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Mechanistic pathways underlying inflammatory injury following exposures to vanadium-containing compounds are not defined. We tested the postulate that the in vitro biological effect of vanadium results from its impact on iron homeostasis. Human bronchial epithelial (HBE) cells exposed to vanadyl sulfate (VOSO 4 ) showed a time- and dose-dependent increase in vanadium relative to PBS. HBE cells exposed to VOSO 4 and then exposed to ferric ammonium citrate (FAC) significantly increased intracellular iron import supporting an interaction between the two metals. Following exposure to VOSO 4 , there was an increase (336 ± 73%) in RNA for divalent metal transporter 1 (DMT1), a major iron importer. With inclusion of VOSO 4 in the incubation, vanadium could be measured in the nuclear and mitochondrial fractions and the supernatant. Non-heme iron in the nuclear and mitochondrial fractions were decreased immediately following VOSO 4 exposure while there was an increased concentration of non-heme iron in the supernatant. Provision of excess iron inhibited changes in the concentration of this metal provoked by VOSO 4 exposures. Using Amplex Red, VOSO 4 was shown to significantly increase oxidant generation by HBE cells in a time- and dose-dependent manner. HBE cells pre-treated with FAC and then exposed to VOSO 4 demonstrated a decreased generation of oxidants. Similarly, activation of the transcription factor NF-ĸB promoter and release of interleukin-6 and -8 were increased following VOSO 4 exposure and these effects were diminished by pre-treatment with FAC. We conclude that an initiating event in biological effect after exposure to vanadyl sulfate is a loss of requisite cell iron. [ABSTRACT FROM AUTHOR]

Exposure to dust, smoke, and fumes containing volatile chemicals and particulate matter (PM) from the World Trade Center (WTC) towers' collapse impacted thousands of citizens and first responders (FR; firefighters, medicals staff, police officers) of New York City. Surviving FR and recovery workers are increasingly prone to age-related diseases that their prior WTC dust exposures might expedite or make worse. This review provides an overview of published WTC studies concerning FR/recovery workers' exposure and causal mechanisms of age-related disease susceptibility, specifically those involving the cardiopulmonary and neurological systems. This review also highlights the recent findings of the major health effects of cardiovascular, pulmonary, and neurological health sequelae from WTC dust exposure. To better treat those that risked their lives during and after the disaster of September 11, 2001, the deleterious mechanisms that WTC dust exposure exerted and continue to exert on the heart, lungs, and brain of FR must be better understood. Overall schematic of the proposed effects of exposure to World Trade Center dust. Created using BioRender.com. [Display omitted] • WTC dust exposure caused short-term effects in the heart, lungs and nervous system. • Long-term effects of WTC dust are evident in many organ systems. • Treatment for survivors of WTC dust exposure should focus on symptom management. [ABSTRACT FROM AUTHOR]

Abstract: The chemical and biological properties of a simple and traditional V(5+) coordination complex, dipicolinatooxovanadium(V) (abbreviated [VO2dipic]−), are described in order to present a hypothesis for a novel mode of action wherein a hydrophobic membrane environment plays a key role. Specifically, we propose that the compartmentalization and both chemical and biological transformations of vanadium-complexes direct whether beneficial or toxic effects will be observed with this class of compounds. This concept is based on the formation of high levels of uncontrollable reactive oxygen species (ROS) from one-electron reactions or alternative events possibly initiated by a two-electron reaction which may be directly or indirectly beneficial by reducing the high levels of ROS. The properties of dipicolinatooxovanadium(V) compounds in aqueous solution (D.C. Crans, et al., Inorg. Chem. 39 (2000) 4409–4416) are very different from those in organic solvents (S.K. Hanson, et al., J. Am. Chem. Soc. 131 (2009) 428–429) and these differences may be key for their mode of action. Since other vanadium complexes are known to hydrolyze upon administration, the low stability of the aqueous complex requires entrapment in hydrophobic environments for such a complex to exist sufficiently long to have an effect. The suggestion that the environment changes the reactivity of the compounds is consistent with the very different modes of action by which one complex act. In short, a novel hypothesis is presented for a mode of action of vanadium compounds based on differences in properties resulting from environmental conditions. These considerations are supported by recent evidence supporting a role for membranes and signal transduction events (D.A. Roess, et al. Chem. Biodivers. 5 (2008) 1558–1570) of the insulin-enhancing properties of these compounds. [Copyright &y& Elsevier]