Papers of the Month
Intramural
By Janelle Weaver
Toxic vanadium compound may impair antibody-mediated immunity
Exposure to sodium metavanadate can adversely affect the immune system by suppressing the responses of cells that produce protective proteins called antibodies, according to researchers from the Division of Translational Toxicology.
Sodium metavanadate is a vanadium compound used in the metal industry and in dietary supplements. Human exposure occurs through inhalation of fumes and dust in the workplace, ingestion of supplements, and contaminated food and water. Exposure to the metal has been associated with therapeutic benefits for immune-relevant diseases such as diabetes.
Because the compound’s potential benefits may be eclipsed by the toxicity reported in previous studies, the researchers evaluated the impact of sodium metavanadate on immune function. In the new study, mice ingested the compound through drinking water for 28 days. Exposure resulted in suppression of the antibody-forming cell response to sheep red blood cells. Specifically, the researchers observed a decrease in antibody-forming cells in the spleen, which is an organ that plays an important role in the immune system. In addition, sodium metavanadate exposure led to a decrease in erythrocyte size and hemoglobin metrics in mice, suggesting erythrocyte microcytosis and anemia.
Collectively, the findings indicate that exposure to the metal impairs the function of B cells, which produce antibodies. According to the authors, the results suggest that people should exert caution in the handling, commercial use, and consumption of sodium metavanadate-containing compounds.
Citation: Frawley R, Johnson VJ, Burleson GR, Shockley KR, Cesta MF, Travlos G, Cora M, Roberts G, Germolec D. 2023. Evaluation of immunotoxicity of sodium metavanadate following drinking water exposure in female B6C3F1/N mice in a 28-day study. J Appl Toxicol; doi: 10.1002/jat.450. [Online 5 Jul 2023].
How glucocorticoids regulate platelet production
Steroid hormones called glucocorticoids facilitate platelet production via a novel mechanism, according to NIEHS researchers. They found glucocorticoids stimulate the production of blood cells called platelets by regulating the activity of genes in megakaryocytes, the cells that produce platelets.
Although glucocorticoids are known to modulate the immune response, their actions on platelet production have not been studied. Dexamethasone, a synthetic analog similar to endogenous glucocorticoids, is used to treat several autoimmune diseases. Immune thrombocytopenia is one such autoimmune disorder that is characterized by a low number of circulating platelets that leads to a high predisposition to internal bleeding.
The researchers discovered that dexamethasone reduces bleeding in mice and rapidly increases the number of circulating young platelets. Glucocorticoids stimulated the production of platelet precursors called proplatelets and the release of platelet-like particles from megakaryocytes. Genome-wide analysis revealed that dexamethasone regulates the expression of more than 1,300 genes in megakaryocytes involved in cellular functions associated with the formation of proplatelets. The study also showed that a protein called guanine deaminase is largely responsible for glucocorticoid stimulation of platelet production.
According to the authors, these findings demonstrate, for the first time, that megakaryocytes are a novel target cell for glucocorticoids. Because these steroid hormones are one of the most widely prescribed medications worldwide for reducing inflammation and treating autoimmune disorders, the study could have an important clinical impact.
Citation: Grodzielski M, Cidlowski JA. 2023. Glucocorticoids regulate thrombopoiesis by remodeling the megakaryocyte transcriptome. J Thromb Haemost; doi: 10.1016/j.jtha.2023.06.012 [Online 17 June 2023].
Metabolic pathway links excessive linoleic acid intake and colon cancer risk
Cytochrome P450 (CYP) monooxygenases may mediate the pro-cancer effects of linoleic acid, according to NIEHS researchers and their collaborators.
Linoleic acid is an essential fatty acid that is abundant in vegetable oils such as corn and soybean oils. Studies suggest that consuming high levels of linoleic acid may increase the risk of colon cancer. Because of the importance of this fatty acid in the human diet, it is crucial to better understand the molecular mechanisms underlying its potential colon cancer-promoting effects.
Toward this goal, the researchers discovered that a diet rich in linoleic acid fails to exacerbate colon cancer in mice that are deficient in the CYP2C subfamily of monooxygenases. Additional experiments revealed that these enzymes convert linoleic acid to epoxyoctadecenoic acids (EpOMEs), which strongly promote the formation of colon tumors via gut microbiota-dependent mechanisms. Overall, these results suggest that CYP2C monooxygenase-mediated conversion of linoleic acid to EpOMEs plays a crucial role in the health effects of this fatty acid.
