Biological definition of multiple chemical sensitivity from redox state and cytokine profiling and not from polymorphisms of xenobiotic-metabolizing enzymes

BACKGROUND: Multiple chemical sensitivity (MCS) is a poorly clinically and biologically defined environment-associated syndrome. Although dysfunctions of phase I/phase II metabolizing enzymes and redox imbalance have been hypothesized, corresponding genetic and metabolic parameters in MCS have not been systematically examined. OBJECTIVES: We sought for genetic, immunological, and metabolic markers in MCS. METHODS: We genotyped patients with diagnosis of MCS, suspected MCS and Italian healthy controls for allelic variants of cytochrome P450 isoforms (CYP2C9, CYP2C19, CYP2D6, and CYP3A5), UDP-glucuronosyl transferase (UGT1A1), and glutathione S-transferases (GSTP1, GSTM1, and GSTT1). Erythrocyte membrane fatty acids, antioxidant (catalase, superoxide dismutase (SOD)) and glutathione metabolizing (GST, glutathione peroxidase (Gpx)) enzymes, whole blood chemiluminescence, total antioxidant capacity, levels of nitrites/nitrates, glutathione, HNE-protein adducts, and a wide spectrum of cytokines in the plasma were determined. RESULTS: Allele and genotype frequencies of CYPs, UGT, GSTM, GSTT, and GSTP were similar in the Italian MCS patients and in the control populations. The activities of erythrocyte catalase and GST were lower, whereas Gpx was higher than normal. Both reduced and oxidised glutathione were decreased, whereas nitrites/nitrates were increased in the MCS groups. The MCS fatty acid profile was shifted to saturated compartment and IFNgamma, IL-8, IL-10, MCP-1, PDGFbb, and VEGF were increased. CONCLUSIONS: Altered redox and cytokine patterns suggest inhibition of expression/activity of metabolizing and antioxidant enzymes in MCS. Metabolic parameters indicating accelerated lipid oxidation, increased nitric oxide production and glutathione depletion in combination with increased plasma inflammatory cytokines should be considered in biological definition and diagnosis of MCS

Rapid coastal deoxygenation due to ocean circulation shift in the northwest Atlantic

Global observations show that the ocean lost approximately 2% of its oxygen inventory over the past five decades1,2,3, with important implications for marine ecosystems4,5. The rate of change varies regionally, with northwest Atlantic coastal waters showing a long-term drop6,7 that vastly outpaces the global and North Atlantic basin mean deoxygenation rates5,8. However, past work has been unable to differentiate the role of large-scale climate forcing from that of local processes. Here, we use hydrographic evidence to show that a Labrador Current retreat is playing a key role in the deoxygenation on the northwest Atlantic shelf. A high-resolution global coupled climate–biogeochemistry model9 reproduces the observed decline of saturation oxygen concentrations in the region, driven by a retreat of the equatorward-flowing Labrador Current and an associated shift towards more oxygen-poor subtropical waters on the shelf. The dynamical changes underlying the shift in shelf water properties are correlated with a slowdown in the simulated Atlantic Meridional Overturning Circulation (AMOC)10. Our results provide strong evidence that a major, centennial-scale change of the Labrador Current is underway, and highlight the potential for ocean dynamics to impact coastal deoxygenation over the coming century