Alzheimer’s disease (AD) is a common neurodegenerative disease in elderly individuals, and effective therapies are unavailable. This study was designed to investigate the neuroprotective effects of sulforaphane (an activator of NF-E2-related factor 2) on mice with AD-like lesions induced by combined administration of aluminum and d-galactose. Step-down-type passive avoidance tests showed sulforaphane ameliorated cognitive impairment in AD-like mice. Immunohistochemistry results indicated sulforaphane attenuated cholinergic neuron loss in the medial septal and hippocampal CA1 regions in AD-like mice. However, spectrophotometry revealed no significant difference in acetylcholine level or the activity of choline acetyltransferase or acetylcholinesterase in the cerebral cortex among groups of control and AD-like mice with and without sulforaphane treatment. Sulforaphane significantly increased the numbers of 5-bromo-2'-deoxyuridine-positive neurons in the subventricular and subgranular zones in AD-like mice which were significantly augmented compared with controls. Atomic absorption spectrometry revealed significantly lower aluminum levels in the brains of sulforaphane-treated AD-like mice than in those that did not receive sulforaphane treatment. In conclusion, sulforaphane ameliorates neurobehavioral deficits by reducing cholinergic neuron loss in the brains of AD-like mice, and the mechanism may be associated with neurogenesis and aluminum load reduction. These findings suggest that phytochemical sulforaphane has potential application in AD therapeutics.

It has been shown that multiple metals exposure is associated with hyperuricemia. However, previous studies on the association and interaction between multiple metals exposure and hyperuricemia have been controversial, and there has been little evaluation of the potential mediating role of estimating glomerular filtration rate (eGFR). In this study, levels of 12 metals in the urine of 3756 study participants were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The associations between urinary metals and the hyperuricemia were analyzed by multivariable logistic regression model and restricted cubic spline (RCS). Weighted Quantile Sum (WQS) regression was used to explore the weight of each metal. Bayesian Kernel Machine Regression (BKMR) was used to explore the join effect of mixed metal exposure. Mediation analysis was used to explore the role of eGFR in relationship between urinary metal concentration and hyperuricemia. In the multi-metal model, the multivariate-adjusted odds ratio (OR) and 95 % confidence interval (CI) of hyperuricemia were 0.89 (0.81,0.99) for Fe, 0.79 (0.70,0.89) for Se, 0.84 (0.75,0.93) for Cd, 0.87 (0.79,0.96) for Pb, 1.36 (1.23,1.51) for Zn (all P < 0.05). The RCS regression indicated signification nonlinear associations for Zn and Pb (all P-non-linear <0.05). The WQS regression model based on the negative fit showed that the maximum weight of Cd is 43.1 %. In the BKMR model, metal mixtures showed an overall negative association with the risk of developing hyperuricemia, and we also found interactions between Zn and Pb. Mediation analysis showed that eGFR mediated the association between Fe, Se, Cd, Pb and hyperuricemia with mediation ratios of 11.18 %, 12.10 %, 9.60 %, and 12.01 %, respectively. The metal mixture in urine is negatively correlated with hyperuricemia, with Cd having the greatest impact. eGFR may play a partial role in association of Fe, Se, Cd and Pb exposure with hyperuricemia.