Epicatechin (EC) was used in this study to antagonize the cognitive dysfunction caused by lead (Pb) exposure in mice. Eight-week-old male Kunming mice were treated with PbCl 2 (20 mg/kg) and/or EC (50 mg/kg) by gavage administration for 4 weeks. Morris water maze test showed that EC could improve memory dysfunction induced by Pb. EC antagonized Ca 2+ overload, activated Nrf2 signaling pathway and reduced the accumulation of Pb in the brain and serum, which suggested that EC might alter Pb distribution in mice. In vitro, spectroscopic analysis, potentiometric titration and docking studies were applied to inquiry into the interaction between bovine serum albumin (BSA) and Pb 2+ in presence or absence of EC. EC was proved to chelate Pb 2+ and reduced the interaction between BSA and Pb 2+ . In summary, EC might protect Pb-induced cognitive impairment by activating Nrf2 signaling pathway, and suppressing Pb accumulation via interference on the binding of Pb to albumin.
Aluminum (Al) is an important environmental neurotoxicity, and the speciation of Al largely determines the absorption and toxic effects in human body. The brain-type creatine kinase (CK-BB), which is an important kinase that regulates energy supply in brain tissue, has been found high affinity to Al. The research was carried to explore the potential neurotoxicity mechanism induced by different speciation of Al. In the current work, the C57BL/6 mice and C6 cells were used to explore the role of Al speciation in Al-induced neurotoxicity. The results showed that the expression levels of F-actin and Cyt C/Caspase 9/Caspase 3 signaling pathways were different in mice treated with AlCl3 and Al(mal)3. In C6 cells, the CK-BB activity decreased by 23.92% after 3.5 mM AlCl3 treatment. AlCl3 treatment resulted in insufficient local ATP supply of cells, thereby affecting the formation of F-actin and cell morphology. After Al(mal)3 treatment, the fluorescence intensity of membrane potential was increased by 141.37%, followed by activating apoptosis pathway of Cyt C/Caspase 9/Caspase 3. In addition, molecular docking showed that the binding site of AlCl3 on CK-BB subunit was closer to the active site. Al(mal)3 enhanced the hydrophobicity of CK-BB. The aim of this study is to demonstrate that CK-BB is an important factor in Al-induced energy metabolism disorder process, in which the speciation of Al compound has revealed particular toxicity mechanisms.
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