Abstract
BACKGROUND/AIM: Tacrolimus (TAC), a cornerstone immunosuppressant in solid organ transplantation, is associated with significant cardiovascular toxicities, including endothelial dysfunction and inflammation. Silymarin (SM), a natural flavonoid complex from milk thistle, possesses known antioxidant and anti-inflammatory properties. This study investigated the pro-inflammatory effects of TAC on human umbilical vein endothelial cells (HUVECs) and evaluated the potential protective capacity of SM. This study aimed to investigate the inflammatory response induced by TAC in HUVECs and to determine whether co-treatment with SM can ameliorate TAC-induced inflammation. MATERIALS AND METHODS: HUVECs were cultured and treated with TAC (20 μg/ml) for varying durations (6, 24, 48, 72 h) under different culture conditions (1% or 2% FBS pre-starvation) to optimize the inflammatory response model. Lipopolysaccharide (LPS) served as a positive control. The optimized condition involved pre-starvation in 2% FBS medium followed by a 6-h induction. In the key experiment, HUVECs were treated with vehicle, TAC (20 μg/ml), or TAC (20 μg/ml) plus SM (50 μg/ml) for 6 h. The expression levels of pro-inflammatory mediators interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) were assessed using western blotting. RESULTS: TAC (20 μg/ml) significantly induced the expression of IL-1β, TNF-α, and COX-2 in HUVECs, particularly after 6 h of induction following pre-starvation in 2% FBS medium. Co-treatment with SM (50 μg/ml) markedly suppressed the TAC-induced up-regulation of all three inflammatory markers (IL-1β, TNF-α, and COX-2) compared to treatment with TAC alone. CONCLUSION: TAC directly promotes an inflammatory phenotype in HUVECs. SM effectively counteracts this TAC-induced endothelial inflammation in vitro. These findings suggest that silymarin, potentially through its antioxidant and NF-κB inhibitory actions, could be explored as a therapeutic agent to mitigate the vascular inflammation and endothelial dysfunction associated with TAC treatment in transplant recipients, potentially reducing cardiovascular complications.