Effects of zinc and manganese on advanced glycation end products (AGEs) formation and AGEs-mediated endothelial cell dysfunction

AimsThe present study investigated the effects of ZnCl2 and MnCl2 supplementations on advanced glycation end products (AGEs) formation and AGEs-mediated endothelial cell dysfunction.Main methodsFluorescence detection was used to monitor the Maillard reaction. Inductively coupled plasma optical emission spectroscopy was used to test cellular zinc and manganese levels. Real-time reverse transcription polymerase chain reaction and western blot were used to analyze the expression of endothelial nitric oxide synthase (eNOS), nuclear transcription factor kappa B (NF-κB), and receptor for AGEs (RAGE). Intracellular reactive oxygen species (ROS) and nitric oxide (NO) production, NOS activity were determined by fluorescent probe assay, superoxide dismutase (SOD) activity was determined by water soluble tetrazolium salt assay.Key findingsMnCl2 showed excellent inhibitory effect on AGEs formation. Primary cultured bovine aortic endothelial cells (BAECs) were exposed to AGEs for 30 min, followed by trace element treatments. Cell viability and the zinc levels declined due to AGEs exposure, which were improved with the supplementations of ZnCl2 and MnCl2. Furthermore, ZnCl2 supplementation effectively enhanced intracellular NO production, elevated eNOS expression and enzymatic activity, and down-regulated NF-κB activation and RAGE expression. MnCl2 dose-dependently impaired ROS formation, down-regulated NF-κB protein expression and nuclear translocation, as well as restored Mn-SOD enzymatic capability.SignificanceOur findings suggested that trace elements relevant to diabetic, such as zinc and manganese played different roles in the formation of AGEs. Both the elements benefited the AGEs-injured BAECs through different mechanisms.