plants are popularly used to reduce diabetes-induced hyperglycemia, either within or outside the context of pregnancy. However, studies examining plant use for diabetes treatment are necessary to confirm its possible effects and its safety for the mother and fetus. The objective of this literature review was to conduct a survey of plant species that are utilized worldwide and their stated therapeutic uses. A literature search was performed using the terms “diabetes and pregnancy”, which resulted in the identification of 31,272 articles. Of these studies, only 12 (0.0038%) were related to medicinal plants, demonstrating that there has been little investigation into this issue. Of the papers analyzed in this review, half evaluated plant leaves, indicating that these scientific studies attempted to reproduce the preparations commonly used by various populations, i.e., in the form of tea. Additionally, more than 90% of studies utilized experimental animals to evaluate the maternal-fetal safety of medicinal plant substances that may potentially be dangerous for humans. Thus, once confidence levels for plant-derived substances are established based on toxicological analyses and safety is confirmed, it is possible that plants will be used to complement conventional diabetes therapies.

s / Placenta 36 (2015) 469e521 513 Methods: Diabetes was induced by streptozotocin (40 mg/kg) in virgin female Wistar rats. After diabetes induction, rats were mated. Hancornia speciosa leaf aqueous extract (600 mg/kg) was administered from day 0 to 20 of pregnancy. On day 21 of pregnancy, all rats were anesthetized and killed. The uteri were removed to obtain maternal-fetal data. Results: Treatment with aqueous extract of H. speciosa showed no hypoglycemic effect in non-diabetic and diabetic animals (p>0.05). However, the plant treatment decreased fetal weight (4.9±0.6 vs control-5.1±0.5) and increased the preimplantation loss rate (23.1% vs control-3.9%) and skeletal anomalies (70.0% vs control-50.0%) in non-diabetic dams. The diabetic group presented a decrease in the number of live fetuses, maternal weight gain, gravid uterus weight and fetal weight, and an increase in the preand post-implantation loss rate, placental weight and index, and visceral and skeletal anomalies. The plant treatment did not alter any parameter in the diabetic group compared to the non-treated diabetic group (p>0.05). Conclusion: The aqueous extract from Hancornia speciosa leaves did not modify the maternal hyperglycemia and fetal anomalies. Therefore, the plant altered the reproductive outcome and was teratogenic in non-diabetic rats, demonstrating the importance of care in the use of substances during pregnancy. PB.23. REPRODUCTIVE AND FETAL REPERCUSSIONS OF TREATMENT WITH AN AQUEOUS EXTRACT OF FLOWERS OF HIBISCUS ROSA SINENSIS IN DIABETIC PREGNANT RATS G.T. Volpato , L.A.F. Afiune , T. Leal-Silva , K.E. Campos , D.C. Damasceno . 1 Institute of Biological and Health Sciences, Federal University of Mato Grosso, Brazil; 2 Laboratory of Experimental Research on Gynecology and Obstetrics, Botucatu Medical School, UNESP, Brazil Hibiscus rosa sinensis, commonly known as rose mallow, is widely used in Brazilian folk medicine for the diabetes treatment. Objective: To evaluate the effect of Hibiscus rosa sinensis aqueous extract treatment on the reproductive outcomes and fetal anomaly incidence in diabetic and non-diabetic rats. Methods: Diabetes was induced by Streptozotocin (40 mg/kg) in virgin female Wistar rats. After diabetes induction, the rats were mated. Oral administration of an aqueous extract of Hibiscus rosa sinensis flowers was given to non-diabetic and diabetic pregnant rats at increasing doses: 100 mg/kg from day 0 to 7 of pregnancy, 200 mg/kg from day 8 to 14 and 400 mg/kg from day 15 to 20. On day 21 of pregnancy, all rats were anesthetized and killed. The uteri were removed to obtain maternal-fetal data. Results: Treatment with aqueous extract of H. rosa sinensis showed no hypoglycemic effect and did not alter the rate of congenital anomalies in non-diabetic and diabetic animals (p>0.05). The diabetic group presented a decrease in the number of live fetuses (9.2±2.7 vs 12.0±1.6-control), maternal weight gain (69.3±21.9 vs 116.7±12.7-control), gravid uterus weight (52.4±24.8 vs 75.9±9.1-control) and fetal weight, and an increase in the pre(21.3% vs 4.0%-control) and post-implantation (18% vs 7.6%control) loss rate, placental weight and index, and visceral and skeletal anomalies. The plant treatment decreased the pre(6.3%) and post-implantation (12.8%) loss rate, improved the gravid uterus weight (69.0±20.8) and maternal weight gain (96.8±43.5). Conclusion: Although we could not confirm its antidiabetic effect, the intervention with the Hibiscus rosa sinensis aqueous extract treatment did not present teratogenic effects and contributed to the improvement in reproductive performance in the diabetic rats. PB.24. REPRODUCTIVE OUTCOME AND BIOCHEMICAL PROFILE OF TREATMENT WITH CROTON URUCURANA LATEX IN PREGNANT RATS G.T. Volpato , T.S. Soares , R.Q. Moares-Souza , N.C. Orleanne , K.E. Campos , D.C. Damasceno . 1 Institute of Biological and Health Sciences, Federal University of Mato Grosso, Brazil; 2 Laboratory of Experimental Research on Gynecology and Obstetrics, Botucatu Medical School, UNESP, Brazil Croton urucurana, commonly known as dragon blood, is widely known in Brazilian folk medicine to have an abortifacient effect. Objective: To evaluate the effect of Croton urucurana latex treatment in pregnant rats on maternal reproductive outcome and biochemical profile. Methods: Virgin female Wistar rats were used and mated. Pregnant rats were randomized into four groups (minimum n1⁄4 12 animals/group): G11⁄4 control, G2 to G41⁄4 treatedwith Croton urucurana latex at doses of 200, 400 and 800mg/kg, respectively. Rats were orally treated by gavage, with plant latex or vehicle during all the gestational period. On gestational day 21, the rats were anesthetized and the blood collected for serum biochemical measurements. The gravid uteri were removed to obtain maternal data. Results: Treatment with the highest dose of C. urucurana showed an increase in protein (5.5±1.5 g/dL), cholesterol (144.0±58.8 mg/dL), alanine aminotransferase (ALT 81.5±20.7 U/L) and aspartate aminotransferase (AST 400.6±90.9 U/L) compared to the other groups (p 0.05). The post-implantation loss increased in the vaccinated group (14.7%), compared to the control (5.0%) and adjuvant (4.4%) groups. The gravid uterus weight was different in the adjuvant group (97.5±17.6 g) compared to the control (71.7 ± 20.2 g) and vaccinated (82.8 ± 17.3 g) groups. Other reproductive outcome parameters presented no alterations. Conclusion: Immunization was confirmed by increased IgG immunoglobulin, which assures the vaccination process, but the protein presented abortive effect. Thus, this vaccine requires carefulness in its use during pregnancy period. PB.26. EXPRESSION OF IGG AND ITS FC GAMMA RECEPTOR IN SWINE PLACENTAL TISSUES IN DIFFERENT GESATIONAL PERIODS Ad.C. Garro , M.G. Garcia , M.A. Koncurat . Biologia General, Facultad de Ciencias Veterinarias, Argentina; Histologia 1 y 2, Facultad de Ciencias Veterinarias, Universidad Nacional de La Pampa, General Pico, La Pampa