According to the authors, the study establishes a unique mechanistic link between dietary fatty acid intake and cancer risk. Moreover, these findings could help in the development of more effective dietary guidelines for optimal linoleic acid intake and the identification of subpopulations that may be especially vulnerable to the negative effects of this fatty acid.
Citation: Zhang J, Yang J, Duval C, Edin ML, Williams A, Lei L, Tu M, Pourmand E, Song R, Graves JP, DeGraff LM, Wong JJ, Wang Y, Sun Q, Sanidad KZ, Wong S, Han Y, Zhang Z, Lee KSS, Park Y, Xiao H, Liu Z, Decker EA, Cui W, Zeldin DC, Zhang G. 2023. CYP eicosanoid pathway mediates colon cancer-promoting effects of dietary linoleic acid. FASEB J 37(7):e23009.
Financial hardship and sleep health varied across groups during pandemic
Financial hardship and sleep disturbances varied by gender, race, and ethnicity during the COVID-19 pandemic, according to NIEHS researchers and their National Institute on Minority Health and Health Disparities collaborators.
In the U.S., the health and financial consequences of COVID-19 have disproportionately affected women and minoritized racial-ethnic groups. Yet, few U.S. studies have investigated financial hardship during the COVID-19 pandemic in relation to sleep health, although sleep is essential for health along with wellbeing and is sensitive to physical as well as psychological stressors.
To address this knowledge gap, the researchers analyzed survey data collected from December 2020 to February 2021 among a nationally representative sample of 5,339 adults in the U.S. Overall, 71% of the participants reported financial hardship, which was more common among women and minoritized racial-ethnic groups except for participants identifying as non-Hispanic Asian. The prevalence of moderate to severe sleep disturbances was 20% on average, 23% among women, 29% among American Indian/Alaska Native adults, and 28% among multiracial adults.
Moreover, people who reported experiencing financial hardship during COVID-19 were more likely to also report sleep disturbances. The strongest associations were generally among Black/African American adults. According to the authors, interventions that alleviate financial insecurity would likely reduce sleep health disparities. Due to disproportionate burdens, tailored interventions may be especially beneficial among women and racial-ethnic minorities, particularly Black/African American adults.
Citation: Gaston SA, Strassle PD, Alhasan DM, Pérez-Stable EJ, Nápoles AM, Jackson CL. 2023. Financial hardship, sleep disturbances, and their relationship among men and women in the United States during the COVID-19 pandemic. Sleep Health; doi: 10.1016/j.sleh.2023.04.007 [Online 4 June 2023].
Assessing the long-term neurological impact of oil spill cleanup
Higher exposures to volatile components of crude oil during the Deepwater Horizon disaster are linked to worse neurologic function among older spill workers up to six years after the disaster, according to NIEHS researchers and their collaborators.
During the 2010 Deepwater Horizon disaster, oil spill response and cleanup workers were exposed to toxic volatile components of crude oil. However, few studies have examined exposure to individual volatile hydrocarbon chemicals in relation to neurologic function among these workers or at levels below occupational exposure limits.
To address this gap, the researchers examined the link between neurologic function and exposure to several spill-related chemicals and total petroleum hydrocarbons among Deepwater Horizon spill workers. The clinical exam occurred four to six years after the disaster. Exposures to the chemicals BTEX and n-hexane were elevated but below occupational limits.
Among workers who were age 50 years or older at study enrollment, higher exposures to volatile components of crude oil were associated with modest neurologic deficits, such as poorer vibrotactile acuity of the great toe, as well as worse performance in postural stability and single-leg stance tests. According to the authors, this study provides evidence that exposure to these agents at levels below current occupational guidelines may induce adverse neurologic effects in susceptible populations.
Citation: Chen D, Werder EJ, Stewart PA, Stenzel MR, Gerr FE, Lawrence KG, Groth CP, Huynh TB, Ramachandran G, Banerjee S, Jackson Ii WB, Christenbury K, Kwok RK, Sandler DP, Engel LS. 2023. Exposure to volatile hydrocarbons and neurologic function among oil spill workers up to 6 years after the Deepwater Horizon disaster. Environ Res 231(Pt 1):116069.
(Janelle Weaver, Ph.D., is a contract writer for the NIEHS Office of Communications and Public Liaison.)
