Papers of the Month
By Janelle Weaver
DNTP study examines oral vanadium toxicity in rodent model
Two vanadium compounds show different absorption, distribution, metabolism, and excretion properties in male and female rats, according to researchers from the NIEHS Division of the National Toxicology Program (DNTP).
Vanadium is a naturally occurring element that is present in a variety of minerals, coal, and crude oils. Low levels of vanadium are detected in many foods and in drinking water, suggesting that there is a potential for human exposure. Although vanadium is an environmental contaminant, little is known about its impact on human health.
To assess vanadium toxicity, the researchers exposed rats to drinking water containing vanadyl sulfate or sodium metavanadate, representing two prevalent oxidation states of vanadium in the environment. Exposure started before birth and lasted for three months after weaning. Vanadium concentration in blood and urine increased with the exposure concentration for both compounds. Compared with males, females had higher levels of vanadium in their blood after vanadyl sulfate exposure, and higher levels in blood and urine after exposure to sodium metavanadate. Animals exposed to sodium metavanadate had up to three-fold higher vanadium levels in blood and urine compared with vanadyl sulfate-exposed animals.
According to the authors, the results will aid in the interpretation of animal data regarding vanadium toxicity and help to determine the relevance of animal toxicity findings to human health.
Citation: Waidyanatha S, Weber FX, Fallacara DM, Harrington JM, Levine K, Robinson VG, Sparrow BR, Stout MD, Fernando R, Hooth MJ, Xie G, Roberts GK. 2022. Systemic exposure and urinary excretion of vanadium following perinatal subchronic exposure to vanadyl sulfate and sodium metavanadate via drinking water. Toxicol Lett 360:53–61.
NIEHS scientists uncover novel targets to treat asthma
An influx of white blood cells called neutrophils into the airway during allergen sensitization can curtail subsequent asthma-like responses in mice, according to NIEHS researchers and their collaborators.
Allergic asthma is a widespread, chronic inflammatory disease of the airways. Many types of environmental exposures have been associated with an increased incidence of asthma, but in most cases, the mechanistic links are not clear. A better understanding of how specific biological pathways give rise to the disease could lead to novel targets and more precise strategies for therapeutic intervention.
Using two mouse models of asthma, the researchers found that neutrophil recruitment to the airway during allergic sensitization promoted the production of a signaling protein called transforming growth factor beta (TGF-beta). This, in turn, blunted the pathogenic potential of allergen-specific T cells and limited the duration of asthma.
According to the authors, most of the known functions of neutrophils are associated with exacerbations of the disease, as opposed to a role for these cells in shaping the initiation of immune responses. The new findings add to a growing body of literature showing that indiscriminate blockade of neutrophil function might not always be helpful in the context of allergic asthma.
Citation: Whitehead GS, Thomas SY, Nakano K, Royer DJ, Burke CG, Nakano H, Cook DN. 2022. A neutrophil/TGF-β axis limits the pathogenicity of allergen-specific CD4+ T cells. JCI Insight 7(4):e150251
A molecule called SIRT1 keeps heart muscle cells in line
A molecule called SIRT1 regulates heart contractions by controlling the alignment and maturation of heart muscle cells and muscle fibers during animal development, according to a study by NIEHS researchers and their collaborators.
SIRT1 is an enzyme that plays critical roles in multiple cellular processes, including metabolism, inflammation, stress responses, and stem cell functions. It is also important for animal development, but how SIRT1 regulates heart maturation and function is still largely unknown. In addition, it has not been clear how heart muscle cells and muscle fibers become aligned during development, thereby contributing to normal heart contractions.
The researchers discovered that SIRT1 regulates the remodeling of heart muscle cells during maturation. Using human embryonic stem cells, they found that SIRT1 deficiency impairs the alignment of heart muscle cells and muscle fibers, and disrupts normal heart beating patterns at late developmental stages. Moreover, deletion of SIRT1 at a late developmental stage in mouse embryos induced irregular distribution of heart muscle cells, misalignment of muscle fibers, and reduced heart size.
Additional results suggest that SIRT1 promotes the alignment of heart muscle cells via the CCL2 signaling pathway. According to the authors, the study highlights the therapeutic potential of SIRT1-activating compounds in the treatment of human heart disease.
Citation: Fang Y, Fan W, Xu X, Janoshazi AK, Fargo DC, Li X. 2022. SIRT1 regulates cardiomyocyte alignment during maturation. J Cell Sci 135(7):jcs259076.
Chemical exposures may affect maternal metabolism, offspring health
Exposure to environmental chemicals during pregnancy is linked to changes in maternal metabolism, with potential implications for child health, according to NIEHS researchers and their Nanjing Medical University collaborators.
Maternal exposure to environmental chemicals during pregnancy can influence various aspects of maternal and offspring health, but the underlying biological mechanisms remain largely unknown. Modification of maternal metabolism by environmental exposure may be an important mechanism. However, there is limited evidence regarding exposure to a wide array of chemicals and related changes to the metabolome — the full suite of metabolites in the human body — during pregnancy.
To address this knowledge gap, the researchers analyzed urine samples collected in the first and third trimesters from 1,024 pregnant women recruited in Nanjing, China. The scientists evaluated relationships between 106 exposures in the first trimester and 139 metabolites in the third trimester.
The results revealed many associations between chemical exposures and changes to maternal metabolism during pregnancy. Among elements, the largest number of metabolic associations were observed for magnesium followed by titanium, and among organic compounds, the largest associations were for a potent endocrine-disrupting chemical called 4-tert-octylphenol. The effects of 10 chemicals on birth weight, gestational age, fat deposition, neurobehavioral development, immunological disorders, and hypertension might be mediated by metabolites associated with these exposures.
According to the authors, the results suggest that environmental modulation of the maternal metabolome may play a role in how prenatal exposures affect child health outcomes.
Citation: Chen M, Guan Y, Huang R, Duan J, Zhou J, Chen T, Wang X, Xia Y, London SJ. 2022. Associations between the maternal exposome and metabolome during pregnancy. Environ Health Perspect 130(3):37003.
Fine particulate matter exposure during oil spill cleanup may affect lung function
Exposure to fine particulate matter (PM 2.5) during oil spill cleanup could impair lung function, according to NIEHS researchers and their collaborators.
The 2010 Deepwater Horizon disaster was the largest marine oil spill in U.S. history.
During the catastrophe, controlled in situ burning and flaring at the wellhead was done to remove oil from the water. Workers near combustion sites were potentially exposed to increased levels of PM 2.5, which has been linked to adverse respiratory health in ambient air pollution studies. But until now, no study had examined impairments in lung function associated with PM 2.5 exposure among oil spill response and cleanup workers.
To address this knowledge gap, NIEHS researchers and collaborators studied 2,316 workers who participated in water-based response and cleanup activities following the Deepwater Horizon disaster and who had lung function measured one to three years later. Among these workers, exposure to PM 2.5 — specifically from burning/flaring of oil/natural gas — was associated with lower lung function compared with not having exposure to the burning/flaring.
According to the authors, additional research is needed to evaluate the persistence of effects of high-level, short-term particulate matter exposure on lung function among cleanup workers.
Citation: Chen D, Lawrence KG, Pratt GC, Stenzel MR, Stewart PA, Groth CP, Banerjee S, Christenbury K, Curry MD, Jackson WB 2nd, Kwok RK, Blair A, Engel LS, Sandler DP. 2022. Fine particulate matter and lung function among burning-exposed Deepwater Horizon oil spill workers. Environ Health Perspect 130(2):27001.