Nanocurcumin Reduces High Glucose and Particulate Matter-Induced Endothelial Inflammation: Mitochondrial Function and Involvement of miR-221/222.

Purpose: Particulate matter (PM) 2.5, harmful air pollutants, and diabetes are associated with high morbidity and mortality from cardiovascular disease (CVD). However, the molecular mechanisms underlying the combined effects of PM and diabetes on CVD remain unclear. Methods: Endothelial cells (ECs) treated with high glucose (HG) and PM mimic hyperglycemia and air pollutant exposure in CVD. Endothelial inflammation was evaluated by Western blot and immunofluorescence of ICAM-1 expression and monocyte adhesion. The mechanisms underlying endothelial inflammation were elucidated through MitoSOX Red analysis, JC-1 staining, MitoTracker analysis, and Western blot analysis of mitochondrial fission-related, autophagy-related, and mitophagy-related proteins. Furthermore. nanocurcumin (NCur) pretreatment was used to test if it has a protective effect. Results: ECs under co-exposure to HG and PM increased ICAM-1 expression and monocyte adhesion, whereas NCur pretreatment attenuated these changes and improved endothelial inflammation. PM exposure increased mitochondrial ROS levels, worsened mitochondrial membrane potential, promoted mitochondrial fission, induced mitophagy, and aggravated inflammation in HG-treated ECs, while NCur reversed these changes. Also, HG and PM-induced endothelial inflammation is through the JNK signaling pathway and miR-221/222 specifically targeting ICAM-1 and BNIP3. PM exposure also aggravated mitochondrial ROS levels, mitochondrial fission, mitophagy, and endothelial inflammation in STZ-induced hyperglycemic mice, whereas NCur attenuated these changes. Conclusion: This study elucidated the mechanisms underlying HG and PM-induced endothelial inflammation in vitro and in vivo. HG and PM treatment increased mitochondrial ROS, mitochondrial fission, and mitophagy in ECs, whereas NCur reversed these conditions. In addition, miR-221/222 plays a role in the amelioration of endothelial inflammation through targeting Bnip3 and ICAM-1, and NCur pretreatment can modulate miR-221/222 levels. Therefore, NCur may be a promising approach to intervene in diabetes and air pollution-induced CVD.

Magnesium sulfate enhances exercise performance and manipulates dynamic changes in peripheral glucose utilization.

The effect of magnesium supplementation on exercise performance remains controversial. In the present study, the effects of magnesium sulfate on exercise performance and blood glucose metabolism were examined. In order to provide a non-invasive measure of continuous exercise, we developed an auto-blood sampling system was coupled to a microdialysis analyzer to detect the dynamic changes in glucose metabolism in conscious and freely moving gerbils subjected to forced swimming. Gerbils were pretreated with saline or magnesium sulfate (90 mg kg(-1), ip) 30 min before exercise. The duration times were significantly increased by 71% in the magnesium sulfate-treated groups (p < 0.01) when compared with those in the control. Another group of gerbils were subjected to blood sampling assay. A catheter was implanted in the jugular vein of each gerbil for collecting blood samples by the computer-aided blood sampler. The basal levels of plasma glucose, lactate, and magnesium were 6,245 +/- 662, 1,067 +/- 309, and 590 +/- 50 microM, respectively, with no significant difference between groups. Plasma glucose, lactate, and magnesium levels increased to 134 and 204%, 369 and 220%, and 155 and 422% of basal levels during swimming in both the control and magnesium sulfate-treated groups, respectively (p < 0.05). Pretreatment with magnesium sulfate elevated glucose and magnesium levels to 175 and 302% of the basal levels (p < 0.05), respectively, whereas pretreatment with magnesium sulfate reduced the lactate levels 150% of the basal level (p < 0.05) during swimming. Furthermore, the magnesium levels increased to about 152-422% of basal levels during forced swimming and the recovery period (p < 0.05). The present study demonstrates that magnesium sulfate improved the duration time of forced swimming exercise. In addition, magnesium raised glucose levels and attenuated lactate levels during forced swimming. These results indicate that positive effects of magnesium supplementation may contribute to the enhancement of exercise performance in athletes.

Effects of magnesium on exercise performance and plasma glucose and lactate concentrations in rats using a novel blood-sampling technique.

Repeated blood sampling in rodents is often necessary and difficult. Magnesium has been touted as an agent for enhancing physical activity. An auto-blood-sampling device coupled with a microdialysis analyzer was developed to determine blood glucose and lactate concentrations in rats subjected to treadmill exercise. The effects of magnesium on exercise performance and blood energy metabolism were also evaluated. Sprague-Dawley rats fed a magnesium-adequate diet were randomly assigned to 2 experimental groups. Exercise performance was evaluated at 3 treadmill speeds (10, 15, and 20 m.min(-1)) with or without magnesium administration (90 mg.kg-1, intraperitoneal) in the first experiment. In the other experiment, each rat was fitted with a catheter in the jugular vein for collection of blood samples during the treadmill exercise at a speed of 20 m.min(-1). Exercise performance was significantly higher at the lower speed of 10 m.min(-1) in the control group. In addition, exercise performance was significantly enhanced only at 20 m.min(-1) in the magnesium-sulfate-treated group when compared with the control group. Blood samples were collected every 15 min. Glucose concentrations increased significantly and then declined immediately after completion of the exercise task at 20 m.min-1 in both groups. However, glucose concentrations increased immediately after administration of magnesium and increased further during exercise when compared with those of the control group. Findings from a repeated blood-sampling assay suggest that increased blood glucose contributes to enhanced exercise performance by rats injected intraperitoneally with magnesium.