benzofurans and Hyperuricemia

Previous studies on the relationship between dioxin exposures and hyperuricemia have usually been based on multi-chemical linear models. However, the complex nonlinear relationship and interaction between mixed dioxin exposures and hyperuricemia have seldom been studied. In this study, we applied three different statistical models to assess the joint effect of 12 dioxins on hyperuricemia.. A total of 7 dioxin-like polychlorinated biphenyls (DL-PCBs), 3 polychlorinated dibenzo-p-dioxins (PCDDs), and 2 polychlorinated dibenzofurans (PCDFs) were measured in the serum of adults by the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2004. We fitted multivariable logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models to estimate the association of individual and mixed dioxin exposures with hyperuricemia.. Among the 1008 individuals included in our analysis, 20.04% had hyperuricemia. In the multivariable logistic regression established for each single dioxin, PCB28, PCB74, PCB105, PCB118, and 1,2,3,4,6,7,8-HPCDD were positively associated with hyperuricemia. With including all dioxins in the multivariable logistic regression model simultaneously, only PCB28 and 1,2,3,4,6,7,8-HPCDD were positively associated with hyperuricemia. In the WQS regression model, the WQS index was significantly associated (OR (95% CI): 2.32 (1.26, 4.28)) with hyperuricemia, and 1,2,3,4,6,7,8-HPCDD (weighted 0.22) had the largest contribution. In BKMR analysis, a significant positive association was found between mixed dioxin exposure and hyperuricemia when all dioxins were at their 60th percentile or above, compared to their 50th percentile. The univariate exposure-response function showed that PCB105 and PCB118 were positively associated with hyperuricemia.. By comparing the three statistical models, we concluded that the whole-body burden of 12 dioxins was significantly positively associated with hyperuricemia. PCB105, PCB118, and 1,2,3,4,6,7,8-HPCDD played the most important roles in hyperuricemia.

Topics: Adult; Bayes Theorem; Benzofurans; Dibenzofurans, Polychlorinated; Dioxins; Humans; Hyperuricemia; Models, Statistical; Nutrition Surveys; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins

Overproduction of uric acid in the body leads to hyperuricemia, which is also closely related to gout. Uric acid production can be lowered by xanthine oxidase (XO) inhibitors. Inhibition of XO has also been proposed as a mechanism for improving cardiovascular health. Therefore, the search for new efficient XO inhibitors is an interesting topic in drug discovery. 3-Phenylcoumarins and 2-phenylbenzofurans are privileged scaffolds in medicinal chemistry. Their structural similarity makes them interesting molecules for a comparative study. Methoxy and nitro substituents were introduced in both scaffolds. The current study gives some insights into the synthesis and biological activity of these molecules against this important target. For the best compound of the series, the 3-(4-methoxyphenyl)-6-nitrocoumarin (4), the IC

Topics: Animals; Benzofurans; Binding Sites; Cell Line; Coumarins; Drug Discovery; Enzyme Inhibitors; Hyperuricemia; Mice; Molecular Conformation; Protein Binding; Structure-Activity Relationship; Xanthine Oxidase

Hyperuricemia (too much uric acid in the blood) is the predisposing condition for gout and is associated with hypertriglyceridemia, diabetes mellitus, and coronary artery disease. Polychlorinated dibenzo-p-dioxins and dibenzo-furans (PCDD/Fs) cause renal toxicity and elevate uric acid. The aim of this analysis was to investigate and clarify the effect of moderate-to-high PCDD/F exposure on hyperuricemia risk.. In this cross-sectional study, we recruited 1531 healthy participants living near a deserted pentachlorophenol factory. We measured serum levels of 17 2,3,7,8-substituted PCDD/Fs, and then examined associations between the main predictor variable, serum TEQ(DF-2005) (total PCDD/Fs 2005 World Health Organization [WHO] toxic equivalency [TEQ]), and dependent variables such as uric acid, glomerular filtration rates, and hyperuricemia risk.. We observed a strong monotonic inverse relationship between serum TEQ(DF-2005) quartiles and the estimated glomerular filtration rate after adjusting for confounding factors (Men: β were 0, -4.7, -6.2, and -14.8; Women: β were 0, -6.7, -12.9, and -21.5). In addition, we observed a suggestive positive trend between serum TEQDF-2005 quartiles and uric acid only in men after adjusting for confounding factors (Men: β were 0, 0.40, 0.36, and 0.59; P for trend <0.05). Men with serum TEQ(DF-2005) higher than the reference group's (<7.4 pg WHO(2005)-TEQ(DF/g) lipid) had a higher hyperuricemia risk after adjusting for confounding factors (25th to <50th percentile, adjusted odds ratio [AOR] = 2.20 [95% confidence interval {CI} = 1.30-3.73]; 50th to <75th percentile, AOR = 1.86 [95% CI = 1.08-3.22]; ≥ 75th percentile, AOR = 3.00 [95% CI = 1.69-5.31]).. We conclude that serum TEQ(DF-2005) is an important determinant of serum uric acid levels and heightens the risk of hyperuricemia in general populations.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzofurans; Cross-Sectional Studies; Environmental Exposure; Environmental Pollutants; Female; Humans; Hyperuricemia; Male; Middle Aged; Polychlorinated Dibenzodioxins; Risk Assessment; Sex Factors; Young Adult

