Associations of co-exposure to metals with serum uric acid and hyperuricemia: A cross-sectional study

While lead exposure is associated with hyperuricemia, there is scarce evidence about whether other metals are associated with serum uric acid (SUA) levels and hyperuricemia, and whether joint effects among metals existed. We conducted a cross-sectional study in 1950 eligible participants with 20 metals measured in urine. We used multivariable linear and logistic regression models to investigate the associations of metals exposure with SUA levels and hyperuricemia risk. We found that urinary vanadium and arsenic concentrations were associated with increased SUA levels in both sexes while urinary selenium concentrations were inversely associated with SUA levels in males. Each doubling of vanadium, arsenic, and selenium concentrations was associated with an adjusted odds ratio of 1.17 (95% CI: 1.03, 1.33), 1.22 (95% CI: 0.99, 1.50), and 0.67 (95% CI: 0.50, 0.88) for hyperuricemia in males, respectively. In addition, under the exposure of vanadium and arsenic, only if high selenium content existed, no significantly increased SUA levels and hyperuricemia risk in both sexes can be found. Vanadium and arsenic exposure were suggested to be associated with elevated SUA levels and hyperuricemia risk with sex difference while high selenium status might counteract their detrimental effects.

Vanadium Derivative Exposure Promotes Functional Alterations of VSMCs and Consequent Atherosclerosis via ROS/p38/NF-κB-Mediated IL-6 Production

Vanadium is a transition metal widely distributed in the Earth’s crust, and is a major contaminant in fossil fuels. Its pathological effect and regulation in atherosclerosis remain unclear. We found that intranasal administration of the vanadium derivative NaVO3 significantly increased plasma and urinary vanadium levels and induced arterial lipid accumulation and atherosclerotic lesions in apolipoprotein E-deficient knockout mice (ApoE−/−) murine aorta compared to those in vehicle-exposed mice. This was accompanied by an increase in plasma reactive oxygen species (ROS) and interleukin 6 (IL-6) levels and a decrease in the vascular smooth muscle cell (VSMC) differentiation marker protein SM22α in the atherosclerotic lesions. Furthermore, exposure to NaVO3 or VOSO4 induced cytosolic ROS generation and IL-6 production in VSMCs and promoted VSMC synthetic differentiation, migration, and proliferation. The anti-oxidant N-acetylcysteine (NAC) not only suppresses IL-6 production and VSMC pathological responses including migration and proliferation but also prevents atherosclerosis in ApoE−/− mice. Inhibition experiments with NAC and pharmacological inhibitors demonstrated that NaVO3-induced IL-6 production is signaled by ROS-triggered p38-mediated NF-κB-dependent pathways. Neutralizing anti-IL-6 antibodies impaired NaVO3-mediated VSMC migration and proliferation. We concluded that NaVO3 exposure activates the ROS-triggering p38 signaling to selectively induce NF-κB-mediated IL-6 production. These signaling pathways induce VSMC synthetic differentiation, migration, and proliferation, leading to lipid accumulation and atherosclerosis.

Association of urinary metal profiles with serum uric acid: a cross-sectional study of traffic policemen in Wuhan, China

ObjectivesSerum uric acid (SUA) is both a strong antioxidant and one of the key risk factors of cardiovascular diseases (CVDs). We aimed to investigate the associations of urinary metal profile with SUA in traffic policemen in Wuhan, China.DesignA cross-sectional study was carried out in traffic policemen.SettingA seriously polluted Chinese city.ParticipantsA total of 186 traffic policemen were recruited in this study. About 56 of them worked in the logistics department and the other 130 maintained traffic order or dealt with traffic accidents on the roads. All these subjects had worked as a policeman for at least 1 year.Main outcome measuresSUA.ResultsThe significantly negative association of lead with SUA was consistent between single-metal and multiple-metal models (p=0.004 and p=0.020, respectively). Vanadium, chromium and tin were reversely associated with SUA levels in the single-metal models after false discovery rate (FDR) adjustment (allP_FDR< 0.05). One IQR increase in vanadium, chromium, tin and lead was associated with 26.9 µmol/L (95% CI −44.6 to −9.2; p=0.003), 27.4 µmol/L (95% CI −46.1 to −8.8; p=0.004), 11.2 µmol/L (95% CI −18.9 to −3.4; p=0.005) and 16.4 µmol/L (95% CI −27.6 to −5.2; p=0.004) decrease in SUA, respectively. Significant interaction between smoking and vanadium on decreased SUV was found (pfor interaction= 0.007 and p_FDR= 0.028).ConclusionsUrinary vanadium, chromium, tin and lead were negatively associated with SUA. Vanadium and cigarette smoking jointly affected SUA levels. Further studies are needed to replicate these findings and to investigate the potential mechanisms.