Levocarnitine inhibits tumor necrosis factor alpha-induced vascular cell adhesion molecule 1 expression

Abstract Background Carnitine is an essential substance for energy metabolism, mainly responsible for intracellular fatty acid transport. Patients undergoing hemodialysis (HD) are prone to carnitine deficiency owing to the removal of carnitine during HD and dietary restrictions. Various diseases caused by carnitine deficiency are treated with biologically active levocarnitine (LC) administration. Vascular cell adhesion molecule 1 (VCAM-1) is an important marker associated with cardiovascular disease, vascular access failure (VAF), and prognosis of patients undergoing HD. While acetyl- l -carnitine inhibits cell adhesion molecules, there are almost no reports that LC inhibits VCAM-1. This study aimed to investigate the inhibitory effect of LC on tumor necrosis factor alpha (TNF-α)-induced VCAM-1. Methods Human umbilical vein endothelial cells were cultured in a medium containing TNF-α and LC for 6 and 24 h, and soluble VCAM-1 (sVCAM-1) in the culture supernatant was measured by enzyme-linked immunosorbent assay. We also measured the expression levels of intracellular reactive oxygen species (ROS), nuclear, and cytoplasmic nuclear factor kappa B (NF-κB/p65) to clarify the site of LC inhibition. NF-κB/p65 translocation into the nucleus was evaluated in intranuclear concentration and the ratio of intranuclear to total NF-κB/p65. Results Cotreatment with LC and TNF-α significantly suppressed sVCAM-1 expression, nuclear NF-κB/p65, and NF-κB/p65 ratio in response to TNF-α-induced inflammation. However, intracellular ROS was not significantly induced by TNF-α. Conclusions LC suppresses TNF-α-induced sVCAM-1 by inhibiting NF-κB/p65 nuclear translocation. LC may reduce the risk of vascular complications and VAF in patients undergoing HD.