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Deoxynivalenol, T-2 toxin, and zearalenone, major Fusarium mycotoxins, contaminate human food on a global level. Exposure to these mycotoxins during pregnancy can lead to abnormalities in neonatal development. Therefore, the aim of this study was to investigate the effects of Fusarium mycotoxins on human placental epithelial cells. As an in vitro model of placental barrier, BeWo cells were exposed to different concentrations of deoxynivalenol, zearalenone or T-2 toxin. Cytotoxicity, effects on barrier integrity, paracellular permeability along with mRNA and protein expression and localization of junctional proteins after exposure were evaluated. Induction of proinflammatory responses was determined by measuring cytokine production. Increasing mycotoxin concentrations affect BeWo cell viability, and T-2 toxin was more toxic compared to other mycotoxins. Deoxynivalenol and T-2 toxin caused significant barrier disruption, altered protein and mRNA expression of junctional proteins, and induced irregular cellular distribution. Although the effects of zearalenone on barrier integrity were less prominent, all tested mycotoxins were able to induce inflammation as measured by IL-6 release. Overall, Fusarium mycotoxins disrupt the barrier of BeWo cells by altering the expression and structure of junctional proteins and trigger proinflammatory responses. These changes in placental barrier may disturb the maternal–fetal interaction and adversely affect fetal development.

IntroductionCoronary artery diseases are the leading cause of wide range of clinical syndromes. Myocardial ischemia is a result of imbalance between coronary blood supply and myocardial demand. The myocardial infarction is the common presentation of ischemic heart disease and occurs when the myocardial ischemia surpasses the critical point for extended time.1 The hypoxia during the ischemia results in various negative alterations in myocardium including the release of proteolytic enzymes, respiratory chain damage, and reduction in the endogenous antioxidant capacity. 2 The main treatment of acute myocardial infarction is known to be the reperfusion of un-perfused area, which in fact leads to several undesirable sequels such as myocyte death, dysrhythmia, myocardial stunning, endothelial and microvascular dysfunction.3 During the reperfusion, restoration of oxygenated blood flow to the ischemic area lead to sudden massive increase in oxygen concentration causing an imbalance between oxidant and anti-oxidative processes.2 Thus, resultant excess production of reactive oxygen species (ROS) initiates lipid peroxidation in the cell membrane and A B S T R A C TBackground: Rosmarinic acid is a polyphenolic compound with considerable antioxidant activities. We aimed to investigate its cardioprotective effects against isoproterenol-induced myocardial infarction (MI) in rats. Methods: Male Wistar rats were assigned to 5 groups of control, isoproterenol, and treatments with 10, 20, 40 mg/kg of rosmarinic acid. Myocardial infarction was induced by subcutaneous injection of isoproterenol (100 mg/kg) once daily for 2 days. Rosmarinic acid was injected intraperitoneally once daily for 4 days, from the day of isoproterenol injection. In the fifth day the animals were anesthetized and hemodynamic and electrocardiographic parameters were recorded. After collecting the blood samples, the hearts were removed, weighed immediately to measure the cardiac enlargement, and kept for further histological studies. Lactate dehydrogenase and malondialdehyde were measured in the heart tissues for evaluating the damages and lipid peroxidation, respectively. Results: Rosmarinic acid revealed a considerable antioxidant activity in vitro, with IC50 of 6.43µg/ml. Isoproterenol induced cardiac arrhythmias, myocardial damage and cardiac enlargement. Rosmarinic acid significantly reduced peripheral neutrophil percentage and inhibited isoproterenol-induced ST-segment elevation and R-amplitude depression in the infarcted hearts. It also significantly increased the mean arterial pressure and heart rate and decreased the left ventricular end diastolic pressure. The ventricular contractility was considerably improved by rosmarinic acid. Histopathological evaluations showed that rosmarinic acid significantly diminished the post-MI necrosis and fibrosis in the myocardium and inhibited the cardiac edematous. Conclusion: It is deducible from the results that rosmarinic acid improves the cardiac performance and inhibits post-MI myocardial depression, probably ...

Deoxynivalenol (DON), a highly prevalent contaminant of grain-based products, is known to induce reproductive- and immunotoxicities. Considering the importance of immune development in early life, the present study investigated the effects of perinatal DON exposure on allergy development and vaccine responsiveness in the offspring. Pregnant mice received control or DON-contaminated diets (12.5 mg/kg diet) during pregnancy and lactation. After weaning, female offspring were sensitized to ovalbumin (OVA) by oral administration of OVA with cholera toxin (CT). Male offspring were injected with Influvac vaccine. OVA-specific acute allergic skin response (ASR) in females and vaccine-specific delayed-type hypersensitivity (DTH) in males were measured upon intradermal antigen challenge. Immune cell populations in spleen and antigen-specific plasma immunoglobulins were analyzed. In female CT+OVA-sensitized offspring of DON-exposed mothers ASR and OVA-specific plasma immunoglobulins were significantly higher, compared to the female offspring of control mothers. In vaccinated male offspring of DON-exposed mothers DTH and vaccine-specific antibody levels were significantly lower, compared to the male offspring of control mothers. In both models a significant reduction in regulatory T cells, Tbet+ Th1 cells and Th1-related cytokine production of the offspring of DON-exposed mothers was observed. In conclusion, early life dietary exposure to DON can adversely influence immune development in the offspring. Consequently, the immune system of the offspring may be skewed towards an imbalanced state, resulting in an increased allergic immune response to food allergens and a decreased immune response to vaccination against influenza virus in these models.