Oil Dispersants and Human Health Effects

The explosion and subsequent blowout of the Deepwater Horizon (DWH) offshore drilling rig on April 20, 2010, led to the largest accidental offshore oil spill since the advent of the petroleum industry, dwarfed only by the deliberate release of crude oil by Iraqi forces during the Persian Gulf War. Over the time until the well was capped on July 15, approximately 200 million gallons of oil spilled into the Gulf of Mexico from the ocean floor beneath the well site located approximately 50 miles off the coast of Louisiana. For perspective, this amount is nearly 20 times the amount of oil discharged during the Exxon Valdez incident in Alaska. As a result, massive mitigation efforts took place during and after the flow of oil which entailed mechanical recovery, controlled burning, and chemical dispersion. As a result unprecedented application of oil dispersant agents was employed by BP during this time until their use was curtailed by the EPA on May 26, 2010. Overall, about 17 - 20% of the crude oil was mechanically recovered and 6 – 8% burned. For the oil remaining in the environment, about 40% (of original input) was evaporated, dissolved, or dispersed into small droplets by natural processes. Initially, it was estimated that only 16.5 million gallons of oil

PRETA Air: Hazardous Air Pollutants

This report shows that people living in a 10-county region of southwestern Pennsylvania have a significantly higher than acceptable risk of developing cancer due to exposure to toxic air pollution released by manufacturing processes, energy production and diesel combustionThe Pittsburgh Regional Environmental Threats Analysis Report -- funded by The Heinz Endowments -- analyzes publicly available data on hazardous air pollutants (HAPs), also known as air toxics. Air toxics include approximately 200 pollutants identified by the U.S. Environmental Protection Agency (EPA) as known or suspected to cause cancer or other serious health effects, such as respiratory, neurological and reproductive disorders. The report is the third in a series as part of a project examining major threats to human health and the environment in southwestern Pennsylvania

Biting the bullet: a call for action on lead-contaminated meat in food-banks

Each year in the United States, food banks receive more than one million kilograms of donated hunted game meat. The National Rifle Association’s (NRA’s) Hunters for the Hungry initiative has established programs in more than 40 states for hunters to take their harvested game animal to a meat processing facility and indicate intent to donate the resulting processed and packaged meat to a local food bank. Most donated game meat is ground deer meat (venison); other donated game includes wild hog and goose. Even though the presence of ammunition-derived metallic lead fragments in donated firearms-hunted meat has been recognized for more than a decade, most of the donated hunted meat is not inspected to discard meat containing lead fragments. An underlying lack of food safety standards for adulterated donated food increases risks to low-income recipients, who are already disproportionately affected by elevated blood lead levels (BLLs).2 Primary prevention is needed for this overlooked source of lead exposure.publishedVersio

Nickel and the Microbial Toxin, MALP-2, Stimulate Proangiogenic Mediators from Human Lung Fibroblasts via a HIF-1α and COX-2–Mediated Pathway

Hypoxia-inducible factor (HIF-1α) and cyclooxygenase-2 (COX-2) have been implicated in the regulation of inflammatory-like processes that lead to angiogenesis and fibrotic disorders. Here we demonstrate that in human lung fibroblasts (HLFs) treated with mixed exposures to chemical and microbial stimuli, HIF-1α stabilization plays a pivotal role in the induction of COX-2 mRNA and protein, driving the release of vascular endothelial growth factor (VEGF) and proangiogenic and profibrotic chemokines. Upon costimulation with Ni and the mycoplasma-derived lipopeptide macrophage-activating lipopeptide-2 (MALP-2), there was a synergistic induction of CXCL1 and CXCL5 mRNA and protein release from HLF, as well as an enhanced response in VEGF compared to either stimulus alone. Consistent with our previous findings that Ni and MALP-2 stimulates the induction of CXCL8 via a COX-2-mediated pathway, CXCL1, CXCL5, and VEGF release were also regulated by COX-2. Ni induced the stabilization of HIF-1α protein in HLF, which was further enhanced in the presence of MALP-2. Depletion of HIF-1α using siRNA blocked COX-2 induction by Ni and MALP-2 along with the release of VEGF, CXCL1, CXCL5, and CXCL8. Our results indicate that Ni and MALP-2 interact to promote an angiogenic profibrotic phenotype in HLF. Moreover, these findings reveal a potential role for HIF-1α in mediating chemical-induced alterations in cellular response to microbial stimuli, modulating pulmonary inflammation and its consequences such as fibrosis and angiogenesis