Background exposure to persistent organic pollutants (POPs) has emerged as a new risk factor for metabolic syndrome (MetS), while hyperuricemia is associated with MetS through unclear mechanisms.. We examined cross-sectional data for consistency with the hypothesis that POPs are a common underlying risk factor of both MetS and hyperuricemia.. We evaluated associations of POPs with hyperuricemia in subjects aged ≥20 years in the population-based National Health and Nutrition Examination Survey (NHANES) 2003-2004. Sample size was n = 1331 for organochlorine (OC) pesticides and n = 1299 for polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs).. Among all subjects, the risk of hyperuricemia was higher for higher serum concentrations of OC pesticides, PCDDs, and dioxin-like PCBs. PCDFs and nondioxin-like PCBs did not show any clear trend. Adjusted odds ratios (ORs) for OC pesticides, PCDDs, and dioxin-like PCBs were 1.0, 2.4, 2.3, 3.0, and 2.5 (P trend = 0.05), 1.0, 1.6, 1.4, 2.1, and 2.5 (P trend = 0.01), and 1.0, 1.3, 1.4, 1.3, and 2.4 (P trend = 0.04). When we restricted the analyses to subjects without MetS, all these associations appeared to strengthen.. This study is consistent with our hypothesis that the risk of hyperuricemia relates to background exposure to a mixture of POPs even among persons without MetS. There should be further research about whether avoiding exposure to POPs and otherwise decreasing body burden of POPs would be helpful to prevent or manage hyperuricemia or gout.

Topics: Adult; Aged; Aged, 80 and over; Benzofurans; Chlorine; Cross-Sectional Studies; Dibenzofurans, Polychlorinated; Dioxins; Environmental Pollutants; Female; Humans; Hyperuricemia; Male; Metabolic Syndrome; Middle Aged; Nutrition Surveys; Odds Ratio; Organic Chemicals; Pesticides; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Risk Factors; United States; Young Adult

Lithospermic acid (LSA) was originally isolated from the roots of Salvia mitiorrhiza, a common herb of oriental medicine. Previous studies demonstrated that LSA has antioxidant effects. In this study, we investigated the in vitro xanthine oxidase (XO) inhibitory activity, and in vivo hypouricemic and anti-inflammatory effects of rats. XO activity was detected by measuring the formation of uric acid or superoxide radicals in the xanthine/xanthine oxidase system. The results showed that LSA inhibited the formation of uric acid and superoxide radicals significantly with an IC50 5.2 and 1.08 microg/ml, respectively, and exhibited competitive inhibition. It was also found that LSA scavenged superoxide radicals directly in the system beta-NADH/PMS and inhibited the production of superoxide in human neutrophils stimulated by PMA and fMLP. LSA was also found to have hypouricemic activity on oxonate-pretreated rats in vivo and have anti-inflammatory effects in a model of gouty arthritis. These results suggested that LSA is a competitive inhibitor of XO, able to directly scavenge superoxide and inhibit superoxide production in vitro, and presents hypouricemic and anti-inflammatory actions in vivo.

Topics: Allopurinol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Benzofurans; Depsides; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Hyperuricemia; Inflammation; Male; Molecular Conformation; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Oxonic Acid; Rats; Rats, Wistar; Reactive Oxygen Species; Tetradecanoylphorbol Acetate; Uric Acid; Xanthine Oxidase