Cerium oxide (CeO2) nanoparticles have been posited to exhibit potent anti-oxidant activity which may allow for the use of these materials in biomedical applications. Herein, we investigate whether CeO2 nanoparticle administration can diminish right ventricular (RV) hypertrophy following four weeks of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male Sprague Dawley rats were randomly divided into three groups: control, MCT only (60 mg/kg), or MCT + CeO2 nanoparticle treatment (60 mg/kg; 0.1 mg/kg). Compared to the control group, the RV weight to body weight ratio was 45% and 22% higher in the MCT and MCT + CeO2 groups, respectively (p < 0.05). Doppler echocardiography demonstrated that CeO2 nanoparticle treatment attenuated monocrotaline-induced changes in pulmonary flow and RV wall thickness. Paralleling these changes in cardiac function, CeO2 nanoparticle treatment also diminished MCT-induced increases in right ventricular (RV) cardiomyocyte cross sectional area, β-myosin heavy chain, fibronectin expression, protein nitrosylation, protein carbonylation and cardiac superoxide levels. These changes with treatment were accompanied by a decrease in the ratio of Bax/Bcl2, diminished caspase-3 activation and reduction in serum inflammatory markers. Taken together, these data suggest that CeO2 nanoparticle administration may attenuate the hypertrophic response of the heart following PAH.
Although food processing can alter food allergenicity, the impact of extrusion processing on in vivo hazelnut allergenicity is unknown. Here, we tested the hypothesis that extrusion processing will alter the immune activation properties of hazelnut protein (HNP) in mice. Soluble extrusion-processed HNP (EHNP) was prepared and evaluated for immune response using an established transdermal sensitization mouse model. Mice were sensitized with identical amounts of EHNP versus raw HNP. After confirming systemic IgE, IgG1 and IgG2a antibody responses, oral hypersensitivity reaction was quantified by hypothermia shock response (HSR). Mechanism was studied by measuring mucosal mast cell (MMC) degranulation. Compared to raw HNP, the EHNP elicited slower but similar IgE antibody (Ab) response, lower IgG1 but higher IgG2a Ab response. The EHNP exhibited significantly lower oral HSR as well as MMC degranulation capacity. These results demonstrate that the extrusion technology can be used to produce soluble HNP with altered immune activation properties.
Food allergies are a significant public health problem because they trigger life-threatening systemic allergic reactions. We have previously reported a novel mouse model that uses transdermal exposure (TDE) to nut protein for sensitization followed by oral challenge (OC) to elicit systemic reactions. Here we evaluated the utility of this model to determine the oral threshold doses for hazelnut (HN). Groups of mice (n=8-10/group) were sensitized with 2, 3, 4 or 5 TDE to HN or saline, followed by OC with HN to induce systemic anaphylaxis. The data demonstrated that a minimum of 4 TDE to HN and a definition of >/=1 o C drop in rectal temperature (RT) at 30 minutes post OC, ensures 100% positive responses and <10% false positive responses. We then evaluated threshold oral elicitation doses in three scenarios: (1) homogeneous 4 TDE to allergen, followed by repeated OC with different doses of HN at weekly intervals; 2) homogeneous 4 TDE to allergen, followed by single OC per dose per group; and 3) heterogeneous (i.e., 4, 5 or 6) TDE with HN followed by single/repeated OC to simulate the human exposure conditions that are generally heterogeneous. The percent responder curves were established for each case and the NOAEL and LOAEL (25 and 50% responses) were estimated. The NOAELs were </=125 mg/Kg; the 25% response LOAELs ranged from 270-312 mg/Kg; and the 50% response LOAELs ranged from 362-412 mg/Kg.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.