Nickel Alterations of TLR2-Dependent Chemokine Profiles in Lung Fibroblasts Are Mediated by COX-2

Particulate matter air pollution (PM) has been linked with chronic respiratory diseases. Real-life exposures are likely to involve a mixture of chemical and microbial stimuli, yet little attention has been paid to the potential interactions between PM components (e.g., Ni) and microbial agents on the development of inflammatory-like conditions in the lung. Using the Toll-like receptor (TLR)-2 agonist MALP-2 as a lipopeptide relevant to microbial colonization, we hypothesized that nickel sensitizes human lung fibroblasts (HLF) for microbial-driven chemokine release through modulation of TLR signaling pathways. NiSO4 (200 μM) synergistically enhanced CXCL8, yet antagonized CXCL10 mRNA expression and protein release from HLF in response to MALP-2. RT2-PCR pathway-focused array results indicated that NiSO4 exposure did not alter the expression of TLRs or their downstream signaling mediators, yet significantly increased the expression of cyclooxygenase 2 (COX-2). Moreover, when NiSO4 was given in combination with MALP-2, there was an amplified induction of COX-2 mRNA and protein along with its metabolic product, PGE2, in HLF. The COX-2 inhibitor, NS-398, attenuated NiSO4 and MALP-2–induced PGE2 and CXCL8 release and partially reversed the NiSO4-dependent inhibition of MALP-2–induced CXCL10 release from HLF. These data indicate that NiSO4 alters the pattern of TLR-2–dependent chemokine release from HLF via a COX-2–mediated pathway. The quantitative and qualitative effects of NiSO4 on microbial-driven chemokine release from HLF shed new light on how PM-derived metals can exacerbate respiratory diseases

Selective Peroxidation and Externalization of Phosphatidylserine in Normal Human Epidermal Keratinocytes During Oxidative Stress Induced by Cumene Hydroperoxide

Reactive oxygen species not only modulate important signal transduction pathways, but also induce DNA damage and cytotoxicity in keratinocytes. Hydrogen peroxide and organic peroxides are particularly important as these chemicals are widely used in dermally applied cosmetics and pharmaceuticals, and also represent endogenous metabolic intermediates. Lipid peroxidation is of fundamental interest in the cellular response to peroxides, as lipids are extremely sensitive to oxidation and lipid-based signaling systems have been implicated in a number of cellular processes, including apoptosis. Oxidation of specific phospholipid classes was measured in normal human epidermal keratinocytes exposed to cumene hydroperoxide after metabolic incorporation of the fluorescent oxidation-sensitive fatty acid, cis-parinaric acid, using a fluorescence high-performance liquid chromatography assay. In addition, lipid oxidation was correlated with changes in membrane phospholipid asymmetry and other markers of apoptosis. Although cumene hydroperoxide produced significant oxidation of cis-parinaric acid in all phospholipid classes, one phospholipid, phosphatidylserine, appeared to be preferentially oxidized above all other species. Using fluorescamine derivatization and annexin V binding it was observed that specific oxidation of phosphatidylserine was accompanied by phosphatidylserine translocation from the inner to the outer plasma membrane surface where it may serve as a recognition signal for interaction with phagocytic macrophages. These effects occurred much earlier than any detectable changes in other apoptotic markers such as caspase-3 activation, DNA fragmentation, or changes in nuclear morphology. Thus, normal human epidermal keratinocytes undergo profound lipid oxidation with preference for phosphatidylserine followed by phosphatidylserine externalization upon exposure to cumene hydroperoxide. It is therefore likely that normal human epidermal keratinocytes exposed to similar oxidative stress in vivo would under go phosphatidylserine oxidation/translocation. This would make them targets for macrophage recognition and phagocytosis, and thus limit their potential to invoke inflammation or give rise to neoplastic transformations