Acute exposure of early-life stage zebrafish (Danio rerio) to Deepwater Horizon crude oil impairs glomerular filtration and renal fluid clearance capacity.

The pronephros (early-stage kidney) is an important osmoregulatory organ, and the onset of its function occurs relatively early in some teleost fishes. As such, any defects in kidney development and function are likely associated with a decreased ability to osmoregulate. Previous work has shown that early-life stage (ELS) zebrafish (Danio rerio) acutely exposed to Deepwater Horizon (DWH) crude oil exhibit transcriptional changes in key genes involved in pronephros development and function, as well as pronephric morphological defects and whole-animal osmoregulatory impairment. The objective of this study was to examine the acute effects of crude oil exposure during zebrafish ELS on pronephros function by assessing its fluid clearance capacity and glomerular filtration integrity. Following a 72-h exposure to control conditions, 20% or 40% dilutions of high-energy water-accommodated fractions (HEWAF) of DWH crude oil, zebrafish were injected into the common cardinal vein either with fluorescein-labeled (FITC) 70-kDa dextran to assess glomerular filtration integrity or with FITC-inulin to assess pronephric clearance capacity. Fluorescence was quantified after the injections at predetermined time intervals by fluorescence microscopy. The results demonstrated a diminished pronephric fluid clearance capacity and failed glomerular perfusion when larvae were exposed to 40% HEWAF dilutions, whereas only a reduced glomerular filtration selectivity was observed in zebrafish previously exposed to the 20% HEWAF dilution.

Exposure to diesel exhaust particles results in altered lung microbial profiles, associated with increased reactive oxygen species/reactive nitrogen species and inflammation, in C57Bl/6 wildtype mice on a high-fat diet.

BACKGROUND: Exposure to traffic-generated emissions is associated with the development and exacerbation of inflammatory lung disorders such as chronic obstructive pulmonary disorder (COPD) and idiopathic pulmonary fibrosis (IPF). Although many lung diseases show an expansion of Proteobacteria, the role of traffic-generated particulate matter pollutants on the lung microbiota has not been well-characterized. Thus, we investigated the hypothesis that exposure to diesel exhaust particles (DEP) can alter commensal lung microbiota, thereby promoting alterations in the lung's immune and inflammatory responses. We aimed to understand whether diet might also contribute to the alteration of the commensal lung microbiome, either alone or related to exposure. To do this, we used male C57Bl/6 mice (4-6-week-old) on either regular chow (LF) or high-fat (HF) diet (45% kcal fat), randomly assigned to be exposed via oropharyngeal aspiration to 35 µg DEP, suspended in 35 µl 0.9% sterile saline or sterile saline only (control) twice a week for 30 days. A separate group of study animals on the HF diet was concurrently treated with 0.3 g/day of Winclove Ecologic® Barrier probiotics in their drinking water throughout the study. RESULTS: Our results show that DEP-exposure increases lung tumor necrosis factor (TNF)-α, interleukin (IL)-10, Toll-like receptor (TLR)-2, TLR-4, and the nuclear factor kappa B (NF-κB) histologically and by RT-qPCR, as well as Immunoglobulin A (IgA) and Immunoglobulin G (IgG) in the bronchoalveolar lavage fluid (BALF), as quantified by ELISA. We also observed an increase in macrophage infiltration and peroxynitrite, a marker of reactive oxygen species (ROS) + reactive nitrogen species (RNS), immunofluorescence staining in the lungs of DEP-exposed and HF-diet animals, which was further exacerbated by concurrent DEP-exposure and HF-diet consumption. Histological examinations revealed enhanced inflammation and collagen deposition in the lungs DEP-exposed mice, regardless of diet. We observed an expansion of Proteobacteria, by qPCR of bacterial 16S rRNA, in the BALF of DEP-exposed mice on the HF diet, which was diminished with probiotic-treatment. CONCLUSIONS: Our findings suggest that exposure to DEP causes persistent and sustained inflammation and bacterial alterations in a ROS-RNS mediated fashion, which is exacerbated by concurrent consumption of an HF diet.

Exposure to Traffic-Generated Pollutants Exacerbates the Expression of Factors Associated with the Pathophysiology of Alzheimer's Disease in Aged C57BL/6 Wild-Type Mice.

BACKGROUND: Multiple studies report a strong correlation between traffic-generated air pollution-exposure and detrimental outcomes in the central nervous system (CNS), including Alzheimer's disease (AD). Incidence of AD is rapidly increasing and, worldwide, many live in regions where pollutants exceed regulatory standards. Thus, it is imperative to identify environmental pollutants that contribute to AD, and the mechanisms involved. OBJECTIVE: We investigated the effects of mixed gasoline and diesel engine emissions (MVE) on the expression of factors involved in progression of AD in the hippocampus and cerebrum in a young versus aged mouse model. METHODS: Young (2 months old) and aged (18 months old) male C57BL/6 mice were exposed to either MVE (300µg/m3 PM) or filtered air (FA) for 6 h/d, 7 d/wk, for 50 d. Immunofluorescence and RT-qPCR were used to quantify oxidative stress (8-OHdG) and expression of amyloid-ß protein precursor (AßPP), ß secretase (BACE1), amyloid-ß (Aß), aryl hydrocarbon receptor (AhR), cytochrome P450 (CYP) 1B1, angiotensin-converting enzyme (ACE1), and angiotensin II type 1 (AT1) receptor in the cerebrum and hippocampus, in addition to cerebral microvascular tight junction (TJ) protein expression. RESULTS: We observed age-related increases in oxidative stress, AhR, CYP1B1, Aß, BACE1, and AT1 receptor in the CA1 region of the hippocampus, and elevation of cerebral AßPP, AhR, and CYP1B1 mRNA, associated with decreased cerebral microvascular TJ protein claudin-5. MVE-exposure resulted in further promotion of oxidative stress, and significant increases in AhR, CYP1B1, BACE1, ACE1, and Aß, compared to the young and aged FA-exposed mice. CONCLUSION: Such findings suggest that MVE-exposure exacerbates the expression of factors in the CNS associated with AD pathogenesis in aged populations.